Research ArticleDevelopment of Corn Starch-Neusilin UFL2Conjugate as Tablet Superdisintegrant Formulation andEvaluation of Fast Disintegrating Tablets
Prateek Juneja1 Birender Kaur1 Oluwatoyin A Odeku2 and Inderbir Singh1
1 Chitkara College of Pharmacy Chitkara University Chandigarh-Patiala National Highway Rajpura Patiala Punjab 140401 India2Department of Pharmaceutics amp Industrial Pharmacy Faculty of Pharmacy University of Ibadan Ibadan 200005 Nigeria
Correspondence should be addressed to Inderbir Singh inderbirsingh2906gmailcom
Received 3 May 2014 Revised 2 September 2014 Accepted 2 September 2014 Published 23 September 2014
Academic Editor Ali Nokhodchi
Copyright copy 2014 Prateek Juneja et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited
In the present study corn Starch-Neusilin UFL2 conjugates were prepared by physical chemical and microwave methods withthe aim of using the conjugates as tablet superdisintegrant Various powder tests namely angle of repose bulk density tappeddensity Hausnerrsquos ratio Carrrsquos index swelling index and powder porosity were conducted on the samples The conjugates werecharacterized by ATR-FTIR XRD DSC and SEM techniques Heckel and Kawakita models were applied to carry out compressionstudies for the prepared conjugates Fast disintegrating tablets of domperidone were prepared using corn starch and corn Starch-Neusilin UFL2 conjugates as tablet superdisintegrants in different concentrations Conjugates were found to possess good powderflow and tabletting properties Heckel analysis indicated that the conjugates prepared by microwave method showed the slowestonset of plastic deformation while Kawakita analysis indicated that the conjugates prepared by microwave method exhibited thehighest amount of total plastic deformation The study revealed that the corn Starch-Neusilin UFL2 conjugates possess improvedpowder flow properties and could be a promising superdisintegrant for preparing fast disintegrating tablet Also the resultssugessted that the microwave method was found to be most effective for the preparation of corn Starch-Neusilin UFL2 conjugates
1 Introduction
Amongst innumerable applications starch and its derivativesare one of the most widely used excipients in the pharma-ceutical industry as they are incorporated in the manufactureof assorted dosage forms due to their biodegradability andbiocompatibility Starches have become a valuable ingredientbecause of their inertness abundance and cost effectivenessin the food industry where they are used as thickenersbulking water retention and gelling agents in the pharma-ceutical industry where they are used as fillers binders anddisintegrants in tablet formulations Commercially starchesare obtained from a variety of cereals (corn waxy corn highamylose corn wheat and various rice varieties) and fromthe tubers and roots (predominantly potato and cassava) Inthe pharmaceutical formulations starch can be used bothas a disintegrant and as a binder depending on the explicitattributes crucial for the formulation As a disintegrant
the mechanism of action of starch includes wicking theimbibitions of water into the tabletmatrix via capillary actionThe concentration of starch used is crucial if it is below theoptimum concentration then there are insufficient channelsfor capillary action and if it is above the optimum concentra-tion then it is difficult to compress the compacts Generallystarch can be used at a concentration range of 2ndash10 wwAs a binding agent in tablet formulations starch is heated insolution enhancing its conversion into a paste before additionto the formula powder blend [1 2] Disintegrants are essentialcomponents of tablet formulations since tablet disintegrationis a prerequisite for dissolution of the active drug fromthe tablet Starch is one of the earliest known disintegrantsalthough in recent times super disintegrants such as sodiumstarch glycolate and croscarmellose sodium offer significantimprovements over the native starches Physical and chemicalmodifications have been used to improve the compactionproperties of some native starches and have yielded starches
Hindawi Publishing CorporationJournal of Drug DeliveryVolume 2014 Article ID 827035 13 pageshttpdxdoiorg1011552014827035
2 Journal of Drug Delivery
with better disintegration properties and some have beenfound to be useful for sustained release dosage forms [3ndash5]Rashid et al [1] developed a directly compressible excipientby coprocessing starch with magnesium silicate which wasachieved either by coprecipitation of magnesium silicate ontodifferent types of starch or by dry granulation of maizestarch with magnesium silicate Magnesium silicate as anantiadhering agent increased the permeability of both maizeand partially pregelatinized starch resulting in compacts ofhigh mechanical strength short disintegration time and lowlubricant sensitivity Formulation with this novel excipientsystem using paracetamol as a model drug indicated itssuitability as a single multifunctional excipient Staroszczyk[6] performed silication of potato starch bymicrowave irradi-ation It was reported thatwhile increasing the silicating agentcross-linking of starchwas increased and silicated starches arethermally more stable A number of modification techniquesnamely physical chemical enzymatic and genetic have beenreported with an aim to enhance the positive attributes andeliminate short coming of the native starches [7]
In recent times advancement in budding new excipientswith multifunctional capabilities (as glidants fillers bindersand disintegrants) has exploited the use of silicates producedsynthetically Silication of excipients resulted in improvementin various properties of the materials namely mechani-cal strength compressibility disintegration and sensitivitytowards lubrication Thus silicatestarch preparations havethe potential to fulfil the requirements of a multifunctionalexcipient In this context the physical properties of compactsproduced (disintegration time tensile strength and powdercompressibility) and sensitivity towards lubrication need tobe investigated On this basis the current study reports theapplication of silicates as an effective tabletting aid when usedwith corn starch [8 9]
Neusilin is a synthetic amorphous form of magnesiumaluminometasilicate which can be used as a multifunctionalexcipient in both direct compression and wet granulationof solid dosage forms Neusilin is widely used in improvingthe quality of tablets (in the terms of its compaction anddisintegration properties) powders granules and capsulesIt does not develop gels with aqueous solutions unlikeother magnesium aluminium silicates The different gradesof Neusilin available are alkaline (FH1 FH2 FL1 FL2 S1 S2and SG2) and neutral (US2 UFL2 NFL2N and NS2N) [10]
The aim of the present study is to evaluate the effi-ciency of a new conjugate of corn starch and Neusilin assuper disintegrating agent in the tablets The corn Starch-Neusilin UFL2 conjugates were prepared by three differentmethods namely physical chemical and microwave andwere used as a superdisintegrant in domperidone tabletformulation and the tablet properties were compared with astandard marketed fast disintegrating tablet Domperidone(C22H24ClN5O2 MW-42591) poorly water-soluble drug
[11] is a potent antidopaminergic drug used orally andintravenously for suppressing nausea and vomiting An adultdose of 10mg domperidone has a modest activity withoutextrapyramidal side effects as it crosses blood brain barrierpoorly Domperidone is absorbed orally and its metabolites
are completely biotransformed and excreted in urineThedis-solution rate and bioavailability of a poorly soluble drug fromsolid dosage formdependmuch on formulation additives andformulation characteristics
2 Materials and Methods
Commercial corn starchwas supplied by IPHZAPharmaceu-ticals Patiala Punjab India Neusilin UFL2 (Fuji ChemicalsJapan) was supplied as gift sample by Gangwal ChemicalsMumbai India Domperidone was gifted by Dr ReddyrsquosLaboratories Baddi (HP) India NaOH was procured fromMerck Specialities Pvt LtdMumbai India All reagents usedwere of analytical grade
21 Preparation of Corn Starch-Neusilin UFL2 ConjugatesThree methods were used in the formulation of the cornStarch-Neusilin UFL2 conjugate physical chemical andmicrowave methods The physical method involved simplemixing of corn starch and Neusilin UFL2 in the ratio 1 1To ensure proper mixing tumbling method was used andthe weighed starch and Neusilin were transferred into abeaker and the mouth of the beaker was closed ensuringthat there is no spillage of the contents from the beakerwhile the mixing is carried out The mixing was carriedout for 15 minutes In chemical method corn starch andNeusilin UFL2 were incorporated in the ratio 1 1 Cornstarch was suspended in distilled water (qs) and kept onmagnetic stirrer at 270 rpm and temperature not more than40∘C To this solution of Neusilin UFL2 in NaOH (qs) wasgradually added with constant stirring After 15ndash20 minutesthe precipitated conjugate was filtered using Whatman filterpaper (GE Healthcare UK Limited) having a pore size of125mm and dried in oven at a temperature not more than 50plusmn 2∘C In microwave method physical mixture of corn starchand Neusilin UFL2 was subjected to microwave radiation at590 watt for not more than 5 minutes
22 Formulation of Fast Disintegration Tablets Fast disin-tegrating tablets of domperidone (10mg) were formulatedby direct compression method using corn starch and thecorn Starch-Neusilin UFL2 conjugates as superdisintegrantaccording to the formulae given in Table 1 The specifiedquantity of the drug diluent and corn starch or corn Starch-Neusilin UFL2 conjugates were weighed accurately passedthrough 60 mesh sieves (250 120583mopening size) and mixed bytumbling method for 15 to 20min (contents were transferredinto a beaker and the mouth of the beaker was closedensuring that there is no spillage of the contents from thebeaker while mixing is carried out)The blend was lubricatedwith talc and magnesium stearate and mixing was done foradditional 5 minutes and the resulting powder mixture wascompressed into tablets usingmultipunch tablettingmachine(AK Industries Nakodar Punjab India) using 675mmbiconcave round die-punches The compression force wasadjusted to give tablet hardness in the pharmacopoeial rangeof fast disintegrating tablets (3ndash5 kgcm2) For each batch 200tablets were formulated
231 Angle of Repose (120579∘) The angle of repose of powder
blends was determined by the funnel method Accuratelyweighed powder blends were taken in a funnel The heightof the funnel was adjusted in such a way that the tip of thefunnel just touched the apex of the heap of the powder blends(2 cm) The powder blends were allowed to flow through thefunnel freely onto its surface The diameter of the powdercone was measured and angle of repose was calculated [12]Three determinations were performed
232 Bulk Density and Tapped Density Both loose bulk den-sity (LBD) and tapped bulk density (TBD) were determinedA quantity of 1 gm of powder was introduced into a 10mLmeasuring cylinder After the initial volume was determinedthe cylinder was tapped onto a hard surface from the heightof 25 cm at 2 seconds intervals Tapping was continued untilno further change in volume was noted The LBD and TBDwere calculated [12] The determination was carried out intriplicate
233 Compressibility Index and Hausner Ratio The com-pressibility index of the powder blends was determined byCarrrsquos compressibility index or Carrrsquos index (CI) Hausnerratio (HR) was also determined for each powder blend [12]
234 Swelling Index Initial bulk volume of the powderwas evaluated using 100mL stoppered graduated cylinderWater was added in sufficient quantity to produce uniformdispersion The sediment volume of the swollen mass was
measured after 24 hours The swelling index was calculatedas
Swelling index = (1198812minus
1198811
1198811
) lowast 100 (1)
where1198811and119881
2are initial volumes of the powder before and
after hydration respectively
235 pH Dispersion (1wv) of the sample was prepared indistilled water and the pHwas determined individually usingdigital pH meter at 37 plusmn 2∘C
236 Loss on Drying Loss on drying (LOD) is used todetermine the levels of moisture or solvents present in thesample The sample was weighed (119882
1) and heated in an
oven at 100 plusmn 5∘C for 2 hrs Sample was cooled in the dryatmosphere of a desiccator and then reweighed (119882
) Effective pore radiusof the powder was determined using method reported byGoel et al [13] A micropipette tip (2mL transparent) wascompletely filled with powder and weighed (119882
119894) Then 119899-
hexane (surface tension (120574) is 184mNm) was poured dropwise on bed top till the solvent filtered out at the bottom of
4 Journal of Drug Delivery
the tip The tip was reweighed (119882119891) and effective pore radius
was calculated by
119877effP = 119882119891minus
119882119894
2120587120574
(3)
24 Attenuated Total Reflectance-Fourier Transform IR Spec-troscopy (ATR-FTIR) The infrared (IR) spectra of sam-ples were obtained using an Attenuated Total Reflectance-Fourier Transform Infra-Red (ATR-FTIR) spectrophotome-ter (Alpha Bruker Japan) The samples were scanned inthe spectral region of 4000 cmminus1 to 400 cmminus1 by KBr pelletmethod
25 X-Ray Powder Diffraction (XRPD) The X-ray powderdiffractograms were registered in an X-Pert Pro (USA) inBragg-Brentano geometry using glass tubing with a Cuanode and graphite monochromator The diffractometer wasoperated at 40mA and 40 kV All the samples being a sizeof less than 250 120583m were randomly placed on a glass sliderespectively The signals of the reflection angle of 2120579 wererecorded from 0∘ to 60∘ at a scanning rate 021∘sec
26 Scanning Electron Microscopy (SEM) The scanning elec-tron micrographs were taken to study the surface morphol-ogy using a Hitachi (Model S 4300 SEN SEM Hitachi HighTechnologies Singapore) at an accelerator potential of 10 kVThe samples were stuck on a specimen holder using a silverplate and then coatedwith palladium in a vacuum evaporator
27 Differential Scanning Calorimetry (DSC) The thermaltransitions of starch samples were investigated with the useof a Perkin Elmer DSC 8000 apparatus (USA) calibrated byusing a high purity indium standard Samples about 10mgwere hermetically sealed in flat bottomed aluminium pansand heated in an atmosphere of nitrogen to eliminate theoxidative and pyrolytic effects The heating rate was 5∘Cminin a temperature range of 25ndash300∘C The DSC thermogramswere recorded
28 Compression Study The two well-known compressionmodels The Heckel andThe Kawakita were used to carry outthe studies [14]
281 Determination of Precompression Density The bulkdensity of each sample at zero pressure was determined bypouring the granules through a funnel into a glass measuringcylinder with a 24mm diameter and a volume of 50mL atan angle of 45∘ Determinations were done in triplicate Therelative density 119863
0 of each formulation was obtained from
the ratio of its bulk density to its particle density [15]
282 Preparation of Tablets for Compression Studies Tablets(400mg) were prepared by compressing the prepared conju-gates for 30 seconds with predetermined loads on a hydraulicpress (Model CAP15T-1233 PCI Analytics Pvt Ltd MumbaiIndia) After ejection the tablets were stored over silica gel
for 24 hours Their masses (119898) and dimensions were thendetermined respectively and their relative densities (119877) werecalculated using the equation
119877 =119898
119881119905120588119904
(4)
where119881119905is the volume (cm3) of the tablet and 120588
119904is the particle
density (gcm3) of the solid material [15]
283 The Heckel Function The deformation mechanism ofthe material was determined using the Heckel model asit is widely used for relating the relative density 119863 of apowder bed during compression to the applied pressure 119875The displacement and force data registered on the simulatorwere transferred to a spreadsheet program (Microsoft Excel2007) The force values were converted into pressures andthe displacement values (in combination with the individualtablet weight determined immediately after compaction)and the true density of the material (determined beforecompaction) were used to calculate the apparent densityof the powder bed 1(1 minus 119863) Using the Heckel plot thecompression stage was subjected to linear regression analysisIt is denoted as
ln [1
(1 minus 119863)
] = 119870119875 + 119860 (5)
The slope of the straight line portion 119870 is the reciprocalof the mean yield pressure 119875
119910 of the material From the
intercept 119860 the relative density 119863119860 can be calculated using
the following equation
119863119860= 1 minus 119890
minus119860 (6)
Relative density of the powder at the point when the appliedpressure equals zero 119863
0 is used to describe the initial
rearrangement phase of densification as a result of die filling
119863119861= 119863119860minus 1198630 (7)
Relative density 119863119861 describes the phase of rearrangement
at low pressures and is the difference between 119863119860
and1198630[15 16]
284 The Kawakita Function In the Kawakita equation theparticle density is not introduced in the calculations since themodel operates on the relative change in volume which givesthe same result whether the relative or the absolute volumeis used The problem in calculation of this equation is to findthe correct initial volume 119881
0 The Kawakita equation is used
to study powder compression using the degree of volumereduction (119862) and is written as
119862 =
(1198810minus 119881119901)
1198810
=119886119887119875
(1 + 119887119875)
(8)
The equation in practice can be rearranged to give
119875
119862
=119875
119886
+1
119886119887
(9)
Journal of Drug Delivery 5
where 1198810is the initial bulk volume of the powder and 119881
119901is
the bulk volume after compression Constant ldquo119886rdquo is equal tothe minimum porosity of the material before compressionwhile constant ldquo119887rdquo is related to the plasticity of the materialThe reciprocal of ldquo119887rdquo gives the pressure term 119875
119896 which is the
pressure required to reduce the powder bed by 50 [14 15]
29 Postcompression Evaluation
291 Diameter and Thickness A calibrated vernier calliper(Ms Mitutoyo Corp Japan) was used for diameter andthickness evaluation of tablets
292 Hardness The tablet hardness is the force required tobreak a tablet in a diametric compression force Hardnesstester (Perfit India) was used to determine the force requiredto break the tablet diametrically The test was performed onsix tablets and the average was calculated
293 Friability Thefriability (119865) of a sample of 20 tabletswasmeasured using Roche Friabilator (Model 902 EI PanchkulaIndia) Twenty tablets were weighed and rotated at 25 rpm for4min Tablets were reweighed after removal of fines (dusted)and the percentage of weight loss was calculated Friabilitybelow 1 was considered acceptable
294 Weight Variation Test Weight variation test was doneby weighing 20 tablets individually calculating the averageweight and comparing the individual tablet weight to theaverage weight
295 Content Uniformity The content uniformity wasassessed according to USP method Ten tablets were pulver-ized and quantity of powder equivalent to 10mg of domperi-done was shaken with 100mL of 01 N HCl for 30 minutesThe contents were filtered through a 045120583mmembrane filterdiluted and analyzed at 284 nmusing aUVVIS double beamspectrophotometer (Model 2202 Systronics AhmedabadIndia) [17]
296 Wetting Time A piece of tissue paper (1075 times 12mm)folded twice was placed in a culture dish (119889 = 65 cm)containing 6mL of water (containing a water soluble dyeeosin) A tablet was carefully placed on the surface of tissuepaper and the time required for water to reach the uppersurface of the tablet was noted as the wetting time [18]
297 Water Absorption Ratio The same procedure used forthe wetting time was used for the water absorption ratioInitial weight of the tablet (119882
119886) was measured before its
placement on the wet tissue and the final weight (119882119887) was
taken after complete wetting Water absorption ratio 119877 wasdetermined using the equation [19]
119877 = 100
(119882119887minus 119882119886)
119882119887
(10)
298 Porosity Porosity is a measure of the void spaces in amaterial and is a fraction of the volume of voids over the totalvolume between 0 and 1 or as a percentage between 0 and 100percent The porosity of the tablets was calculated as follows
Porosity =1 minus 119898
120588truelowast 119881 (11)
where 120588true is the true density of the mixture and 119898 and 119881
are the weight and volume of the tablet respectively Thetrue density of the powder was found using true densitymeter (SMART PYCNO 30 Smart Instruments Maharash-tra India)
299 Tablet Packing Fraction (119875119891) The tablet packing
fraction 119875119891 is a measure of the degree of consolida-
tioncompactness of the tablet Tablet packing fraction wasdetermined by the equation
Packing fraction (119875119891) =
119908
1205871199032119905120588
(12)
where119908 is the weight of a tablet 119903 is radius 119905 is thickness and120588 is the particle density
The radius and thickness of 10 tablets were measuredusing a vernier calliper The apparent particle density of thedrug powder was determined using liquid paraffin displace-ment method Firstly the weight of a specific gravity bottlefilledwith liquid paraffin and theweight of the specific gravitybottle containing a sample of the drug powder were notedThe final weight was determined The determination wasexecuted in triplicate and mean results were used in thecalculation of 119875
119891[20]
2910 In Vitro Disintegration Time In vitro disintegrationtime for the tablets was determined using USP disintegrationapparatus (EI Product Panchkula India) using 01 NHCl (pH1-2 900mL at 37∘C) as the disintegrating medium
2911 In Vitro Dissolution Studies In vitro dissolution ofthe fast disintegrating tablets was studied in USP XXIVdissolution apparatus II (DS 8000 Lab India Pune India)employing a paddle stirrer at 50 rpm using 900mL of pH12 01 N HCl at 37 plusmn 05∘C as a dissolution mediumAliquots of 5mL eachwere withdrawn at predetermined timeintervals and replaced with equal volume of fresh mediumAliquots were filtered through a 045120583m membrane filterand analyzed for drug content using a UVVIS double beamspectrophotometer (2202 Systronics Ahmedabad India) at284 nm Drug concentration was calculated and expressed ascumulative percent of the drug releasedThe similarity factor(1198912) is a logarithmic transformation of the sum-squared
error of differences between the test (119879119895) and reference
(119877119895) products over all time points It is a useful tool for
comparison of dissolution profiles when more than three orfour dissolution time points are available It is calculated as
(119882119895) is an optional weight factor The similarity factor fits
result between 0 and 100 It is 100 when the test and referenceprofiles are identical and tends to be 0 as the dissimilarityincreases In order to consider similar dissolution profiles 119891
2
values should be close to 100
3 Result and Discussion
31 Precompression Evaluation
311 Micromeritics Study The result of the micromeriticstudies for corn starch and the prepared corn Starch-NeusilinUFL2 conjugates were conducted and results are listed inTable 2 Angle of repose (120579∘) is a characteristic of the internalfriction or cohesion of the particles Its value will be highif the powder is cohesive and low if the powder is non-cohesive Flow property of the corn starch was improvedby the addition of Neusilin UFL2 as compared formulationswith conjugates showed good to excellent flow properties asindicated by the values of angle of repose (3669ndash2767∘) to thecorn starch (4325∘) Carrrsquos index showed values 225 to 125denoting that these formulations were of acceptable to goodflowability compared to the corn starch (3428) Hausnerrsquosratio showed that powders with low interparticle frictionhad ratios of approximately 129 to 114 indicating good flowproperties as compared to the corn starch (152) Swellingindex of the conjugates prepared by physical chemical andmicrowave method were found to be 40 65 and 95respectively which was far better than the swelling index ofcorn starch that is 18 which is in context with the effectivepore radius of the conjugates and corn starch The resultsof both swelling and effective pore radius point towardsmore wicking action capability and hence disintegrationpotential of the conjugates over the pure corn starch Theresult of micromeritic study indicates that conjugates pre-pared by microwave method were the most effective methodfollowed by chemical and physical method as they gave bettermicromeritic properties as evidenced from the Table 2
312 ATR-FTIR Analysis Corn starch and Neusilin UFL2interactions studies were carried out using ATR-FTIR spec-trophotometer and the spectra for the samples are shownin Figure 1 The IR spectra of corn starch showed a peakat 3434 cmminus1 and 2931 cmminus1 representing OndashH and CndashHstretching respectively The absorption band at 1652 cmminus1is due to absorbed water in amorphous region of starchPeak at 1241 cmminus1 represents CH
2OH group whereas peak
at 1159 cmminus1 represents coupling mode of CndashC and CndashOstretching vibrations The band at 1080 cmminus1 represents CndashOndashH bending vibration whereas peak at 929 cmminus1 could beascribed to the skeletal mode vibration of 120572-14-glycosidiclinkage The corn Starch-Neusilin UFL2 conjugates preparedby different methods namely physical microwave andchemical exhibit a sharp peak near 3480 cmminus1 which isotherwise observed at 3434 cmminus1 in the pure corn starchThisshift and sharpening of peak indicate the formation of SindashOndashC bridging bond between corn starch and Neusilin UFL2Moreover reduction in the intensity of peak at 1241 cmminus1
4000 3000 2000 1500 1000 400
(cmminus1)
T(
)
(A)
(B)
(C)
(D)
Figure 1 IR spectra of (A) native corn starch corn Starch-NeusilinUFL2 conjugates by (B) physical method (C) chemical method and(D) microwave method
1159 cmminus1 and 1080 cmminus1 confirms intermolecular bridgingbetween corn starch and Neusilin UFL2 Thus the additionof Neusilin changed the properties of corn starch forming anew excipient with different functional properties
313 XRD Analysis The XRD patterns of the samples areshown in Figure 2 The structure of corn starch is char-acterized by the presence of broad peak at 2456∘2120579 angleAppearance of sharp peak at 2740∘2120579 3172∘2120579 4560∘21205795391∘2120579 and 5647∘2120579 angles respectively in case of conju-gates prepared bymicrowavemethod gives clear indication ofreduction in amorphous nature or otherwise increase in thecrystalline behavior of the corn starch that could be correlatedwith the increase in swelling and hence superdisintegrantpotential of conjugates prepared by different methods Crys-tallinity and hence the superdisintegrant property (Table 4)of conjugates prepared by different methods were in therank order of microwave gt chemical gt physical mixtureHigh proportion of longer chains might form more stablecrystallites in the pure corn starch The swelling powerof corn starch depends on the water holding capacity ofthe starch molecule by hydrogen bonding Hence higherdegree of intermolecular bonding between corn starch andNeusilin UFL2 favors the long chain crystalline structureand hence the swelling of the conjugates which in turnpotentiates the use of corn Starch-Neusilin UFL2 as a tabletsuperdisintegrant [21]
314 DSC Analysis Figure 3 shows the DSC thermogramsof the pure corn starch and corn Starch-Neusilin UFL2conjugates prepared by physical chemical and microwavemethods Corn starch has a discrete structure and pos-sesses partially crystalline microscopic granules that are
Figure 2 XRD pattern of (A) native corn starch corn Starch-Neusilin UFL2 conjugates by (B) physical method (C) chemicalmethod and (D) microwave method
held together by intended micellar network of associatedmolecules so it does not show obvious Tg or Tm untilpyrogenation Melting range was found to be extended andbroadened with the incorporation of Neusilin UFL2 Broad-ening and shifting of the melting range in the DSC spectracould be attributed to intermolecular bonding between cornstarch and Neusilin UFL2 indicating that the Neusilin UFL2molecules were restrained by the corn starch molecules Thebroadening of themelting range could be due to the regularityof the OH group that already existed in corn starch whichhad disappeared by the interaction with Neusilin UFL2 TheTm and ΔH of the melting peak are significantly lower inthe pure corn starch than the conjugates which indicate thatthere is an interaction between corn starch and NeusilinUFL2 which has enhanced the crystallization of the purecorn starch This increase in crystalline behaviour of thepure corn starch could be correlated to increase in swelling
40 50 60 70 80 90 100 110 120 130 140
Temperature (∘C)
(A)
(B)
(C)(D)
Figure 3 DSC pattern of (A) native corn starch corn Starch-Neusilin UFL2 conjugates by (B) physical method (C) chemicalmethod and (D) microwave method
and hence superdisintegrant potential of conjugates preparedby different methods Crystallinity and superdisintegrantbehaviour of conjugates prepared by different methods couldbe arranged as microwave gt chemical gt physical mixtureFurthermore the crystalline structure contributes towardsthe swelling behaviour of the conjugates responsible for thetablet superdisintegrant activity
315 SEM Analysis Surface morphology of the corn starchand corn Starch-Neusilin UFL2 conjugates was studied bySEManalysis as shown in Figure 4The corn starch undergoesa change in its native structure from thin smooth flatsurface structure with folded edges to three dimensionalcompacts upon conjugation with the Neusilin UFL2 SEMmicrograph of the prepared conjugates showed the presenceof interparticulate voids and channels that are responsible forthe increase in water absorption and swelling capacity of theconjugates as compared to the pure corn starch Furthermorethese voidschannels contributed to the wicking behaviorresponsible for the tablet superdisintegrant property of thecorn Starch-Neusilin UFL2 conjugates Conjugates preparedbymicrowavemethod illustrated the presence ofmore porous
8 Journal of Drug Delivery
structure as compared to conjugates prepared by physicaland chemical methods The results are in line with the betterin vitro disintegration performance of FDT prepared withconjugates of microwave method compared to the other twomethods
316 Heckel FunctionAnalysis Figure 5 shows representativeHeckel plots for the conjugates prepared by physical chem-ical and microwave methods The Heckel plots showed aninitial linear portion with an increase slope at pressure of100MPa followed by another linear region for the conjugatesprepared by physical and chemical methods while for theconjugate prepared by microwave method the second linearregion was from 175MPaThe mean yield pressure values forthe conjugates were calculated from the slope of the portionshowing the highest linearity of the Heckel plots and theintercept 119860 was determined from the extrapolation of theregionThe values of119863
119860and119863
119861were calculated respectively
The values of 119875119910 1198630 119863119860 and 119863
119861for the formulations are
presented in Table 3 The value of 1198630which represents the
degree of initial packing in the die as a result of die fillingfor the conjugates indicates that the conjugates preparedby microwave method exhibited highest degree of packingin the die as a result of die filling while the conjugatesprepared by physical method exhibited the lowest valuesThevalue of 119863
119861represents the phase of rearrangement of the
particles in the early stages of compression119863119861values tend to
indicate the extent of fragmentation of particles or granulesalthough fragmentation can occur concurrently with plasticand elastic deformation of constituent particles The chemi-cally prepared conjugates exhibited the highest values whilethe one prepared by microwave method exhibited the lowestvalues This indicates that fragmentation occurs more withthe chemically prepared conjugates [22 23]The values of119863
119860
which represents the total degree of packing achieved at zeroand low pressures was also in the rank order of microwave gtchemical gt physical for the methods to prepare conjugatesThis indicates that the conjugates prepared by microwavemethod showed higher degree of packing at low pressuresThe mean yield pressure 119875
119910is inversely related to the ability
of the formulations to deform plastically under pressureThe result indicates that the conjugates prepared by physicalmethod showed the fastest onset of plastic deformation whilethe conjugates prepared by microwave method showed theslowest onset Materials with high yield pressure are classifiedas brittle or fragmenting materials whereas those with lowervalues are classified as plasticallyelastically deforming mate-rials [24] Generally during compression plastic deformationand fragmentation are known to occur concurrently Starcheshave been known to deform plastically under compressionpressure
317 Kawakita Function Analysis TheKawakita plots for theconjugates are presented in Figure 6 A linear relationshipwas obtained at all compression pressures employed withcorrelation coefficient of 0999 for the conjugates preparedby different methods The values of 119886 and 119886119887 were obtainedfrom the slope and intercept respectivelyThe value of (1minus119886)
gives the initial relative density of the starch 119863119868 while 119875
119896
values were obtained from the reciprocal of values of 119887The values of 119863
119868and 119875
119896are shown in Table 3 The value
of 119863119868is a measure of the packed initial relative density of
the formulation with the application of small pressure ortapping The ranking of 119863
119868for the conjugates was chemical
method gt microwave method gt physical method The valueof 119875119896which is an inverse measure of the amount of plastic
deformation occurring during the compression process wasfound to be maximum for tablets formulated using conju-gates prepared by chemical method followed by microwavemethod and physical method [23]Thus conjugates preparedby microwave method exhibited the highest amount of totalplastic deformation while conjugates prepared by physicalmethod exhibited the lowest values The ranking was seen tobe in the reverse order as that of the 119875
119910values It has been
shown that while119875119910relates to the onset of plastic deformation
during compression the 119875119896relates to the amount of plastic
deformation that occurs during the compression processThus the conjugates prepared by physical method showedthe slowest onset of plastic deformation but the highest totalamount of plastic deformation
32 Postcompression Evaluation Tablets require certainamount of strength and resistance to friability to withstandmechanical shock of handling during manufacturingshipping and packaging Hardness of the tablets formulatedusing the corn starch-Neusilin UFL2 conjugates assuperdisintegrant was found to vary from 43 to 35 kgcm2compared to 315 to 309 kgcm2 of tablets formulatedusing the native corn starch Percentage friability of allformulations was less than 1 indicating good mechanicalcharacteristics Wetting time was observed to be decreasedfrom 68 seconds for the tablets incorporating native cornstarch to 33 22 and 14 seconds for the tablets incorporatingconjugates prepared by physical chemical and microwavemethods Disintegration time was also observed to decreasefrom 83 seconds for the tablets incorporating native cornstarch to 40 35 and 22 seconds for the tablets incorporatingconjugates prepared by physical chemical and microwavemethods respectively Water absorption ratio was found tobe inversely proportional to the wetting and disintegratingtime of the tablets The increase in water absorption ratioand decrease in wetting and disintegration times in allformulations may be attributed to the modification of thecorn starch by Neusilin UFL2 to yield a novel conjugatewhich acts as superdisintegrant which absorbs water andswells causing rupture of the tablets Tablet propertiessuch as mechanical strength tablet packing fraction anddisintegration are in turn affected by the porosity [25]Tablets with low packing fraction have high porosity andpores facilitates the penetration of dissolution media intothe tablet leading to disintegration of the tablet Whereashigher tablet packing fraction leads to reduction in porositywhich inhibits the penetration of dissolution media resultingin slower disintegration rate of the tablet [26] Tabletpacking fraction was found to be decreased in the tabletsincorporating conjugates (063ndash041) compared to the tablets
Journal of Drug Delivery 9
(a) (b)
(c) (d)
Figure 4 SEM photomicrographs of (A) corn starch and corn Starch-Neusilin UFL2 conjugates prepared by (B) physical method (C)chemical method and (D) microwave method
Table 3 Parameters derived from the Heckel and Kawakita plots for tablet incorporating corn Starch-Neusilin UFL2 conjugate as asuperdisintegrant prepared by (A) physical method (B) chemical method and (C) microwave method
Figure 5 Heckel plots for the tablet incorporating corn Starch-Neusilin UFL2 conjugate as a superdisintegrant prepared by (A)physical method (B) chemical method and (C)microwavemethod
with corn starch (082) The results are in line with thepowder evaluation results where conjugates prepared byphysical chemical and microwave methods were showing
0
50
100
150
200
250
300
0 50 100 150 200 250
PC
Applied pressure (MPa)
ABC
Figure 6 Kawakita plots for the tablet incorporating corn Starch-Neusilin UFL2 conjugate as a superdisintegrant prepared by (A)physical method (B) chemical method and (C)microwavemethod
better swelling and effective pore radius compared to thenative corn starch The fast disintegration of tablets is dueto the presence of pores resulting in faster penetration of
10 Journal of Drug Delivery
Table4Differentp
ropertieso
fthe
form
ulated
FDTs
Cod
eParameter
Diameter
(mm)
Thickn
ess(mm)
Friability(
)Hardn
ess(kgcm
2 )TSlowast(M
Nm
2 )WTlowast
(Sec)
WARlowast
()
DTlowast
(Sec)
CUlowast(
)TP
Flowast119875lowast(
)1198652
F1674
plusmn003
356
plusmn003
089
plusmn004
311
plusmn010
047
plusmn015
68plusmn113
40plusmn011
73plusmn3
9899plusmn02
081
189
19F2
673
plusmn004
351
plusmn004
091
plusmn002
315
plusmn007
047
plusmn005
68plusmn12
942
plusmn011
73plusmn1
991plusmn015
082
175
24F3
674
plusmn005
355
plusmn005
089
plusmn005
309
plusmn011
047
plusmn011
67plusmn111
46plusmn009
71plusmn2
9727plusmn09
081
187
21F4
673
plusmn001
359
plusmn005
090
plusmn003
310
plusmn002
047
plusmn009
66plusmn114
46plusmn010
71plusmn3
9659plusmn05
080
194
25F5
674
plusmn001
351
plusmn005
076
plusmn004
350
plusmn011
048
plusmn005
33plusmn114
98plusmn004
48plusmn2
9650plusmn03
063
367
43F6
674
plusmn002
355
plusmn004
073
plusmn005
356
plusmn008
048
plusmn001
33plusmn16
796
plusmn004
46plusmn3
991plusmn015
062
373
43F7
674
plusmn001
355
plusmn005
071
plusmn002
370
plusmn015
056
plusmn018
32plusmn110
101plusmn
005
44plusmn1
9835plusmn02
062
373
45F8
674
plusmn003
356
plusmn003
067
plusmn003
375
plusmn021
055
plusmn008
31plusmn14
0103plusmn002
40plusmn2
9923plusmn05
062
375
47F9
673
plusmn004
355
plusmn002
055
plusmn001
400
plusmn018
060
plusmn019
23plusmn13
4108plusmn003
40plusmn6
9912
plusmn04
054
426
50F10
674
plusmn005
354
plusmn007
054
plusmn005
380
plusmn015
057
plusmn006
22plusmn12
5100plusmn002
35plusmn3
9892plusmn07
057
435
50F11
673
plusmn003
356
plusmn004
055
plusmn003
370
plusmn017
056
plusmn011
23plusmn10
5106plusmn006
36plusmn2
9727plusmn09
057
423
55F12
673
plusmn002
353
plusmn003
051
plusmn004
410
plusmn02
062
plusmn015
23plusmn13
8110
plusmn004
32plusmn7
9659plusmn05
056
426
53F13
674
plusmn003
355
plusmn004
041
plusmn007
420
plusmn027
073
plusmn008
14plusmn15
2121plusmn
008
26plusmn2
9915
plusmn01
041
582
50F14
673
plusmn001
351
plusmn004
042
plusmn002
425
plusmn02
073
plusmn020
14plusmn12
6124plusmn007
24plusmn5
9899plusmn02
039
595
52F15
674
plusmn003
355
plusmn006
044
plusmn004
430
plusmn010
076
plusmn018
13plusmn115
125plusmn003
22plusmn3
9975plusmn10
040
599
62F16
674
plusmn001
359
plusmn005
047
plusmn007
420
plusmn045
079
plusmn019
14plusmn14
0128plusmn005
22plusmn4
9912
plusmn03
041
612
64TSlowasttensiles
treng
thW
Tlowastw
ettin
gtim
eWARlowast
water
absorptio
nratio
DTlowast
disintegratio
ntim
eCUlowastcon
tent
unifo
rmity
TPFlowasttabletp
acking
fractio
n119875lowastporosity
Journal of Drug Delivery 11
the dissolution media leading to swelling and wicking of theprepared conjugate creating hydrodynamic pressure insidethe tablets hence responsible for the quick and completedisintegration of tablets indicating the superdisintegrantactivity of conjugates prepared by physical chemical andmicrowave methods over the native corn starch
The results obtained from the in vitro dissolution studyare presented in Figures 7 8 9 and 10 ldquoMKTDrdquo representsthe standard marketed domperidone formulation to whichthe formulated FDTs were compared The similarity factor(1198912) is a logarithmic transformation of the sum-squared
error of differences between test and reference productsover all time points It was observed that the three differentapproaches used for the preparation of conjugate in thisstudy namely physical chemical and microwave methodsincreased the dissolution rate of the drug compared to thetablet prepared with the native corn starch and standardmarketed formulation of the drug The order of increaseddrug dissolution using the different approaches was asfollows microwave gt chemical gt physical In case of theFDTs prepared by using native corn starch (F1ndashF4) thepercentage cumulative drug release was found to be verypoor as compared to the standard marketed formulation ofdomperidone (MKTD)The119891
2value for formulation (F1ndashF4)
was below 50 depicting the dissimilarity between the drugreleases Formulations (F5ndashF8) (F9ndashF12) and (F13ndashF16)werecontaining corn starch-Neusilin UFL2 conjugate prepared byphysical chemical and microwave methods The percentagecumulative drug release for these formulations were found tobe comparable to the standardmarketed formulation of dom-peridone The 119891
2values for these formulations were found
to be over 50 evidencing the similarity between the drugreleases Results of various tablet evaluation tests as evidencedfrom Table 4 indicate that among the three methods usedfor the preparation of conjugates microwave was the mosteffectivemethod followed by chemical and physical methodsMoreover by increasing the concentration of conjugates thetablet did not show much effect on drug release from theformulated FDTs Hence from the commercial point of viewlowest concentration of superdisintegrant showing optimumtabletting results should be recommended
4 Conculsions
In present work an attempt was made to modify the cornstarch to develop corn starch-Neusilin UFL2 conjugatesusing different methods namely physical chemical andmicrowave The prepared conjugates and the corn starchwere characterised for powder flow pH viscosity swellingand effective pore radius Evaluation of precompressionparameter indicates good flow properties The preparedconjugates were also subjected to the compression studiesnamely Heckel and Kawakita function The Heckel plot isusually correlated with the speed of the tablet machine whilethe Kawakita plot is related to the crushing or tensile strengthof the tablet Fast disintegrating tablets of domperidone wereformulated by direct compression technique employing thecorn starch and the prepared conjugates The tablets were
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F1F2F3
F4MKTD
Figure 7 Dissolution rate profiles of FDTs (F1ndashF4) formulated byincorporating native corn starch as a superdisintegrant compared toa standard marketed formulation of domperidone (MKTD)
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F5F6F7
F8MKTD
Figure 8 Dissolution rate profiles of FDTs (F5ndashF8) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates preparedby physical method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
evaluated for physical parametric tests wetting time waterabsorption ratio porosity tablet packing fraction in vitrodisintegration time drug content in vitro dissolution andstability studies Extensive swelling porosity and wickingaction of the prepared corn Starch-Neusilin UFL2 conjugatesin the prepared fast disintegrating tablets were found to becontributing to its superdisintegrant action
In conclusion the prepared conjugates can be effectivelyused as superdisintegrant in order to develop a faster disin-tegrating tablet formulation Future challenges for many fastdisintegrating tablet manufacturers include reducing costsby finding ways to manufacture with conventional equip-ment using versatile packaging and improving mechanical
12 Journal of Drug Delivery
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F9F10F11
F12MKTD
Figure 9 Dissolution rate profiles of FDTs (F9ndashF12) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates preparedby chemical method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
F13F14F15
F16MKTD
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
Figure 10 Dissolution rate profiles of FDTs (F13ndashF16) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates prepared bymicrowave method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
strength Such products provide an opportunity for theproduct line extension in the market place and extensionof patent term of innovator Due to its wide significancethis drug delivery system may lead to better patient com-pliance and ultimate clinical output Future might witnessnovel technologies for development and utilization of themodified starches as tablet superdisintegrant for cost effectiveformulation of fast disintegrating tablets
Conflict of Interests
The authors declare that they have no conflict of interests
Acknowledgments
The authors gratefully acknowledge Dr Madhu ChitkaraVice Chancellor Chitkara University Rajpura Punjab IndiaDr Ashok Chitkara Chairman Chitkara Educational TrustChandigarh India and Dr Sandeep Arora Dean ChitkaraUniversity Rajpura Punjab India for support and institu-tional facilities
References
[1] I Rashid M Al-Remawi S A Leharne B Z Chowdhry andA Badwan ldquoA novel multifunctional pharmaceutical excipientmodification of the permeability of starch by processing withmagnesium silicaterdquo International Journal of Pharmaceutics vol411 no 1-2 pp 18ndash26 2011
[2] O A Odeku and K M Picker-Freyer ldquoAnalysis of the materialand tablet formation properties of four Dioscorea starchesrdquoStarchStarke vol 59 no 9 pp 430ndash444 2007
[3] N Visavarungroj and J P Remon ldquoAn evaluation of hydrox-ypropyl starch an disintegrant and binder in tablet formulationrdquoDrug Development and Industrial Pharmacy vol 17 no 10 pp1389ndash1396 1991
[4] M Nakano N Nakazono and N Inotsume ldquoPreparation andevaluation of sustained release tablets prepared with 120572-starchrdquoChemical and Pharmaceutical Bulletin vol 35 no 10 pp 4346ndash4350 1987
[5] O A Odeku and K M Picker-Freyer ldquoFreeze-dried prege-latinized Dioscorea starches as tablet matrix for sustainedreleaserdquo Journal of Excipients and Food Chemicals vol 1 no 2pp 21ndash32 2010
[6] H Staroszczyk ldquoMicrowave-assisted silication of potato starchrdquoCarbohydrate Polymers vol 77 no 3 pp 506ndash515 2009
[7] J Singh L Kaur and O J McCarthy ldquoFactors influencingthe physico-chemical morphological thermal and rheologicalproperties of some chemically modified starches for foodapplications a reviewrdquo Food Hydrocolloids vol 21 no 1 pp 1ndash22 2007
[8] I Rashid N Daraghmeh M Al-Remawi S A Leharne B ZChowdhry and A Badwan ldquoCharacterization of chitin-metalsilicates as binding superdisintegrantsrdquo Journal of Pharmaceuti-cal Sciences vol 98 no 12 pp 4887ndash4901 2009
[9] I Rashid N Daraghmeh M Al-Remawi S A Leharne B ZChowdhry and A Badwan ldquoCharacterization of the impactof magnesium stearate lubrication on the tableting propertiesof chitin-Mg silicate as a superdisintegrating binder whencompared to Avicel 200rdquo Powder Technology vol 203 no 3 pp609ndash619 2010
[10] Y Asai M Nohara S Fujioka K Isaji and S Nagira ldquoApplica-tion of Neusilin UFL2 on manufacturing of tablets using directcompression method Development of core tablets containingthe function of small degree of decrease of hardness at thehumid conditionsrdquoPharmaceutical Technical Newsletter vol 25pp 67ndash70 2009
[11] B G Prajapati and D V Patel ldquoFormulation and optimiza-tion of domperidone fast dissolving tablet by wet granulationtechniques using factorial designrdquo International Journal ofPharmTech Research vol 2 no 1 pp 292ndash299 2010
[12] J Cooper and C Gunn ldquoPowder flow and compactionrdquo inTutorial Pharmacy S J Carter Ed pp 211ndash233 CBS Publishersand Distributors New Delhi India 1986
Journal of Drug Delivery 13
[13] H Goel G Kaur A K Tiwary and V Rana ldquoFormulationdevelopment of stronger and quick disintegrating tablets acrucial effect of chitinrdquoYakugaku Zasshi vol 130 no 5 pp 729ndash735 2010
[14] J M Sonnergaard ldquoImpact of particle density and initial vol-ume on mathematical compression modelsrdquo European Journalof Pharmaceutical Sciences vol 11 no 4 pp 307ndash315 2000
[15] O A Odeku ldquoAssessment of Albizia zygia gum as a bindingagent in tablet formulationsrdquo Acta Pharmaceutica vol 55 no3 pp 263ndash276 2005
[16] F Kiekens A Debunne C Vervaet et al ldquoInfluence of thepunch diameter and curvature on the yield pressure of MCC-compacts duringHeckel analysisrdquo European Journal of Pharma-ceutical Sciences vol 22 no 2-3 pp 117ndash126 2004
[17] ldquoUnited States Pharmacopeia 24NF19rdquo inTheOfficial Compen-dia of Standards M D Asian Rockville Ed pp 1913ndash1914 USPharmacopeial Convention 2000
[18] T Y Puttewar M D Kshirsagar A V Chandewar and R VChikhale ldquoFormulation and evaluation of orodispersible tabletof tastemasked doxylamine succinate using ion exchange resinrdquoJournal of King Saud UniversitymdashScience vol 22 no 4 pp 229ndash240 2010
[19] A Fini V Bergamante G C Ceschel C Ronchi and C A Fde Moraes ldquoFast dispersibleslow releasing ibuprofen tabletsrdquoEuropean Journal of Pharmaceutics and Biopharmaceutics vol69 no 1 pp 335ndash341 2008
[20] M U Uhumwangho and R S Okor ldquoEffect of humidity on thedisintegrant property of 120572-cellulose Part II A technical noterdquoAAPS PharmSciTech vol 6 no 1 article no 7 pp E31ndashE342005
[21] T Sasaki and J Matsuki ldquoEffect of wheat starch structure onswelling powerrdquo Cereal Chemistry vol 75 no 4 pp 525ndash5291998
[22] O A Itiola and N Pilpel ldquoTableting characteristics of metron-idazole formulationsrdquo International Journal of Pharmaceuticsvol 31 no 1-2 pp 99ndash105 1986
[23] O A Odeku and O A Itiola ldquoEvaluation of khaya gum asa binder in a paracetamol tablet formulationrdquo Pharmacy andPharmacology Communications vol 4 no 4 pp 183ndash188 1998
[24] O A Odeku and J T Fell ldquoEffects of the method of preparationon the compression mechanical and release properties ofkhaya gum matricesrdquo Pharmaceutical Development and Tech-nology vol 11 no 4 pp 435ndash441 2006
[25] O A Odeku and B L Akinwande ldquoEffect of the mode ofincorporation on the disintegrant properties of acid modifiedwater and white yam starchesrdquo Saudi Pharmaceutical Journalvol 20 no 2 pp 171ndash175 2012
[26] R Shangraw A Mitrevej and M Shah ldquoA new era of tabletdisintegrantsrdquo Pharmaceutical Technology vol 4 no 10 pp 49ndash57 1980
2 Journal of Drug Delivery
with better disintegration properties and some have beenfound to be useful for sustained release dosage forms [3ndash5]Rashid et al [1] developed a directly compressible excipientby coprocessing starch with magnesium silicate which wasachieved either by coprecipitation of magnesium silicate ontodifferent types of starch or by dry granulation of maizestarch with magnesium silicate Magnesium silicate as anantiadhering agent increased the permeability of both maizeand partially pregelatinized starch resulting in compacts ofhigh mechanical strength short disintegration time and lowlubricant sensitivity Formulation with this novel excipientsystem using paracetamol as a model drug indicated itssuitability as a single multifunctional excipient Staroszczyk[6] performed silication of potato starch bymicrowave irradi-ation It was reported thatwhile increasing the silicating agentcross-linking of starchwas increased and silicated starches arethermally more stable A number of modification techniquesnamely physical chemical enzymatic and genetic have beenreported with an aim to enhance the positive attributes andeliminate short coming of the native starches [7]
In recent times advancement in budding new excipientswith multifunctional capabilities (as glidants fillers bindersand disintegrants) has exploited the use of silicates producedsynthetically Silication of excipients resulted in improvementin various properties of the materials namely mechani-cal strength compressibility disintegration and sensitivitytowards lubrication Thus silicatestarch preparations havethe potential to fulfil the requirements of a multifunctionalexcipient In this context the physical properties of compactsproduced (disintegration time tensile strength and powdercompressibility) and sensitivity towards lubrication need tobe investigated On this basis the current study reports theapplication of silicates as an effective tabletting aid when usedwith corn starch [8 9]
Neusilin is a synthetic amorphous form of magnesiumaluminometasilicate which can be used as a multifunctionalexcipient in both direct compression and wet granulationof solid dosage forms Neusilin is widely used in improvingthe quality of tablets (in the terms of its compaction anddisintegration properties) powders granules and capsulesIt does not develop gels with aqueous solutions unlikeother magnesium aluminium silicates The different gradesof Neusilin available are alkaline (FH1 FH2 FL1 FL2 S1 S2and SG2) and neutral (US2 UFL2 NFL2N and NS2N) [10]
The aim of the present study is to evaluate the effi-ciency of a new conjugate of corn starch and Neusilin assuper disintegrating agent in the tablets The corn Starch-Neusilin UFL2 conjugates were prepared by three differentmethods namely physical chemical and microwave andwere used as a superdisintegrant in domperidone tabletformulation and the tablet properties were compared with astandard marketed fast disintegrating tablet Domperidone(C22H24ClN5O2 MW-42591) poorly water-soluble drug
[11] is a potent antidopaminergic drug used orally andintravenously for suppressing nausea and vomiting An adultdose of 10mg domperidone has a modest activity withoutextrapyramidal side effects as it crosses blood brain barrierpoorly Domperidone is absorbed orally and its metabolites
are completely biotransformed and excreted in urineThedis-solution rate and bioavailability of a poorly soluble drug fromsolid dosage formdependmuch on formulation additives andformulation characteristics
2 Materials and Methods
Commercial corn starchwas supplied by IPHZAPharmaceu-ticals Patiala Punjab India Neusilin UFL2 (Fuji ChemicalsJapan) was supplied as gift sample by Gangwal ChemicalsMumbai India Domperidone was gifted by Dr ReddyrsquosLaboratories Baddi (HP) India NaOH was procured fromMerck Specialities Pvt LtdMumbai India All reagents usedwere of analytical grade
21 Preparation of Corn Starch-Neusilin UFL2 ConjugatesThree methods were used in the formulation of the cornStarch-Neusilin UFL2 conjugate physical chemical andmicrowave methods The physical method involved simplemixing of corn starch and Neusilin UFL2 in the ratio 1 1To ensure proper mixing tumbling method was used andthe weighed starch and Neusilin were transferred into abeaker and the mouth of the beaker was closed ensuringthat there is no spillage of the contents from the beakerwhile the mixing is carried out The mixing was carriedout for 15 minutes In chemical method corn starch andNeusilin UFL2 were incorporated in the ratio 1 1 Cornstarch was suspended in distilled water (qs) and kept onmagnetic stirrer at 270 rpm and temperature not more than40∘C To this solution of Neusilin UFL2 in NaOH (qs) wasgradually added with constant stirring After 15ndash20 minutesthe precipitated conjugate was filtered using Whatman filterpaper (GE Healthcare UK Limited) having a pore size of125mm and dried in oven at a temperature not more than 50plusmn 2∘C In microwave method physical mixture of corn starchand Neusilin UFL2 was subjected to microwave radiation at590 watt for not more than 5 minutes
22 Formulation of Fast Disintegration Tablets Fast disin-tegrating tablets of domperidone (10mg) were formulatedby direct compression method using corn starch and thecorn Starch-Neusilin UFL2 conjugates as superdisintegrantaccording to the formulae given in Table 1 The specifiedquantity of the drug diluent and corn starch or corn Starch-Neusilin UFL2 conjugates were weighed accurately passedthrough 60 mesh sieves (250 120583mopening size) and mixed bytumbling method for 15 to 20min (contents were transferredinto a beaker and the mouth of the beaker was closedensuring that there is no spillage of the contents from thebeaker while mixing is carried out)The blend was lubricatedwith talc and magnesium stearate and mixing was done foradditional 5 minutes and the resulting powder mixture wascompressed into tablets usingmultipunch tablettingmachine(AK Industries Nakodar Punjab India) using 675mmbiconcave round die-punches The compression force wasadjusted to give tablet hardness in the pharmacopoeial rangeof fast disintegrating tablets (3ndash5 kgcm2) For each batch 200tablets were formulated
231 Angle of Repose (120579∘) The angle of repose of powder
blends was determined by the funnel method Accuratelyweighed powder blends were taken in a funnel The heightof the funnel was adjusted in such a way that the tip of thefunnel just touched the apex of the heap of the powder blends(2 cm) The powder blends were allowed to flow through thefunnel freely onto its surface The diameter of the powdercone was measured and angle of repose was calculated [12]Three determinations were performed
232 Bulk Density and Tapped Density Both loose bulk den-sity (LBD) and tapped bulk density (TBD) were determinedA quantity of 1 gm of powder was introduced into a 10mLmeasuring cylinder After the initial volume was determinedthe cylinder was tapped onto a hard surface from the heightof 25 cm at 2 seconds intervals Tapping was continued untilno further change in volume was noted The LBD and TBDwere calculated [12] The determination was carried out intriplicate
233 Compressibility Index and Hausner Ratio The com-pressibility index of the powder blends was determined byCarrrsquos compressibility index or Carrrsquos index (CI) Hausnerratio (HR) was also determined for each powder blend [12]
234 Swelling Index Initial bulk volume of the powderwas evaluated using 100mL stoppered graduated cylinderWater was added in sufficient quantity to produce uniformdispersion The sediment volume of the swollen mass was
measured after 24 hours The swelling index was calculatedas
Swelling index = (1198812minus
1198811
1198811
) lowast 100 (1)
where1198811and119881
2are initial volumes of the powder before and
after hydration respectively
235 pH Dispersion (1wv) of the sample was prepared indistilled water and the pHwas determined individually usingdigital pH meter at 37 plusmn 2∘C
236 Loss on Drying Loss on drying (LOD) is used todetermine the levels of moisture or solvents present in thesample The sample was weighed (119882
1) and heated in an
oven at 100 plusmn 5∘C for 2 hrs Sample was cooled in the dryatmosphere of a desiccator and then reweighed (119882
) Effective pore radiusof the powder was determined using method reported byGoel et al [13] A micropipette tip (2mL transparent) wascompletely filled with powder and weighed (119882
119894) Then 119899-
hexane (surface tension (120574) is 184mNm) was poured dropwise on bed top till the solvent filtered out at the bottom of
4 Journal of Drug Delivery
the tip The tip was reweighed (119882119891) and effective pore radius
was calculated by
119877effP = 119882119891minus
119882119894
2120587120574
(3)
24 Attenuated Total Reflectance-Fourier Transform IR Spec-troscopy (ATR-FTIR) The infrared (IR) spectra of sam-ples were obtained using an Attenuated Total Reflectance-Fourier Transform Infra-Red (ATR-FTIR) spectrophotome-ter (Alpha Bruker Japan) The samples were scanned inthe spectral region of 4000 cmminus1 to 400 cmminus1 by KBr pelletmethod
25 X-Ray Powder Diffraction (XRPD) The X-ray powderdiffractograms were registered in an X-Pert Pro (USA) inBragg-Brentano geometry using glass tubing with a Cuanode and graphite monochromator The diffractometer wasoperated at 40mA and 40 kV All the samples being a sizeof less than 250 120583m were randomly placed on a glass sliderespectively The signals of the reflection angle of 2120579 wererecorded from 0∘ to 60∘ at a scanning rate 021∘sec
26 Scanning Electron Microscopy (SEM) The scanning elec-tron micrographs were taken to study the surface morphol-ogy using a Hitachi (Model S 4300 SEN SEM Hitachi HighTechnologies Singapore) at an accelerator potential of 10 kVThe samples were stuck on a specimen holder using a silverplate and then coatedwith palladium in a vacuum evaporator
27 Differential Scanning Calorimetry (DSC) The thermaltransitions of starch samples were investigated with the useof a Perkin Elmer DSC 8000 apparatus (USA) calibrated byusing a high purity indium standard Samples about 10mgwere hermetically sealed in flat bottomed aluminium pansand heated in an atmosphere of nitrogen to eliminate theoxidative and pyrolytic effects The heating rate was 5∘Cminin a temperature range of 25ndash300∘C The DSC thermogramswere recorded
28 Compression Study The two well-known compressionmodels The Heckel andThe Kawakita were used to carry outthe studies [14]
281 Determination of Precompression Density The bulkdensity of each sample at zero pressure was determined bypouring the granules through a funnel into a glass measuringcylinder with a 24mm diameter and a volume of 50mL atan angle of 45∘ Determinations were done in triplicate Therelative density 119863
0 of each formulation was obtained from
the ratio of its bulk density to its particle density [15]
282 Preparation of Tablets for Compression Studies Tablets(400mg) were prepared by compressing the prepared conju-gates for 30 seconds with predetermined loads on a hydraulicpress (Model CAP15T-1233 PCI Analytics Pvt Ltd MumbaiIndia) After ejection the tablets were stored over silica gel
for 24 hours Their masses (119898) and dimensions were thendetermined respectively and their relative densities (119877) werecalculated using the equation
119877 =119898
119881119905120588119904
(4)
where119881119905is the volume (cm3) of the tablet and 120588
119904is the particle
density (gcm3) of the solid material [15]
283 The Heckel Function The deformation mechanism ofthe material was determined using the Heckel model asit is widely used for relating the relative density 119863 of apowder bed during compression to the applied pressure 119875The displacement and force data registered on the simulatorwere transferred to a spreadsheet program (Microsoft Excel2007) The force values were converted into pressures andthe displacement values (in combination with the individualtablet weight determined immediately after compaction)and the true density of the material (determined beforecompaction) were used to calculate the apparent densityof the powder bed 1(1 minus 119863) Using the Heckel plot thecompression stage was subjected to linear regression analysisIt is denoted as
ln [1
(1 minus 119863)
] = 119870119875 + 119860 (5)
The slope of the straight line portion 119870 is the reciprocalof the mean yield pressure 119875
119910 of the material From the
intercept 119860 the relative density 119863119860 can be calculated using
the following equation
119863119860= 1 minus 119890
minus119860 (6)
Relative density of the powder at the point when the appliedpressure equals zero 119863
0 is used to describe the initial
rearrangement phase of densification as a result of die filling
119863119861= 119863119860minus 1198630 (7)
Relative density 119863119861 describes the phase of rearrangement
at low pressures and is the difference between 119863119860
and1198630[15 16]
284 The Kawakita Function In the Kawakita equation theparticle density is not introduced in the calculations since themodel operates on the relative change in volume which givesthe same result whether the relative or the absolute volumeis used The problem in calculation of this equation is to findthe correct initial volume 119881
0 The Kawakita equation is used
to study powder compression using the degree of volumereduction (119862) and is written as
119862 =
(1198810minus 119881119901)
1198810
=119886119887119875
(1 + 119887119875)
(8)
The equation in practice can be rearranged to give
119875
119862
=119875
119886
+1
119886119887
(9)
Journal of Drug Delivery 5
where 1198810is the initial bulk volume of the powder and 119881
119901is
the bulk volume after compression Constant ldquo119886rdquo is equal tothe minimum porosity of the material before compressionwhile constant ldquo119887rdquo is related to the plasticity of the materialThe reciprocal of ldquo119887rdquo gives the pressure term 119875
119896 which is the
pressure required to reduce the powder bed by 50 [14 15]
29 Postcompression Evaluation
291 Diameter and Thickness A calibrated vernier calliper(Ms Mitutoyo Corp Japan) was used for diameter andthickness evaluation of tablets
292 Hardness The tablet hardness is the force required tobreak a tablet in a diametric compression force Hardnesstester (Perfit India) was used to determine the force requiredto break the tablet diametrically The test was performed onsix tablets and the average was calculated
293 Friability Thefriability (119865) of a sample of 20 tabletswasmeasured using Roche Friabilator (Model 902 EI PanchkulaIndia) Twenty tablets were weighed and rotated at 25 rpm for4min Tablets were reweighed after removal of fines (dusted)and the percentage of weight loss was calculated Friabilitybelow 1 was considered acceptable
294 Weight Variation Test Weight variation test was doneby weighing 20 tablets individually calculating the averageweight and comparing the individual tablet weight to theaverage weight
295 Content Uniformity The content uniformity wasassessed according to USP method Ten tablets were pulver-ized and quantity of powder equivalent to 10mg of domperi-done was shaken with 100mL of 01 N HCl for 30 minutesThe contents were filtered through a 045120583mmembrane filterdiluted and analyzed at 284 nmusing aUVVIS double beamspectrophotometer (Model 2202 Systronics AhmedabadIndia) [17]
296 Wetting Time A piece of tissue paper (1075 times 12mm)folded twice was placed in a culture dish (119889 = 65 cm)containing 6mL of water (containing a water soluble dyeeosin) A tablet was carefully placed on the surface of tissuepaper and the time required for water to reach the uppersurface of the tablet was noted as the wetting time [18]
297 Water Absorption Ratio The same procedure used forthe wetting time was used for the water absorption ratioInitial weight of the tablet (119882
119886) was measured before its
placement on the wet tissue and the final weight (119882119887) was
taken after complete wetting Water absorption ratio 119877 wasdetermined using the equation [19]
119877 = 100
(119882119887minus 119882119886)
119882119887
(10)
298 Porosity Porosity is a measure of the void spaces in amaterial and is a fraction of the volume of voids over the totalvolume between 0 and 1 or as a percentage between 0 and 100percent The porosity of the tablets was calculated as follows
Porosity =1 minus 119898
120588truelowast 119881 (11)
where 120588true is the true density of the mixture and 119898 and 119881
are the weight and volume of the tablet respectively Thetrue density of the powder was found using true densitymeter (SMART PYCNO 30 Smart Instruments Maharash-tra India)
299 Tablet Packing Fraction (119875119891) The tablet packing
fraction 119875119891 is a measure of the degree of consolida-
tioncompactness of the tablet Tablet packing fraction wasdetermined by the equation
Packing fraction (119875119891) =
119908
1205871199032119905120588
(12)
where119908 is the weight of a tablet 119903 is radius 119905 is thickness and120588 is the particle density
The radius and thickness of 10 tablets were measuredusing a vernier calliper The apparent particle density of thedrug powder was determined using liquid paraffin displace-ment method Firstly the weight of a specific gravity bottlefilledwith liquid paraffin and theweight of the specific gravitybottle containing a sample of the drug powder were notedThe final weight was determined The determination wasexecuted in triplicate and mean results were used in thecalculation of 119875
119891[20]
2910 In Vitro Disintegration Time In vitro disintegrationtime for the tablets was determined using USP disintegrationapparatus (EI Product Panchkula India) using 01 NHCl (pH1-2 900mL at 37∘C) as the disintegrating medium
2911 In Vitro Dissolution Studies In vitro dissolution ofthe fast disintegrating tablets was studied in USP XXIVdissolution apparatus II (DS 8000 Lab India Pune India)employing a paddle stirrer at 50 rpm using 900mL of pH12 01 N HCl at 37 plusmn 05∘C as a dissolution mediumAliquots of 5mL eachwere withdrawn at predetermined timeintervals and replaced with equal volume of fresh mediumAliquots were filtered through a 045120583m membrane filterand analyzed for drug content using a UVVIS double beamspectrophotometer (2202 Systronics Ahmedabad India) at284 nm Drug concentration was calculated and expressed ascumulative percent of the drug releasedThe similarity factor(1198912) is a logarithmic transformation of the sum-squared
error of differences between the test (119879119895) and reference
(119877119895) products over all time points It is a useful tool for
comparison of dissolution profiles when more than three orfour dissolution time points are available It is calculated as
(119882119895) is an optional weight factor The similarity factor fits
result between 0 and 100 It is 100 when the test and referenceprofiles are identical and tends to be 0 as the dissimilarityincreases In order to consider similar dissolution profiles 119891
2
values should be close to 100
3 Result and Discussion
31 Precompression Evaluation
311 Micromeritics Study The result of the micromeriticstudies for corn starch and the prepared corn Starch-NeusilinUFL2 conjugates were conducted and results are listed inTable 2 Angle of repose (120579∘) is a characteristic of the internalfriction or cohesion of the particles Its value will be highif the powder is cohesive and low if the powder is non-cohesive Flow property of the corn starch was improvedby the addition of Neusilin UFL2 as compared formulationswith conjugates showed good to excellent flow properties asindicated by the values of angle of repose (3669ndash2767∘) to thecorn starch (4325∘) Carrrsquos index showed values 225 to 125denoting that these formulations were of acceptable to goodflowability compared to the corn starch (3428) Hausnerrsquosratio showed that powders with low interparticle frictionhad ratios of approximately 129 to 114 indicating good flowproperties as compared to the corn starch (152) Swellingindex of the conjugates prepared by physical chemical andmicrowave method were found to be 40 65 and 95respectively which was far better than the swelling index ofcorn starch that is 18 which is in context with the effectivepore radius of the conjugates and corn starch The resultsof both swelling and effective pore radius point towardsmore wicking action capability and hence disintegrationpotential of the conjugates over the pure corn starch Theresult of micromeritic study indicates that conjugates pre-pared by microwave method were the most effective methodfollowed by chemical and physical method as they gave bettermicromeritic properties as evidenced from the Table 2
312 ATR-FTIR Analysis Corn starch and Neusilin UFL2interactions studies were carried out using ATR-FTIR spec-trophotometer and the spectra for the samples are shownin Figure 1 The IR spectra of corn starch showed a peakat 3434 cmminus1 and 2931 cmminus1 representing OndashH and CndashHstretching respectively The absorption band at 1652 cmminus1is due to absorbed water in amorphous region of starchPeak at 1241 cmminus1 represents CH
2OH group whereas peak
at 1159 cmminus1 represents coupling mode of CndashC and CndashOstretching vibrations The band at 1080 cmminus1 represents CndashOndashH bending vibration whereas peak at 929 cmminus1 could beascribed to the skeletal mode vibration of 120572-14-glycosidiclinkage The corn Starch-Neusilin UFL2 conjugates preparedby different methods namely physical microwave andchemical exhibit a sharp peak near 3480 cmminus1 which isotherwise observed at 3434 cmminus1 in the pure corn starchThisshift and sharpening of peak indicate the formation of SindashOndashC bridging bond between corn starch and Neusilin UFL2Moreover reduction in the intensity of peak at 1241 cmminus1
4000 3000 2000 1500 1000 400
(cmminus1)
T(
)
(A)
(B)
(C)
(D)
Figure 1 IR spectra of (A) native corn starch corn Starch-NeusilinUFL2 conjugates by (B) physical method (C) chemical method and(D) microwave method
1159 cmminus1 and 1080 cmminus1 confirms intermolecular bridgingbetween corn starch and Neusilin UFL2 Thus the additionof Neusilin changed the properties of corn starch forming anew excipient with different functional properties
313 XRD Analysis The XRD patterns of the samples areshown in Figure 2 The structure of corn starch is char-acterized by the presence of broad peak at 2456∘2120579 angleAppearance of sharp peak at 2740∘2120579 3172∘2120579 4560∘21205795391∘2120579 and 5647∘2120579 angles respectively in case of conju-gates prepared bymicrowavemethod gives clear indication ofreduction in amorphous nature or otherwise increase in thecrystalline behavior of the corn starch that could be correlatedwith the increase in swelling and hence superdisintegrantpotential of conjugates prepared by different methods Crys-tallinity and hence the superdisintegrant property (Table 4)of conjugates prepared by different methods were in therank order of microwave gt chemical gt physical mixtureHigh proportion of longer chains might form more stablecrystallites in the pure corn starch The swelling powerof corn starch depends on the water holding capacity ofthe starch molecule by hydrogen bonding Hence higherdegree of intermolecular bonding between corn starch andNeusilin UFL2 favors the long chain crystalline structureand hence the swelling of the conjugates which in turnpotentiates the use of corn Starch-Neusilin UFL2 as a tabletsuperdisintegrant [21]
314 DSC Analysis Figure 3 shows the DSC thermogramsof the pure corn starch and corn Starch-Neusilin UFL2conjugates prepared by physical chemical and microwavemethods Corn starch has a discrete structure and pos-sesses partially crystalline microscopic granules that are
Figure 2 XRD pattern of (A) native corn starch corn Starch-Neusilin UFL2 conjugates by (B) physical method (C) chemicalmethod and (D) microwave method
held together by intended micellar network of associatedmolecules so it does not show obvious Tg or Tm untilpyrogenation Melting range was found to be extended andbroadened with the incorporation of Neusilin UFL2 Broad-ening and shifting of the melting range in the DSC spectracould be attributed to intermolecular bonding between cornstarch and Neusilin UFL2 indicating that the Neusilin UFL2molecules were restrained by the corn starch molecules Thebroadening of themelting range could be due to the regularityof the OH group that already existed in corn starch whichhad disappeared by the interaction with Neusilin UFL2 TheTm and ΔH of the melting peak are significantly lower inthe pure corn starch than the conjugates which indicate thatthere is an interaction between corn starch and NeusilinUFL2 which has enhanced the crystallization of the purecorn starch This increase in crystalline behaviour of thepure corn starch could be correlated to increase in swelling
40 50 60 70 80 90 100 110 120 130 140
Temperature (∘C)
(A)
(B)
(C)(D)
Figure 3 DSC pattern of (A) native corn starch corn Starch-Neusilin UFL2 conjugates by (B) physical method (C) chemicalmethod and (D) microwave method
and hence superdisintegrant potential of conjugates preparedby different methods Crystallinity and superdisintegrantbehaviour of conjugates prepared by different methods couldbe arranged as microwave gt chemical gt physical mixtureFurthermore the crystalline structure contributes towardsthe swelling behaviour of the conjugates responsible for thetablet superdisintegrant activity
315 SEM Analysis Surface morphology of the corn starchand corn Starch-Neusilin UFL2 conjugates was studied bySEManalysis as shown in Figure 4The corn starch undergoesa change in its native structure from thin smooth flatsurface structure with folded edges to three dimensionalcompacts upon conjugation with the Neusilin UFL2 SEMmicrograph of the prepared conjugates showed the presenceof interparticulate voids and channels that are responsible forthe increase in water absorption and swelling capacity of theconjugates as compared to the pure corn starch Furthermorethese voidschannels contributed to the wicking behaviorresponsible for the tablet superdisintegrant property of thecorn Starch-Neusilin UFL2 conjugates Conjugates preparedbymicrowavemethod illustrated the presence ofmore porous
8 Journal of Drug Delivery
structure as compared to conjugates prepared by physicaland chemical methods The results are in line with the betterin vitro disintegration performance of FDT prepared withconjugates of microwave method compared to the other twomethods
316 Heckel FunctionAnalysis Figure 5 shows representativeHeckel plots for the conjugates prepared by physical chem-ical and microwave methods The Heckel plots showed aninitial linear portion with an increase slope at pressure of100MPa followed by another linear region for the conjugatesprepared by physical and chemical methods while for theconjugate prepared by microwave method the second linearregion was from 175MPaThe mean yield pressure values forthe conjugates were calculated from the slope of the portionshowing the highest linearity of the Heckel plots and theintercept 119860 was determined from the extrapolation of theregionThe values of119863
119860and119863
119861were calculated respectively
The values of 119875119910 1198630 119863119860 and 119863
119861for the formulations are
presented in Table 3 The value of 1198630which represents the
degree of initial packing in the die as a result of die fillingfor the conjugates indicates that the conjugates preparedby microwave method exhibited highest degree of packingin the die as a result of die filling while the conjugatesprepared by physical method exhibited the lowest valuesThevalue of 119863
119861represents the phase of rearrangement of the
particles in the early stages of compression119863119861values tend to
indicate the extent of fragmentation of particles or granulesalthough fragmentation can occur concurrently with plasticand elastic deformation of constituent particles The chemi-cally prepared conjugates exhibited the highest values whilethe one prepared by microwave method exhibited the lowestvalues This indicates that fragmentation occurs more withthe chemically prepared conjugates [22 23]The values of119863
119860
which represents the total degree of packing achieved at zeroand low pressures was also in the rank order of microwave gtchemical gt physical for the methods to prepare conjugatesThis indicates that the conjugates prepared by microwavemethod showed higher degree of packing at low pressuresThe mean yield pressure 119875
119910is inversely related to the ability
of the formulations to deform plastically under pressureThe result indicates that the conjugates prepared by physicalmethod showed the fastest onset of plastic deformation whilethe conjugates prepared by microwave method showed theslowest onset Materials with high yield pressure are classifiedas brittle or fragmenting materials whereas those with lowervalues are classified as plasticallyelastically deforming mate-rials [24] Generally during compression plastic deformationand fragmentation are known to occur concurrently Starcheshave been known to deform plastically under compressionpressure
317 Kawakita Function Analysis TheKawakita plots for theconjugates are presented in Figure 6 A linear relationshipwas obtained at all compression pressures employed withcorrelation coefficient of 0999 for the conjugates preparedby different methods The values of 119886 and 119886119887 were obtainedfrom the slope and intercept respectivelyThe value of (1minus119886)
gives the initial relative density of the starch 119863119868 while 119875
119896
values were obtained from the reciprocal of values of 119887The values of 119863
119868and 119875
119896are shown in Table 3 The value
of 119863119868is a measure of the packed initial relative density of
the formulation with the application of small pressure ortapping The ranking of 119863
119868for the conjugates was chemical
method gt microwave method gt physical method The valueof 119875119896which is an inverse measure of the amount of plastic
deformation occurring during the compression process wasfound to be maximum for tablets formulated using conju-gates prepared by chemical method followed by microwavemethod and physical method [23]Thus conjugates preparedby microwave method exhibited the highest amount of totalplastic deformation while conjugates prepared by physicalmethod exhibited the lowest values The ranking was seen tobe in the reverse order as that of the 119875
119910values It has been
shown that while119875119910relates to the onset of plastic deformation
during compression the 119875119896relates to the amount of plastic
deformation that occurs during the compression processThus the conjugates prepared by physical method showedthe slowest onset of plastic deformation but the highest totalamount of plastic deformation
32 Postcompression Evaluation Tablets require certainamount of strength and resistance to friability to withstandmechanical shock of handling during manufacturingshipping and packaging Hardness of the tablets formulatedusing the corn starch-Neusilin UFL2 conjugates assuperdisintegrant was found to vary from 43 to 35 kgcm2compared to 315 to 309 kgcm2 of tablets formulatedusing the native corn starch Percentage friability of allformulations was less than 1 indicating good mechanicalcharacteristics Wetting time was observed to be decreasedfrom 68 seconds for the tablets incorporating native cornstarch to 33 22 and 14 seconds for the tablets incorporatingconjugates prepared by physical chemical and microwavemethods Disintegration time was also observed to decreasefrom 83 seconds for the tablets incorporating native cornstarch to 40 35 and 22 seconds for the tablets incorporatingconjugates prepared by physical chemical and microwavemethods respectively Water absorption ratio was found tobe inversely proportional to the wetting and disintegratingtime of the tablets The increase in water absorption ratioand decrease in wetting and disintegration times in allformulations may be attributed to the modification of thecorn starch by Neusilin UFL2 to yield a novel conjugatewhich acts as superdisintegrant which absorbs water andswells causing rupture of the tablets Tablet propertiessuch as mechanical strength tablet packing fraction anddisintegration are in turn affected by the porosity [25]Tablets with low packing fraction have high porosity andpores facilitates the penetration of dissolution media intothe tablet leading to disintegration of the tablet Whereashigher tablet packing fraction leads to reduction in porositywhich inhibits the penetration of dissolution media resultingin slower disintegration rate of the tablet [26] Tabletpacking fraction was found to be decreased in the tabletsincorporating conjugates (063ndash041) compared to the tablets
Journal of Drug Delivery 9
(a) (b)
(c) (d)
Figure 4 SEM photomicrographs of (A) corn starch and corn Starch-Neusilin UFL2 conjugates prepared by (B) physical method (C)chemical method and (D) microwave method
Table 3 Parameters derived from the Heckel and Kawakita plots for tablet incorporating corn Starch-Neusilin UFL2 conjugate as asuperdisintegrant prepared by (A) physical method (B) chemical method and (C) microwave method
Figure 5 Heckel plots for the tablet incorporating corn Starch-Neusilin UFL2 conjugate as a superdisintegrant prepared by (A)physical method (B) chemical method and (C)microwavemethod
with corn starch (082) The results are in line with thepowder evaluation results where conjugates prepared byphysical chemical and microwave methods were showing
0
50
100
150
200
250
300
0 50 100 150 200 250
PC
Applied pressure (MPa)
ABC
Figure 6 Kawakita plots for the tablet incorporating corn Starch-Neusilin UFL2 conjugate as a superdisintegrant prepared by (A)physical method (B) chemical method and (C)microwavemethod
better swelling and effective pore radius compared to thenative corn starch The fast disintegration of tablets is dueto the presence of pores resulting in faster penetration of
10 Journal of Drug Delivery
Table4Differentp
ropertieso
fthe
form
ulated
FDTs
Cod
eParameter
Diameter
(mm)
Thickn
ess(mm)
Friability(
)Hardn
ess(kgcm
2 )TSlowast(M
Nm
2 )WTlowast
(Sec)
WARlowast
()
DTlowast
(Sec)
CUlowast(
)TP
Flowast119875lowast(
)1198652
F1674
plusmn003
356
plusmn003
089
plusmn004
311
plusmn010
047
plusmn015
68plusmn113
40plusmn011
73plusmn3
9899plusmn02
081
189
19F2
673
plusmn004
351
plusmn004
091
plusmn002
315
plusmn007
047
plusmn005
68plusmn12
942
plusmn011
73plusmn1
991plusmn015
082
175
24F3
674
plusmn005
355
plusmn005
089
plusmn005
309
plusmn011
047
plusmn011
67plusmn111
46plusmn009
71plusmn2
9727plusmn09
081
187
21F4
673
plusmn001
359
plusmn005
090
plusmn003
310
plusmn002
047
plusmn009
66plusmn114
46plusmn010
71plusmn3
9659plusmn05
080
194
25F5
674
plusmn001
351
plusmn005
076
plusmn004
350
plusmn011
048
plusmn005
33plusmn114
98plusmn004
48plusmn2
9650plusmn03
063
367
43F6
674
plusmn002
355
plusmn004
073
plusmn005
356
plusmn008
048
plusmn001
33plusmn16
796
plusmn004
46plusmn3
991plusmn015
062
373
43F7
674
plusmn001
355
plusmn005
071
plusmn002
370
plusmn015
056
plusmn018
32plusmn110
101plusmn
005
44plusmn1
9835plusmn02
062
373
45F8
674
plusmn003
356
plusmn003
067
plusmn003
375
plusmn021
055
plusmn008
31plusmn14
0103plusmn002
40plusmn2
9923plusmn05
062
375
47F9
673
plusmn004
355
plusmn002
055
plusmn001
400
plusmn018
060
plusmn019
23plusmn13
4108plusmn003
40plusmn6
9912
plusmn04
054
426
50F10
674
plusmn005
354
plusmn007
054
plusmn005
380
plusmn015
057
plusmn006
22plusmn12
5100plusmn002
35plusmn3
9892plusmn07
057
435
50F11
673
plusmn003
356
plusmn004
055
plusmn003
370
plusmn017
056
plusmn011
23plusmn10
5106plusmn006
36plusmn2
9727plusmn09
057
423
55F12
673
plusmn002
353
plusmn003
051
plusmn004
410
plusmn02
062
plusmn015
23plusmn13
8110
plusmn004
32plusmn7
9659plusmn05
056
426
53F13
674
plusmn003
355
plusmn004
041
plusmn007
420
plusmn027
073
plusmn008
14plusmn15
2121plusmn
008
26plusmn2
9915
plusmn01
041
582
50F14
673
plusmn001
351
plusmn004
042
plusmn002
425
plusmn02
073
plusmn020
14plusmn12
6124plusmn007
24plusmn5
9899plusmn02
039
595
52F15
674
plusmn003
355
plusmn006
044
plusmn004
430
plusmn010
076
plusmn018
13plusmn115
125plusmn003
22plusmn3
9975plusmn10
040
599
62F16
674
plusmn001
359
plusmn005
047
plusmn007
420
plusmn045
079
plusmn019
14plusmn14
0128plusmn005
22plusmn4
9912
plusmn03
041
612
64TSlowasttensiles
treng
thW
Tlowastw
ettin
gtim
eWARlowast
water
absorptio
nratio
DTlowast
disintegratio
ntim
eCUlowastcon
tent
unifo
rmity
TPFlowasttabletp
acking
fractio
n119875lowastporosity
Journal of Drug Delivery 11
the dissolution media leading to swelling and wicking of theprepared conjugate creating hydrodynamic pressure insidethe tablets hence responsible for the quick and completedisintegration of tablets indicating the superdisintegrantactivity of conjugates prepared by physical chemical andmicrowave methods over the native corn starch
The results obtained from the in vitro dissolution studyare presented in Figures 7 8 9 and 10 ldquoMKTDrdquo representsthe standard marketed domperidone formulation to whichthe formulated FDTs were compared The similarity factor(1198912) is a logarithmic transformation of the sum-squared
error of differences between test and reference productsover all time points It was observed that the three differentapproaches used for the preparation of conjugate in thisstudy namely physical chemical and microwave methodsincreased the dissolution rate of the drug compared to thetablet prepared with the native corn starch and standardmarketed formulation of the drug The order of increaseddrug dissolution using the different approaches was asfollows microwave gt chemical gt physical In case of theFDTs prepared by using native corn starch (F1ndashF4) thepercentage cumulative drug release was found to be verypoor as compared to the standard marketed formulation ofdomperidone (MKTD)The119891
2value for formulation (F1ndashF4)
was below 50 depicting the dissimilarity between the drugreleases Formulations (F5ndashF8) (F9ndashF12) and (F13ndashF16)werecontaining corn starch-Neusilin UFL2 conjugate prepared byphysical chemical and microwave methods The percentagecumulative drug release for these formulations were found tobe comparable to the standardmarketed formulation of dom-peridone The 119891
2values for these formulations were found
to be over 50 evidencing the similarity between the drugreleases Results of various tablet evaluation tests as evidencedfrom Table 4 indicate that among the three methods usedfor the preparation of conjugates microwave was the mosteffectivemethod followed by chemical and physical methodsMoreover by increasing the concentration of conjugates thetablet did not show much effect on drug release from theformulated FDTs Hence from the commercial point of viewlowest concentration of superdisintegrant showing optimumtabletting results should be recommended
4 Conculsions
In present work an attempt was made to modify the cornstarch to develop corn starch-Neusilin UFL2 conjugatesusing different methods namely physical chemical andmicrowave The prepared conjugates and the corn starchwere characterised for powder flow pH viscosity swellingand effective pore radius Evaluation of precompressionparameter indicates good flow properties The preparedconjugates were also subjected to the compression studiesnamely Heckel and Kawakita function The Heckel plot isusually correlated with the speed of the tablet machine whilethe Kawakita plot is related to the crushing or tensile strengthof the tablet Fast disintegrating tablets of domperidone wereformulated by direct compression technique employing thecorn starch and the prepared conjugates The tablets were
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F1F2F3
F4MKTD
Figure 7 Dissolution rate profiles of FDTs (F1ndashF4) formulated byincorporating native corn starch as a superdisintegrant compared toa standard marketed formulation of domperidone (MKTD)
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F5F6F7
F8MKTD
Figure 8 Dissolution rate profiles of FDTs (F5ndashF8) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates preparedby physical method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
evaluated for physical parametric tests wetting time waterabsorption ratio porosity tablet packing fraction in vitrodisintegration time drug content in vitro dissolution andstability studies Extensive swelling porosity and wickingaction of the prepared corn Starch-Neusilin UFL2 conjugatesin the prepared fast disintegrating tablets were found to becontributing to its superdisintegrant action
In conclusion the prepared conjugates can be effectivelyused as superdisintegrant in order to develop a faster disin-tegrating tablet formulation Future challenges for many fastdisintegrating tablet manufacturers include reducing costsby finding ways to manufacture with conventional equip-ment using versatile packaging and improving mechanical
12 Journal of Drug Delivery
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F9F10F11
F12MKTD
Figure 9 Dissolution rate profiles of FDTs (F9ndashF12) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates preparedby chemical method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
F13F14F15
F16MKTD
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
Figure 10 Dissolution rate profiles of FDTs (F13ndashF16) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates prepared bymicrowave method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
strength Such products provide an opportunity for theproduct line extension in the market place and extensionof patent term of innovator Due to its wide significancethis drug delivery system may lead to better patient com-pliance and ultimate clinical output Future might witnessnovel technologies for development and utilization of themodified starches as tablet superdisintegrant for cost effectiveformulation of fast disintegrating tablets
Conflict of Interests
The authors declare that they have no conflict of interests
Acknowledgments
The authors gratefully acknowledge Dr Madhu ChitkaraVice Chancellor Chitkara University Rajpura Punjab IndiaDr Ashok Chitkara Chairman Chitkara Educational TrustChandigarh India and Dr Sandeep Arora Dean ChitkaraUniversity Rajpura Punjab India for support and institu-tional facilities
References
[1] I Rashid M Al-Remawi S A Leharne B Z Chowdhry andA Badwan ldquoA novel multifunctional pharmaceutical excipientmodification of the permeability of starch by processing withmagnesium silicaterdquo International Journal of Pharmaceutics vol411 no 1-2 pp 18ndash26 2011
[2] O A Odeku and K M Picker-Freyer ldquoAnalysis of the materialand tablet formation properties of four Dioscorea starchesrdquoStarchStarke vol 59 no 9 pp 430ndash444 2007
[3] N Visavarungroj and J P Remon ldquoAn evaluation of hydrox-ypropyl starch an disintegrant and binder in tablet formulationrdquoDrug Development and Industrial Pharmacy vol 17 no 10 pp1389ndash1396 1991
[4] M Nakano N Nakazono and N Inotsume ldquoPreparation andevaluation of sustained release tablets prepared with 120572-starchrdquoChemical and Pharmaceutical Bulletin vol 35 no 10 pp 4346ndash4350 1987
[5] O A Odeku and K M Picker-Freyer ldquoFreeze-dried prege-latinized Dioscorea starches as tablet matrix for sustainedreleaserdquo Journal of Excipients and Food Chemicals vol 1 no 2pp 21ndash32 2010
[6] H Staroszczyk ldquoMicrowave-assisted silication of potato starchrdquoCarbohydrate Polymers vol 77 no 3 pp 506ndash515 2009
[7] J Singh L Kaur and O J McCarthy ldquoFactors influencingthe physico-chemical morphological thermal and rheologicalproperties of some chemically modified starches for foodapplications a reviewrdquo Food Hydrocolloids vol 21 no 1 pp 1ndash22 2007
[8] I Rashid N Daraghmeh M Al-Remawi S A Leharne B ZChowdhry and A Badwan ldquoCharacterization of chitin-metalsilicates as binding superdisintegrantsrdquo Journal of Pharmaceuti-cal Sciences vol 98 no 12 pp 4887ndash4901 2009
[9] I Rashid N Daraghmeh M Al-Remawi S A Leharne B ZChowdhry and A Badwan ldquoCharacterization of the impactof magnesium stearate lubrication on the tableting propertiesof chitin-Mg silicate as a superdisintegrating binder whencompared to Avicel 200rdquo Powder Technology vol 203 no 3 pp609ndash619 2010
[10] Y Asai M Nohara S Fujioka K Isaji and S Nagira ldquoApplica-tion of Neusilin UFL2 on manufacturing of tablets using directcompression method Development of core tablets containingthe function of small degree of decrease of hardness at thehumid conditionsrdquoPharmaceutical Technical Newsletter vol 25pp 67ndash70 2009
[11] B G Prajapati and D V Patel ldquoFormulation and optimiza-tion of domperidone fast dissolving tablet by wet granulationtechniques using factorial designrdquo International Journal ofPharmTech Research vol 2 no 1 pp 292ndash299 2010
[12] J Cooper and C Gunn ldquoPowder flow and compactionrdquo inTutorial Pharmacy S J Carter Ed pp 211ndash233 CBS Publishersand Distributors New Delhi India 1986
Journal of Drug Delivery 13
[13] H Goel G Kaur A K Tiwary and V Rana ldquoFormulationdevelopment of stronger and quick disintegrating tablets acrucial effect of chitinrdquoYakugaku Zasshi vol 130 no 5 pp 729ndash735 2010
[14] J M Sonnergaard ldquoImpact of particle density and initial vol-ume on mathematical compression modelsrdquo European Journalof Pharmaceutical Sciences vol 11 no 4 pp 307ndash315 2000
[15] O A Odeku ldquoAssessment of Albizia zygia gum as a bindingagent in tablet formulationsrdquo Acta Pharmaceutica vol 55 no3 pp 263ndash276 2005
[16] F Kiekens A Debunne C Vervaet et al ldquoInfluence of thepunch diameter and curvature on the yield pressure of MCC-compacts duringHeckel analysisrdquo European Journal of Pharma-ceutical Sciences vol 22 no 2-3 pp 117ndash126 2004
[17] ldquoUnited States Pharmacopeia 24NF19rdquo inTheOfficial Compen-dia of Standards M D Asian Rockville Ed pp 1913ndash1914 USPharmacopeial Convention 2000
[18] T Y Puttewar M D Kshirsagar A V Chandewar and R VChikhale ldquoFormulation and evaluation of orodispersible tabletof tastemasked doxylamine succinate using ion exchange resinrdquoJournal of King Saud UniversitymdashScience vol 22 no 4 pp 229ndash240 2010
[19] A Fini V Bergamante G C Ceschel C Ronchi and C A Fde Moraes ldquoFast dispersibleslow releasing ibuprofen tabletsrdquoEuropean Journal of Pharmaceutics and Biopharmaceutics vol69 no 1 pp 335ndash341 2008
[20] M U Uhumwangho and R S Okor ldquoEffect of humidity on thedisintegrant property of 120572-cellulose Part II A technical noterdquoAAPS PharmSciTech vol 6 no 1 article no 7 pp E31ndashE342005
[21] T Sasaki and J Matsuki ldquoEffect of wheat starch structure onswelling powerrdquo Cereal Chemistry vol 75 no 4 pp 525ndash5291998
[22] O A Itiola and N Pilpel ldquoTableting characteristics of metron-idazole formulationsrdquo International Journal of Pharmaceuticsvol 31 no 1-2 pp 99ndash105 1986
[23] O A Odeku and O A Itiola ldquoEvaluation of khaya gum asa binder in a paracetamol tablet formulationrdquo Pharmacy andPharmacology Communications vol 4 no 4 pp 183ndash188 1998
[24] O A Odeku and J T Fell ldquoEffects of the method of preparationon the compression mechanical and release properties ofkhaya gum matricesrdquo Pharmaceutical Development and Tech-nology vol 11 no 4 pp 435ndash441 2006
[25] O A Odeku and B L Akinwande ldquoEffect of the mode ofincorporation on the disintegrant properties of acid modifiedwater and white yam starchesrdquo Saudi Pharmaceutical Journalvol 20 no 2 pp 171ndash175 2012
[26] R Shangraw A Mitrevej and M Shah ldquoA new era of tabletdisintegrantsrdquo Pharmaceutical Technology vol 4 no 10 pp 49ndash57 1980
231 Angle of Repose (120579∘) The angle of repose of powder
blends was determined by the funnel method Accuratelyweighed powder blends were taken in a funnel The heightof the funnel was adjusted in such a way that the tip of thefunnel just touched the apex of the heap of the powder blends(2 cm) The powder blends were allowed to flow through thefunnel freely onto its surface The diameter of the powdercone was measured and angle of repose was calculated [12]Three determinations were performed
232 Bulk Density and Tapped Density Both loose bulk den-sity (LBD) and tapped bulk density (TBD) were determinedA quantity of 1 gm of powder was introduced into a 10mLmeasuring cylinder After the initial volume was determinedthe cylinder was tapped onto a hard surface from the heightof 25 cm at 2 seconds intervals Tapping was continued untilno further change in volume was noted The LBD and TBDwere calculated [12] The determination was carried out intriplicate
233 Compressibility Index and Hausner Ratio The com-pressibility index of the powder blends was determined byCarrrsquos compressibility index or Carrrsquos index (CI) Hausnerratio (HR) was also determined for each powder blend [12]
234 Swelling Index Initial bulk volume of the powderwas evaluated using 100mL stoppered graduated cylinderWater was added in sufficient quantity to produce uniformdispersion The sediment volume of the swollen mass was
measured after 24 hours The swelling index was calculatedas
Swelling index = (1198812minus
1198811
1198811
) lowast 100 (1)
where1198811and119881
2are initial volumes of the powder before and
after hydration respectively
235 pH Dispersion (1wv) of the sample was prepared indistilled water and the pHwas determined individually usingdigital pH meter at 37 plusmn 2∘C
236 Loss on Drying Loss on drying (LOD) is used todetermine the levels of moisture or solvents present in thesample The sample was weighed (119882
1) and heated in an
oven at 100 plusmn 5∘C for 2 hrs Sample was cooled in the dryatmosphere of a desiccator and then reweighed (119882
) Effective pore radiusof the powder was determined using method reported byGoel et al [13] A micropipette tip (2mL transparent) wascompletely filled with powder and weighed (119882
119894) Then 119899-
hexane (surface tension (120574) is 184mNm) was poured dropwise on bed top till the solvent filtered out at the bottom of
4 Journal of Drug Delivery
the tip The tip was reweighed (119882119891) and effective pore radius
was calculated by
119877effP = 119882119891minus
119882119894
2120587120574
(3)
24 Attenuated Total Reflectance-Fourier Transform IR Spec-troscopy (ATR-FTIR) The infrared (IR) spectra of sam-ples were obtained using an Attenuated Total Reflectance-Fourier Transform Infra-Red (ATR-FTIR) spectrophotome-ter (Alpha Bruker Japan) The samples were scanned inthe spectral region of 4000 cmminus1 to 400 cmminus1 by KBr pelletmethod
25 X-Ray Powder Diffraction (XRPD) The X-ray powderdiffractograms were registered in an X-Pert Pro (USA) inBragg-Brentano geometry using glass tubing with a Cuanode and graphite monochromator The diffractometer wasoperated at 40mA and 40 kV All the samples being a sizeof less than 250 120583m were randomly placed on a glass sliderespectively The signals of the reflection angle of 2120579 wererecorded from 0∘ to 60∘ at a scanning rate 021∘sec
26 Scanning Electron Microscopy (SEM) The scanning elec-tron micrographs were taken to study the surface morphol-ogy using a Hitachi (Model S 4300 SEN SEM Hitachi HighTechnologies Singapore) at an accelerator potential of 10 kVThe samples were stuck on a specimen holder using a silverplate and then coatedwith palladium in a vacuum evaporator
27 Differential Scanning Calorimetry (DSC) The thermaltransitions of starch samples were investigated with the useof a Perkin Elmer DSC 8000 apparatus (USA) calibrated byusing a high purity indium standard Samples about 10mgwere hermetically sealed in flat bottomed aluminium pansand heated in an atmosphere of nitrogen to eliminate theoxidative and pyrolytic effects The heating rate was 5∘Cminin a temperature range of 25ndash300∘C The DSC thermogramswere recorded
28 Compression Study The two well-known compressionmodels The Heckel andThe Kawakita were used to carry outthe studies [14]
281 Determination of Precompression Density The bulkdensity of each sample at zero pressure was determined bypouring the granules through a funnel into a glass measuringcylinder with a 24mm diameter and a volume of 50mL atan angle of 45∘ Determinations were done in triplicate Therelative density 119863
0 of each formulation was obtained from
the ratio of its bulk density to its particle density [15]
282 Preparation of Tablets for Compression Studies Tablets(400mg) were prepared by compressing the prepared conju-gates for 30 seconds with predetermined loads on a hydraulicpress (Model CAP15T-1233 PCI Analytics Pvt Ltd MumbaiIndia) After ejection the tablets were stored over silica gel
for 24 hours Their masses (119898) and dimensions were thendetermined respectively and their relative densities (119877) werecalculated using the equation
119877 =119898
119881119905120588119904
(4)
where119881119905is the volume (cm3) of the tablet and 120588
119904is the particle
density (gcm3) of the solid material [15]
283 The Heckel Function The deformation mechanism ofthe material was determined using the Heckel model asit is widely used for relating the relative density 119863 of apowder bed during compression to the applied pressure 119875The displacement and force data registered on the simulatorwere transferred to a spreadsheet program (Microsoft Excel2007) The force values were converted into pressures andthe displacement values (in combination with the individualtablet weight determined immediately after compaction)and the true density of the material (determined beforecompaction) were used to calculate the apparent densityof the powder bed 1(1 minus 119863) Using the Heckel plot thecompression stage was subjected to linear regression analysisIt is denoted as
ln [1
(1 minus 119863)
] = 119870119875 + 119860 (5)
The slope of the straight line portion 119870 is the reciprocalof the mean yield pressure 119875
119910 of the material From the
intercept 119860 the relative density 119863119860 can be calculated using
the following equation
119863119860= 1 minus 119890
minus119860 (6)
Relative density of the powder at the point when the appliedpressure equals zero 119863
0 is used to describe the initial
rearrangement phase of densification as a result of die filling
119863119861= 119863119860minus 1198630 (7)
Relative density 119863119861 describes the phase of rearrangement
at low pressures and is the difference between 119863119860
and1198630[15 16]
284 The Kawakita Function In the Kawakita equation theparticle density is not introduced in the calculations since themodel operates on the relative change in volume which givesthe same result whether the relative or the absolute volumeis used The problem in calculation of this equation is to findthe correct initial volume 119881
0 The Kawakita equation is used
to study powder compression using the degree of volumereduction (119862) and is written as
119862 =
(1198810minus 119881119901)
1198810
=119886119887119875
(1 + 119887119875)
(8)
The equation in practice can be rearranged to give
119875
119862
=119875
119886
+1
119886119887
(9)
Journal of Drug Delivery 5
where 1198810is the initial bulk volume of the powder and 119881
119901is
the bulk volume after compression Constant ldquo119886rdquo is equal tothe minimum porosity of the material before compressionwhile constant ldquo119887rdquo is related to the plasticity of the materialThe reciprocal of ldquo119887rdquo gives the pressure term 119875
119896 which is the
pressure required to reduce the powder bed by 50 [14 15]
29 Postcompression Evaluation
291 Diameter and Thickness A calibrated vernier calliper(Ms Mitutoyo Corp Japan) was used for diameter andthickness evaluation of tablets
292 Hardness The tablet hardness is the force required tobreak a tablet in a diametric compression force Hardnesstester (Perfit India) was used to determine the force requiredto break the tablet diametrically The test was performed onsix tablets and the average was calculated
293 Friability Thefriability (119865) of a sample of 20 tabletswasmeasured using Roche Friabilator (Model 902 EI PanchkulaIndia) Twenty tablets were weighed and rotated at 25 rpm for4min Tablets were reweighed after removal of fines (dusted)and the percentage of weight loss was calculated Friabilitybelow 1 was considered acceptable
294 Weight Variation Test Weight variation test was doneby weighing 20 tablets individually calculating the averageweight and comparing the individual tablet weight to theaverage weight
295 Content Uniformity The content uniformity wasassessed according to USP method Ten tablets were pulver-ized and quantity of powder equivalent to 10mg of domperi-done was shaken with 100mL of 01 N HCl for 30 minutesThe contents were filtered through a 045120583mmembrane filterdiluted and analyzed at 284 nmusing aUVVIS double beamspectrophotometer (Model 2202 Systronics AhmedabadIndia) [17]
296 Wetting Time A piece of tissue paper (1075 times 12mm)folded twice was placed in a culture dish (119889 = 65 cm)containing 6mL of water (containing a water soluble dyeeosin) A tablet was carefully placed on the surface of tissuepaper and the time required for water to reach the uppersurface of the tablet was noted as the wetting time [18]
297 Water Absorption Ratio The same procedure used forthe wetting time was used for the water absorption ratioInitial weight of the tablet (119882
119886) was measured before its
placement on the wet tissue and the final weight (119882119887) was
taken after complete wetting Water absorption ratio 119877 wasdetermined using the equation [19]
119877 = 100
(119882119887minus 119882119886)
119882119887
(10)
298 Porosity Porosity is a measure of the void spaces in amaterial and is a fraction of the volume of voids over the totalvolume between 0 and 1 or as a percentage between 0 and 100percent The porosity of the tablets was calculated as follows
Porosity =1 minus 119898
120588truelowast 119881 (11)
where 120588true is the true density of the mixture and 119898 and 119881
are the weight and volume of the tablet respectively Thetrue density of the powder was found using true densitymeter (SMART PYCNO 30 Smart Instruments Maharash-tra India)
299 Tablet Packing Fraction (119875119891) The tablet packing
fraction 119875119891 is a measure of the degree of consolida-
tioncompactness of the tablet Tablet packing fraction wasdetermined by the equation
Packing fraction (119875119891) =
119908
1205871199032119905120588
(12)
where119908 is the weight of a tablet 119903 is radius 119905 is thickness and120588 is the particle density
The radius and thickness of 10 tablets were measuredusing a vernier calliper The apparent particle density of thedrug powder was determined using liquid paraffin displace-ment method Firstly the weight of a specific gravity bottlefilledwith liquid paraffin and theweight of the specific gravitybottle containing a sample of the drug powder were notedThe final weight was determined The determination wasexecuted in triplicate and mean results were used in thecalculation of 119875
119891[20]
2910 In Vitro Disintegration Time In vitro disintegrationtime for the tablets was determined using USP disintegrationapparatus (EI Product Panchkula India) using 01 NHCl (pH1-2 900mL at 37∘C) as the disintegrating medium
2911 In Vitro Dissolution Studies In vitro dissolution ofthe fast disintegrating tablets was studied in USP XXIVdissolution apparatus II (DS 8000 Lab India Pune India)employing a paddle stirrer at 50 rpm using 900mL of pH12 01 N HCl at 37 plusmn 05∘C as a dissolution mediumAliquots of 5mL eachwere withdrawn at predetermined timeintervals and replaced with equal volume of fresh mediumAliquots were filtered through a 045120583m membrane filterand analyzed for drug content using a UVVIS double beamspectrophotometer (2202 Systronics Ahmedabad India) at284 nm Drug concentration was calculated and expressed ascumulative percent of the drug releasedThe similarity factor(1198912) is a logarithmic transformation of the sum-squared
error of differences between the test (119879119895) and reference
(119877119895) products over all time points It is a useful tool for
comparison of dissolution profiles when more than three orfour dissolution time points are available It is calculated as
(119882119895) is an optional weight factor The similarity factor fits
result between 0 and 100 It is 100 when the test and referenceprofiles are identical and tends to be 0 as the dissimilarityincreases In order to consider similar dissolution profiles 119891
2
values should be close to 100
3 Result and Discussion
31 Precompression Evaluation
311 Micromeritics Study The result of the micromeriticstudies for corn starch and the prepared corn Starch-NeusilinUFL2 conjugates were conducted and results are listed inTable 2 Angle of repose (120579∘) is a characteristic of the internalfriction or cohesion of the particles Its value will be highif the powder is cohesive and low if the powder is non-cohesive Flow property of the corn starch was improvedby the addition of Neusilin UFL2 as compared formulationswith conjugates showed good to excellent flow properties asindicated by the values of angle of repose (3669ndash2767∘) to thecorn starch (4325∘) Carrrsquos index showed values 225 to 125denoting that these formulations were of acceptable to goodflowability compared to the corn starch (3428) Hausnerrsquosratio showed that powders with low interparticle frictionhad ratios of approximately 129 to 114 indicating good flowproperties as compared to the corn starch (152) Swellingindex of the conjugates prepared by physical chemical andmicrowave method were found to be 40 65 and 95respectively which was far better than the swelling index ofcorn starch that is 18 which is in context with the effectivepore radius of the conjugates and corn starch The resultsof both swelling and effective pore radius point towardsmore wicking action capability and hence disintegrationpotential of the conjugates over the pure corn starch Theresult of micromeritic study indicates that conjugates pre-pared by microwave method were the most effective methodfollowed by chemical and physical method as they gave bettermicromeritic properties as evidenced from the Table 2
312 ATR-FTIR Analysis Corn starch and Neusilin UFL2interactions studies were carried out using ATR-FTIR spec-trophotometer and the spectra for the samples are shownin Figure 1 The IR spectra of corn starch showed a peakat 3434 cmminus1 and 2931 cmminus1 representing OndashH and CndashHstretching respectively The absorption band at 1652 cmminus1is due to absorbed water in amorphous region of starchPeak at 1241 cmminus1 represents CH
2OH group whereas peak
at 1159 cmminus1 represents coupling mode of CndashC and CndashOstretching vibrations The band at 1080 cmminus1 represents CndashOndashH bending vibration whereas peak at 929 cmminus1 could beascribed to the skeletal mode vibration of 120572-14-glycosidiclinkage The corn Starch-Neusilin UFL2 conjugates preparedby different methods namely physical microwave andchemical exhibit a sharp peak near 3480 cmminus1 which isotherwise observed at 3434 cmminus1 in the pure corn starchThisshift and sharpening of peak indicate the formation of SindashOndashC bridging bond between corn starch and Neusilin UFL2Moreover reduction in the intensity of peak at 1241 cmminus1
4000 3000 2000 1500 1000 400
(cmminus1)
T(
)
(A)
(B)
(C)
(D)
Figure 1 IR spectra of (A) native corn starch corn Starch-NeusilinUFL2 conjugates by (B) physical method (C) chemical method and(D) microwave method
1159 cmminus1 and 1080 cmminus1 confirms intermolecular bridgingbetween corn starch and Neusilin UFL2 Thus the additionof Neusilin changed the properties of corn starch forming anew excipient with different functional properties
313 XRD Analysis The XRD patterns of the samples areshown in Figure 2 The structure of corn starch is char-acterized by the presence of broad peak at 2456∘2120579 angleAppearance of sharp peak at 2740∘2120579 3172∘2120579 4560∘21205795391∘2120579 and 5647∘2120579 angles respectively in case of conju-gates prepared bymicrowavemethod gives clear indication ofreduction in amorphous nature or otherwise increase in thecrystalline behavior of the corn starch that could be correlatedwith the increase in swelling and hence superdisintegrantpotential of conjugates prepared by different methods Crys-tallinity and hence the superdisintegrant property (Table 4)of conjugates prepared by different methods were in therank order of microwave gt chemical gt physical mixtureHigh proportion of longer chains might form more stablecrystallites in the pure corn starch The swelling powerof corn starch depends on the water holding capacity ofthe starch molecule by hydrogen bonding Hence higherdegree of intermolecular bonding between corn starch andNeusilin UFL2 favors the long chain crystalline structureand hence the swelling of the conjugates which in turnpotentiates the use of corn Starch-Neusilin UFL2 as a tabletsuperdisintegrant [21]
314 DSC Analysis Figure 3 shows the DSC thermogramsof the pure corn starch and corn Starch-Neusilin UFL2conjugates prepared by physical chemical and microwavemethods Corn starch has a discrete structure and pos-sesses partially crystalline microscopic granules that are
Figure 2 XRD pattern of (A) native corn starch corn Starch-Neusilin UFL2 conjugates by (B) physical method (C) chemicalmethod and (D) microwave method
held together by intended micellar network of associatedmolecules so it does not show obvious Tg or Tm untilpyrogenation Melting range was found to be extended andbroadened with the incorporation of Neusilin UFL2 Broad-ening and shifting of the melting range in the DSC spectracould be attributed to intermolecular bonding between cornstarch and Neusilin UFL2 indicating that the Neusilin UFL2molecules were restrained by the corn starch molecules Thebroadening of themelting range could be due to the regularityof the OH group that already existed in corn starch whichhad disappeared by the interaction with Neusilin UFL2 TheTm and ΔH of the melting peak are significantly lower inthe pure corn starch than the conjugates which indicate thatthere is an interaction between corn starch and NeusilinUFL2 which has enhanced the crystallization of the purecorn starch This increase in crystalline behaviour of thepure corn starch could be correlated to increase in swelling
40 50 60 70 80 90 100 110 120 130 140
Temperature (∘C)
(A)
(B)
(C)(D)
Figure 3 DSC pattern of (A) native corn starch corn Starch-Neusilin UFL2 conjugates by (B) physical method (C) chemicalmethod and (D) microwave method
and hence superdisintegrant potential of conjugates preparedby different methods Crystallinity and superdisintegrantbehaviour of conjugates prepared by different methods couldbe arranged as microwave gt chemical gt physical mixtureFurthermore the crystalline structure contributes towardsthe swelling behaviour of the conjugates responsible for thetablet superdisintegrant activity
315 SEM Analysis Surface morphology of the corn starchand corn Starch-Neusilin UFL2 conjugates was studied bySEManalysis as shown in Figure 4The corn starch undergoesa change in its native structure from thin smooth flatsurface structure with folded edges to three dimensionalcompacts upon conjugation with the Neusilin UFL2 SEMmicrograph of the prepared conjugates showed the presenceof interparticulate voids and channels that are responsible forthe increase in water absorption and swelling capacity of theconjugates as compared to the pure corn starch Furthermorethese voidschannels contributed to the wicking behaviorresponsible for the tablet superdisintegrant property of thecorn Starch-Neusilin UFL2 conjugates Conjugates preparedbymicrowavemethod illustrated the presence ofmore porous
8 Journal of Drug Delivery
structure as compared to conjugates prepared by physicaland chemical methods The results are in line with the betterin vitro disintegration performance of FDT prepared withconjugates of microwave method compared to the other twomethods
316 Heckel FunctionAnalysis Figure 5 shows representativeHeckel plots for the conjugates prepared by physical chem-ical and microwave methods The Heckel plots showed aninitial linear portion with an increase slope at pressure of100MPa followed by another linear region for the conjugatesprepared by physical and chemical methods while for theconjugate prepared by microwave method the second linearregion was from 175MPaThe mean yield pressure values forthe conjugates were calculated from the slope of the portionshowing the highest linearity of the Heckel plots and theintercept 119860 was determined from the extrapolation of theregionThe values of119863
119860and119863
119861were calculated respectively
The values of 119875119910 1198630 119863119860 and 119863
119861for the formulations are
presented in Table 3 The value of 1198630which represents the
degree of initial packing in the die as a result of die fillingfor the conjugates indicates that the conjugates preparedby microwave method exhibited highest degree of packingin the die as a result of die filling while the conjugatesprepared by physical method exhibited the lowest valuesThevalue of 119863
119861represents the phase of rearrangement of the
particles in the early stages of compression119863119861values tend to
indicate the extent of fragmentation of particles or granulesalthough fragmentation can occur concurrently with plasticand elastic deformation of constituent particles The chemi-cally prepared conjugates exhibited the highest values whilethe one prepared by microwave method exhibited the lowestvalues This indicates that fragmentation occurs more withthe chemically prepared conjugates [22 23]The values of119863
119860
which represents the total degree of packing achieved at zeroand low pressures was also in the rank order of microwave gtchemical gt physical for the methods to prepare conjugatesThis indicates that the conjugates prepared by microwavemethod showed higher degree of packing at low pressuresThe mean yield pressure 119875
119910is inversely related to the ability
of the formulations to deform plastically under pressureThe result indicates that the conjugates prepared by physicalmethod showed the fastest onset of plastic deformation whilethe conjugates prepared by microwave method showed theslowest onset Materials with high yield pressure are classifiedas brittle or fragmenting materials whereas those with lowervalues are classified as plasticallyelastically deforming mate-rials [24] Generally during compression plastic deformationand fragmentation are known to occur concurrently Starcheshave been known to deform plastically under compressionpressure
317 Kawakita Function Analysis TheKawakita plots for theconjugates are presented in Figure 6 A linear relationshipwas obtained at all compression pressures employed withcorrelation coefficient of 0999 for the conjugates preparedby different methods The values of 119886 and 119886119887 were obtainedfrom the slope and intercept respectivelyThe value of (1minus119886)
gives the initial relative density of the starch 119863119868 while 119875
119896
values were obtained from the reciprocal of values of 119887The values of 119863
119868and 119875
119896are shown in Table 3 The value
of 119863119868is a measure of the packed initial relative density of
the formulation with the application of small pressure ortapping The ranking of 119863
119868for the conjugates was chemical
method gt microwave method gt physical method The valueof 119875119896which is an inverse measure of the amount of plastic
deformation occurring during the compression process wasfound to be maximum for tablets formulated using conju-gates prepared by chemical method followed by microwavemethod and physical method [23]Thus conjugates preparedby microwave method exhibited the highest amount of totalplastic deformation while conjugates prepared by physicalmethod exhibited the lowest values The ranking was seen tobe in the reverse order as that of the 119875
119910values It has been
shown that while119875119910relates to the onset of plastic deformation
during compression the 119875119896relates to the amount of plastic
deformation that occurs during the compression processThus the conjugates prepared by physical method showedthe slowest onset of plastic deformation but the highest totalamount of plastic deformation
32 Postcompression Evaluation Tablets require certainamount of strength and resistance to friability to withstandmechanical shock of handling during manufacturingshipping and packaging Hardness of the tablets formulatedusing the corn starch-Neusilin UFL2 conjugates assuperdisintegrant was found to vary from 43 to 35 kgcm2compared to 315 to 309 kgcm2 of tablets formulatedusing the native corn starch Percentage friability of allformulations was less than 1 indicating good mechanicalcharacteristics Wetting time was observed to be decreasedfrom 68 seconds for the tablets incorporating native cornstarch to 33 22 and 14 seconds for the tablets incorporatingconjugates prepared by physical chemical and microwavemethods Disintegration time was also observed to decreasefrom 83 seconds for the tablets incorporating native cornstarch to 40 35 and 22 seconds for the tablets incorporatingconjugates prepared by physical chemical and microwavemethods respectively Water absorption ratio was found tobe inversely proportional to the wetting and disintegratingtime of the tablets The increase in water absorption ratioand decrease in wetting and disintegration times in allformulations may be attributed to the modification of thecorn starch by Neusilin UFL2 to yield a novel conjugatewhich acts as superdisintegrant which absorbs water andswells causing rupture of the tablets Tablet propertiessuch as mechanical strength tablet packing fraction anddisintegration are in turn affected by the porosity [25]Tablets with low packing fraction have high porosity andpores facilitates the penetration of dissolution media intothe tablet leading to disintegration of the tablet Whereashigher tablet packing fraction leads to reduction in porositywhich inhibits the penetration of dissolution media resultingin slower disintegration rate of the tablet [26] Tabletpacking fraction was found to be decreased in the tabletsincorporating conjugates (063ndash041) compared to the tablets
Journal of Drug Delivery 9
(a) (b)
(c) (d)
Figure 4 SEM photomicrographs of (A) corn starch and corn Starch-Neusilin UFL2 conjugates prepared by (B) physical method (C)chemical method and (D) microwave method
Table 3 Parameters derived from the Heckel and Kawakita plots for tablet incorporating corn Starch-Neusilin UFL2 conjugate as asuperdisintegrant prepared by (A) physical method (B) chemical method and (C) microwave method
Figure 5 Heckel plots for the tablet incorporating corn Starch-Neusilin UFL2 conjugate as a superdisintegrant prepared by (A)physical method (B) chemical method and (C)microwavemethod
with corn starch (082) The results are in line with thepowder evaluation results where conjugates prepared byphysical chemical and microwave methods were showing
0
50
100
150
200
250
300
0 50 100 150 200 250
PC
Applied pressure (MPa)
ABC
Figure 6 Kawakita plots for the tablet incorporating corn Starch-Neusilin UFL2 conjugate as a superdisintegrant prepared by (A)physical method (B) chemical method and (C)microwavemethod
better swelling and effective pore radius compared to thenative corn starch The fast disintegration of tablets is dueto the presence of pores resulting in faster penetration of
10 Journal of Drug Delivery
Table4Differentp
ropertieso
fthe
form
ulated
FDTs
Cod
eParameter
Diameter
(mm)
Thickn
ess(mm)
Friability(
)Hardn
ess(kgcm
2 )TSlowast(M
Nm
2 )WTlowast
(Sec)
WARlowast
()
DTlowast
(Sec)
CUlowast(
)TP
Flowast119875lowast(
)1198652
F1674
plusmn003
356
plusmn003
089
plusmn004
311
plusmn010
047
plusmn015
68plusmn113
40plusmn011
73plusmn3
9899plusmn02
081
189
19F2
673
plusmn004
351
plusmn004
091
plusmn002
315
plusmn007
047
plusmn005
68plusmn12
942
plusmn011
73plusmn1
991plusmn015
082
175
24F3
674
plusmn005
355
plusmn005
089
plusmn005
309
plusmn011
047
plusmn011
67plusmn111
46plusmn009
71plusmn2
9727plusmn09
081
187
21F4
673
plusmn001
359
plusmn005
090
plusmn003
310
plusmn002
047
plusmn009
66plusmn114
46plusmn010
71plusmn3
9659plusmn05
080
194
25F5
674
plusmn001
351
plusmn005
076
plusmn004
350
plusmn011
048
plusmn005
33plusmn114
98plusmn004
48plusmn2
9650plusmn03
063
367
43F6
674
plusmn002
355
plusmn004
073
plusmn005
356
plusmn008
048
plusmn001
33plusmn16
796
plusmn004
46plusmn3
991plusmn015
062
373
43F7
674
plusmn001
355
plusmn005
071
plusmn002
370
plusmn015
056
plusmn018
32plusmn110
101plusmn
005
44plusmn1
9835plusmn02
062
373
45F8
674
plusmn003
356
plusmn003
067
plusmn003
375
plusmn021
055
plusmn008
31plusmn14
0103plusmn002
40plusmn2
9923plusmn05
062
375
47F9
673
plusmn004
355
plusmn002
055
plusmn001
400
plusmn018
060
plusmn019
23plusmn13
4108plusmn003
40plusmn6
9912
plusmn04
054
426
50F10
674
plusmn005
354
plusmn007
054
plusmn005
380
plusmn015
057
plusmn006
22plusmn12
5100plusmn002
35plusmn3
9892plusmn07
057
435
50F11
673
plusmn003
356
plusmn004
055
plusmn003
370
plusmn017
056
plusmn011
23plusmn10
5106plusmn006
36plusmn2
9727plusmn09
057
423
55F12
673
plusmn002
353
plusmn003
051
plusmn004
410
plusmn02
062
plusmn015
23plusmn13
8110
plusmn004
32plusmn7
9659plusmn05
056
426
53F13
674
plusmn003
355
plusmn004
041
plusmn007
420
plusmn027
073
plusmn008
14plusmn15
2121plusmn
008
26plusmn2
9915
plusmn01
041
582
50F14
673
plusmn001
351
plusmn004
042
plusmn002
425
plusmn02
073
plusmn020
14plusmn12
6124plusmn007
24plusmn5
9899plusmn02
039
595
52F15
674
plusmn003
355
plusmn006
044
plusmn004
430
plusmn010
076
plusmn018
13plusmn115
125plusmn003
22plusmn3
9975plusmn10
040
599
62F16
674
plusmn001
359
plusmn005
047
plusmn007
420
plusmn045
079
plusmn019
14plusmn14
0128plusmn005
22plusmn4
9912
plusmn03
041
612
64TSlowasttensiles
treng
thW
Tlowastw
ettin
gtim
eWARlowast
water
absorptio
nratio
DTlowast
disintegratio
ntim
eCUlowastcon
tent
unifo
rmity
TPFlowasttabletp
acking
fractio
n119875lowastporosity
Journal of Drug Delivery 11
the dissolution media leading to swelling and wicking of theprepared conjugate creating hydrodynamic pressure insidethe tablets hence responsible for the quick and completedisintegration of tablets indicating the superdisintegrantactivity of conjugates prepared by physical chemical andmicrowave methods over the native corn starch
The results obtained from the in vitro dissolution studyare presented in Figures 7 8 9 and 10 ldquoMKTDrdquo representsthe standard marketed domperidone formulation to whichthe formulated FDTs were compared The similarity factor(1198912) is a logarithmic transformation of the sum-squared
error of differences between test and reference productsover all time points It was observed that the three differentapproaches used for the preparation of conjugate in thisstudy namely physical chemical and microwave methodsincreased the dissolution rate of the drug compared to thetablet prepared with the native corn starch and standardmarketed formulation of the drug The order of increaseddrug dissolution using the different approaches was asfollows microwave gt chemical gt physical In case of theFDTs prepared by using native corn starch (F1ndashF4) thepercentage cumulative drug release was found to be verypoor as compared to the standard marketed formulation ofdomperidone (MKTD)The119891
2value for formulation (F1ndashF4)
was below 50 depicting the dissimilarity between the drugreleases Formulations (F5ndashF8) (F9ndashF12) and (F13ndashF16)werecontaining corn starch-Neusilin UFL2 conjugate prepared byphysical chemical and microwave methods The percentagecumulative drug release for these formulations were found tobe comparable to the standardmarketed formulation of dom-peridone The 119891
2values for these formulations were found
to be over 50 evidencing the similarity between the drugreleases Results of various tablet evaluation tests as evidencedfrom Table 4 indicate that among the three methods usedfor the preparation of conjugates microwave was the mosteffectivemethod followed by chemical and physical methodsMoreover by increasing the concentration of conjugates thetablet did not show much effect on drug release from theformulated FDTs Hence from the commercial point of viewlowest concentration of superdisintegrant showing optimumtabletting results should be recommended
4 Conculsions
In present work an attempt was made to modify the cornstarch to develop corn starch-Neusilin UFL2 conjugatesusing different methods namely physical chemical andmicrowave The prepared conjugates and the corn starchwere characterised for powder flow pH viscosity swellingand effective pore radius Evaluation of precompressionparameter indicates good flow properties The preparedconjugates were also subjected to the compression studiesnamely Heckel and Kawakita function The Heckel plot isusually correlated with the speed of the tablet machine whilethe Kawakita plot is related to the crushing or tensile strengthof the tablet Fast disintegrating tablets of domperidone wereformulated by direct compression technique employing thecorn starch and the prepared conjugates The tablets were
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F1F2F3
F4MKTD
Figure 7 Dissolution rate profiles of FDTs (F1ndashF4) formulated byincorporating native corn starch as a superdisintegrant compared toa standard marketed formulation of domperidone (MKTD)
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F5F6F7
F8MKTD
Figure 8 Dissolution rate profiles of FDTs (F5ndashF8) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates preparedby physical method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
evaluated for physical parametric tests wetting time waterabsorption ratio porosity tablet packing fraction in vitrodisintegration time drug content in vitro dissolution andstability studies Extensive swelling porosity and wickingaction of the prepared corn Starch-Neusilin UFL2 conjugatesin the prepared fast disintegrating tablets were found to becontributing to its superdisintegrant action
In conclusion the prepared conjugates can be effectivelyused as superdisintegrant in order to develop a faster disin-tegrating tablet formulation Future challenges for many fastdisintegrating tablet manufacturers include reducing costsby finding ways to manufacture with conventional equip-ment using versatile packaging and improving mechanical
12 Journal of Drug Delivery
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F9F10F11
F12MKTD
Figure 9 Dissolution rate profiles of FDTs (F9ndashF12) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates preparedby chemical method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
F13F14F15
F16MKTD
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
Figure 10 Dissolution rate profiles of FDTs (F13ndashF16) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates prepared bymicrowave method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
strength Such products provide an opportunity for theproduct line extension in the market place and extensionof patent term of innovator Due to its wide significancethis drug delivery system may lead to better patient com-pliance and ultimate clinical output Future might witnessnovel technologies for development and utilization of themodified starches as tablet superdisintegrant for cost effectiveformulation of fast disintegrating tablets
Conflict of Interests
The authors declare that they have no conflict of interests
Acknowledgments
The authors gratefully acknowledge Dr Madhu ChitkaraVice Chancellor Chitkara University Rajpura Punjab IndiaDr Ashok Chitkara Chairman Chitkara Educational TrustChandigarh India and Dr Sandeep Arora Dean ChitkaraUniversity Rajpura Punjab India for support and institu-tional facilities
References
[1] I Rashid M Al-Remawi S A Leharne B Z Chowdhry andA Badwan ldquoA novel multifunctional pharmaceutical excipientmodification of the permeability of starch by processing withmagnesium silicaterdquo International Journal of Pharmaceutics vol411 no 1-2 pp 18ndash26 2011
[2] O A Odeku and K M Picker-Freyer ldquoAnalysis of the materialand tablet formation properties of four Dioscorea starchesrdquoStarchStarke vol 59 no 9 pp 430ndash444 2007
[3] N Visavarungroj and J P Remon ldquoAn evaluation of hydrox-ypropyl starch an disintegrant and binder in tablet formulationrdquoDrug Development and Industrial Pharmacy vol 17 no 10 pp1389ndash1396 1991
[4] M Nakano N Nakazono and N Inotsume ldquoPreparation andevaluation of sustained release tablets prepared with 120572-starchrdquoChemical and Pharmaceutical Bulletin vol 35 no 10 pp 4346ndash4350 1987
[5] O A Odeku and K M Picker-Freyer ldquoFreeze-dried prege-latinized Dioscorea starches as tablet matrix for sustainedreleaserdquo Journal of Excipients and Food Chemicals vol 1 no 2pp 21ndash32 2010
[6] H Staroszczyk ldquoMicrowave-assisted silication of potato starchrdquoCarbohydrate Polymers vol 77 no 3 pp 506ndash515 2009
[7] J Singh L Kaur and O J McCarthy ldquoFactors influencingthe physico-chemical morphological thermal and rheologicalproperties of some chemically modified starches for foodapplications a reviewrdquo Food Hydrocolloids vol 21 no 1 pp 1ndash22 2007
[8] I Rashid N Daraghmeh M Al-Remawi S A Leharne B ZChowdhry and A Badwan ldquoCharacterization of chitin-metalsilicates as binding superdisintegrantsrdquo Journal of Pharmaceuti-cal Sciences vol 98 no 12 pp 4887ndash4901 2009
[9] I Rashid N Daraghmeh M Al-Remawi S A Leharne B ZChowdhry and A Badwan ldquoCharacterization of the impactof magnesium stearate lubrication on the tableting propertiesof chitin-Mg silicate as a superdisintegrating binder whencompared to Avicel 200rdquo Powder Technology vol 203 no 3 pp609ndash619 2010
[10] Y Asai M Nohara S Fujioka K Isaji and S Nagira ldquoApplica-tion of Neusilin UFL2 on manufacturing of tablets using directcompression method Development of core tablets containingthe function of small degree of decrease of hardness at thehumid conditionsrdquoPharmaceutical Technical Newsletter vol 25pp 67ndash70 2009
[11] B G Prajapati and D V Patel ldquoFormulation and optimiza-tion of domperidone fast dissolving tablet by wet granulationtechniques using factorial designrdquo International Journal ofPharmTech Research vol 2 no 1 pp 292ndash299 2010
[12] J Cooper and C Gunn ldquoPowder flow and compactionrdquo inTutorial Pharmacy S J Carter Ed pp 211ndash233 CBS Publishersand Distributors New Delhi India 1986
Journal of Drug Delivery 13
[13] H Goel G Kaur A K Tiwary and V Rana ldquoFormulationdevelopment of stronger and quick disintegrating tablets acrucial effect of chitinrdquoYakugaku Zasshi vol 130 no 5 pp 729ndash735 2010
[14] J M Sonnergaard ldquoImpact of particle density and initial vol-ume on mathematical compression modelsrdquo European Journalof Pharmaceutical Sciences vol 11 no 4 pp 307ndash315 2000
[15] O A Odeku ldquoAssessment of Albizia zygia gum as a bindingagent in tablet formulationsrdquo Acta Pharmaceutica vol 55 no3 pp 263ndash276 2005
[16] F Kiekens A Debunne C Vervaet et al ldquoInfluence of thepunch diameter and curvature on the yield pressure of MCC-compacts duringHeckel analysisrdquo European Journal of Pharma-ceutical Sciences vol 22 no 2-3 pp 117ndash126 2004
[17] ldquoUnited States Pharmacopeia 24NF19rdquo inTheOfficial Compen-dia of Standards M D Asian Rockville Ed pp 1913ndash1914 USPharmacopeial Convention 2000
[18] T Y Puttewar M D Kshirsagar A V Chandewar and R VChikhale ldquoFormulation and evaluation of orodispersible tabletof tastemasked doxylamine succinate using ion exchange resinrdquoJournal of King Saud UniversitymdashScience vol 22 no 4 pp 229ndash240 2010
[19] A Fini V Bergamante G C Ceschel C Ronchi and C A Fde Moraes ldquoFast dispersibleslow releasing ibuprofen tabletsrdquoEuropean Journal of Pharmaceutics and Biopharmaceutics vol69 no 1 pp 335ndash341 2008
[20] M U Uhumwangho and R S Okor ldquoEffect of humidity on thedisintegrant property of 120572-cellulose Part II A technical noterdquoAAPS PharmSciTech vol 6 no 1 article no 7 pp E31ndashE342005
[21] T Sasaki and J Matsuki ldquoEffect of wheat starch structure onswelling powerrdquo Cereal Chemistry vol 75 no 4 pp 525ndash5291998
[22] O A Itiola and N Pilpel ldquoTableting characteristics of metron-idazole formulationsrdquo International Journal of Pharmaceuticsvol 31 no 1-2 pp 99ndash105 1986
[23] O A Odeku and O A Itiola ldquoEvaluation of khaya gum asa binder in a paracetamol tablet formulationrdquo Pharmacy andPharmacology Communications vol 4 no 4 pp 183ndash188 1998
[24] O A Odeku and J T Fell ldquoEffects of the method of preparationon the compression mechanical and release properties ofkhaya gum matricesrdquo Pharmaceutical Development and Tech-nology vol 11 no 4 pp 435ndash441 2006
[25] O A Odeku and B L Akinwande ldquoEffect of the mode ofincorporation on the disintegrant properties of acid modifiedwater and white yam starchesrdquo Saudi Pharmaceutical Journalvol 20 no 2 pp 171ndash175 2012
[26] R Shangraw A Mitrevej and M Shah ldquoA new era of tabletdisintegrantsrdquo Pharmaceutical Technology vol 4 no 10 pp 49ndash57 1980
4 Journal of Drug Delivery
the tip The tip was reweighed (119882119891) and effective pore radius
was calculated by
119877effP = 119882119891minus
119882119894
2120587120574
(3)
24 Attenuated Total Reflectance-Fourier Transform IR Spec-troscopy (ATR-FTIR) The infrared (IR) spectra of sam-ples were obtained using an Attenuated Total Reflectance-Fourier Transform Infra-Red (ATR-FTIR) spectrophotome-ter (Alpha Bruker Japan) The samples were scanned inthe spectral region of 4000 cmminus1 to 400 cmminus1 by KBr pelletmethod
25 X-Ray Powder Diffraction (XRPD) The X-ray powderdiffractograms were registered in an X-Pert Pro (USA) inBragg-Brentano geometry using glass tubing with a Cuanode and graphite monochromator The diffractometer wasoperated at 40mA and 40 kV All the samples being a sizeof less than 250 120583m were randomly placed on a glass sliderespectively The signals of the reflection angle of 2120579 wererecorded from 0∘ to 60∘ at a scanning rate 021∘sec
26 Scanning Electron Microscopy (SEM) The scanning elec-tron micrographs were taken to study the surface morphol-ogy using a Hitachi (Model S 4300 SEN SEM Hitachi HighTechnologies Singapore) at an accelerator potential of 10 kVThe samples were stuck on a specimen holder using a silverplate and then coatedwith palladium in a vacuum evaporator
27 Differential Scanning Calorimetry (DSC) The thermaltransitions of starch samples were investigated with the useof a Perkin Elmer DSC 8000 apparatus (USA) calibrated byusing a high purity indium standard Samples about 10mgwere hermetically sealed in flat bottomed aluminium pansand heated in an atmosphere of nitrogen to eliminate theoxidative and pyrolytic effects The heating rate was 5∘Cminin a temperature range of 25ndash300∘C The DSC thermogramswere recorded
28 Compression Study The two well-known compressionmodels The Heckel andThe Kawakita were used to carry outthe studies [14]
281 Determination of Precompression Density The bulkdensity of each sample at zero pressure was determined bypouring the granules through a funnel into a glass measuringcylinder with a 24mm diameter and a volume of 50mL atan angle of 45∘ Determinations were done in triplicate Therelative density 119863
0 of each formulation was obtained from
the ratio of its bulk density to its particle density [15]
282 Preparation of Tablets for Compression Studies Tablets(400mg) were prepared by compressing the prepared conju-gates for 30 seconds with predetermined loads on a hydraulicpress (Model CAP15T-1233 PCI Analytics Pvt Ltd MumbaiIndia) After ejection the tablets were stored over silica gel
for 24 hours Their masses (119898) and dimensions were thendetermined respectively and their relative densities (119877) werecalculated using the equation
119877 =119898
119881119905120588119904
(4)
where119881119905is the volume (cm3) of the tablet and 120588
119904is the particle
density (gcm3) of the solid material [15]
283 The Heckel Function The deformation mechanism ofthe material was determined using the Heckel model asit is widely used for relating the relative density 119863 of apowder bed during compression to the applied pressure 119875The displacement and force data registered on the simulatorwere transferred to a spreadsheet program (Microsoft Excel2007) The force values were converted into pressures andthe displacement values (in combination with the individualtablet weight determined immediately after compaction)and the true density of the material (determined beforecompaction) were used to calculate the apparent densityof the powder bed 1(1 minus 119863) Using the Heckel plot thecompression stage was subjected to linear regression analysisIt is denoted as
ln [1
(1 minus 119863)
] = 119870119875 + 119860 (5)
The slope of the straight line portion 119870 is the reciprocalof the mean yield pressure 119875
119910 of the material From the
intercept 119860 the relative density 119863119860 can be calculated using
the following equation
119863119860= 1 minus 119890
minus119860 (6)
Relative density of the powder at the point when the appliedpressure equals zero 119863
0 is used to describe the initial
rearrangement phase of densification as a result of die filling
119863119861= 119863119860minus 1198630 (7)
Relative density 119863119861 describes the phase of rearrangement
at low pressures and is the difference between 119863119860
and1198630[15 16]
284 The Kawakita Function In the Kawakita equation theparticle density is not introduced in the calculations since themodel operates on the relative change in volume which givesthe same result whether the relative or the absolute volumeis used The problem in calculation of this equation is to findthe correct initial volume 119881
0 The Kawakita equation is used
to study powder compression using the degree of volumereduction (119862) and is written as
119862 =
(1198810minus 119881119901)
1198810
=119886119887119875
(1 + 119887119875)
(8)
The equation in practice can be rearranged to give
119875
119862
=119875
119886
+1
119886119887
(9)
Journal of Drug Delivery 5
where 1198810is the initial bulk volume of the powder and 119881
119901is
the bulk volume after compression Constant ldquo119886rdquo is equal tothe minimum porosity of the material before compressionwhile constant ldquo119887rdquo is related to the plasticity of the materialThe reciprocal of ldquo119887rdquo gives the pressure term 119875
119896 which is the
pressure required to reduce the powder bed by 50 [14 15]
29 Postcompression Evaluation
291 Diameter and Thickness A calibrated vernier calliper(Ms Mitutoyo Corp Japan) was used for diameter andthickness evaluation of tablets
292 Hardness The tablet hardness is the force required tobreak a tablet in a diametric compression force Hardnesstester (Perfit India) was used to determine the force requiredto break the tablet diametrically The test was performed onsix tablets and the average was calculated
293 Friability Thefriability (119865) of a sample of 20 tabletswasmeasured using Roche Friabilator (Model 902 EI PanchkulaIndia) Twenty tablets were weighed and rotated at 25 rpm for4min Tablets were reweighed after removal of fines (dusted)and the percentage of weight loss was calculated Friabilitybelow 1 was considered acceptable
294 Weight Variation Test Weight variation test was doneby weighing 20 tablets individually calculating the averageweight and comparing the individual tablet weight to theaverage weight
295 Content Uniformity The content uniformity wasassessed according to USP method Ten tablets were pulver-ized and quantity of powder equivalent to 10mg of domperi-done was shaken with 100mL of 01 N HCl for 30 minutesThe contents were filtered through a 045120583mmembrane filterdiluted and analyzed at 284 nmusing aUVVIS double beamspectrophotometer (Model 2202 Systronics AhmedabadIndia) [17]
296 Wetting Time A piece of tissue paper (1075 times 12mm)folded twice was placed in a culture dish (119889 = 65 cm)containing 6mL of water (containing a water soluble dyeeosin) A tablet was carefully placed on the surface of tissuepaper and the time required for water to reach the uppersurface of the tablet was noted as the wetting time [18]
297 Water Absorption Ratio The same procedure used forthe wetting time was used for the water absorption ratioInitial weight of the tablet (119882
119886) was measured before its
placement on the wet tissue and the final weight (119882119887) was
taken after complete wetting Water absorption ratio 119877 wasdetermined using the equation [19]
119877 = 100
(119882119887minus 119882119886)
119882119887
(10)
298 Porosity Porosity is a measure of the void spaces in amaterial and is a fraction of the volume of voids over the totalvolume between 0 and 1 or as a percentage between 0 and 100percent The porosity of the tablets was calculated as follows
Porosity =1 minus 119898
120588truelowast 119881 (11)
where 120588true is the true density of the mixture and 119898 and 119881
are the weight and volume of the tablet respectively Thetrue density of the powder was found using true densitymeter (SMART PYCNO 30 Smart Instruments Maharash-tra India)
299 Tablet Packing Fraction (119875119891) The tablet packing
fraction 119875119891 is a measure of the degree of consolida-
tioncompactness of the tablet Tablet packing fraction wasdetermined by the equation
Packing fraction (119875119891) =
119908
1205871199032119905120588
(12)
where119908 is the weight of a tablet 119903 is radius 119905 is thickness and120588 is the particle density
The radius and thickness of 10 tablets were measuredusing a vernier calliper The apparent particle density of thedrug powder was determined using liquid paraffin displace-ment method Firstly the weight of a specific gravity bottlefilledwith liquid paraffin and theweight of the specific gravitybottle containing a sample of the drug powder were notedThe final weight was determined The determination wasexecuted in triplicate and mean results were used in thecalculation of 119875
119891[20]
2910 In Vitro Disintegration Time In vitro disintegrationtime for the tablets was determined using USP disintegrationapparatus (EI Product Panchkula India) using 01 NHCl (pH1-2 900mL at 37∘C) as the disintegrating medium
2911 In Vitro Dissolution Studies In vitro dissolution ofthe fast disintegrating tablets was studied in USP XXIVdissolution apparatus II (DS 8000 Lab India Pune India)employing a paddle stirrer at 50 rpm using 900mL of pH12 01 N HCl at 37 plusmn 05∘C as a dissolution mediumAliquots of 5mL eachwere withdrawn at predetermined timeintervals and replaced with equal volume of fresh mediumAliquots were filtered through a 045120583m membrane filterand analyzed for drug content using a UVVIS double beamspectrophotometer (2202 Systronics Ahmedabad India) at284 nm Drug concentration was calculated and expressed ascumulative percent of the drug releasedThe similarity factor(1198912) is a logarithmic transformation of the sum-squared
error of differences between the test (119879119895) and reference
(119877119895) products over all time points It is a useful tool for
comparison of dissolution profiles when more than three orfour dissolution time points are available It is calculated as
(119882119895) is an optional weight factor The similarity factor fits
result between 0 and 100 It is 100 when the test and referenceprofiles are identical and tends to be 0 as the dissimilarityincreases In order to consider similar dissolution profiles 119891
2
values should be close to 100
3 Result and Discussion
31 Precompression Evaluation
311 Micromeritics Study The result of the micromeriticstudies for corn starch and the prepared corn Starch-NeusilinUFL2 conjugates were conducted and results are listed inTable 2 Angle of repose (120579∘) is a characteristic of the internalfriction or cohesion of the particles Its value will be highif the powder is cohesive and low if the powder is non-cohesive Flow property of the corn starch was improvedby the addition of Neusilin UFL2 as compared formulationswith conjugates showed good to excellent flow properties asindicated by the values of angle of repose (3669ndash2767∘) to thecorn starch (4325∘) Carrrsquos index showed values 225 to 125denoting that these formulations were of acceptable to goodflowability compared to the corn starch (3428) Hausnerrsquosratio showed that powders with low interparticle frictionhad ratios of approximately 129 to 114 indicating good flowproperties as compared to the corn starch (152) Swellingindex of the conjugates prepared by physical chemical andmicrowave method were found to be 40 65 and 95respectively which was far better than the swelling index ofcorn starch that is 18 which is in context with the effectivepore radius of the conjugates and corn starch The resultsof both swelling and effective pore radius point towardsmore wicking action capability and hence disintegrationpotential of the conjugates over the pure corn starch Theresult of micromeritic study indicates that conjugates pre-pared by microwave method were the most effective methodfollowed by chemical and physical method as they gave bettermicromeritic properties as evidenced from the Table 2
312 ATR-FTIR Analysis Corn starch and Neusilin UFL2interactions studies were carried out using ATR-FTIR spec-trophotometer and the spectra for the samples are shownin Figure 1 The IR spectra of corn starch showed a peakat 3434 cmminus1 and 2931 cmminus1 representing OndashH and CndashHstretching respectively The absorption band at 1652 cmminus1is due to absorbed water in amorphous region of starchPeak at 1241 cmminus1 represents CH
2OH group whereas peak
at 1159 cmminus1 represents coupling mode of CndashC and CndashOstretching vibrations The band at 1080 cmminus1 represents CndashOndashH bending vibration whereas peak at 929 cmminus1 could beascribed to the skeletal mode vibration of 120572-14-glycosidiclinkage The corn Starch-Neusilin UFL2 conjugates preparedby different methods namely physical microwave andchemical exhibit a sharp peak near 3480 cmminus1 which isotherwise observed at 3434 cmminus1 in the pure corn starchThisshift and sharpening of peak indicate the formation of SindashOndashC bridging bond between corn starch and Neusilin UFL2Moreover reduction in the intensity of peak at 1241 cmminus1
4000 3000 2000 1500 1000 400
(cmminus1)
T(
)
(A)
(B)
(C)
(D)
Figure 1 IR spectra of (A) native corn starch corn Starch-NeusilinUFL2 conjugates by (B) physical method (C) chemical method and(D) microwave method
1159 cmminus1 and 1080 cmminus1 confirms intermolecular bridgingbetween corn starch and Neusilin UFL2 Thus the additionof Neusilin changed the properties of corn starch forming anew excipient with different functional properties
313 XRD Analysis The XRD patterns of the samples areshown in Figure 2 The structure of corn starch is char-acterized by the presence of broad peak at 2456∘2120579 angleAppearance of sharp peak at 2740∘2120579 3172∘2120579 4560∘21205795391∘2120579 and 5647∘2120579 angles respectively in case of conju-gates prepared bymicrowavemethod gives clear indication ofreduction in amorphous nature or otherwise increase in thecrystalline behavior of the corn starch that could be correlatedwith the increase in swelling and hence superdisintegrantpotential of conjugates prepared by different methods Crys-tallinity and hence the superdisintegrant property (Table 4)of conjugates prepared by different methods were in therank order of microwave gt chemical gt physical mixtureHigh proportion of longer chains might form more stablecrystallites in the pure corn starch The swelling powerof corn starch depends on the water holding capacity ofthe starch molecule by hydrogen bonding Hence higherdegree of intermolecular bonding between corn starch andNeusilin UFL2 favors the long chain crystalline structureand hence the swelling of the conjugates which in turnpotentiates the use of corn Starch-Neusilin UFL2 as a tabletsuperdisintegrant [21]
314 DSC Analysis Figure 3 shows the DSC thermogramsof the pure corn starch and corn Starch-Neusilin UFL2conjugates prepared by physical chemical and microwavemethods Corn starch has a discrete structure and pos-sesses partially crystalline microscopic granules that are
Figure 2 XRD pattern of (A) native corn starch corn Starch-Neusilin UFL2 conjugates by (B) physical method (C) chemicalmethod and (D) microwave method
held together by intended micellar network of associatedmolecules so it does not show obvious Tg or Tm untilpyrogenation Melting range was found to be extended andbroadened with the incorporation of Neusilin UFL2 Broad-ening and shifting of the melting range in the DSC spectracould be attributed to intermolecular bonding between cornstarch and Neusilin UFL2 indicating that the Neusilin UFL2molecules were restrained by the corn starch molecules Thebroadening of themelting range could be due to the regularityof the OH group that already existed in corn starch whichhad disappeared by the interaction with Neusilin UFL2 TheTm and ΔH of the melting peak are significantly lower inthe pure corn starch than the conjugates which indicate thatthere is an interaction between corn starch and NeusilinUFL2 which has enhanced the crystallization of the purecorn starch This increase in crystalline behaviour of thepure corn starch could be correlated to increase in swelling
40 50 60 70 80 90 100 110 120 130 140
Temperature (∘C)
(A)
(B)
(C)(D)
Figure 3 DSC pattern of (A) native corn starch corn Starch-Neusilin UFL2 conjugates by (B) physical method (C) chemicalmethod and (D) microwave method
and hence superdisintegrant potential of conjugates preparedby different methods Crystallinity and superdisintegrantbehaviour of conjugates prepared by different methods couldbe arranged as microwave gt chemical gt physical mixtureFurthermore the crystalline structure contributes towardsthe swelling behaviour of the conjugates responsible for thetablet superdisintegrant activity
315 SEM Analysis Surface morphology of the corn starchand corn Starch-Neusilin UFL2 conjugates was studied bySEManalysis as shown in Figure 4The corn starch undergoesa change in its native structure from thin smooth flatsurface structure with folded edges to three dimensionalcompacts upon conjugation with the Neusilin UFL2 SEMmicrograph of the prepared conjugates showed the presenceof interparticulate voids and channels that are responsible forthe increase in water absorption and swelling capacity of theconjugates as compared to the pure corn starch Furthermorethese voidschannels contributed to the wicking behaviorresponsible for the tablet superdisintegrant property of thecorn Starch-Neusilin UFL2 conjugates Conjugates preparedbymicrowavemethod illustrated the presence ofmore porous
8 Journal of Drug Delivery
structure as compared to conjugates prepared by physicaland chemical methods The results are in line with the betterin vitro disintegration performance of FDT prepared withconjugates of microwave method compared to the other twomethods
316 Heckel FunctionAnalysis Figure 5 shows representativeHeckel plots for the conjugates prepared by physical chem-ical and microwave methods The Heckel plots showed aninitial linear portion with an increase slope at pressure of100MPa followed by another linear region for the conjugatesprepared by physical and chemical methods while for theconjugate prepared by microwave method the second linearregion was from 175MPaThe mean yield pressure values forthe conjugates were calculated from the slope of the portionshowing the highest linearity of the Heckel plots and theintercept 119860 was determined from the extrapolation of theregionThe values of119863
119860and119863
119861were calculated respectively
The values of 119875119910 1198630 119863119860 and 119863
119861for the formulations are
presented in Table 3 The value of 1198630which represents the
degree of initial packing in the die as a result of die fillingfor the conjugates indicates that the conjugates preparedby microwave method exhibited highest degree of packingin the die as a result of die filling while the conjugatesprepared by physical method exhibited the lowest valuesThevalue of 119863
119861represents the phase of rearrangement of the
particles in the early stages of compression119863119861values tend to
indicate the extent of fragmentation of particles or granulesalthough fragmentation can occur concurrently with plasticand elastic deformation of constituent particles The chemi-cally prepared conjugates exhibited the highest values whilethe one prepared by microwave method exhibited the lowestvalues This indicates that fragmentation occurs more withthe chemically prepared conjugates [22 23]The values of119863
119860
which represents the total degree of packing achieved at zeroand low pressures was also in the rank order of microwave gtchemical gt physical for the methods to prepare conjugatesThis indicates that the conjugates prepared by microwavemethod showed higher degree of packing at low pressuresThe mean yield pressure 119875
119910is inversely related to the ability
of the formulations to deform plastically under pressureThe result indicates that the conjugates prepared by physicalmethod showed the fastest onset of plastic deformation whilethe conjugates prepared by microwave method showed theslowest onset Materials with high yield pressure are classifiedas brittle or fragmenting materials whereas those with lowervalues are classified as plasticallyelastically deforming mate-rials [24] Generally during compression plastic deformationand fragmentation are known to occur concurrently Starcheshave been known to deform plastically under compressionpressure
317 Kawakita Function Analysis TheKawakita plots for theconjugates are presented in Figure 6 A linear relationshipwas obtained at all compression pressures employed withcorrelation coefficient of 0999 for the conjugates preparedby different methods The values of 119886 and 119886119887 were obtainedfrom the slope and intercept respectivelyThe value of (1minus119886)
gives the initial relative density of the starch 119863119868 while 119875
119896
values were obtained from the reciprocal of values of 119887The values of 119863
119868and 119875
119896are shown in Table 3 The value
of 119863119868is a measure of the packed initial relative density of
the formulation with the application of small pressure ortapping The ranking of 119863
119868for the conjugates was chemical
method gt microwave method gt physical method The valueof 119875119896which is an inverse measure of the amount of plastic
deformation occurring during the compression process wasfound to be maximum for tablets formulated using conju-gates prepared by chemical method followed by microwavemethod and physical method [23]Thus conjugates preparedby microwave method exhibited the highest amount of totalplastic deformation while conjugates prepared by physicalmethod exhibited the lowest values The ranking was seen tobe in the reverse order as that of the 119875
119910values It has been
shown that while119875119910relates to the onset of plastic deformation
during compression the 119875119896relates to the amount of plastic
deformation that occurs during the compression processThus the conjugates prepared by physical method showedthe slowest onset of plastic deformation but the highest totalamount of plastic deformation
32 Postcompression Evaluation Tablets require certainamount of strength and resistance to friability to withstandmechanical shock of handling during manufacturingshipping and packaging Hardness of the tablets formulatedusing the corn starch-Neusilin UFL2 conjugates assuperdisintegrant was found to vary from 43 to 35 kgcm2compared to 315 to 309 kgcm2 of tablets formulatedusing the native corn starch Percentage friability of allformulations was less than 1 indicating good mechanicalcharacteristics Wetting time was observed to be decreasedfrom 68 seconds for the tablets incorporating native cornstarch to 33 22 and 14 seconds for the tablets incorporatingconjugates prepared by physical chemical and microwavemethods Disintegration time was also observed to decreasefrom 83 seconds for the tablets incorporating native cornstarch to 40 35 and 22 seconds for the tablets incorporatingconjugates prepared by physical chemical and microwavemethods respectively Water absorption ratio was found tobe inversely proportional to the wetting and disintegratingtime of the tablets The increase in water absorption ratioand decrease in wetting and disintegration times in allformulations may be attributed to the modification of thecorn starch by Neusilin UFL2 to yield a novel conjugatewhich acts as superdisintegrant which absorbs water andswells causing rupture of the tablets Tablet propertiessuch as mechanical strength tablet packing fraction anddisintegration are in turn affected by the porosity [25]Tablets with low packing fraction have high porosity andpores facilitates the penetration of dissolution media intothe tablet leading to disintegration of the tablet Whereashigher tablet packing fraction leads to reduction in porositywhich inhibits the penetration of dissolution media resultingin slower disintegration rate of the tablet [26] Tabletpacking fraction was found to be decreased in the tabletsincorporating conjugates (063ndash041) compared to the tablets
Journal of Drug Delivery 9
(a) (b)
(c) (d)
Figure 4 SEM photomicrographs of (A) corn starch and corn Starch-Neusilin UFL2 conjugates prepared by (B) physical method (C)chemical method and (D) microwave method
Table 3 Parameters derived from the Heckel and Kawakita plots for tablet incorporating corn Starch-Neusilin UFL2 conjugate as asuperdisintegrant prepared by (A) physical method (B) chemical method and (C) microwave method
Figure 5 Heckel plots for the tablet incorporating corn Starch-Neusilin UFL2 conjugate as a superdisintegrant prepared by (A)physical method (B) chemical method and (C)microwavemethod
with corn starch (082) The results are in line with thepowder evaluation results where conjugates prepared byphysical chemical and microwave methods were showing
0
50
100
150
200
250
300
0 50 100 150 200 250
PC
Applied pressure (MPa)
ABC
Figure 6 Kawakita plots for the tablet incorporating corn Starch-Neusilin UFL2 conjugate as a superdisintegrant prepared by (A)physical method (B) chemical method and (C)microwavemethod
better swelling and effective pore radius compared to thenative corn starch The fast disintegration of tablets is dueto the presence of pores resulting in faster penetration of
10 Journal of Drug Delivery
Table4Differentp
ropertieso
fthe
form
ulated
FDTs
Cod
eParameter
Diameter
(mm)
Thickn
ess(mm)
Friability(
)Hardn
ess(kgcm
2 )TSlowast(M
Nm
2 )WTlowast
(Sec)
WARlowast
()
DTlowast
(Sec)
CUlowast(
)TP
Flowast119875lowast(
)1198652
F1674
plusmn003
356
plusmn003
089
plusmn004
311
plusmn010
047
plusmn015
68plusmn113
40plusmn011
73plusmn3
9899plusmn02
081
189
19F2
673
plusmn004
351
plusmn004
091
plusmn002
315
plusmn007
047
plusmn005
68plusmn12
942
plusmn011
73plusmn1
991plusmn015
082
175
24F3
674
plusmn005
355
plusmn005
089
plusmn005
309
plusmn011
047
plusmn011
67plusmn111
46plusmn009
71plusmn2
9727plusmn09
081
187
21F4
673
plusmn001
359
plusmn005
090
plusmn003
310
plusmn002
047
plusmn009
66plusmn114
46plusmn010
71plusmn3
9659plusmn05
080
194
25F5
674
plusmn001
351
plusmn005
076
plusmn004
350
plusmn011
048
plusmn005
33plusmn114
98plusmn004
48plusmn2
9650plusmn03
063
367
43F6
674
plusmn002
355
plusmn004
073
plusmn005
356
plusmn008
048
plusmn001
33plusmn16
796
plusmn004
46plusmn3
991plusmn015
062
373
43F7
674
plusmn001
355
plusmn005
071
plusmn002
370
plusmn015
056
plusmn018
32plusmn110
101plusmn
005
44plusmn1
9835plusmn02
062
373
45F8
674
plusmn003
356
plusmn003
067
plusmn003
375
plusmn021
055
plusmn008
31plusmn14
0103plusmn002
40plusmn2
9923plusmn05
062
375
47F9
673
plusmn004
355
plusmn002
055
plusmn001
400
plusmn018
060
plusmn019
23plusmn13
4108plusmn003
40plusmn6
9912
plusmn04
054
426
50F10
674
plusmn005
354
plusmn007
054
plusmn005
380
plusmn015
057
plusmn006
22plusmn12
5100plusmn002
35plusmn3
9892plusmn07
057
435
50F11
673
plusmn003
356
plusmn004
055
plusmn003
370
plusmn017
056
plusmn011
23plusmn10
5106plusmn006
36plusmn2
9727plusmn09
057
423
55F12
673
plusmn002
353
plusmn003
051
plusmn004
410
plusmn02
062
plusmn015
23plusmn13
8110
plusmn004
32plusmn7
9659plusmn05
056
426
53F13
674
plusmn003
355
plusmn004
041
plusmn007
420
plusmn027
073
plusmn008
14plusmn15
2121plusmn
008
26plusmn2
9915
plusmn01
041
582
50F14
673
plusmn001
351
plusmn004
042
plusmn002
425
plusmn02
073
plusmn020
14plusmn12
6124plusmn007
24plusmn5
9899plusmn02
039
595
52F15
674
plusmn003
355
plusmn006
044
plusmn004
430
plusmn010
076
plusmn018
13plusmn115
125plusmn003
22plusmn3
9975plusmn10
040
599
62F16
674
plusmn001
359
plusmn005
047
plusmn007
420
plusmn045
079
plusmn019
14plusmn14
0128plusmn005
22plusmn4
9912
plusmn03
041
612
64TSlowasttensiles
treng
thW
Tlowastw
ettin
gtim
eWARlowast
water
absorptio
nratio
DTlowast
disintegratio
ntim
eCUlowastcon
tent
unifo
rmity
TPFlowasttabletp
acking
fractio
n119875lowastporosity
Journal of Drug Delivery 11
the dissolution media leading to swelling and wicking of theprepared conjugate creating hydrodynamic pressure insidethe tablets hence responsible for the quick and completedisintegration of tablets indicating the superdisintegrantactivity of conjugates prepared by physical chemical andmicrowave methods over the native corn starch
The results obtained from the in vitro dissolution studyare presented in Figures 7 8 9 and 10 ldquoMKTDrdquo representsthe standard marketed domperidone formulation to whichthe formulated FDTs were compared The similarity factor(1198912) is a logarithmic transformation of the sum-squared
error of differences between test and reference productsover all time points It was observed that the three differentapproaches used for the preparation of conjugate in thisstudy namely physical chemical and microwave methodsincreased the dissolution rate of the drug compared to thetablet prepared with the native corn starch and standardmarketed formulation of the drug The order of increaseddrug dissolution using the different approaches was asfollows microwave gt chemical gt physical In case of theFDTs prepared by using native corn starch (F1ndashF4) thepercentage cumulative drug release was found to be verypoor as compared to the standard marketed formulation ofdomperidone (MKTD)The119891
2value for formulation (F1ndashF4)
was below 50 depicting the dissimilarity between the drugreleases Formulations (F5ndashF8) (F9ndashF12) and (F13ndashF16)werecontaining corn starch-Neusilin UFL2 conjugate prepared byphysical chemical and microwave methods The percentagecumulative drug release for these formulations were found tobe comparable to the standardmarketed formulation of dom-peridone The 119891
2values for these formulations were found
to be over 50 evidencing the similarity between the drugreleases Results of various tablet evaluation tests as evidencedfrom Table 4 indicate that among the three methods usedfor the preparation of conjugates microwave was the mosteffectivemethod followed by chemical and physical methodsMoreover by increasing the concentration of conjugates thetablet did not show much effect on drug release from theformulated FDTs Hence from the commercial point of viewlowest concentration of superdisintegrant showing optimumtabletting results should be recommended
4 Conculsions
In present work an attempt was made to modify the cornstarch to develop corn starch-Neusilin UFL2 conjugatesusing different methods namely physical chemical andmicrowave The prepared conjugates and the corn starchwere characterised for powder flow pH viscosity swellingand effective pore radius Evaluation of precompressionparameter indicates good flow properties The preparedconjugates were also subjected to the compression studiesnamely Heckel and Kawakita function The Heckel plot isusually correlated with the speed of the tablet machine whilethe Kawakita plot is related to the crushing or tensile strengthof the tablet Fast disintegrating tablets of domperidone wereformulated by direct compression technique employing thecorn starch and the prepared conjugates The tablets were
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F1F2F3
F4MKTD
Figure 7 Dissolution rate profiles of FDTs (F1ndashF4) formulated byincorporating native corn starch as a superdisintegrant compared toa standard marketed formulation of domperidone (MKTD)
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F5F6F7
F8MKTD
Figure 8 Dissolution rate profiles of FDTs (F5ndashF8) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates preparedby physical method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
evaluated for physical parametric tests wetting time waterabsorption ratio porosity tablet packing fraction in vitrodisintegration time drug content in vitro dissolution andstability studies Extensive swelling porosity and wickingaction of the prepared corn Starch-Neusilin UFL2 conjugatesin the prepared fast disintegrating tablets were found to becontributing to its superdisintegrant action
In conclusion the prepared conjugates can be effectivelyused as superdisintegrant in order to develop a faster disin-tegrating tablet formulation Future challenges for many fastdisintegrating tablet manufacturers include reducing costsby finding ways to manufacture with conventional equip-ment using versatile packaging and improving mechanical
12 Journal of Drug Delivery
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F9F10F11
F12MKTD
Figure 9 Dissolution rate profiles of FDTs (F9ndashF12) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates preparedby chemical method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
F13F14F15
F16MKTD
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
Figure 10 Dissolution rate profiles of FDTs (F13ndashF16) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates prepared bymicrowave method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
strength Such products provide an opportunity for theproduct line extension in the market place and extensionof patent term of innovator Due to its wide significancethis drug delivery system may lead to better patient com-pliance and ultimate clinical output Future might witnessnovel technologies for development and utilization of themodified starches as tablet superdisintegrant for cost effectiveformulation of fast disintegrating tablets
Conflict of Interests
The authors declare that they have no conflict of interests
Acknowledgments
The authors gratefully acknowledge Dr Madhu ChitkaraVice Chancellor Chitkara University Rajpura Punjab IndiaDr Ashok Chitkara Chairman Chitkara Educational TrustChandigarh India and Dr Sandeep Arora Dean ChitkaraUniversity Rajpura Punjab India for support and institu-tional facilities
References
[1] I Rashid M Al-Remawi S A Leharne B Z Chowdhry andA Badwan ldquoA novel multifunctional pharmaceutical excipientmodification of the permeability of starch by processing withmagnesium silicaterdquo International Journal of Pharmaceutics vol411 no 1-2 pp 18ndash26 2011
[2] O A Odeku and K M Picker-Freyer ldquoAnalysis of the materialand tablet formation properties of four Dioscorea starchesrdquoStarchStarke vol 59 no 9 pp 430ndash444 2007
[3] N Visavarungroj and J P Remon ldquoAn evaluation of hydrox-ypropyl starch an disintegrant and binder in tablet formulationrdquoDrug Development and Industrial Pharmacy vol 17 no 10 pp1389ndash1396 1991
[4] M Nakano N Nakazono and N Inotsume ldquoPreparation andevaluation of sustained release tablets prepared with 120572-starchrdquoChemical and Pharmaceutical Bulletin vol 35 no 10 pp 4346ndash4350 1987
[5] O A Odeku and K M Picker-Freyer ldquoFreeze-dried prege-latinized Dioscorea starches as tablet matrix for sustainedreleaserdquo Journal of Excipients and Food Chemicals vol 1 no 2pp 21ndash32 2010
[6] H Staroszczyk ldquoMicrowave-assisted silication of potato starchrdquoCarbohydrate Polymers vol 77 no 3 pp 506ndash515 2009
[7] J Singh L Kaur and O J McCarthy ldquoFactors influencingthe physico-chemical morphological thermal and rheologicalproperties of some chemically modified starches for foodapplications a reviewrdquo Food Hydrocolloids vol 21 no 1 pp 1ndash22 2007
[8] I Rashid N Daraghmeh M Al-Remawi S A Leharne B ZChowdhry and A Badwan ldquoCharacterization of chitin-metalsilicates as binding superdisintegrantsrdquo Journal of Pharmaceuti-cal Sciences vol 98 no 12 pp 4887ndash4901 2009
[9] I Rashid N Daraghmeh M Al-Remawi S A Leharne B ZChowdhry and A Badwan ldquoCharacterization of the impactof magnesium stearate lubrication on the tableting propertiesof chitin-Mg silicate as a superdisintegrating binder whencompared to Avicel 200rdquo Powder Technology vol 203 no 3 pp609ndash619 2010
[10] Y Asai M Nohara S Fujioka K Isaji and S Nagira ldquoApplica-tion of Neusilin UFL2 on manufacturing of tablets using directcompression method Development of core tablets containingthe function of small degree of decrease of hardness at thehumid conditionsrdquoPharmaceutical Technical Newsletter vol 25pp 67ndash70 2009
[11] B G Prajapati and D V Patel ldquoFormulation and optimiza-tion of domperidone fast dissolving tablet by wet granulationtechniques using factorial designrdquo International Journal ofPharmTech Research vol 2 no 1 pp 292ndash299 2010
[12] J Cooper and C Gunn ldquoPowder flow and compactionrdquo inTutorial Pharmacy S J Carter Ed pp 211ndash233 CBS Publishersand Distributors New Delhi India 1986
Journal of Drug Delivery 13
[13] H Goel G Kaur A K Tiwary and V Rana ldquoFormulationdevelopment of stronger and quick disintegrating tablets acrucial effect of chitinrdquoYakugaku Zasshi vol 130 no 5 pp 729ndash735 2010
[14] J M Sonnergaard ldquoImpact of particle density and initial vol-ume on mathematical compression modelsrdquo European Journalof Pharmaceutical Sciences vol 11 no 4 pp 307ndash315 2000
[15] O A Odeku ldquoAssessment of Albizia zygia gum as a bindingagent in tablet formulationsrdquo Acta Pharmaceutica vol 55 no3 pp 263ndash276 2005
[16] F Kiekens A Debunne C Vervaet et al ldquoInfluence of thepunch diameter and curvature on the yield pressure of MCC-compacts duringHeckel analysisrdquo European Journal of Pharma-ceutical Sciences vol 22 no 2-3 pp 117ndash126 2004
[17] ldquoUnited States Pharmacopeia 24NF19rdquo inTheOfficial Compen-dia of Standards M D Asian Rockville Ed pp 1913ndash1914 USPharmacopeial Convention 2000
[18] T Y Puttewar M D Kshirsagar A V Chandewar and R VChikhale ldquoFormulation and evaluation of orodispersible tabletof tastemasked doxylamine succinate using ion exchange resinrdquoJournal of King Saud UniversitymdashScience vol 22 no 4 pp 229ndash240 2010
[19] A Fini V Bergamante G C Ceschel C Ronchi and C A Fde Moraes ldquoFast dispersibleslow releasing ibuprofen tabletsrdquoEuropean Journal of Pharmaceutics and Biopharmaceutics vol69 no 1 pp 335ndash341 2008
[20] M U Uhumwangho and R S Okor ldquoEffect of humidity on thedisintegrant property of 120572-cellulose Part II A technical noterdquoAAPS PharmSciTech vol 6 no 1 article no 7 pp E31ndashE342005
[21] T Sasaki and J Matsuki ldquoEffect of wheat starch structure onswelling powerrdquo Cereal Chemistry vol 75 no 4 pp 525ndash5291998
[22] O A Itiola and N Pilpel ldquoTableting characteristics of metron-idazole formulationsrdquo International Journal of Pharmaceuticsvol 31 no 1-2 pp 99ndash105 1986
[23] O A Odeku and O A Itiola ldquoEvaluation of khaya gum asa binder in a paracetamol tablet formulationrdquo Pharmacy andPharmacology Communications vol 4 no 4 pp 183ndash188 1998
[24] O A Odeku and J T Fell ldquoEffects of the method of preparationon the compression mechanical and release properties ofkhaya gum matricesrdquo Pharmaceutical Development and Tech-nology vol 11 no 4 pp 435ndash441 2006
[25] O A Odeku and B L Akinwande ldquoEffect of the mode ofincorporation on the disintegrant properties of acid modifiedwater and white yam starchesrdquo Saudi Pharmaceutical Journalvol 20 no 2 pp 171ndash175 2012
[26] R Shangraw A Mitrevej and M Shah ldquoA new era of tabletdisintegrantsrdquo Pharmaceutical Technology vol 4 no 10 pp 49ndash57 1980
Journal of Drug Delivery 5
where 1198810is the initial bulk volume of the powder and 119881
119901is
the bulk volume after compression Constant ldquo119886rdquo is equal tothe minimum porosity of the material before compressionwhile constant ldquo119887rdquo is related to the plasticity of the materialThe reciprocal of ldquo119887rdquo gives the pressure term 119875
119896 which is the
pressure required to reduce the powder bed by 50 [14 15]
29 Postcompression Evaluation
291 Diameter and Thickness A calibrated vernier calliper(Ms Mitutoyo Corp Japan) was used for diameter andthickness evaluation of tablets
292 Hardness The tablet hardness is the force required tobreak a tablet in a diametric compression force Hardnesstester (Perfit India) was used to determine the force requiredto break the tablet diametrically The test was performed onsix tablets and the average was calculated
293 Friability Thefriability (119865) of a sample of 20 tabletswasmeasured using Roche Friabilator (Model 902 EI PanchkulaIndia) Twenty tablets were weighed and rotated at 25 rpm for4min Tablets were reweighed after removal of fines (dusted)and the percentage of weight loss was calculated Friabilitybelow 1 was considered acceptable
294 Weight Variation Test Weight variation test was doneby weighing 20 tablets individually calculating the averageweight and comparing the individual tablet weight to theaverage weight
295 Content Uniformity The content uniformity wasassessed according to USP method Ten tablets were pulver-ized and quantity of powder equivalent to 10mg of domperi-done was shaken with 100mL of 01 N HCl for 30 minutesThe contents were filtered through a 045120583mmembrane filterdiluted and analyzed at 284 nmusing aUVVIS double beamspectrophotometer (Model 2202 Systronics AhmedabadIndia) [17]
296 Wetting Time A piece of tissue paper (1075 times 12mm)folded twice was placed in a culture dish (119889 = 65 cm)containing 6mL of water (containing a water soluble dyeeosin) A tablet was carefully placed on the surface of tissuepaper and the time required for water to reach the uppersurface of the tablet was noted as the wetting time [18]
297 Water Absorption Ratio The same procedure used forthe wetting time was used for the water absorption ratioInitial weight of the tablet (119882
119886) was measured before its
placement on the wet tissue and the final weight (119882119887) was
taken after complete wetting Water absorption ratio 119877 wasdetermined using the equation [19]
119877 = 100
(119882119887minus 119882119886)
119882119887
(10)
298 Porosity Porosity is a measure of the void spaces in amaterial and is a fraction of the volume of voids over the totalvolume between 0 and 1 or as a percentage between 0 and 100percent The porosity of the tablets was calculated as follows
Porosity =1 minus 119898
120588truelowast 119881 (11)
where 120588true is the true density of the mixture and 119898 and 119881
are the weight and volume of the tablet respectively Thetrue density of the powder was found using true densitymeter (SMART PYCNO 30 Smart Instruments Maharash-tra India)
299 Tablet Packing Fraction (119875119891) The tablet packing
fraction 119875119891 is a measure of the degree of consolida-
tioncompactness of the tablet Tablet packing fraction wasdetermined by the equation
Packing fraction (119875119891) =
119908
1205871199032119905120588
(12)
where119908 is the weight of a tablet 119903 is radius 119905 is thickness and120588 is the particle density
The radius and thickness of 10 tablets were measuredusing a vernier calliper The apparent particle density of thedrug powder was determined using liquid paraffin displace-ment method Firstly the weight of a specific gravity bottlefilledwith liquid paraffin and theweight of the specific gravitybottle containing a sample of the drug powder were notedThe final weight was determined The determination wasexecuted in triplicate and mean results were used in thecalculation of 119875
119891[20]
2910 In Vitro Disintegration Time In vitro disintegrationtime for the tablets was determined using USP disintegrationapparatus (EI Product Panchkula India) using 01 NHCl (pH1-2 900mL at 37∘C) as the disintegrating medium
2911 In Vitro Dissolution Studies In vitro dissolution ofthe fast disintegrating tablets was studied in USP XXIVdissolution apparatus II (DS 8000 Lab India Pune India)employing a paddle stirrer at 50 rpm using 900mL of pH12 01 N HCl at 37 plusmn 05∘C as a dissolution mediumAliquots of 5mL eachwere withdrawn at predetermined timeintervals and replaced with equal volume of fresh mediumAliquots were filtered through a 045120583m membrane filterand analyzed for drug content using a UVVIS double beamspectrophotometer (2202 Systronics Ahmedabad India) at284 nm Drug concentration was calculated and expressed ascumulative percent of the drug releasedThe similarity factor(1198912) is a logarithmic transformation of the sum-squared
error of differences between the test (119879119895) and reference
(119877119895) products over all time points It is a useful tool for
comparison of dissolution profiles when more than three orfour dissolution time points are available It is calculated as
(119882119895) is an optional weight factor The similarity factor fits
result between 0 and 100 It is 100 when the test and referenceprofiles are identical and tends to be 0 as the dissimilarityincreases In order to consider similar dissolution profiles 119891
2
values should be close to 100
3 Result and Discussion
31 Precompression Evaluation
311 Micromeritics Study The result of the micromeriticstudies for corn starch and the prepared corn Starch-NeusilinUFL2 conjugates were conducted and results are listed inTable 2 Angle of repose (120579∘) is a characteristic of the internalfriction or cohesion of the particles Its value will be highif the powder is cohesive and low if the powder is non-cohesive Flow property of the corn starch was improvedby the addition of Neusilin UFL2 as compared formulationswith conjugates showed good to excellent flow properties asindicated by the values of angle of repose (3669ndash2767∘) to thecorn starch (4325∘) Carrrsquos index showed values 225 to 125denoting that these formulations were of acceptable to goodflowability compared to the corn starch (3428) Hausnerrsquosratio showed that powders with low interparticle frictionhad ratios of approximately 129 to 114 indicating good flowproperties as compared to the corn starch (152) Swellingindex of the conjugates prepared by physical chemical andmicrowave method were found to be 40 65 and 95respectively which was far better than the swelling index ofcorn starch that is 18 which is in context with the effectivepore radius of the conjugates and corn starch The resultsof both swelling and effective pore radius point towardsmore wicking action capability and hence disintegrationpotential of the conjugates over the pure corn starch Theresult of micromeritic study indicates that conjugates pre-pared by microwave method were the most effective methodfollowed by chemical and physical method as they gave bettermicromeritic properties as evidenced from the Table 2
312 ATR-FTIR Analysis Corn starch and Neusilin UFL2interactions studies were carried out using ATR-FTIR spec-trophotometer and the spectra for the samples are shownin Figure 1 The IR spectra of corn starch showed a peakat 3434 cmminus1 and 2931 cmminus1 representing OndashH and CndashHstretching respectively The absorption band at 1652 cmminus1is due to absorbed water in amorphous region of starchPeak at 1241 cmminus1 represents CH
2OH group whereas peak
at 1159 cmminus1 represents coupling mode of CndashC and CndashOstretching vibrations The band at 1080 cmminus1 represents CndashOndashH bending vibration whereas peak at 929 cmminus1 could beascribed to the skeletal mode vibration of 120572-14-glycosidiclinkage The corn Starch-Neusilin UFL2 conjugates preparedby different methods namely physical microwave andchemical exhibit a sharp peak near 3480 cmminus1 which isotherwise observed at 3434 cmminus1 in the pure corn starchThisshift and sharpening of peak indicate the formation of SindashOndashC bridging bond between corn starch and Neusilin UFL2Moreover reduction in the intensity of peak at 1241 cmminus1
4000 3000 2000 1500 1000 400
(cmminus1)
T(
)
(A)
(B)
(C)
(D)
Figure 1 IR spectra of (A) native corn starch corn Starch-NeusilinUFL2 conjugates by (B) physical method (C) chemical method and(D) microwave method
1159 cmminus1 and 1080 cmminus1 confirms intermolecular bridgingbetween corn starch and Neusilin UFL2 Thus the additionof Neusilin changed the properties of corn starch forming anew excipient with different functional properties
313 XRD Analysis The XRD patterns of the samples areshown in Figure 2 The structure of corn starch is char-acterized by the presence of broad peak at 2456∘2120579 angleAppearance of sharp peak at 2740∘2120579 3172∘2120579 4560∘21205795391∘2120579 and 5647∘2120579 angles respectively in case of conju-gates prepared bymicrowavemethod gives clear indication ofreduction in amorphous nature or otherwise increase in thecrystalline behavior of the corn starch that could be correlatedwith the increase in swelling and hence superdisintegrantpotential of conjugates prepared by different methods Crys-tallinity and hence the superdisintegrant property (Table 4)of conjugates prepared by different methods were in therank order of microwave gt chemical gt physical mixtureHigh proportion of longer chains might form more stablecrystallites in the pure corn starch The swelling powerof corn starch depends on the water holding capacity ofthe starch molecule by hydrogen bonding Hence higherdegree of intermolecular bonding between corn starch andNeusilin UFL2 favors the long chain crystalline structureand hence the swelling of the conjugates which in turnpotentiates the use of corn Starch-Neusilin UFL2 as a tabletsuperdisintegrant [21]
314 DSC Analysis Figure 3 shows the DSC thermogramsof the pure corn starch and corn Starch-Neusilin UFL2conjugates prepared by physical chemical and microwavemethods Corn starch has a discrete structure and pos-sesses partially crystalline microscopic granules that are
Figure 2 XRD pattern of (A) native corn starch corn Starch-Neusilin UFL2 conjugates by (B) physical method (C) chemicalmethod and (D) microwave method
held together by intended micellar network of associatedmolecules so it does not show obvious Tg or Tm untilpyrogenation Melting range was found to be extended andbroadened with the incorporation of Neusilin UFL2 Broad-ening and shifting of the melting range in the DSC spectracould be attributed to intermolecular bonding between cornstarch and Neusilin UFL2 indicating that the Neusilin UFL2molecules were restrained by the corn starch molecules Thebroadening of themelting range could be due to the regularityof the OH group that already existed in corn starch whichhad disappeared by the interaction with Neusilin UFL2 TheTm and ΔH of the melting peak are significantly lower inthe pure corn starch than the conjugates which indicate thatthere is an interaction between corn starch and NeusilinUFL2 which has enhanced the crystallization of the purecorn starch This increase in crystalline behaviour of thepure corn starch could be correlated to increase in swelling
40 50 60 70 80 90 100 110 120 130 140
Temperature (∘C)
(A)
(B)
(C)(D)
Figure 3 DSC pattern of (A) native corn starch corn Starch-Neusilin UFL2 conjugates by (B) physical method (C) chemicalmethod and (D) microwave method
and hence superdisintegrant potential of conjugates preparedby different methods Crystallinity and superdisintegrantbehaviour of conjugates prepared by different methods couldbe arranged as microwave gt chemical gt physical mixtureFurthermore the crystalline structure contributes towardsthe swelling behaviour of the conjugates responsible for thetablet superdisintegrant activity
315 SEM Analysis Surface morphology of the corn starchand corn Starch-Neusilin UFL2 conjugates was studied bySEManalysis as shown in Figure 4The corn starch undergoesa change in its native structure from thin smooth flatsurface structure with folded edges to three dimensionalcompacts upon conjugation with the Neusilin UFL2 SEMmicrograph of the prepared conjugates showed the presenceof interparticulate voids and channels that are responsible forthe increase in water absorption and swelling capacity of theconjugates as compared to the pure corn starch Furthermorethese voidschannels contributed to the wicking behaviorresponsible for the tablet superdisintegrant property of thecorn Starch-Neusilin UFL2 conjugates Conjugates preparedbymicrowavemethod illustrated the presence ofmore porous
8 Journal of Drug Delivery
structure as compared to conjugates prepared by physicaland chemical methods The results are in line with the betterin vitro disintegration performance of FDT prepared withconjugates of microwave method compared to the other twomethods
316 Heckel FunctionAnalysis Figure 5 shows representativeHeckel plots for the conjugates prepared by physical chem-ical and microwave methods The Heckel plots showed aninitial linear portion with an increase slope at pressure of100MPa followed by another linear region for the conjugatesprepared by physical and chemical methods while for theconjugate prepared by microwave method the second linearregion was from 175MPaThe mean yield pressure values forthe conjugates were calculated from the slope of the portionshowing the highest linearity of the Heckel plots and theintercept 119860 was determined from the extrapolation of theregionThe values of119863
119860and119863
119861were calculated respectively
The values of 119875119910 1198630 119863119860 and 119863
119861for the formulations are
presented in Table 3 The value of 1198630which represents the
degree of initial packing in the die as a result of die fillingfor the conjugates indicates that the conjugates preparedby microwave method exhibited highest degree of packingin the die as a result of die filling while the conjugatesprepared by physical method exhibited the lowest valuesThevalue of 119863
119861represents the phase of rearrangement of the
particles in the early stages of compression119863119861values tend to
indicate the extent of fragmentation of particles or granulesalthough fragmentation can occur concurrently with plasticand elastic deformation of constituent particles The chemi-cally prepared conjugates exhibited the highest values whilethe one prepared by microwave method exhibited the lowestvalues This indicates that fragmentation occurs more withthe chemically prepared conjugates [22 23]The values of119863
119860
which represents the total degree of packing achieved at zeroand low pressures was also in the rank order of microwave gtchemical gt physical for the methods to prepare conjugatesThis indicates that the conjugates prepared by microwavemethod showed higher degree of packing at low pressuresThe mean yield pressure 119875
119910is inversely related to the ability
of the formulations to deform plastically under pressureThe result indicates that the conjugates prepared by physicalmethod showed the fastest onset of plastic deformation whilethe conjugates prepared by microwave method showed theslowest onset Materials with high yield pressure are classifiedas brittle or fragmenting materials whereas those with lowervalues are classified as plasticallyelastically deforming mate-rials [24] Generally during compression plastic deformationand fragmentation are known to occur concurrently Starcheshave been known to deform plastically under compressionpressure
317 Kawakita Function Analysis TheKawakita plots for theconjugates are presented in Figure 6 A linear relationshipwas obtained at all compression pressures employed withcorrelation coefficient of 0999 for the conjugates preparedby different methods The values of 119886 and 119886119887 were obtainedfrom the slope and intercept respectivelyThe value of (1minus119886)
gives the initial relative density of the starch 119863119868 while 119875
119896
values were obtained from the reciprocal of values of 119887The values of 119863
119868and 119875
119896are shown in Table 3 The value
of 119863119868is a measure of the packed initial relative density of
the formulation with the application of small pressure ortapping The ranking of 119863
119868for the conjugates was chemical
method gt microwave method gt physical method The valueof 119875119896which is an inverse measure of the amount of plastic
deformation occurring during the compression process wasfound to be maximum for tablets formulated using conju-gates prepared by chemical method followed by microwavemethod and physical method [23]Thus conjugates preparedby microwave method exhibited the highest amount of totalplastic deformation while conjugates prepared by physicalmethod exhibited the lowest values The ranking was seen tobe in the reverse order as that of the 119875
119910values It has been
shown that while119875119910relates to the onset of plastic deformation
during compression the 119875119896relates to the amount of plastic
deformation that occurs during the compression processThus the conjugates prepared by physical method showedthe slowest onset of plastic deformation but the highest totalamount of plastic deformation
32 Postcompression Evaluation Tablets require certainamount of strength and resistance to friability to withstandmechanical shock of handling during manufacturingshipping and packaging Hardness of the tablets formulatedusing the corn starch-Neusilin UFL2 conjugates assuperdisintegrant was found to vary from 43 to 35 kgcm2compared to 315 to 309 kgcm2 of tablets formulatedusing the native corn starch Percentage friability of allformulations was less than 1 indicating good mechanicalcharacteristics Wetting time was observed to be decreasedfrom 68 seconds for the tablets incorporating native cornstarch to 33 22 and 14 seconds for the tablets incorporatingconjugates prepared by physical chemical and microwavemethods Disintegration time was also observed to decreasefrom 83 seconds for the tablets incorporating native cornstarch to 40 35 and 22 seconds for the tablets incorporatingconjugates prepared by physical chemical and microwavemethods respectively Water absorption ratio was found tobe inversely proportional to the wetting and disintegratingtime of the tablets The increase in water absorption ratioand decrease in wetting and disintegration times in allformulations may be attributed to the modification of thecorn starch by Neusilin UFL2 to yield a novel conjugatewhich acts as superdisintegrant which absorbs water andswells causing rupture of the tablets Tablet propertiessuch as mechanical strength tablet packing fraction anddisintegration are in turn affected by the porosity [25]Tablets with low packing fraction have high porosity andpores facilitates the penetration of dissolution media intothe tablet leading to disintegration of the tablet Whereashigher tablet packing fraction leads to reduction in porositywhich inhibits the penetration of dissolution media resultingin slower disintegration rate of the tablet [26] Tabletpacking fraction was found to be decreased in the tabletsincorporating conjugates (063ndash041) compared to the tablets
Journal of Drug Delivery 9
(a) (b)
(c) (d)
Figure 4 SEM photomicrographs of (A) corn starch and corn Starch-Neusilin UFL2 conjugates prepared by (B) physical method (C)chemical method and (D) microwave method
Table 3 Parameters derived from the Heckel and Kawakita plots for tablet incorporating corn Starch-Neusilin UFL2 conjugate as asuperdisintegrant prepared by (A) physical method (B) chemical method and (C) microwave method
Figure 5 Heckel plots for the tablet incorporating corn Starch-Neusilin UFL2 conjugate as a superdisintegrant prepared by (A)physical method (B) chemical method and (C)microwavemethod
with corn starch (082) The results are in line with thepowder evaluation results where conjugates prepared byphysical chemical and microwave methods were showing
0
50
100
150
200
250
300
0 50 100 150 200 250
PC
Applied pressure (MPa)
ABC
Figure 6 Kawakita plots for the tablet incorporating corn Starch-Neusilin UFL2 conjugate as a superdisintegrant prepared by (A)physical method (B) chemical method and (C)microwavemethod
better swelling and effective pore radius compared to thenative corn starch The fast disintegration of tablets is dueto the presence of pores resulting in faster penetration of
10 Journal of Drug Delivery
Table4Differentp
ropertieso
fthe
form
ulated
FDTs
Cod
eParameter
Diameter
(mm)
Thickn
ess(mm)
Friability(
)Hardn
ess(kgcm
2 )TSlowast(M
Nm
2 )WTlowast
(Sec)
WARlowast
()
DTlowast
(Sec)
CUlowast(
)TP
Flowast119875lowast(
)1198652
F1674
plusmn003
356
plusmn003
089
plusmn004
311
plusmn010
047
plusmn015
68plusmn113
40plusmn011
73plusmn3
9899plusmn02
081
189
19F2
673
plusmn004
351
plusmn004
091
plusmn002
315
plusmn007
047
plusmn005
68plusmn12
942
plusmn011
73plusmn1
991plusmn015
082
175
24F3
674
plusmn005
355
plusmn005
089
plusmn005
309
plusmn011
047
plusmn011
67plusmn111
46plusmn009
71plusmn2
9727plusmn09
081
187
21F4
673
plusmn001
359
plusmn005
090
plusmn003
310
plusmn002
047
plusmn009
66plusmn114
46plusmn010
71plusmn3
9659plusmn05
080
194
25F5
674
plusmn001
351
plusmn005
076
plusmn004
350
plusmn011
048
plusmn005
33plusmn114
98plusmn004
48plusmn2
9650plusmn03
063
367
43F6
674
plusmn002
355
plusmn004
073
plusmn005
356
plusmn008
048
plusmn001
33plusmn16
796
plusmn004
46plusmn3
991plusmn015
062
373
43F7
674
plusmn001
355
plusmn005
071
plusmn002
370
plusmn015
056
plusmn018
32plusmn110
101plusmn
005
44plusmn1
9835plusmn02
062
373
45F8
674
plusmn003
356
plusmn003
067
plusmn003
375
plusmn021
055
plusmn008
31plusmn14
0103plusmn002
40plusmn2
9923plusmn05
062
375
47F9
673
plusmn004
355
plusmn002
055
plusmn001
400
plusmn018
060
plusmn019
23plusmn13
4108plusmn003
40plusmn6
9912
plusmn04
054
426
50F10
674
plusmn005
354
plusmn007
054
plusmn005
380
plusmn015
057
plusmn006
22plusmn12
5100plusmn002
35plusmn3
9892plusmn07
057
435
50F11
673
plusmn003
356
plusmn004
055
plusmn003
370
plusmn017
056
plusmn011
23plusmn10
5106plusmn006
36plusmn2
9727plusmn09
057
423
55F12
673
plusmn002
353
plusmn003
051
plusmn004
410
plusmn02
062
plusmn015
23plusmn13
8110
plusmn004
32plusmn7
9659plusmn05
056
426
53F13
674
plusmn003
355
plusmn004
041
plusmn007
420
plusmn027
073
plusmn008
14plusmn15
2121plusmn
008
26plusmn2
9915
plusmn01
041
582
50F14
673
plusmn001
351
plusmn004
042
plusmn002
425
plusmn02
073
plusmn020
14plusmn12
6124plusmn007
24plusmn5
9899plusmn02
039
595
52F15
674
plusmn003
355
plusmn006
044
plusmn004
430
plusmn010
076
plusmn018
13plusmn115
125plusmn003
22plusmn3
9975plusmn10
040
599
62F16
674
plusmn001
359
plusmn005
047
plusmn007
420
plusmn045
079
plusmn019
14plusmn14
0128plusmn005
22plusmn4
9912
plusmn03
041
612
64TSlowasttensiles
treng
thW
Tlowastw
ettin
gtim
eWARlowast
water
absorptio
nratio
DTlowast
disintegratio
ntim
eCUlowastcon
tent
unifo
rmity
TPFlowasttabletp
acking
fractio
n119875lowastporosity
Journal of Drug Delivery 11
the dissolution media leading to swelling and wicking of theprepared conjugate creating hydrodynamic pressure insidethe tablets hence responsible for the quick and completedisintegration of tablets indicating the superdisintegrantactivity of conjugates prepared by physical chemical andmicrowave methods over the native corn starch
The results obtained from the in vitro dissolution studyare presented in Figures 7 8 9 and 10 ldquoMKTDrdquo representsthe standard marketed domperidone formulation to whichthe formulated FDTs were compared The similarity factor(1198912) is a logarithmic transformation of the sum-squared
error of differences between test and reference productsover all time points It was observed that the three differentapproaches used for the preparation of conjugate in thisstudy namely physical chemical and microwave methodsincreased the dissolution rate of the drug compared to thetablet prepared with the native corn starch and standardmarketed formulation of the drug The order of increaseddrug dissolution using the different approaches was asfollows microwave gt chemical gt physical In case of theFDTs prepared by using native corn starch (F1ndashF4) thepercentage cumulative drug release was found to be verypoor as compared to the standard marketed formulation ofdomperidone (MKTD)The119891
2value for formulation (F1ndashF4)
was below 50 depicting the dissimilarity between the drugreleases Formulations (F5ndashF8) (F9ndashF12) and (F13ndashF16)werecontaining corn starch-Neusilin UFL2 conjugate prepared byphysical chemical and microwave methods The percentagecumulative drug release for these formulations were found tobe comparable to the standardmarketed formulation of dom-peridone The 119891
2values for these formulations were found
to be over 50 evidencing the similarity between the drugreleases Results of various tablet evaluation tests as evidencedfrom Table 4 indicate that among the three methods usedfor the preparation of conjugates microwave was the mosteffectivemethod followed by chemical and physical methodsMoreover by increasing the concentration of conjugates thetablet did not show much effect on drug release from theformulated FDTs Hence from the commercial point of viewlowest concentration of superdisintegrant showing optimumtabletting results should be recommended
4 Conculsions
In present work an attempt was made to modify the cornstarch to develop corn starch-Neusilin UFL2 conjugatesusing different methods namely physical chemical andmicrowave The prepared conjugates and the corn starchwere characterised for powder flow pH viscosity swellingand effective pore radius Evaluation of precompressionparameter indicates good flow properties The preparedconjugates were also subjected to the compression studiesnamely Heckel and Kawakita function The Heckel plot isusually correlated with the speed of the tablet machine whilethe Kawakita plot is related to the crushing or tensile strengthof the tablet Fast disintegrating tablets of domperidone wereformulated by direct compression technique employing thecorn starch and the prepared conjugates The tablets were
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F1F2F3
F4MKTD
Figure 7 Dissolution rate profiles of FDTs (F1ndashF4) formulated byincorporating native corn starch as a superdisintegrant compared toa standard marketed formulation of domperidone (MKTD)
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F5F6F7
F8MKTD
Figure 8 Dissolution rate profiles of FDTs (F5ndashF8) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates preparedby physical method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
evaluated for physical parametric tests wetting time waterabsorption ratio porosity tablet packing fraction in vitrodisintegration time drug content in vitro dissolution andstability studies Extensive swelling porosity and wickingaction of the prepared corn Starch-Neusilin UFL2 conjugatesin the prepared fast disintegrating tablets were found to becontributing to its superdisintegrant action
In conclusion the prepared conjugates can be effectivelyused as superdisintegrant in order to develop a faster disin-tegrating tablet formulation Future challenges for many fastdisintegrating tablet manufacturers include reducing costsby finding ways to manufacture with conventional equip-ment using versatile packaging and improving mechanical
12 Journal of Drug Delivery
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F9F10F11
F12MKTD
Figure 9 Dissolution rate profiles of FDTs (F9ndashF12) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates preparedby chemical method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
F13F14F15
F16MKTD
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
Figure 10 Dissolution rate profiles of FDTs (F13ndashF16) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates prepared bymicrowave method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
strength Such products provide an opportunity for theproduct line extension in the market place and extensionof patent term of innovator Due to its wide significancethis drug delivery system may lead to better patient com-pliance and ultimate clinical output Future might witnessnovel technologies for development and utilization of themodified starches as tablet superdisintegrant for cost effectiveformulation of fast disintegrating tablets
Conflict of Interests
The authors declare that they have no conflict of interests
Acknowledgments
The authors gratefully acknowledge Dr Madhu ChitkaraVice Chancellor Chitkara University Rajpura Punjab IndiaDr Ashok Chitkara Chairman Chitkara Educational TrustChandigarh India and Dr Sandeep Arora Dean ChitkaraUniversity Rajpura Punjab India for support and institu-tional facilities
References
[1] I Rashid M Al-Remawi S A Leharne B Z Chowdhry andA Badwan ldquoA novel multifunctional pharmaceutical excipientmodification of the permeability of starch by processing withmagnesium silicaterdquo International Journal of Pharmaceutics vol411 no 1-2 pp 18ndash26 2011
[2] O A Odeku and K M Picker-Freyer ldquoAnalysis of the materialand tablet formation properties of four Dioscorea starchesrdquoStarchStarke vol 59 no 9 pp 430ndash444 2007
[3] N Visavarungroj and J P Remon ldquoAn evaluation of hydrox-ypropyl starch an disintegrant and binder in tablet formulationrdquoDrug Development and Industrial Pharmacy vol 17 no 10 pp1389ndash1396 1991
[4] M Nakano N Nakazono and N Inotsume ldquoPreparation andevaluation of sustained release tablets prepared with 120572-starchrdquoChemical and Pharmaceutical Bulletin vol 35 no 10 pp 4346ndash4350 1987
[5] O A Odeku and K M Picker-Freyer ldquoFreeze-dried prege-latinized Dioscorea starches as tablet matrix for sustainedreleaserdquo Journal of Excipients and Food Chemicals vol 1 no 2pp 21ndash32 2010
[6] H Staroszczyk ldquoMicrowave-assisted silication of potato starchrdquoCarbohydrate Polymers vol 77 no 3 pp 506ndash515 2009
[7] J Singh L Kaur and O J McCarthy ldquoFactors influencingthe physico-chemical morphological thermal and rheologicalproperties of some chemically modified starches for foodapplications a reviewrdquo Food Hydrocolloids vol 21 no 1 pp 1ndash22 2007
[8] I Rashid N Daraghmeh M Al-Remawi S A Leharne B ZChowdhry and A Badwan ldquoCharacterization of chitin-metalsilicates as binding superdisintegrantsrdquo Journal of Pharmaceuti-cal Sciences vol 98 no 12 pp 4887ndash4901 2009
[9] I Rashid N Daraghmeh M Al-Remawi S A Leharne B ZChowdhry and A Badwan ldquoCharacterization of the impactof magnesium stearate lubrication on the tableting propertiesof chitin-Mg silicate as a superdisintegrating binder whencompared to Avicel 200rdquo Powder Technology vol 203 no 3 pp609ndash619 2010
[10] Y Asai M Nohara S Fujioka K Isaji and S Nagira ldquoApplica-tion of Neusilin UFL2 on manufacturing of tablets using directcompression method Development of core tablets containingthe function of small degree of decrease of hardness at thehumid conditionsrdquoPharmaceutical Technical Newsletter vol 25pp 67ndash70 2009
[11] B G Prajapati and D V Patel ldquoFormulation and optimiza-tion of domperidone fast dissolving tablet by wet granulationtechniques using factorial designrdquo International Journal ofPharmTech Research vol 2 no 1 pp 292ndash299 2010
[12] J Cooper and C Gunn ldquoPowder flow and compactionrdquo inTutorial Pharmacy S J Carter Ed pp 211ndash233 CBS Publishersand Distributors New Delhi India 1986
Journal of Drug Delivery 13
[13] H Goel G Kaur A K Tiwary and V Rana ldquoFormulationdevelopment of stronger and quick disintegrating tablets acrucial effect of chitinrdquoYakugaku Zasshi vol 130 no 5 pp 729ndash735 2010
[14] J M Sonnergaard ldquoImpact of particle density and initial vol-ume on mathematical compression modelsrdquo European Journalof Pharmaceutical Sciences vol 11 no 4 pp 307ndash315 2000
[15] O A Odeku ldquoAssessment of Albizia zygia gum as a bindingagent in tablet formulationsrdquo Acta Pharmaceutica vol 55 no3 pp 263ndash276 2005
[16] F Kiekens A Debunne C Vervaet et al ldquoInfluence of thepunch diameter and curvature on the yield pressure of MCC-compacts duringHeckel analysisrdquo European Journal of Pharma-ceutical Sciences vol 22 no 2-3 pp 117ndash126 2004
[17] ldquoUnited States Pharmacopeia 24NF19rdquo inTheOfficial Compen-dia of Standards M D Asian Rockville Ed pp 1913ndash1914 USPharmacopeial Convention 2000
[18] T Y Puttewar M D Kshirsagar A V Chandewar and R VChikhale ldquoFormulation and evaluation of orodispersible tabletof tastemasked doxylamine succinate using ion exchange resinrdquoJournal of King Saud UniversitymdashScience vol 22 no 4 pp 229ndash240 2010
[19] A Fini V Bergamante G C Ceschel C Ronchi and C A Fde Moraes ldquoFast dispersibleslow releasing ibuprofen tabletsrdquoEuropean Journal of Pharmaceutics and Biopharmaceutics vol69 no 1 pp 335ndash341 2008
[20] M U Uhumwangho and R S Okor ldquoEffect of humidity on thedisintegrant property of 120572-cellulose Part II A technical noterdquoAAPS PharmSciTech vol 6 no 1 article no 7 pp E31ndashE342005
[21] T Sasaki and J Matsuki ldquoEffect of wheat starch structure onswelling powerrdquo Cereal Chemistry vol 75 no 4 pp 525ndash5291998
[22] O A Itiola and N Pilpel ldquoTableting characteristics of metron-idazole formulationsrdquo International Journal of Pharmaceuticsvol 31 no 1-2 pp 99ndash105 1986
[23] O A Odeku and O A Itiola ldquoEvaluation of khaya gum asa binder in a paracetamol tablet formulationrdquo Pharmacy andPharmacology Communications vol 4 no 4 pp 183ndash188 1998
[24] O A Odeku and J T Fell ldquoEffects of the method of preparationon the compression mechanical and release properties ofkhaya gum matricesrdquo Pharmaceutical Development and Tech-nology vol 11 no 4 pp 435ndash441 2006
[25] O A Odeku and B L Akinwande ldquoEffect of the mode ofincorporation on the disintegrant properties of acid modifiedwater and white yam starchesrdquo Saudi Pharmaceutical Journalvol 20 no 2 pp 171ndash175 2012
[26] R Shangraw A Mitrevej and M Shah ldquoA new era of tabletdisintegrantsrdquo Pharmaceutical Technology vol 4 no 10 pp 49ndash57 1980
6 Journal of Drug Delivery
(119882119895) is an optional weight factor The similarity factor fits
result between 0 and 100 It is 100 when the test and referenceprofiles are identical and tends to be 0 as the dissimilarityincreases In order to consider similar dissolution profiles 119891
2
values should be close to 100
3 Result and Discussion
31 Precompression Evaluation
311 Micromeritics Study The result of the micromeriticstudies for corn starch and the prepared corn Starch-NeusilinUFL2 conjugates were conducted and results are listed inTable 2 Angle of repose (120579∘) is a characteristic of the internalfriction or cohesion of the particles Its value will be highif the powder is cohesive and low if the powder is non-cohesive Flow property of the corn starch was improvedby the addition of Neusilin UFL2 as compared formulationswith conjugates showed good to excellent flow properties asindicated by the values of angle of repose (3669ndash2767∘) to thecorn starch (4325∘) Carrrsquos index showed values 225 to 125denoting that these formulations were of acceptable to goodflowability compared to the corn starch (3428) Hausnerrsquosratio showed that powders with low interparticle frictionhad ratios of approximately 129 to 114 indicating good flowproperties as compared to the corn starch (152) Swellingindex of the conjugates prepared by physical chemical andmicrowave method were found to be 40 65 and 95respectively which was far better than the swelling index ofcorn starch that is 18 which is in context with the effectivepore radius of the conjugates and corn starch The resultsof both swelling and effective pore radius point towardsmore wicking action capability and hence disintegrationpotential of the conjugates over the pure corn starch Theresult of micromeritic study indicates that conjugates pre-pared by microwave method were the most effective methodfollowed by chemical and physical method as they gave bettermicromeritic properties as evidenced from the Table 2
312 ATR-FTIR Analysis Corn starch and Neusilin UFL2interactions studies were carried out using ATR-FTIR spec-trophotometer and the spectra for the samples are shownin Figure 1 The IR spectra of corn starch showed a peakat 3434 cmminus1 and 2931 cmminus1 representing OndashH and CndashHstretching respectively The absorption band at 1652 cmminus1is due to absorbed water in amorphous region of starchPeak at 1241 cmminus1 represents CH
2OH group whereas peak
at 1159 cmminus1 represents coupling mode of CndashC and CndashOstretching vibrations The band at 1080 cmminus1 represents CndashOndashH bending vibration whereas peak at 929 cmminus1 could beascribed to the skeletal mode vibration of 120572-14-glycosidiclinkage The corn Starch-Neusilin UFL2 conjugates preparedby different methods namely physical microwave andchemical exhibit a sharp peak near 3480 cmminus1 which isotherwise observed at 3434 cmminus1 in the pure corn starchThisshift and sharpening of peak indicate the formation of SindashOndashC bridging bond between corn starch and Neusilin UFL2Moreover reduction in the intensity of peak at 1241 cmminus1
4000 3000 2000 1500 1000 400
(cmminus1)
T(
)
(A)
(B)
(C)
(D)
Figure 1 IR spectra of (A) native corn starch corn Starch-NeusilinUFL2 conjugates by (B) physical method (C) chemical method and(D) microwave method
1159 cmminus1 and 1080 cmminus1 confirms intermolecular bridgingbetween corn starch and Neusilin UFL2 Thus the additionof Neusilin changed the properties of corn starch forming anew excipient with different functional properties
313 XRD Analysis The XRD patterns of the samples areshown in Figure 2 The structure of corn starch is char-acterized by the presence of broad peak at 2456∘2120579 angleAppearance of sharp peak at 2740∘2120579 3172∘2120579 4560∘21205795391∘2120579 and 5647∘2120579 angles respectively in case of conju-gates prepared bymicrowavemethod gives clear indication ofreduction in amorphous nature or otherwise increase in thecrystalline behavior of the corn starch that could be correlatedwith the increase in swelling and hence superdisintegrantpotential of conjugates prepared by different methods Crys-tallinity and hence the superdisintegrant property (Table 4)of conjugates prepared by different methods were in therank order of microwave gt chemical gt physical mixtureHigh proportion of longer chains might form more stablecrystallites in the pure corn starch The swelling powerof corn starch depends on the water holding capacity ofthe starch molecule by hydrogen bonding Hence higherdegree of intermolecular bonding between corn starch andNeusilin UFL2 favors the long chain crystalline structureand hence the swelling of the conjugates which in turnpotentiates the use of corn Starch-Neusilin UFL2 as a tabletsuperdisintegrant [21]
314 DSC Analysis Figure 3 shows the DSC thermogramsof the pure corn starch and corn Starch-Neusilin UFL2conjugates prepared by physical chemical and microwavemethods Corn starch has a discrete structure and pos-sesses partially crystalline microscopic granules that are
Figure 2 XRD pattern of (A) native corn starch corn Starch-Neusilin UFL2 conjugates by (B) physical method (C) chemicalmethod and (D) microwave method
held together by intended micellar network of associatedmolecules so it does not show obvious Tg or Tm untilpyrogenation Melting range was found to be extended andbroadened with the incorporation of Neusilin UFL2 Broad-ening and shifting of the melting range in the DSC spectracould be attributed to intermolecular bonding between cornstarch and Neusilin UFL2 indicating that the Neusilin UFL2molecules were restrained by the corn starch molecules Thebroadening of themelting range could be due to the regularityof the OH group that already existed in corn starch whichhad disappeared by the interaction with Neusilin UFL2 TheTm and ΔH of the melting peak are significantly lower inthe pure corn starch than the conjugates which indicate thatthere is an interaction between corn starch and NeusilinUFL2 which has enhanced the crystallization of the purecorn starch This increase in crystalline behaviour of thepure corn starch could be correlated to increase in swelling
40 50 60 70 80 90 100 110 120 130 140
Temperature (∘C)
(A)
(B)
(C)(D)
Figure 3 DSC pattern of (A) native corn starch corn Starch-Neusilin UFL2 conjugates by (B) physical method (C) chemicalmethod and (D) microwave method
and hence superdisintegrant potential of conjugates preparedby different methods Crystallinity and superdisintegrantbehaviour of conjugates prepared by different methods couldbe arranged as microwave gt chemical gt physical mixtureFurthermore the crystalline structure contributes towardsthe swelling behaviour of the conjugates responsible for thetablet superdisintegrant activity
315 SEM Analysis Surface morphology of the corn starchand corn Starch-Neusilin UFL2 conjugates was studied bySEManalysis as shown in Figure 4The corn starch undergoesa change in its native structure from thin smooth flatsurface structure with folded edges to three dimensionalcompacts upon conjugation with the Neusilin UFL2 SEMmicrograph of the prepared conjugates showed the presenceof interparticulate voids and channels that are responsible forthe increase in water absorption and swelling capacity of theconjugates as compared to the pure corn starch Furthermorethese voidschannels contributed to the wicking behaviorresponsible for the tablet superdisintegrant property of thecorn Starch-Neusilin UFL2 conjugates Conjugates preparedbymicrowavemethod illustrated the presence ofmore porous
8 Journal of Drug Delivery
structure as compared to conjugates prepared by physicaland chemical methods The results are in line with the betterin vitro disintegration performance of FDT prepared withconjugates of microwave method compared to the other twomethods
316 Heckel FunctionAnalysis Figure 5 shows representativeHeckel plots for the conjugates prepared by physical chem-ical and microwave methods The Heckel plots showed aninitial linear portion with an increase slope at pressure of100MPa followed by another linear region for the conjugatesprepared by physical and chemical methods while for theconjugate prepared by microwave method the second linearregion was from 175MPaThe mean yield pressure values forthe conjugates were calculated from the slope of the portionshowing the highest linearity of the Heckel plots and theintercept 119860 was determined from the extrapolation of theregionThe values of119863
119860and119863
119861were calculated respectively
The values of 119875119910 1198630 119863119860 and 119863
119861for the formulations are
presented in Table 3 The value of 1198630which represents the
degree of initial packing in the die as a result of die fillingfor the conjugates indicates that the conjugates preparedby microwave method exhibited highest degree of packingin the die as a result of die filling while the conjugatesprepared by physical method exhibited the lowest valuesThevalue of 119863
119861represents the phase of rearrangement of the
particles in the early stages of compression119863119861values tend to
indicate the extent of fragmentation of particles or granulesalthough fragmentation can occur concurrently with plasticand elastic deformation of constituent particles The chemi-cally prepared conjugates exhibited the highest values whilethe one prepared by microwave method exhibited the lowestvalues This indicates that fragmentation occurs more withthe chemically prepared conjugates [22 23]The values of119863
119860
which represents the total degree of packing achieved at zeroand low pressures was also in the rank order of microwave gtchemical gt physical for the methods to prepare conjugatesThis indicates that the conjugates prepared by microwavemethod showed higher degree of packing at low pressuresThe mean yield pressure 119875
119910is inversely related to the ability
of the formulations to deform plastically under pressureThe result indicates that the conjugates prepared by physicalmethod showed the fastest onset of plastic deformation whilethe conjugates prepared by microwave method showed theslowest onset Materials with high yield pressure are classifiedas brittle or fragmenting materials whereas those with lowervalues are classified as plasticallyelastically deforming mate-rials [24] Generally during compression plastic deformationand fragmentation are known to occur concurrently Starcheshave been known to deform plastically under compressionpressure
317 Kawakita Function Analysis TheKawakita plots for theconjugates are presented in Figure 6 A linear relationshipwas obtained at all compression pressures employed withcorrelation coefficient of 0999 for the conjugates preparedby different methods The values of 119886 and 119886119887 were obtainedfrom the slope and intercept respectivelyThe value of (1minus119886)
gives the initial relative density of the starch 119863119868 while 119875
119896
values were obtained from the reciprocal of values of 119887The values of 119863
119868and 119875
119896are shown in Table 3 The value
of 119863119868is a measure of the packed initial relative density of
the formulation with the application of small pressure ortapping The ranking of 119863
119868for the conjugates was chemical
method gt microwave method gt physical method The valueof 119875119896which is an inverse measure of the amount of plastic
deformation occurring during the compression process wasfound to be maximum for tablets formulated using conju-gates prepared by chemical method followed by microwavemethod and physical method [23]Thus conjugates preparedby microwave method exhibited the highest amount of totalplastic deformation while conjugates prepared by physicalmethod exhibited the lowest values The ranking was seen tobe in the reverse order as that of the 119875
119910values It has been
shown that while119875119910relates to the onset of plastic deformation
during compression the 119875119896relates to the amount of plastic
deformation that occurs during the compression processThus the conjugates prepared by physical method showedthe slowest onset of plastic deformation but the highest totalamount of plastic deformation
32 Postcompression Evaluation Tablets require certainamount of strength and resistance to friability to withstandmechanical shock of handling during manufacturingshipping and packaging Hardness of the tablets formulatedusing the corn starch-Neusilin UFL2 conjugates assuperdisintegrant was found to vary from 43 to 35 kgcm2compared to 315 to 309 kgcm2 of tablets formulatedusing the native corn starch Percentage friability of allformulations was less than 1 indicating good mechanicalcharacteristics Wetting time was observed to be decreasedfrom 68 seconds for the tablets incorporating native cornstarch to 33 22 and 14 seconds for the tablets incorporatingconjugates prepared by physical chemical and microwavemethods Disintegration time was also observed to decreasefrom 83 seconds for the tablets incorporating native cornstarch to 40 35 and 22 seconds for the tablets incorporatingconjugates prepared by physical chemical and microwavemethods respectively Water absorption ratio was found tobe inversely proportional to the wetting and disintegratingtime of the tablets The increase in water absorption ratioand decrease in wetting and disintegration times in allformulations may be attributed to the modification of thecorn starch by Neusilin UFL2 to yield a novel conjugatewhich acts as superdisintegrant which absorbs water andswells causing rupture of the tablets Tablet propertiessuch as mechanical strength tablet packing fraction anddisintegration are in turn affected by the porosity [25]Tablets with low packing fraction have high porosity andpores facilitates the penetration of dissolution media intothe tablet leading to disintegration of the tablet Whereashigher tablet packing fraction leads to reduction in porositywhich inhibits the penetration of dissolution media resultingin slower disintegration rate of the tablet [26] Tabletpacking fraction was found to be decreased in the tabletsincorporating conjugates (063ndash041) compared to the tablets
Journal of Drug Delivery 9
(a) (b)
(c) (d)
Figure 4 SEM photomicrographs of (A) corn starch and corn Starch-Neusilin UFL2 conjugates prepared by (B) physical method (C)chemical method and (D) microwave method
Table 3 Parameters derived from the Heckel and Kawakita plots for tablet incorporating corn Starch-Neusilin UFL2 conjugate as asuperdisintegrant prepared by (A) physical method (B) chemical method and (C) microwave method
Figure 5 Heckel plots for the tablet incorporating corn Starch-Neusilin UFL2 conjugate as a superdisintegrant prepared by (A)physical method (B) chemical method and (C)microwavemethod
with corn starch (082) The results are in line with thepowder evaluation results where conjugates prepared byphysical chemical and microwave methods were showing
0
50
100
150
200
250
300
0 50 100 150 200 250
PC
Applied pressure (MPa)
ABC
Figure 6 Kawakita plots for the tablet incorporating corn Starch-Neusilin UFL2 conjugate as a superdisintegrant prepared by (A)physical method (B) chemical method and (C)microwavemethod
better swelling and effective pore radius compared to thenative corn starch The fast disintegration of tablets is dueto the presence of pores resulting in faster penetration of
10 Journal of Drug Delivery
Table4Differentp
ropertieso
fthe
form
ulated
FDTs
Cod
eParameter
Diameter
(mm)
Thickn
ess(mm)
Friability(
)Hardn
ess(kgcm
2 )TSlowast(M
Nm
2 )WTlowast
(Sec)
WARlowast
()
DTlowast
(Sec)
CUlowast(
)TP
Flowast119875lowast(
)1198652
F1674
plusmn003
356
plusmn003
089
plusmn004
311
plusmn010
047
plusmn015
68plusmn113
40plusmn011
73plusmn3
9899plusmn02
081
189
19F2
673
plusmn004
351
plusmn004
091
plusmn002
315
plusmn007
047
plusmn005
68plusmn12
942
plusmn011
73plusmn1
991plusmn015
082
175
24F3
674
plusmn005
355
plusmn005
089
plusmn005
309
plusmn011
047
plusmn011
67plusmn111
46plusmn009
71plusmn2
9727plusmn09
081
187
21F4
673
plusmn001
359
plusmn005
090
plusmn003
310
plusmn002
047
plusmn009
66plusmn114
46plusmn010
71plusmn3
9659plusmn05
080
194
25F5
674
plusmn001
351
plusmn005
076
plusmn004
350
plusmn011
048
plusmn005
33plusmn114
98plusmn004
48plusmn2
9650plusmn03
063
367
43F6
674
plusmn002
355
plusmn004
073
plusmn005
356
plusmn008
048
plusmn001
33plusmn16
796
plusmn004
46plusmn3
991plusmn015
062
373
43F7
674
plusmn001
355
plusmn005
071
plusmn002
370
plusmn015
056
plusmn018
32plusmn110
101plusmn
005
44plusmn1
9835plusmn02
062
373
45F8
674
plusmn003
356
plusmn003
067
plusmn003
375
plusmn021
055
plusmn008
31plusmn14
0103plusmn002
40plusmn2
9923plusmn05
062
375
47F9
673
plusmn004
355
plusmn002
055
plusmn001
400
plusmn018
060
plusmn019
23plusmn13
4108plusmn003
40plusmn6
9912
plusmn04
054
426
50F10
674
plusmn005
354
plusmn007
054
plusmn005
380
plusmn015
057
plusmn006
22plusmn12
5100plusmn002
35plusmn3
9892plusmn07
057
435
50F11
673
plusmn003
356
plusmn004
055
plusmn003
370
plusmn017
056
plusmn011
23plusmn10
5106plusmn006
36plusmn2
9727plusmn09
057
423
55F12
673
plusmn002
353
plusmn003
051
plusmn004
410
plusmn02
062
plusmn015
23plusmn13
8110
plusmn004
32plusmn7
9659plusmn05
056
426
53F13
674
plusmn003
355
plusmn004
041
plusmn007
420
plusmn027
073
plusmn008
14plusmn15
2121plusmn
008
26plusmn2
9915
plusmn01
041
582
50F14
673
plusmn001
351
plusmn004
042
plusmn002
425
plusmn02
073
plusmn020
14plusmn12
6124plusmn007
24plusmn5
9899plusmn02
039
595
52F15
674
plusmn003
355
plusmn006
044
plusmn004
430
plusmn010
076
plusmn018
13plusmn115
125plusmn003
22plusmn3
9975plusmn10
040
599
62F16
674
plusmn001
359
plusmn005
047
plusmn007
420
plusmn045
079
plusmn019
14plusmn14
0128plusmn005
22plusmn4
9912
plusmn03
041
612
64TSlowasttensiles
treng
thW
Tlowastw
ettin
gtim
eWARlowast
water
absorptio
nratio
DTlowast
disintegratio
ntim
eCUlowastcon
tent
unifo
rmity
TPFlowasttabletp
acking
fractio
n119875lowastporosity
Journal of Drug Delivery 11
the dissolution media leading to swelling and wicking of theprepared conjugate creating hydrodynamic pressure insidethe tablets hence responsible for the quick and completedisintegration of tablets indicating the superdisintegrantactivity of conjugates prepared by physical chemical andmicrowave methods over the native corn starch
The results obtained from the in vitro dissolution studyare presented in Figures 7 8 9 and 10 ldquoMKTDrdquo representsthe standard marketed domperidone formulation to whichthe formulated FDTs were compared The similarity factor(1198912) is a logarithmic transformation of the sum-squared
error of differences between test and reference productsover all time points It was observed that the three differentapproaches used for the preparation of conjugate in thisstudy namely physical chemical and microwave methodsincreased the dissolution rate of the drug compared to thetablet prepared with the native corn starch and standardmarketed formulation of the drug The order of increaseddrug dissolution using the different approaches was asfollows microwave gt chemical gt physical In case of theFDTs prepared by using native corn starch (F1ndashF4) thepercentage cumulative drug release was found to be verypoor as compared to the standard marketed formulation ofdomperidone (MKTD)The119891
2value for formulation (F1ndashF4)
was below 50 depicting the dissimilarity between the drugreleases Formulations (F5ndashF8) (F9ndashF12) and (F13ndashF16)werecontaining corn starch-Neusilin UFL2 conjugate prepared byphysical chemical and microwave methods The percentagecumulative drug release for these formulations were found tobe comparable to the standardmarketed formulation of dom-peridone The 119891
2values for these formulations were found
to be over 50 evidencing the similarity between the drugreleases Results of various tablet evaluation tests as evidencedfrom Table 4 indicate that among the three methods usedfor the preparation of conjugates microwave was the mosteffectivemethod followed by chemical and physical methodsMoreover by increasing the concentration of conjugates thetablet did not show much effect on drug release from theformulated FDTs Hence from the commercial point of viewlowest concentration of superdisintegrant showing optimumtabletting results should be recommended
4 Conculsions
In present work an attempt was made to modify the cornstarch to develop corn starch-Neusilin UFL2 conjugatesusing different methods namely physical chemical andmicrowave The prepared conjugates and the corn starchwere characterised for powder flow pH viscosity swellingand effective pore radius Evaluation of precompressionparameter indicates good flow properties The preparedconjugates were also subjected to the compression studiesnamely Heckel and Kawakita function The Heckel plot isusually correlated with the speed of the tablet machine whilethe Kawakita plot is related to the crushing or tensile strengthof the tablet Fast disintegrating tablets of domperidone wereformulated by direct compression technique employing thecorn starch and the prepared conjugates The tablets were
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F1F2F3
F4MKTD
Figure 7 Dissolution rate profiles of FDTs (F1ndashF4) formulated byincorporating native corn starch as a superdisintegrant compared toa standard marketed formulation of domperidone (MKTD)
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F5F6F7
F8MKTD
Figure 8 Dissolution rate profiles of FDTs (F5ndashF8) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates preparedby physical method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
evaluated for physical parametric tests wetting time waterabsorption ratio porosity tablet packing fraction in vitrodisintegration time drug content in vitro dissolution andstability studies Extensive swelling porosity and wickingaction of the prepared corn Starch-Neusilin UFL2 conjugatesin the prepared fast disintegrating tablets were found to becontributing to its superdisintegrant action
In conclusion the prepared conjugates can be effectivelyused as superdisintegrant in order to develop a faster disin-tegrating tablet formulation Future challenges for many fastdisintegrating tablet manufacturers include reducing costsby finding ways to manufacture with conventional equip-ment using versatile packaging and improving mechanical
12 Journal of Drug Delivery
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F9F10F11
F12MKTD
Figure 9 Dissolution rate profiles of FDTs (F9ndashF12) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates preparedby chemical method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
F13F14F15
F16MKTD
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
Figure 10 Dissolution rate profiles of FDTs (F13ndashF16) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates prepared bymicrowave method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
strength Such products provide an opportunity for theproduct line extension in the market place and extensionof patent term of innovator Due to its wide significancethis drug delivery system may lead to better patient com-pliance and ultimate clinical output Future might witnessnovel technologies for development and utilization of themodified starches as tablet superdisintegrant for cost effectiveformulation of fast disintegrating tablets
Conflict of Interests
The authors declare that they have no conflict of interests
Acknowledgments
The authors gratefully acknowledge Dr Madhu ChitkaraVice Chancellor Chitkara University Rajpura Punjab IndiaDr Ashok Chitkara Chairman Chitkara Educational TrustChandigarh India and Dr Sandeep Arora Dean ChitkaraUniversity Rajpura Punjab India for support and institu-tional facilities
References
[1] I Rashid M Al-Remawi S A Leharne B Z Chowdhry andA Badwan ldquoA novel multifunctional pharmaceutical excipientmodification of the permeability of starch by processing withmagnesium silicaterdquo International Journal of Pharmaceutics vol411 no 1-2 pp 18ndash26 2011
[2] O A Odeku and K M Picker-Freyer ldquoAnalysis of the materialand tablet formation properties of four Dioscorea starchesrdquoStarchStarke vol 59 no 9 pp 430ndash444 2007
[3] N Visavarungroj and J P Remon ldquoAn evaluation of hydrox-ypropyl starch an disintegrant and binder in tablet formulationrdquoDrug Development and Industrial Pharmacy vol 17 no 10 pp1389ndash1396 1991
[4] M Nakano N Nakazono and N Inotsume ldquoPreparation andevaluation of sustained release tablets prepared with 120572-starchrdquoChemical and Pharmaceutical Bulletin vol 35 no 10 pp 4346ndash4350 1987
[5] O A Odeku and K M Picker-Freyer ldquoFreeze-dried prege-latinized Dioscorea starches as tablet matrix for sustainedreleaserdquo Journal of Excipients and Food Chemicals vol 1 no 2pp 21ndash32 2010
[6] H Staroszczyk ldquoMicrowave-assisted silication of potato starchrdquoCarbohydrate Polymers vol 77 no 3 pp 506ndash515 2009
[7] J Singh L Kaur and O J McCarthy ldquoFactors influencingthe physico-chemical morphological thermal and rheologicalproperties of some chemically modified starches for foodapplications a reviewrdquo Food Hydrocolloids vol 21 no 1 pp 1ndash22 2007
[8] I Rashid N Daraghmeh M Al-Remawi S A Leharne B ZChowdhry and A Badwan ldquoCharacterization of chitin-metalsilicates as binding superdisintegrantsrdquo Journal of Pharmaceuti-cal Sciences vol 98 no 12 pp 4887ndash4901 2009
[9] I Rashid N Daraghmeh M Al-Remawi S A Leharne B ZChowdhry and A Badwan ldquoCharacterization of the impactof magnesium stearate lubrication on the tableting propertiesof chitin-Mg silicate as a superdisintegrating binder whencompared to Avicel 200rdquo Powder Technology vol 203 no 3 pp609ndash619 2010
[10] Y Asai M Nohara S Fujioka K Isaji and S Nagira ldquoApplica-tion of Neusilin UFL2 on manufacturing of tablets using directcompression method Development of core tablets containingthe function of small degree of decrease of hardness at thehumid conditionsrdquoPharmaceutical Technical Newsletter vol 25pp 67ndash70 2009
[11] B G Prajapati and D V Patel ldquoFormulation and optimiza-tion of domperidone fast dissolving tablet by wet granulationtechniques using factorial designrdquo International Journal ofPharmTech Research vol 2 no 1 pp 292ndash299 2010
[12] J Cooper and C Gunn ldquoPowder flow and compactionrdquo inTutorial Pharmacy S J Carter Ed pp 211ndash233 CBS Publishersand Distributors New Delhi India 1986
Journal of Drug Delivery 13
[13] H Goel G Kaur A K Tiwary and V Rana ldquoFormulationdevelopment of stronger and quick disintegrating tablets acrucial effect of chitinrdquoYakugaku Zasshi vol 130 no 5 pp 729ndash735 2010
[14] J M Sonnergaard ldquoImpact of particle density and initial vol-ume on mathematical compression modelsrdquo European Journalof Pharmaceutical Sciences vol 11 no 4 pp 307ndash315 2000
[15] O A Odeku ldquoAssessment of Albizia zygia gum as a bindingagent in tablet formulationsrdquo Acta Pharmaceutica vol 55 no3 pp 263ndash276 2005
[16] F Kiekens A Debunne C Vervaet et al ldquoInfluence of thepunch diameter and curvature on the yield pressure of MCC-compacts duringHeckel analysisrdquo European Journal of Pharma-ceutical Sciences vol 22 no 2-3 pp 117ndash126 2004
[17] ldquoUnited States Pharmacopeia 24NF19rdquo inTheOfficial Compen-dia of Standards M D Asian Rockville Ed pp 1913ndash1914 USPharmacopeial Convention 2000
[18] T Y Puttewar M D Kshirsagar A V Chandewar and R VChikhale ldquoFormulation and evaluation of orodispersible tabletof tastemasked doxylamine succinate using ion exchange resinrdquoJournal of King Saud UniversitymdashScience vol 22 no 4 pp 229ndash240 2010
[19] A Fini V Bergamante G C Ceschel C Ronchi and C A Fde Moraes ldquoFast dispersibleslow releasing ibuprofen tabletsrdquoEuropean Journal of Pharmaceutics and Biopharmaceutics vol69 no 1 pp 335ndash341 2008
[20] M U Uhumwangho and R S Okor ldquoEffect of humidity on thedisintegrant property of 120572-cellulose Part II A technical noterdquoAAPS PharmSciTech vol 6 no 1 article no 7 pp E31ndashE342005
[21] T Sasaki and J Matsuki ldquoEffect of wheat starch structure onswelling powerrdquo Cereal Chemistry vol 75 no 4 pp 525ndash5291998
[22] O A Itiola and N Pilpel ldquoTableting characteristics of metron-idazole formulationsrdquo International Journal of Pharmaceuticsvol 31 no 1-2 pp 99ndash105 1986
[23] O A Odeku and O A Itiola ldquoEvaluation of khaya gum asa binder in a paracetamol tablet formulationrdquo Pharmacy andPharmacology Communications vol 4 no 4 pp 183ndash188 1998
[24] O A Odeku and J T Fell ldquoEffects of the method of preparationon the compression mechanical and release properties ofkhaya gum matricesrdquo Pharmaceutical Development and Tech-nology vol 11 no 4 pp 435ndash441 2006
[25] O A Odeku and B L Akinwande ldquoEffect of the mode ofincorporation on the disintegrant properties of acid modifiedwater and white yam starchesrdquo Saudi Pharmaceutical Journalvol 20 no 2 pp 171ndash175 2012
[26] R Shangraw A Mitrevej and M Shah ldquoA new era of tabletdisintegrantsrdquo Pharmaceutical Technology vol 4 no 10 pp 49ndash57 1980
Figure 2 XRD pattern of (A) native corn starch corn Starch-Neusilin UFL2 conjugates by (B) physical method (C) chemicalmethod and (D) microwave method
held together by intended micellar network of associatedmolecules so it does not show obvious Tg or Tm untilpyrogenation Melting range was found to be extended andbroadened with the incorporation of Neusilin UFL2 Broad-ening and shifting of the melting range in the DSC spectracould be attributed to intermolecular bonding between cornstarch and Neusilin UFL2 indicating that the Neusilin UFL2molecules were restrained by the corn starch molecules Thebroadening of themelting range could be due to the regularityof the OH group that already existed in corn starch whichhad disappeared by the interaction with Neusilin UFL2 TheTm and ΔH of the melting peak are significantly lower inthe pure corn starch than the conjugates which indicate thatthere is an interaction between corn starch and NeusilinUFL2 which has enhanced the crystallization of the purecorn starch This increase in crystalline behaviour of thepure corn starch could be correlated to increase in swelling
40 50 60 70 80 90 100 110 120 130 140
Temperature (∘C)
(A)
(B)
(C)(D)
Figure 3 DSC pattern of (A) native corn starch corn Starch-Neusilin UFL2 conjugates by (B) physical method (C) chemicalmethod and (D) microwave method
and hence superdisintegrant potential of conjugates preparedby different methods Crystallinity and superdisintegrantbehaviour of conjugates prepared by different methods couldbe arranged as microwave gt chemical gt physical mixtureFurthermore the crystalline structure contributes towardsthe swelling behaviour of the conjugates responsible for thetablet superdisintegrant activity
315 SEM Analysis Surface morphology of the corn starchand corn Starch-Neusilin UFL2 conjugates was studied bySEManalysis as shown in Figure 4The corn starch undergoesa change in its native structure from thin smooth flatsurface structure with folded edges to three dimensionalcompacts upon conjugation with the Neusilin UFL2 SEMmicrograph of the prepared conjugates showed the presenceof interparticulate voids and channels that are responsible forthe increase in water absorption and swelling capacity of theconjugates as compared to the pure corn starch Furthermorethese voidschannels contributed to the wicking behaviorresponsible for the tablet superdisintegrant property of thecorn Starch-Neusilin UFL2 conjugates Conjugates preparedbymicrowavemethod illustrated the presence ofmore porous
8 Journal of Drug Delivery
structure as compared to conjugates prepared by physicaland chemical methods The results are in line with the betterin vitro disintegration performance of FDT prepared withconjugates of microwave method compared to the other twomethods
316 Heckel FunctionAnalysis Figure 5 shows representativeHeckel plots for the conjugates prepared by physical chem-ical and microwave methods The Heckel plots showed aninitial linear portion with an increase slope at pressure of100MPa followed by another linear region for the conjugatesprepared by physical and chemical methods while for theconjugate prepared by microwave method the second linearregion was from 175MPaThe mean yield pressure values forthe conjugates were calculated from the slope of the portionshowing the highest linearity of the Heckel plots and theintercept 119860 was determined from the extrapolation of theregionThe values of119863
119860and119863
119861were calculated respectively
The values of 119875119910 1198630 119863119860 and 119863
119861for the formulations are
presented in Table 3 The value of 1198630which represents the
degree of initial packing in the die as a result of die fillingfor the conjugates indicates that the conjugates preparedby microwave method exhibited highest degree of packingin the die as a result of die filling while the conjugatesprepared by physical method exhibited the lowest valuesThevalue of 119863
119861represents the phase of rearrangement of the
particles in the early stages of compression119863119861values tend to
indicate the extent of fragmentation of particles or granulesalthough fragmentation can occur concurrently with plasticand elastic deformation of constituent particles The chemi-cally prepared conjugates exhibited the highest values whilethe one prepared by microwave method exhibited the lowestvalues This indicates that fragmentation occurs more withthe chemically prepared conjugates [22 23]The values of119863
119860
which represents the total degree of packing achieved at zeroand low pressures was also in the rank order of microwave gtchemical gt physical for the methods to prepare conjugatesThis indicates that the conjugates prepared by microwavemethod showed higher degree of packing at low pressuresThe mean yield pressure 119875
119910is inversely related to the ability
of the formulations to deform plastically under pressureThe result indicates that the conjugates prepared by physicalmethod showed the fastest onset of plastic deformation whilethe conjugates prepared by microwave method showed theslowest onset Materials with high yield pressure are classifiedas brittle or fragmenting materials whereas those with lowervalues are classified as plasticallyelastically deforming mate-rials [24] Generally during compression plastic deformationand fragmentation are known to occur concurrently Starcheshave been known to deform plastically under compressionpressure
317 Kawakita Function Analysis TheKawakita plots for theconjugates are presented in Figure 6 A linear relationshipwas obtained at all compression pressures employed withcorrelation coefficient of 0999 for the conjugates preparedby different methods The values of 119886 and 119886119887 were obtainedfrom the slope and intercept respectivelyThe value of (1minus119886)
gives the initial relative density of the starch 119863119868 while 119875
119896
values were obtained from the reciprocal of values of 119887The values of 119863
119868and 119875
119896are shown in Table 3 The value
of 119863119868is a measure of the packed initial relative density of
the formulation with the application of small pressure ortapping The ranking of 119863
119868for the conjugates was chemical
method gt microwave method gt physical method The valueof 119875119896which is an inverse measure of the amount of plastic
deformation occurring during the compression process wasfound to be maximum for tablets formulated using conju-gates prepared by chemical method followed by microwavemethod and physical method [23]Thus conjugates preparedby microwave method exhibited the highest amount of totalplastic deformation while conjugates prepared by physicalmethod exhibited the lowest values The ranking was seen tobe in the reverse order as that of the 119875
119910values It has been
shown that while119875119910relates to the onset of plastic deformation
during compression the 119875119896relates to the amount of plastic
deformation that occurs during the compression processThus the conjugates prepared by physical method showedthe slowest onset of plastic deformation but the highest totalamount of plastic deformation
32 Postcompression Evaluation Tablets require certainamount of strength and resistance to friability to withstandmechanical shock of handling during manufacturingshipping and packaging Hardness of the tablets formulatedusing the corn starch-Neusilin UFL2 conjugates assuperdisintegrant was found to vary from 43 to 35 kgcm2compared to 315 to 309 kgcm2 of tablets formulatedusing the native corn starch Percentage friability of allformulations was less than 1 indicating good mechanicalcharacteristics Wetting time was observed to be decreasedfrom 68 seconds for the tablets incorporating native cornstarch to 33 22 and 14 seconds for the tablets incorporatingconjugates prepared by physical chemical and microwavemethods Disintegration time was also observed to decreasefrom 83 seconds for the tablets incorporating native cornstarch to 40 35 and 22 seconds for the tablets incorporatingconjugates prepared by physical chemical and microwavemethods respectively Water absorption ratio was found tobe inversely proportional to the wetting and disintegratingtime of the tablets The increase in water absorption ratioand decrease in wetting and disintegration times in allformulations may be attributed to the modification of thecorn starch by Neusilin UFL2 to yield a novel conjugatewhich acts as superdisintegrant which absorbs water andswells causing rupture of the tablets Tablet propertiessuch as mechanical strength tablet packing fraction anddisintegration are in turn affected by the porosity [25]Tablets with low packing fraction have high porosity andpores facilitates the penetration of dissolution media intothe tablet leading to disintegration of the tablet Whereashigher tablet packing fraction leads to reduction in porositywhich inhibits the penetration of dissolution media resultingin slower disintegration rate of the tablet [26] Tabletpacking fraction was found to be decreased in the tabletsincorporating conjugates (063ndash041) compared to the tablets
Journal of Drug Delivery 9
(a) (b)
(c) (d)
Figure 4 SEM photomicrographs of (A) corn starch and corn Starch-Neusilin UFL2 conjugates prepared by (B) physical method (C)chemical method and (D) microwave method
Table 3 Parameters derived from the Heckel and Kawakita plots for tablet incorporating corn Starch-Neusilin UFL2 conjugate as asuperdisintegrant prepared by (A) physical method (B) chemical method and (C) microwave method
Figure 5 Heckel plots for the tablet incorporating corn Starch-Neusilin UFL2 conjugate as a superdisintegrant prepared by (A)physical method (B) chemical method and (C)microwavemethod
with corn starch (082) The results are in line with thepowder evaluation results where conjugates prepared byphysical chemical and microwave methods were showing
0
50
100
150
200
250
300
0 50 100 150 200 250
PC
Applied pressure (MPa)
ABC
Figure 6 Kawakita plots for the tablet incorporating corn Starch-Neusilin UFL2 conjugate as a superdisintegrant prepared by (A)physical method (B) chemical method and (C)microwavemethod
better swelling and effective pore radius compared to thenative corn starch The fast disintegration of tablets is dueto the presence of pores resulting in faster penetration of
10 Journal of Drug Delivery
Table4Differentp
ropertieso
fthe
form
ulated
FDTs
Cod
eParameter
Diameter
(mm)
Thickn
ess(mm)
Friability(
)Hardn
ess(kgcm
2 )TSlowast(M
Nm
2 )WTlowast
(Sec)
WARlowast
()
DTlowast
(Sec)
CUlowast(
)TP
Flowast119875lowast(
)1198652
F1674
plusmn003
356
plusmn003
089
plusmn004
311
plusmn010
047
plusmn015
68plusmn113
40plusmn011
73plusmn3
9899plusmn02
081
189
19F2
673
plusmn004
351
plusmn004
091
plusmn002
315
plusmn007
047
plusmn005
68plusmn12
942
plusmn011
73plusmn1
991plusmn015
082
175
24F3
674
plusmn005
355
plusmn005
089
plusmn005
309
plusmn011
047
plusmn011
67plusmn111
46plusmn009
71plusmn2
9727plusmn09
081
187
21F4
673
plusmn001
359
plusmn005
090
plusmn003
310
plusmn002
047
plusmn009
66plusmn114
46plusmn010
71plusmn3
9659plusmn05
080
194
25F5
674
plusmn001
351
plusmn005
076
plusmn004
350
plusmn011
048
plusmn005
33plusmn114
98plusmn004
48plusmn2
9650plusmn03
063
367
43F6
674
plusmn002
355
plusmn004
073
plusmn005
356
plusmn008
048
plusmn001
33plusmn16
796
plusmn004
46plusmn3
991plusmn015
062
373
43F7
674
plusmn001
355
plusmn005
071
plusmn002
370
plusmn015
056
plusmn018
32plusmn110
101plusmn
005
44plusmn1
9835plusmn02
062
373
45F8
674
plusmn003
356
plusmn003
067
plusmn003
375
plusmn021
055
plusmn008
31plusmn14
0103plusmn002
40plusmn2
9923plusmn05
062
375
47F9
673
plusmn004
355
plusmn002
055
plusmn001
400
plusmn018
060
plusmn019
23plusmn13
4108plusmn003
40plusmn6
9912
plusmn04
054
426
50F10
674
plusmn005
354
plusmn007
054
plusmn005
380
plusmn015
057
plusmn006
22plusmn12
5100plusmn002
35plusmn3
9892plusmn07
057
435
50F11
673
plusmn003
356
plusmn004
055
plusmn003
370
plusmn017
056
plusmn011
23plusmn10
5106plusmn006
36plusmn2
9727plusmn09
057
423
55F12
673
plusmn002
353
plusmn003
051
plusmn004
410
plusmn02
062
plusmn015
23plusmn13
8110
plusmn004
32plusmn7
9659plusmn05
056
426
53F13
674
plusmn003
355
plusmn004
041
plusmn007
420
plusmn027
073
plusmn008
14plusmn15
2121plusmn
008
26plusmn2
9915
plusmn01
041
582
50F14
673
plusmn001
351
plusmn004
042
plusmn002
425
plusmn02
073
plusmn020
14plusmn12
6124plusmn007
24plusmn5
9899plusmn02
039
595
52F15
674
plusmn003
355
plusmn006
044
plusmn004
430
plusmn010
076
plusmn018
13plusmn115
125plusmn003
22plusmn3
9975plusmn10
040
599
62F16
674
plusmn001
359
plusmn005
047
plusmn007
420
plusmn045
079
plusmn019
14plusmn14
0128plusmn005
22plusmn4
9912
plusmn03
041
612
64TSlowasttensiles
treng
thW
Tlowastw
ettin
gtim
eWARlowast
water
absorptio
nratio
DTlowast
disintegratio
ntim
eCUlowastcon
tent
unifo
rmity
TPFlowasttabletp
acking
fractio
n119875lowastporosity
Journal of Drug Delivery 11
the dissolution media leading to swelling and wicking of theprepared conjugate creating hydrodynamic pressure insidethe tablets hence responsible for the quick and completedisintegration of tablets indicating the superdisintegrantactivity of conjugates prepared by physical chemical andmicrowave methods over the native corn starch
The results obtained from the in vitro dissolution studyare presented in Figures 7 8 9 and 10 ldquoMKTDrdquo representsthe standard marketed domperidone formulation to whichthe formulated FDTs were compared The similarity factor(1198912) is a logarithmic transformation of the sum-squared
error of differences between test and reference productsover all time points It was observed that the three differentapproaches used for the preparation of conjugate in thisstudy namely physical chemical and microwave methodsincreased the dissolution rate of the drug compared to thetablet prepared with the native corn starch and standardmarketed formulation of the drug The order of increaseddrug dissolution using the different approaches was asfollows microwave gt chemical gt physical In case of theFDTs prepared by using native corn starch (F1ndashF4) thepercentage cumulative drug release was found to be verypoor as compared to the standard marketed formulation ofdomperidone (MKTD)The119891
2value for formulation (F1ndashF4)
was below 50 depicting the dissimilarity between the drugreleases Formulations (F5ndashF8) (F9ndashF12) and (F13ndashF16)werecontaining corn starch-Neusilin UFL2 conjugate prepared byphysical chemical and microwave methods The percentagecumulative drug release for these formulations were found tobe comparable to the standardmarketed formulation of dom-peridone The 119891
2values for these formulations were found
to be over 50 evidencing the similarity between the drugreleases Results of various tablet evaluation tests as evidencedfrom Table 4 indicate that among the three methods usedfor the preparation of conjugates microwave was the mosteffectivemethod followed by chemical and physical methodsMoreover by increasing the concentration of conjugates thetablet did not show much effect on drug release from theformulated FDTs Hence from the commercial point of viewlowest concentration of superdisintegrant showing optimumtabletting results should be recommended
4 Conculsions
In present work an attempt was made to modify the cornstarch to develop corn starch-Neusilin UFL2 conjugatesusing different methods namely physical chemical andmicrowave The prepared conjugates and the corn starchwere characterised for powder flow pH viscosity swellingand effective pore radius Evaluation of precompressionparameter indicates good flow properties The preparedconjugates were also subjected to the compression studiesnamely Heckel and Kawakita function The Heckel plot isusually correlated with the speed of the tablet machine whilethe Kawakita plot is related to the crushing or tensile strengthof the tablet Fast disintegrating tablets of domperidone wereformulated by direct compression technique employing thecorn starch and the prepared conjugates The tablets were
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F1F2F3
F4MKTD
Figure 7 Dissolution rate profiles of FDTs (F1ndashF4) formulated byincorporating native corn starch as a superdisintegrant compared toa standard marketed formulation of domperidone (MKTD)
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F5F6F7
F8MKTD
Figure 8 Dissolution rate profiles of FDTs (F5ndashF8) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates preparedby physical method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
evaluated for physical parametric tests wetting time waterabsorption ratio porosity tablet packing fraction in vitrodisintegration time drug content in vitro dissolution andstability studies Extensive swelling porosity and wickingaction of the prepared corn Starch-Neusilin UFL2 conjugatesin the prepared fast disintegrating tablets were found to becontributing to its superdisintegrant action
In conclusion the prepared conjugates can be effectivelyused as superdisintegrant in order to develop a faster disin-tegrating tablet formulation Future challenges for many fastdisintegrating tablet manufacturers include reducing costsby finding ways to manufacture with conventional equip-ment using versatile packaging and improving mechanical
12 Journal of Drug Delivery
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F9F10F11
F12MKTD
Figure 9 Dissolution rate profiles of FDTs (F9ndashF12) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates preparedby chemical method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
F13F14F15
F16MKTD
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
Figure 10 Dissolution rate profiles of FDTs (F13ndashF16) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates prepared bymicrowave method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
strength Such products provide an opportunity for theproduct line extension in the market place and extensionof patent term of innovator Due to its wide significancethis drug delivery system may lead to better patient com-pliance and ultimate clinical output Future might witnessnovel technologies for development and utilization of themodified starches as tablet superdisintegrant for cost effectiveformulation of fast disintegrating tablets
Conflict of Interests
The authors declare that they have no conflict of interests
Acknowledgments
The authors gratefully acknowledge Dr Madhu ChitkaraVice Chancellor Chitkara University Rajpura Punjab IndiaDr Ashok Chitkara Chairman Chitkara Educational TrustChandigarh India and Dr Sandeep Arora Dean ChitkaraUniversity Rajpura Punjab India for support and institu-tional facilities
References
[1] I Rashid M Al-Remawi S A Leharne B Z Chowdhry andA Badwan ldquoA novel multifunctional pharmaceutical excipientmodification of the permeability of starch by processing withmagnesium silicaterdquo International Journal of Pharmaceutics vol411 no 1-2 pp 18ndash26 2011
[2] O A Odeku and K M Picker-Freyer ldquoAnalysis of the materialand tablet formation properties of four Dioscorea starchesrdquoStarchStarke vol 59 no 9 pp 430ndash444 2007
[3] N Visavarungroj and J P Remon ldquoAn evaluation of hydrox-ypropyl starch an disintegrant and binder in tablet formulationrdquoDrug Development and Industrial Pharmacy vol 17 no 10 pp1389ndash1396 1991
[4] M Nakano N Nakazono and N Inotsume ldquoPreparation andevaluation of sustained release tablets prepared with 120572-starchrdquoChemical and Pharmaceutical Bulletin vol 35 no 10 pp 4346ndash4350 1987
[5] O A Odeku and K M Picker-Freyer ldquoFreeze-dried prege-latinized Dioscorea starches as tablet matrix for sustainedreleaserdquo Journal of Excipients and Food Chemicals vol 1 no 2pp 21ndash32 2010
[6] H Staroszczyk ldquoMicrowave-assisted silication of potato starchrdquoCarbohydrate Polymers vol 77 no 3 pp 506ndash515 2009
[7] J Singh L Kaur and O J McCarthy ldquoFactors influencingthe physico-chemical morphological thermal and rheologicalproperties of some chemically modified starches for foodapplications a reviewrdquo Food Hydrocolloids vol 21 no 1 pp 1ndash22 2007
[8] I Rashid N Daraghmeh M Al-Remawi S A Leharne B ZChowdhry and A Badwan ldquoCharacterization of chitin-metalsilicates as binding superdisintegrantsrdquo Journal of Pharmaceuti-cal Sciences vol 98 no 12 pp 4887ndash4901 2009
[9] I Rashid N Daraghmeh M Al-Remawi S A Leharne B ZChowdhry and A Badwan ldquoCharacterization of the impactof magnesium stearate lubrication on the tableting propertiesof chitin-Mg silicate as a superdisintegrating binder whencompared to Avicel 200rdquo Powder Technology vol 203 no 3 pp609ndash619 2010
[10] Y Asai M Nohara S Fujioka K Isaji and S Nagira ldquoApplica-tion of Neusilin UFL2 on manufacturing of tablets using directcompression method Development of core tablets containingthe function of small degree of decrease of hardness at thehumid conditionsrdquoPharmaceutical Technical Newsletter vol 25pp 67ndash70 2009
[11] B G Prajapati and D V Patel ldquoFormulation and optimiza-tion of domperidone fast dissolving tablet by wet granulationtechniques using factorial designrdquo International Journal ofPharmTech Research vol 2 no 1 pp 292ndash299 2010
[12] J Cooper and C Gunn ldquoPowder flow and compactionrdquo inTutorial Pharmacy S J Carter Ed pp 211ndash233 CBS Publishersand Distributors New Delhi India 1986
Journal of Drug Delivery 13
[13] H Goel G Kaur A K Tiwary and V Rana ldquoFormulationdevelopment of stronger and quick disintegrating tablets acrucial effect of chitinrdquoYakugaku Zasshi vol 130 no 5 pp 729ndash735 2010
[14] J M Sonnergaard ldquoImpact of particle density and initial vol-ume on mathematical compression modelsrdquo European Journalof Pharmaceutical Sciences vol 11 no 4 pp 307ndash315 2000
[15] O A Odeku ldquoAssessment of Albizia zygia gum as a bindingagent in tablet formulationsrdquo Acta Pharmaceutica vol 55 no3 pp 263ndash276 2005
[16] F Kiekens A Debunne C Vervaet et al ldquoInfluence of thepunch diameter and curvature on the yield pressure of MCC-compacts duringHeckel analysisrdquo European Journal of Pharma-ceutical Sciences vol 22 no 2-3 pp 117ndash126 2004
[17] ldquoUnited States Pharmacopeia 24NF19rdquo inTheOfficial Compen-dia of Standards M D Asian Rockville Ed pp 1913ndash1914 USPharmacopeial Convention 2000
[18] T Y Puttewar M D Kshirsagar A V Chandewar and R VChikhale ldquoFormulation and evaluation of orodispersible tabletof tastemasked doxylamine succinate using ion exchange resinrdquoJournal of King Saud UniversitymdashScience vol 22 no 4 pp 229ndash240 2010
[19] A Fini V Bergamante G C Ceschel C Ronchi and C A Fde Moraes ldquoFast dispersibleslow releasing ibuprofen tabletsrdquoEuropean Journal of Pharmaceutics and Biopharmaceutics vol69 no 1 pp 335ndash341 2008
[20] M U Uhumwangho and R S Okor ldquoEffect of humidity on thedisintegrant property of 120572-cellulose Part II A technical noterdquoAAPS PharmSciTech vol 6 no 1 article no 7 pp E31ndashE342005
[21] T Sasaki and J Matsuki ldquoEffect of wheat starch structure onswelling powerrdquo Cereal Chemistry vol 75 no 4 pp 525ndash5291998
[22] O A Itiola and N Pilpel ldquoTableting characteristics of metron-idazole formulationsrdquo International Journal of Pharmaceuticsvol 31 no 1-2 pp 99ndash105 1986
[23] O A Odeku and O A Itiola ldquoEvaluation of khaya gum asa binder in a paracetamol tablet formulationrdquo Pharmacy andPharmacology Communications vol 4 no 4 pp 183ndash188 1998
[24] O A Odeku and J T Fell ldquoEffects of the method of preparationon the compression mechanical and release properties ofkhaya gum matricesrdquo Pharmaceutical Development and Tech-nology vol 11 no 4 pp 435ndash441 2006
[25] O A Odeku and B L Akinwande ldquoEffect of the mode ofincorporation on the disintegrant properties of acid modifiedwater and white yam starchesrdquo Saudi Pharmaceutical Journalvol 20 no 2 pp 171ndash175 2012
[26] R Shangraw A Mitrevej and M Shah ldquoA new era of tabletdisintegrantsrdquo Pharmaceutical Technology vol 4 no 10 pp 49ndash57 1980
8 Journal of Drug Delivery
structure as compared to conjugates prepared by physicaland chemical methods The results are in line with the betterin vitro disintegration performance of FDT prepared withconjugates of microwave method compared to the other twomethods
316 Heckel FunctionAnalysis Figure 5 shows representativeHeckel plots for the conjugates prepared by physical chem-ical and microwave methods The Heckel plots showed aninitial linear portion with an increase slope at pressure of100MPa followed by another linear region for the conjugatesprepared by physical and chemical methods while for theconjugate prepared by microwave method the second linearregion was from 175MPaThe mean yield pressure values forthe conjugates were calculated from the slope of the portionshowing the highest linearity of the Heckel plots and theintercept 119860 was determined from the extrapolation of theregionThe values of119863
119860and119863
119861were calculated respectively
The values of 119875119910 1198630 119863119860 and 119863
119861for the formulations are
presented in Table 3 The value of 1198630which represents the
degree of initial packing in the die as a result of die fillingfor the conjugates indicates that the conjugates preparedby microwave method exhibited highest degree of packingin the die as a result of die filling while the conjugatesprepared by physical method exhibited the lowest valuesThevalue of 119863
119861represents the phase of rearrangement of the
particles in the early stages of compression119863119861values tend to
indicate the extent of fragmentation of particles or granulesalthough fragmentation can occur concurrently with plasticand elastic deformation of constituent particles The chemi-cally prepared conjugates exhibited the highest values whilethe one prepared by microwave method exhibited the lowestvalues This indicates that fragmentation occurs more withthe chemically prepared conjugates [22 23]The values of119863
119860
which represents the total degree of packing achieved at zeroand low pressures was also in the rank order of microwave gtchemical gt physical for the methods to prepare conjugatesThis indicates that the conjugates prepared by microwavemethod showed higher degree of packing at low pressuresThe mean yield pressure 119875
119910is inversely related to the ability
of the formulations to deform plastically under pressureThe result indicates that the conjugates prepared by physicalmethod showed the fastest onset of plastic deformation whilethe conjugates prepared by microwave method showed theslowest onset Materials with high yield pressure are classifiedas brittle or fragmenting materials whereas those with lowervalues are classified as plasticallyelastically deforming mate-rials [24] Generally during compression plastic deformationand fragmentation are known to occur concurrently Starcheshave been known to deform plastically under compressionpressure
317 Kawakita Function Analysis TheKawakita plots for theconjugates are presented in Figure 6 A linear relationshipwas obtained at all compression pressures employed withcorrelation coefficient of 0999 for the conjugates preparedby different methods The values of 119886 and 119886119887 were obtainedfrom the slope and intercept respectivelyThe value of (1minus119886)
gives the initial relative density of the starch 119863119868 while 119875
119896
values were obtained from the reciprocal of values of 119887The values of 119863
119868and 119875
119896are shown in Table 3 The value
of 119863119868is a measure of the packed initial relative density of
the formulation with the application of small pressure ortapping The ranking of 119863
119868for the conjugates was chemical
method gt microwave method gt physical method The valueof 119875119896which is an inverse measure of the amount of plastic
deformation occurring during the compression process wasfound to be maximum for tablets formulated using conju-gates prepared by chemical method followed by microwavemethod and physical method [23]Thus conjugates preparedby microwave method exhibited the highest amount of totalplastic deformation while conjugates prepared by physicalmethod exhibited the lowest values The ranking was seen tobe in the reverse order as that of the 119875
119910values It has been
shown that while119875119910relates to the onset of plastic deformation
during compression the 119875119896relates to the amount of plastic
deformation that occurs during the compression processThus the conjugates prepared by physical method showedthe slowest onset of plastic deformation but the highest totalamount of plastic deformation
32 Postcompression Evaluation Tablets require certainamount of strength and resistance to friability to withstandmechanical shock of handling during manufacturingshipping and packaging Hardness of the tablets formulatedusing the corn starch-Neusilin UFL2 conjugates assuperdisintegrant was found to vary from 43 to 35 kgcm2compared to 315 to 309 kgcm2 of tablets formulatedusing the native corn starch Percentage friability of allformulations was less than 1 indicating good mechanicalcharacteristics Wetting time was observed to be decreasedfrom 68 seconds for the tablets incorporating native cornstarch to 33 22 and 14 seconds for the tablets incorporatingconjugates prepared by physical chemical and microwavemethods Disintegration time was also observed to decreasefrom 83 seconds for the tablets incorporating native cornstarch to 40 35 and 22 seconds for the tablets incorporatingconjugates prepared by physical chemical and microwavemethods respectively Water absorption ratio was found tobe inversely proportional to the wetting and disintegratingtime of the tablets The increase in water absorption ratioand decrease in wetting and disintegration times in allformulations may be attributed to the modification of thecorn starch by Neusilin UFL2 to yield a novel conjugatewhich acts as superdisintegrant which absorbs water andswells causing rupture of the tablets Tablet propertiessuch as mechanical strength tablet packing fraction anddisintegration are in turn affected by the porosity [25]Tablets with low packing fraction have high porosity andpores facilitates the penetration of dissolution media intothe tablet leading to disintegration of the tablet Whereashigher tablet packing fraction leads to reduction in porositywhich inhibits the penetration of dissolution media resultingin slower disintegration rate of the tablet [26] Tabletpacking fraction was found to be decreased in the tabletsincorporating conjugates (063ndash041) compared to the tablets
Journal of Drug Delivery 9
(a) (b)
(c) (d)
Figure 4 SEM photomicrographs of (A) corn starch and corn Starch-Neusilin UFL2 conjugates prepared by (B) physical method (C)chemical method and (D) microwave method
Table 3 Parameters derived from the Heckel and Kawakita plots for tablet incorporating corn Starch-Neusilin UFL2 conjugate as asuperdisintegrant prepared by (A) physical method (B) chemical method and (C) microwave method
Figure 5 Heckel plots for the tablet incorporating corn Starch-Neusilin UFL2 conjugate as a superdisintegrant prepared by (A)physical method (B) chemical method and (C)microwavemethod
with corn starch (082) The results are in line with thepowder evaluation results where conjugates prepared byphysical chemical and microwave methods were showing
0
50
100
150
200
250
300
0 50 100 150 200 250
PC
Applied pressure (MPa)
ABC
Figure 6 Kawakita plots for the tablet incorporating corn Starch-Neusilin UFL2 conjugate as a superdisintegrant prepared by (A)physical method (B) chemical method and (C)microwavemethod
better swelling and effective pore radius compared to thenative corn starch The fast disintegration of tablets is dueto the presence of pores resulting in faster penetration of
10 Journal of Drug Delivery
Table4Differentp
ropertieso
fthe
form
ulated
FDTs
Cod
eParameter
Diameter
(mm)
Thickn
ess(mm)
Friability(
)Hardn
ess(kgcm
2 )TSlowast(M
Nm
2 )WTlowast
(Sec)
WARlowast
()
DTlowast
(Sec)
CUlowast(
)TP
Flowast119875lowast(
)1198652
F1674
plusmn003
356
plusmn003
089
plusmn004
311
plusmn010
047
plusmn015
68plusmn113
40plusmn011
73plusmn3
9899plusmn02
081
189
19F2
673
plusmn004
351
plusmn004
091
plusmn002
315
plusmn007
047
plusmn005
68plusmn12
942
plusmn011
73plusmn1
991plusmn015
082
175
24F3
674
plusmn005
355
plusmn005
089
plusmn005
309
plusmn011
047
plusmn011
67plusmn111
46plusmn009
71plusmn2
9727plusmn09
081
187
21F4
673
plusmn001
359
plusmn005
090
plusmn003
310
plusmn002
047
plusmn009
66plusmn114
46plusmn010
71plusmn3
9659plusmn05
080
194
25F5
674
plusmn001
351
plusmn005
076
plusmn004
350
plusmn011
048
plusmn005
33plusmn114
98plusmn004
48plusmn2
9650plusmn03
063
367
43F6
674
plusmn002
355
plusmn004
073
plusmn005
356
plusmn008
048
plusmn001
33plusmn16
796
plusmn004
46plusmn3
991plusmn015
062
373
43F7
674
plusmn001
355
plusmn005
071
plusmn002
370
plusmn015
056
plusmn018
32plusmn110
101plusmn
005
44plusmn1
9835plusmn02
062
373
45F8
674
plusmn003
356
plusmn003
067
plusmn003
375
plusmn021
055
plusmn008
31plusmn14
0103plusmn002
40plusmn2
9923plusmn05
062
375
47F9
673
plusmn004
355
plusmn002
055
plusmn001
400
plusmn018
060
plusmn019
23plusmn13
4108plusmn003
40plusmn6
9912
plusmn04
054
426
50F10
674
plusmn005
354
plusmn007
054
plusmn005
380
plusmn015
057
plusmn006
22plusmn12
5100plusmn002
35plusmn3
9892plusmn07
057
435
50F11
673
plusmn003
356
plusmn004
055
plusmn003
370
plusmn017
056
plusmn011
23plusmn10
5106plusmn006
36plusmn2
9727plusmn09
057
423
55F12
673
plusmn002
353
plusmn003
051
plusmn004
410
plusmn02
062
plusmn015
23plusmn13
8110
plusmn004
32plusmn7
9659plusmn05
056
426
53F13
674
plusmn003
355
plusmn004
041
plusmn007
420
plusmn027
073
plusmn008
14plusmn15
2121plusmn
008
26plusmn2
9915
plusmn01
041
582
50F14
673
plusmn001
351
plusmn004
042
plusmn002
425
plusmn02
073
plusmn020
14plusmn12
6124plusmn007
24plusmn5
9899plusmn02
039
595
52F15
674
plusmn003
355
plusmn006
044
plusmn004
430
plusmn010
076
plusmn018
13plusmn115
125plusmn003
22plusmn3
9975plusmn10
040
599
62F16
674
plusmn001
359
plusmn005
047
plusmn007
420
plusmn045
079
plusmn019
14plusmn14
0128plusmn005
22plusmn4
9912
plusmn03
041
612
64TSlowasttensiles
treng
thW
Tlowastw
ettin
gtim
eWARlowast
water
absorptio
nratio
DTlowast
disintegratio
ntim
eCUlowastcon
tent
unifo
rmity
TPFlowasttabletp
acking
fractio
n119875lowastporosity
Journal of Drug Delivery 11
the dissolution media leading to swelling and wicking of theprepared conjugate creating hydrodynamic pressure insidethe tablets hence responsible for the quick and completedisintegration of tablets indicating the superdisintegrantactivity of conjugates prepared by physical chemical andmicrowave methods over the native corn starch
The results obtained from the in vitro dissolution studyare presented in Figures 7 8 9 and 10 ldquoMKTDrdquo representsthe standard marketed domperidone formulation to whichthe formulated FDTs were compared The similarity factor(1198912) is a logarithmic transformation of the sum-squared
error of differences between test and reference productsover all time points It was observed that the three differentapproaches used for the preparation of conjugate in thisstudy namely physical chemical and microwave methodsincreased the dissolution rate of the drug compared to thetablet prepared with the native corn starch and standardmarketed formulation of the drug The order of increaseddrug dissolution using the different approaches was asfollows microwave gt chemical gt physical In case of theFDTs prepared by using native corn starch (F1ndashF4) thepercentage cumulative drug release was found to be verypoor as compared to the standard marketed formulation ofdomperidone (MKTD)The119891
2value for formulation (F1ndashF4)
was below 50 depicting the dissimilarity between the drugreleases Formulations (F5ndashF8) (F9ndashF12) and (F13ndashF16)werecontaining corn starch-Neusilin UFL2 conjugate prepared byphysical chemical and microwave methods The percentagecumulative drug release for these formulations were found tobe comparable to the standardmarketed formulation of dom-peridone The 119891
2values for these formulations were found
to be over 50 evidencing the similarity between the drugreleases Results of various tablet evaluation tests as evidencedfrom Table 4 indicate that among the three methods usedfor the preparation of conjugates microwave was the mosteffectivemethod followed by chemical and physical methodsMoreover by increasing the concentration of conjugates thetablet did not show much effect on drug release from theformulated FDTs Hence from the commercial point of viewlowest concentration of superdisintegrant showing optimumtabletting results should be recommended
4 Conculsions
In present work an attempt was made to modify the cornstarch to develop corn starch-Neusilin UFL2 conjugatesusing different methods namely physical chemical andmicrowave The prepared conjugates and the corn starchwere characterised for powder flow pH viscosity swellingand effective pore radius Evaluation of precompressionparameter indicates good flow properties The preparedconjugates were also subjected to the compression studiesnamely Heckel and Kawakita function The Heckel plot isusually correlated with the speed of the tablet machine whilethe Kawakita plot is related to the crushing or tensile strengthof the tablet Fast disintegrating tablets of domperidone wereformulated by direct compression technique employing thecorn starch and the prepared conjugates The tablets were
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F1F2F3
F4MKTD
Figure 7 Dissolution rate profiles of FDTs (F1ndashF4) formulated byincorporating native corn starch as a superdisintegrant compared toa standard marketed formulation of domperidone (MKTD)
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F5F6F7
F8MKTD
Figure 8 Dissolution rate profiles of FDTs (F5ndashF8) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates preparedby physical method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
evaluated for physical parametric tests wetting time waterabsorption ratio porosity tablet packing fraction in vitrodisintegration time drug content in vitro dissolution andstability studies Extensive swelling porosity and wickingaction of the prepared corn Starch-Neusilin UFL2 conjugatesin the prepared fast disintegrating tablets were found to becontributing to its superdisintegrant action
In conclusion the prepared conjugates can be effectivelyused as superdisintegrant in order to develop a faster disin-tegrating tablet formulation Future challenges for many fastdisintegrating tablet manufacturers include reducing costsby finding ways to manufacture with conventional equip-ment using versatile packaging and improving mechanical
12 Journal of Drug Delivery
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F9F10F11
F12MKTD
Figure 9 Dissolution rate profiles of FDTs (F9ndashF12) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates preparedby chemical method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
F13F14F15
F16MKTD
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
Figure 10 Dissolution rate profiles of FDTs (F13ndashF16) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates prepared bymicrowave method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
strength Such products provide an opportunity for theproduct line extension in the market place and extensionof patent term of innovator Due to its wide significancethis drug delivery system may lead to better patient com-pliance and ultimate clinical output Future might witnessnovel technologies for development and utilization of themodified starches as tablet superdisintegrant for cost effectiveformulation of fast disintegrating tablets
Conflict of Interests
The authors declare that they have no conflict of interests
Acknowledgments
The authors gratefully acknowledge Dr Madhu ChitkaraVice Chancellor Chitkara University Rajpura Punjab IndiaDr Ashok Chitkara Chairman Chitkara Educational TrustChandigarh India and Dr Sandeep Arora Dean ChitkaraUniversity Rajpura Punjab India for support and institu-tional facilities
References
[1] I Rashid M Al-Remawi S A Leharne B Z Chowdhry andA Badwan ldquoA novel multifunctional pharmaceutical excipientmodification of the permeability of starch by processing withmagnesium silicaterdquo International Journal of Pharmaceutics vol411 no 1-2 pp 18ndash26 2011
[2] O A Odeku and K M Picker-Freyer ldquoAnalysis of the materialand tablet formation properties of four Dioscorea starchesrdquoStarchStarke vol 59 no 9 pp 430ndash444 2007
[3] N Visavarungroj and J P Remon ldquoAn evaluation of hydrox-ypropyl starch an disintegrant and binder in tablet formulationrdquoDrug Development and Industrial Pharmacy vol 17 no 10 pp1389ndash1396 1991
[4] M Nakano N Nakazono and N Inotsume ldquoPreparation andevaluation of sustained release tablets prepared with 120572-starchrdquoChemical and Pharmaceutical Bulletin vol 35 no 10 pp 4346ndash4350 1987
[5] O A Odeku and K M Picker-Freyer ldquoFreeze-dried prege-latinized Dioscorea starches as tablet matrix for sustainedreleaserdquo Journal of Excipients and Food Chemicals vol 1 no 2pp 21ndash32 2010
[6] H Staroszczyk ldquoMicrowave-assisted silication of potato starchrdquoCarbohydrate Polymers vol 77 no 3 pp 506ndash515 2009
[7] J Singh L Kaur and O J McCarthy ldquoFactors influencingthe physico-chemical morphological thermal and rheologicalproperties of some chemically modified starches for foodapplications a reviewrdquo Food Hydrocolloids vol 21 no 1 pp 1ndash22 2007
[8] I Rashid N Daraghmeh M Al-Remawi S A Leharne B ZChowdhry and A Badwan ldquoCharacterization of chitin-metalsilicates as binding superdisintegrantsrdquo Journal of Pharmaceuti-cal Sciences vol 98 no 12 pp 4887ndash4901 2009
[9] I Rashid N Daraghmeh M Al-Remawi S A Leharne B ZChowdhry and A Badwan ldquoCharacterization of the impactof magnesium stearate lubrication on the tableting propertiesof chitin-Mg silicate as a superdisintegrating binder whencompared to Avicel 200rdquo Powder Technology vol 203 no 3 pp609ndash619 2010
[10] Y Asai M Nohara S Fujioka K Isaji and S Nagira ldquoApplica-tion of Neusilin UFL2 on manufacturing of tablets using directcompression method Development of core tablets containingthe function of small degree of decrease of hardness at thehumid conditionsrdquoPharmaceutical Technical Newsletter vol 25pp 67ndash70 2009
[11] B G Prajapati and D V Patel ldquoFormulation and optimiza-tion of domperidone fast dissolving tablet by wet granulationtechniques using factorial designrdquo International Journal ofPharmTech Research vol 2 no 1 pp 292ndash299 2010
[12] J Cooper and C Gunn ldquoPowder flow and compactionrdquo inTutorial Pharmacy S J Carter Ed pp 211ndash233 CBS Publishersand Distributors New Delhi India 1986
Journal of Drug Delivery 13
[13] H Goel G Kaur A K Tiwary and V Rana ldquoFormulationdevelopment of stronger and quick disintegrating tablets acrucial effect of chitinrdquoYakugaku Zasshi vol 130 no 5 pp 729ndash735 2010
[14] J M Sonnergaard ldquoImpact of particle density and initial vol-ume on mathematical compression modelsrdquo European Journalof Pharmaceutical Sciences vol 11 no 4 pp 307ndash315 2000
[15] O A Odeku ldquoAssessment of Albizia zygia gum as a bindingagent in tablet formulationsrdquo Acta Pharmaceutica vol 55 no3 pp 263ndash276 2005
[16] F Kiekens A Debunne C Vervaet et al ldquoInfluence of thepunch diameter and curvature on the yield pressure of MCC-compacts duringHeckel analysisrdquo European Journal of Pharma-ceutical Sciences vol 22 no 2-3 pp 117ndash126 2004
[17] ldquoUnited States Pharmacopeia 24NF19rdquo inTheOfficial Compen-dia of Standards M D Asian Rockville Ed pp 1913ndash1914 USPharmacopeial Convention 2000
[18] T Y Puttewar M D Kshirsagar A V Chandewar and R VChikhale ldquoFormulation and evaluation of orodispersible tabletof tastemasked doxylamine succinate using ion exchange resinrdquoJournal of King Saud UniversitymdashScience vol 22 no 4 pp 229ndash240 2010
[19] A Fini V Bergamante G C Ceschel C Ronchi and C A Fde Moraes ldquoFast dispersibleslow releasing ibuprofen tabletsrdquoEuropean Journal of Pharmaceutics and Biopharmaceutics vol69 no 1 pp 335ndash341 2008
[20] M U Uhumwangho and R S Okor ldquoEffect of humidity on thedisintegrant property of 120572-cellulose Part II A technical noterdquoAAPS PharmSciTech vol 6 no 1 article no 7 pp E31ndashE342005
[21] T Sasaki and J Matsuki ldquoEffect of wheat starch structure onswelling powerrdquo Cereal Chemistry vol 75 no 4 pp 525ndash5291998
[22] O A Itiola and N Pilpel ldquoTableting characteristics of metron-idazole formulationsrdquo International Journal of Pharmaceuticsvol 31 no 1-2 pp 99ndash105 1986
[23] O A Odeku and O A Itiola ldquoEvaluation of khaya gum asa binder in a paracetamol tablet formulationrdquo Pharmacy andPharmacology Communications vol 4 no 4 pp 183ndash188 1998
[24] O A Odeku and J T Fell ldquoEffects of the method of preparationon the compression mechanical and release properties ofkhaya gum matricesrdquo Pharmaceutical Development and Tech-nology vol 11 no 4 pp 435ndash441 2006
[25] O A Odeku and B L Akinwande ldquoEffect of the mode ofincorporation on the disintegrant properties of acid modifiedwater and white yam starchesrdquo Saudi Pharmaceutical Journalvol 20 no 2 pp 171ndash175 2012
[26] R Shangraw A Mitrevej and M Shah ldquoA new era of tabletdisintegrantsrdquo Pharmaceutical Technology vol 4 no 10 pp 49ndash57 1980
Journal of Drug Delivery 9
(a) (b)
(c) (d)
Figure 4 SEM photomicrographs of (A) corn starch and corn Starch-Neusilin UFL2 conjugates prepared by (B) physical method (C)chemical method and (D) microwave method
Table 3 Parameters derived from the Heckel and Kawakita plots for tablet incorporating corn Starch-Neusilin UFL2 conjugate as asuperdisintegrant prepared by (A) physical method (B) chemical method and (C) microwave method
Figure 5 Heckel plots for the tablet incorporating corn Starch-Neusilin UFL2 conjugate as a superdisintegrant prepared by (A)physical method (B) chemical method and (C)microwavemethod
with corn starch (082) The results are in line with thepowder evaluation results where conjugates prepared byphysical chemical and microwave methods were showing
0
50
100
150
200
250
300
0 50 100 150 200 250
PC
Applied pressure (MPa)
ABC
Figure 6 Kawakita plots for the tablet incorporating corn Starch-Neusilin UFL2 conjugate as a superdisintegrant prepared by (A)physical method (B) chemical method and (C)microwavemethod
better swelling and effective pore radius compared to thenative corn starch The fast disintegration of tablets is dueto the presence of pores resulting in faster penetration of
10 Journal of Drug Delivery
Table4Differentp
ropertieso
fthe
form
ulated
FDTs
Cod
eParameter
Diameter
(mm)
Thickn
ess(mm)
Friability(
)Hardn
ess(kgcm
2 )TSlowast(M
Nm
2 )WTlowast
(Sec)
WARlowast
()
DTlowast
(Sec)
CUlowast(
)TP
Flowast119875lowast(
)1198652
F1674
plusmn003
356
plusmn003
089
plusmn004
311
plusmn010
047
plusmn015
68plusmn113
40plusmn011
73plusmn3
9899plusmn02
081
189
19F2
673
plusmn004
351
plusmn004
091
plusmn002
315
plusmn007
047
plusmn005
68plusmn12
942
plusmn011
73plusmn1
991plusmn015
082
175
24F3
674
plusmn005
355
plusmn005
089
plusmn005
309
plusmn011
047
plusmn011
67plusmn111
46plusmn009
71plusmn2
9727plusmn09
081
187
21F4
673
plusmn001
359
plusmn005
090
plusmn003
310
plusmn002
047
plusmn009
66plusmn114
46plusmn010
71plusmn3
9659plusmn05
080
194
25F5
674
plusmn001
351
plusmn005
076
plusmn004
350
plusmn011
048
plusmn005
33plusmn114
98plusmn004
48plusmn2
9650plusmn03
063
367
43F6
674
plusmn002
355
plusmn004
073
plusmn005
356
plusmn008
048
plusmn001
33plusmn16
796
plusmn004
46plusmn3
991plusmn015
062
373
43F7
674
plusmn001
355
plusmn005
071
plusmn002
370
plusmn015
056
plusmn018
32plusmn110
101plusmn
005
44plusmn1
9835plusmn02
062
373
45F8
674
plusmn003
356
plusmn003
067
plusmn003
375
plusmn021
055
plusmn008
31plusmn14
0103plusmn002
40plusmn2
9923plusmn05
062
375
47F9
673
plusmn004
355
plusmn002
055
plusmn001
400
plusmn018
060
plusmn019
23plusmn13
4108plusmn003
40plusmn6
9912
plusmn04
054
426
50F10
674
plusmn005
354
plusmn007
054
plusmn005
380
plusmn015
057
plusmn006
22plusmn12
5100plusmn002
35plusmn3
9892plusmn07
057
435
50F11
673
plusmn003
356
plusmn004
055
plusmn003
370
plusmn017
056
plusmn011
23plusmn10
5106plusmn006
36plusmn2
9727plusmn09
057
423
55F12
673
plusmn002
353
plusmn003
051
plusmn004
410
plusmn02
062
plusmn015
23plusmn13
8110
plusmn004
32plusmn7
9659plusmn05
056
426
53F13
674
plusmn003
355
plusmn004
041
plusmn007
420
plusmn027
073
plusmn008
14plusmn15
2121plusmn
008
26plusmn2
9915
plusmn01
041
582
50F14
673
plusmn001
351
plusmn004
042
plusmn002
425
plusmn02
073
plusmn020
14plusmn12
6124plusmn007
24plusmn5
9899plusmn02
039
595
52F15
674
plusmn003
355
plusmn006
044
plusmn004
430
plusmn010
076
plusmn018
13plusmn115
125plusmn003
22plusmn3
9975plusmn10
040
599
62F16
674
plusmn001
359
plusmn005
047
plusmn007
420
plusmn045
079
plusmn019
14plusmn14
0128plusmn005
22plusmn4
9912
plusmn03
041
612
64TSlowasttensiles
treng
thW
Tlowastw
ettin
gtim
eWARlowast
water
absorptio
nratio
DTlowast
disintegratio
ntim
eCUlowastcon
tent
unifo
rmity
TPFlowasttabletp
acking
fractio
n119875lowastporosity
Journal of Drug Delivery 11
the dissolution media leading to swelling and wicking of theprepared conjugate creating hydrodynamic pressure insidethe tablets hence responsible for the quick and completedisintegration of tablets indicating the superdisintegrantactivity of conjugates prepared by physical chemical andmicrowave methods over the native corn starch
The results obtained from the in vitro dissolution studyare presented in Figures 7 8 9 and 10 ldquoMKTDrdquo representsthe standard marketed domperidone formulation to whichthe formulated FDTs were compared The similarity factor(1198912) is a logarithmic transformation of the sum-squared
error of differences between test and reference productsover all time points It was observed that the three differentapproaches used for the preparation of conjugate in thisstudy namely physical chemical and microwave methodsincreased the dissolution rate of the drug compared to thetablet prepared with the native corn starch and standardmarketed formulation of the drug The order of increaseddrug dissolution using the different approaches was asfollows microwave gt chemical gt physical In case of theFDTs prepared by using native corn starch (F1ndashF4) thepercentage cumulative drug release was found to be verypoor as compared to the standard marketed formulation ofdomperidone (MKTD)The119891
2value for formulation (F1ndashF4)
was below 50 depicting the dissimilarity between the drugreleases Formulations (F5ndashF8) (F9ndashF12) and (F13ndashF16)werecontaining corn starch-Neusilin UFL2 conjugate prepared byphysical chemical and microwave methods The percentagecumulative drug release for these formulations were found tobe comparable to the standardmarketed formulation of dom-peridone The 119891
2values for these formulations were found
to be over 50 evidencing the similarity between the drugreleases Results of various tablet evaluation tests as evidencedfrom Table 4 indicate that among the three methods usedfor the preparation of conjugates microwave was the mosteffectivemethod followed by chemical and physical methodsMoreover by increasing the concentration of conjugates thetablet did not show much effect on drug release from theformulated FDTs Hence from the commercial point of viewlowest concentration of superdisintegrant showing optimumtabletting results should be recommended
4 Conculsions
In present work an attempt was made to modify the cornstarch to develop corn starch-Neusilin UFL2 conjugatesusing different methods namely physical chemical andmicrowave The prepared conjugates and the corn starchwere characterised for powder flow pH viscosity swellingand effective pore radius Evaluation of precompressionparameter indicates good flow properties The preparedconjugates were also subjected to the compression studiesnamely Heckel and Kawakita function The Heckel plot isusually correlated with the speed of the tablet machine whilethe Kawakita plot is related to the crushing or tensile strengthof the tablet Fast disintegrating tablets of domperidone wereformulated by direct compression technique employing thecorn starch and the prepared conjugates The tablets were
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F1F2F3
F4MKTD
Figure 7 Dissolution rate profiles of FDTs (F1ndashF4) formulated byincorporating native corn starch as a superdisintegrant compared toa standard marketed formulation of domperidone (MKTD)
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F5F6F7
F8MKTD
Figure 8 Dissolution rate profiles of FDTs (F5ndashF8) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates preparedby physical method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
evaluated for physical parametric tests wetting time waterabsorption ratio porosity tablet packing fraction in vitrodisintegration time drug content in vitro dissolution andstability studies Extensive swelling porosity and wickingaction of the prepared corn Starch-Neusilin UFL2 conjugatesin the prepared fast disintegrating tablets were found to becontributing to its superdisintegrant action
In conclusion the prepared conjugates can be effectivelyused as superdisintegrant in order to develop a faster disin-tegrating tablet formulation Future challenges for many fastdisintegrating tablet manufacturers include reducing costsby finding ways to manufacture with conventional equip-ment using versatile packaging and improving mechanical
12 Journal of Drug Delivery
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F9F10F11
F12MKTD
Figure 9 Dissolution rate profiles of FDTs (F9ndashF12) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates preparedby chemical method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
F13F14F15
F16MKTD
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
Figure 10 Dissolution rate profiles of FDTs (F13ndashF16) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates prepared bymicrowave method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
strength Such products provide an opportunity for theproduct line extension in the market place and extensionof patent term of innovator Due to its wide significancethis drug delivery system may lead to better patient com-pliance and ultimate clinical output Future might witnessnovel technologies for development and utilization of themodified starches as tablet superdisintegrant for cost effectiveformulation of fast disintegrating tablets
Conflict of Interests
The authors declare that they have no conflict of interests
Acknowledgments
The authors gratefully acknowledge Dr Madhu ChitkaraVice Chancellor Chitkara University Rajpura Punjab IndiaDr Ashok Chitkara Chairman Chitkara Educational TrustChandigarh India and Dr Sandeep Arora Dean ChitkaraUniversity Rajpura Punjab India for support and institu-tional facilities
References
[1] I Rashid M Al-Remawi S A Leharne B Z Chowdhry andA Badwan ldquoA novel multifunctional pharmaceutical excipientmodification of the permeability of starch by processing withmagnesium silicaterdquo International Journal of Pharmaceutics vol411 no 1-2 pp 18ndash26 2011
[2] O A Odeku and K M Picker-Freyer ldquoAnalysis of the materialand tablet formation properties of four Dioscorea starchesrdquoStarchStarke vol 59 no 9 pp 430ndash444 2007
[3] N Visavarungroj and J P Remon ldquoAn evaluation of hydrox-ypropyl starch an disintegrant and binder in tablet formulationrdquoDrug Development and Industrial Pharmacy vol 17 no 10 pp1389ndash1396 1991
[4] M Nakano N Nakazono and N Inotsume ldquoPreparation andevaluation of sustained release tablets prepared with 120572-starchrdquoChemical and Pharmaceutical Bulletin vol 35 no 10 pp 4346ndash4350 1987
[5] O A Odeku and K M Picker-Freyer ldquoFreeze-dried prege-latinized Dioscorea starches as tablet matrix for sustainedreleaserdquo Journal of Excipients and Food Chemicals vol 1 no 2pp 21ndash32 2010
[6] H Staroszczyk ldquoMicrowave-assisted silication of potato starchrdquoCarbohydrate Polymers vol 77 no 3 pp 506ndash515 2009
[7] J Singh L Kaur and O J McCarthy ldquoFactors influencingthe physico-chemical morphological thermal and rheologicalproperties of some chemically modified starches for foodapplications a reviewrdquo Food Hydrocolloids vol 21 no 1 pp 1ndash22 2007
[8] I Rashid N Daraghmeh M Al-Remawi S A Leharne B ZChowdhry and A Badwan ldquoCharacterization of chitin-metalsilicates as binding superdisintegrantsrdquo Journal of Pharmaceuti-cal Sciences vol 98 no 12 pp 4887ndash4901 2009
[9] I Rashid N Daraghmeh M Al-Remawi S A Leharne B ZChowdhry and A Badwan ldquoCharacterization of the impactof magnesium stearate lubrication on the tableting propertiesof chitin-Mg silicate as a superdisintegrating binder whencompared to Avicel 200rdquo Powder Technology vol 203 no 3 pp609ndash619 2010
[10] Y Asai M Nohara S Fujioka K Isaji and S Nagira ldquoApplica-tion of Neusilin UFL2 on manufacturing of tablets using directcompression method Development of core tablets containingthe function of small degree of decrease of hardness at thehumid conditionsrdquoPharmaceutical Technical Newsletter vol 25pp 67ndash70 2009
[11] B G Prajapati and D V Patel ldquoFormulation and optimiza-tion of domperidone fast dissolving tablet by wet granulationtechniques using factorial designrdquo International Journal ofPharmTech Research vol 2 no 1 pp 292ndash299 2010
[12] J Cooper and C Gunn ldquoPowder flow and compactionrdquo inTutorial Pharmacy S J Carter Ed pp 211ndash233 CBS Publishersand Distributors New Delhi India 1986
Journal of Drug Delivery 13
[13] H Goel G Kaur A K Tiwary and V Rana ldquoFormulationdevelopment of stronger and quick disintegrating tablets acrucial effect of chitinrdquoYakugaku Zasshi vol 130 no 5 pp 729ndash735 2010
[14] J M Sonnergaard ldquoImpact of particle density and initial vol-ume on mathematical compression modelsrdquo European Journalof Pharmaceutical Sciences vol 11 no 4 pp 307ndash315 2000
[15] O A Odeku ldquoAssessment of Albizia zygia gum as a bindingagent in tablet formulationsrdquo Acta Pharmaceutica vol 55 no3 pp 263ndash276 2005
[16] F Kiekens A Debunne C Vervaet et al ldquoInfluence of thepunch diameter and curvature on the yield pressure of MCC-compacts duringHeckel analysisrdquo European Journal of Pharma-ceutical Sciences vol 22 no 2-3 pp 117ndash126 2004
[17] ldquoUnited States Pharmacopeia 24NF19rdquo inTheOfficial Compen-dia of Standards M D Asian Rockville Ed pp 1913ndash1914 USPharmacopeial Convention 2000
[18] T Y Puttewar M D Kshirsagar A V Chandewar and R VChikhale ldquoFormulation and evaluation of orodispersible tabletof tastemasked doxylamine succinate using ion exchange resinrdquoJournal of King Saud UniversitymdashScience vol 22 no 4 pp 229ndash240 2010
[19] A Fini V Bergamante G C Ceschel C Ronchi and C A Fde Moraes ldquoFast dispersibleslow releasing ibuprofen tabletsrdquoEuropean Journal of Pharmaceutics and Biopharmaceutics vol69 no 1 pp 335ndash341 2008
[20] M U Uhumwangho and R S Okor ldquoEffect of humidity on thedisintegrant property of 120572-cellulose Part II A technical noterdquoAAPS PharmSciTech vol 6 no 1 article no 7 pp E31ndashE342005
[21] T Sasaki and J Matsuki ldquoEffect of wheat starch structure onswelling powerrdquo Cereal Chemistry vol 75 no 4 pp 525ndash5291998
[22] O A Itiola and N Pilpel ldquoTableting characteristics of metron-idazole formulationsrdquo International Journal of Pharmaceuticsvol 31 no 1-2 pp 99ndash105 1986
[23] O A Odeku and O A Itiola ldquoEvaluation of khaya gum asa binder in a paracetamol tablet formulationrdquo Pharmacy andPharmacology Communications vol 4 no 4 pp 183ndash188 1998
[24] O A Odeku and J T Fell ldquoEffects of the method of preparationon the compression mechanical and release properties ofkhaya gum matricesrdquo Pharmaceutical Development and Tech-nology vol 11 no 4 pp 435ndash441 2006
[25] O A Odeku and B L Akinwande ldquoEffect of the mode ofincorporation on the disintegrant properties of acid modifiedwater and white yam starchesrdquo Saudi Pharmaceutical Journalvol 20 no 2 pp 171ndash175 2012
[26] R Shangraw A Mitrevej and M Shah ldquoA new era of tabletdisintegrantsrdquo Pharmaceutical Technology vol 4 no 10 pp 49ndash57 1980
10 Journal of Drug Delivery
Table4Differentp
ropertieso
fthe
form
ulated
FDTs
Cod
eParameter
Diameter
(mm)
Thickn
ess(mm)
Friability(
)Hardn
ess(kgcm
2 )TSlowast(M
Nm
2 )WTlowast
(Sec)
WARlowast
()
DTlowast
(Sec)
CUlowast(
)TP
Flowast119875lowast(
)1198652
F1674
plusmn003
356
plusmn003
089
plusmn004
311
plusmn010
047
plusmn015
68plusmn113
40plusmn011
73plusmn3
9899plusmn02
081
189
19F2
673
plusmn004
351
plusmn004
091
plusmn002
315
plusmn007
047
plusmn005
68plusmn12
942
plusmn011
73plusmn1
991plusmn015
082
175
24F3
674
plusmn005
355
plusmn005
089
plusmn005
309
plusmn011
047
plusmn011
67plusmn111
46plusmn009
71plusmn2
9727plusmn09
081
187
21F4
673
plusmn001
359
plusmn005
090
plusmn003
310
plusmn002
047
plusmn009
66plusmn114
46plusmn010
71plusmn3
9659plusmn05
080
194
25F5
674
plusmn001
351
plusmn005
076
plusmn004
350
plusmn011
048
plusmn005
33plusmn114
98plusmn004
48plusmn2
9650plusmn03
063
367
43F6
674
plusmn002
355
plusmn004
073
plusmn005
356
plusmn008
048
plusmn001
33plusmn16
796
plusmn004
46plusmn3
991plusmn015
062
373
43F7
674
plusmn001
355
plusmn005
071
plusmn002
370
plusmn015
056
plusmn018
32plusmn110
101plusmn
005
44plusmn1
9835plusmn02
062
373
45F8
674
plusmn003
356
plusmn003
067
plusmn003
375
plusmn021
055
plusmn008
31plusmn14
0103plusmn002
40plusmn2
9923plusmn05
062
375
47F9
673
plusmn004
355
plusmn002
055
plusmn001
400
plusmn018
060
plusmn019
23plusmn13
4108plusmn003
40plusmn6
9912
plusmn04
054
426
50F10
674
plusmn005
354
plusmn007
054
plusmn005
380
plusmn015
057
plusmn006
22plusmn12
5100plusmn002
35plusmn3
9892plusmn07
057
435
50F11
673
plusmn003
356
plusmn004
055
plusmn003
370
plusmn017
056
plusmn011
23plusmn10
5106plusmn006
36plusmn2
9727plusmn09
057
423
55F12
673
plusmn002
353
plusmn003
051
plusmn004
410
plusmn02
062
plusmn015
23plusmn13
8110
plusmn004
32plusmn7
9659plusmn05
056
426
53F13
674
plusmn003
355
plusmn004
041
plusmn007
420
plusmn027
073
plusmn008
14plusmn15
2121plusmn
008
26plusmn2
9915
plusmn01
041
582
50F14
673
plusmn001
351
plusmn004
042
plusmn002
425
plusmn02
073
plusmn020
14plusmn12
6124plusmn007
24plusmn5
9899plusmn02
039
595
52F15
674
plusmn003
355
plusmn006
044
plusmn004
430
plusmn010
076
plusmn018
13plusmn115
125plusmn003
22plusmn3
9975plusmn10
040
599
62F16
674
plusmn001
359
plusmn005
047
plusmn007
420
plusmn045
079
plusmn019
14plusmn14
0128plusmn005
22plusmn4
9912
plusmn03
041
612
64TSlowasttensiles
treng
thW
Tlowastw
ettin
gtim
eWARlowast
water
absorptio
nratio
DTlowast
disintegratio
ntim
eCUlowastcon
tent
unifo
rmity
TPFlowasttabletp
acking
fractio
n119875lowastporosity
Journal of Drug Delivery 11
the dissolution media leading to swelling and wicking of theprepared conjugate creating hydrodynamic pressure insidethe tablets hence responsible for the quick and completedisintegration of tablets indicating the superdisintegrantactivity of conjugates prepared by physical chemical andmicrowave methods over the native corn starch
The results obtained from the in vitro dissolution studyare presented in Figures 7 8 9 and 10 ldquoMKTDrdquo representsthe standard marketed domperidone formulation to whichthe formulated FDTs were compared The similarity factor(1198912) is a logarithmic transformation of the sum-squared
error of differences between test and reference productsover all time points It was observed that the three differentapproaches used for the preparation of conjugate in thisstudy namely physical chemical and microwave methodsincreased the dissolution rate of the drug compared to thetablet prepared with the native corn starch and standardmarketed formulation of the drug The order of increaseddrug dissolution using the different approaches was asfollows microwave gt chemical gt physical In case of theFDTs prepared by using native corn starch (F1ndashF4) thepercentage cumulative drug release was found to be verypoor as compared to the standard marketed formulation ofdomperidone (MKTD)The119891
2value for formulation (F1ndashF4)
was below 50 depicting the dissimilarity between the drugreleases Formulations (F5ndashF8) (F9ndashF12) and (F13ndashF16)werecontaining corn starch-Neusilin UFL2 conjugate prepared byphysical chemical and microwave methods The percentagecumulative drug release for these formulations were found tobe comparable to the standardmarketed formulation of dom-peridone The 119891
2values for these formulations were found
to be over 50 evidencing the similarity between the drugreleases Results of various tablet evaluation tests as evidencedfrom Table 4 indicate that among the three methods usedfor the preparation of conjugates microwave was the mosteffectivemethod followed by chemical and physical methodsMoreover by increasing the concentration of conjugates thetablet did not show much effect on drug release from theformulated FDTs Hence from the commercial point of viewlowest concentration of superdisintegrant showing optimumtabletting results should be recommended
4 Conculsions
In present work an attempt was made to modify the cornstarch to develop corn starch-Neusilin UFL2 conjugatesusing different methods namely physical chemical andmicrowave The prepared conjugates and the corn starchwere characterised for powder flow pH viscosity swellingand effective pore radius Evaluation of precompressionparameter indicates good flow properties The preparedconjugates were also subjected to the compression studiesnamely Heckel and Kawakita function The Heckel plot isusually correlated with the speed of the tablet machine whilethe Kawakita plot is related to the crushing or tensile strengthof the tablet Fast disintegrating tablets of domperidone wereformulated by direct compression technique employing thecorn starch and the prepared conjugates The tablets were
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F1F2F3
F4MKTD
Figure 7 Dissolution rate profiles of FDTs (F1ndashF4) formulated byincorporating native corn starch as a superdisintegrant compared toa standard marketed formulation of domperidone (MKTD)
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F5F6F7
F8MKTD
Figure 8 Dissolution rate profiles of FDTs (F5ndashF8) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates preparedby physical method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
evaluated for physical parametric tests wetting time waterabsorption ratio porosity tablet packing fraction in vitrodisintegration time drug content in vitro dissolution andstability studies Extensive swelling porosity and wickingaction of the prepared corn Starch-Neusilin UFL2 conjugatesin the prepared fast disintegrating tablets were found to becontributing to its superdisintegrant action
In conclusion the prepared conjugates can be effectivelyused as superdisintegrant in order to develop a faster disin-tegrating tablet formulation Future challenges for many fastdisintegrating tablet manufacturers include reducing costsby finding ways to manufacture with conventional equip-ment using versatile packaging and improving mechanical
12 Journal of Drug Delivery
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F9F10F11
F12MKTD
Figure 9 Dissolution rate profiles of FDTs (F9ndashF12) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates preparedby chemical method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
F13F14F15
F16MKTD
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
Figure 10 Dissolution rate profiles of FDTs (F13ndashF16) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates prepared bymicrowave method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
strength Such products provide an opportunity for theproduct line extension in the market place and extensionof patent term of innovator Due to its wide significancethis drug delivery system may lead to better patient com-pliance and ultimate clinical output Future might witnessnovel technologies for development and utilization of themodified starches as tablet superdisintegrant for cost effectiveformulation of fast disintegrating tablets
Conflict of Interests
The authors declare that they have no conflict of interests
Acknowledgments
The authors gratefully acknowledge Dr Madhu ChitkaraVice Chancellor Chitkara University Rajpura Punjab IndiaDr Ashok Chitkara Chairman Chitkara Educational TrustChandigarh India and Dr Sandeep Arora Dean ChitkaraUniversity Rajpura Punjab India for support and institu-tional facilities
References
[1] I Rashid M Al-Remawi S A Leharne B Z Chowdhry andA Badwan ldquoA novel multifunctional pharmaceutical excipientmodification of the permeability of starch by processing withmagnesium silicaterdquo International Journal of Pharmaceutics vol411 no 1-2 pp 18ndash26 2011
[2] O A Odeku and K M Picker-Freyer ldquoAnalysis of the materialand tablet formation properties of four Dioscorea starchesrdquoStarchStarke vol 59 no 9 pp 430ndash444 2007
[3] N Visavarungroj and J P Remon ldquoAn evaluation of hydrox-ypropyl starch an disintegrant and binder in tablet formulationrdquoDrug Development and Industrial Pharmacy vol 17 no 10 pp1389ndash1396 1991
[4] M Nakano N Nakazono and N Inotsume ldquoPreparation andevaluation of sustained release tablets prepared with 120572-starchrdquoChemical and Pharmaceutical Bulletin vol 35 no 10 pp 4346ndash4350 1987
[5] O A Odeku and K M Picker-Freyer ldquoFreeze-dried prege-latinized Dioscorea starches as tablet matrix for sustainedreleaserdquo Journal of Excipients and Food Chemicals vol 1 no 2pp 21ndash32 2010
[6] H Staroszczyk ldquoMicrowave-assisted silication of potato starchrdquoCarbohydrate Polymers vol 77 no 3 pp 506ndash515 2009
[7] J Singh L Kaur and O J McCarthy ldquoFactors influencingthe physico-chemical morphological thermal and rheologicalproperties of some chemically modified starches for foodapplications a reviewrdquo Food Hydrocolloids vol 21 no 1 pp 1ndash22 2007
[8] I Rashid N Daraghmeh M Al-Remawi S A Leharne B ZChowdhry and A Badwan ldquoCharacterization of chitin-metalsilicates as binding superdisintegrantsrdquo Journal of Pharmaceuti-cal Sciences vol 98 no 12 pp 4887ndash4901 2009
[9] I Rashid N Daraghmeh M Al-Remawi S A Leharne B ZChowdhry and A Badwan ldquoCharacterization of the impactof magnesium stearate lubrication on the tableting propertiesof chitin-Mg silicate as a superdisintegrating binder whencompared to Avicel 200rdquo Powder Technology vol 203 no 3 pp609ndash619 2010
[10] Y Asai M Nohara S Fujioka K Isaji and S Nagira ldquoApplica-tion of Neusilin UFL2 on manufacturing of tablets using directcompression method Development of core tablets containingthe function of small degree of decrease of hardness at thehumid conditionsrdquoPharmaceutical Technical Newsletter vol 25pp 67ndash70 2009
[11] B G Prajapati and D V Patel ldquoFormulation and optimiza-tion of domperidone fast dissolving tablet by wet granulationtechniques using factorial designrdquo International Journal ofPharmTech Research vol 2 no 1 pp 292ndash299 2010
[12] J Cooper and C Gunn ldquoPowder flow and compactionrdquo inTutorial Pharmacy S J Carter Ed pp 211ndash233 CBS Publishersand Distributors New Delhi India 1986
Journal of Drug Delivery 13
[13] H Goel G Kaur A K Tiwary and V Rana ldquoFormulationdevelopment of stronger and quick disintegrating tablets acrucial effect of chitinrdquoYakugaku Zasshi vol 130 no 5 pp 729ndash735 2010
[14] J M Sonnergaard ldquoImpact of particle density and initial vol-ume on mathematical compression modelsrdquo European Journalof Pharmaceutical Sciences vol 11 no 4 pp 307ndash315 2000
[15] O A Odeku ldquoAssessment of Albizia zygia gum as a bindingagent in tablet formulationsrdquo Acta Pharmaceutica vol 55 no3 pp 263ndash276 2005
[16] F Kiekens A Debunne C Vervaet et al ldquoInfluence of thepunch diameter and curvature on the yield pressure of MCC-compacts duringHeckel analysisrdquo European Journal of Pharma-ceutical Sciences vol 22 no 2-3 pp 117ndash126 2004
[17] ldquoUnited States Pharmacopeia 24NF19rdquo inTheOfficial Compen-dia of Standards M D Asian Rockville Ed pp 1913ndash1914 USPharmacopeial Convention 2000
[18] T Y Puttewar M D Kshirsagar A V Chandewar and R VChikhale ldquoFormulation and evaluation of orodispersible tabletof tastemasked doxylamine succinate using ion exchange resinrdquoJournal of King Saud UniversitymdashScience vol 22 no 4 pp 229ndash240 2010
[19] A Fini V Bergamante G C Ceschel C Ronchi and C A Fde Moraes ldquoFast dispersibleslow releasing ibuprofen tabletsrdquoEuropean Journal of Pharmaceutics and Biopharmaceutics vol69 no 1 pp 335ndash341 2008
[20] M U Uhumwangho and R S Okor ldquoEffect of humidity on thedisintegrant property of 120572-cellulose Part II A technical noterdquoAAPS PharmSciTech vol 6 no 1 article no 7 pp E31ndashE342005
[21] T Sasaki and J Matsuki ldquoEffect of wheat starch structure onswelling powerrdquo Cereal Chemistry vol 75 no 4 pp 525ndash5291998
[22] O A Itiola and N Pilpel ldquoTableting characteristics of metron-idazole formulationsrdquo International Journal of Pharmaceuticsvol 31 no 1-2 pp 99ndash105 1986
[23] O A Odeku and O A Itiola ldquoEvaluation of khaya gum asa binder in a paracetamol tablet formulationrdquo Pharmacy andPharmacology Communications vol 4 no 4 pp 183ndash188 1998
[24] O A Odeku and J T Fell ldquoEffects of the method of preparationon the compression mechanical and release properties ofkhaya gum matricesrdquo Pharmaceutical Development and Tech-nology vol 11 no 4 pp 435ndash441 2006
[25] O A Odeku and B L Akinwande ldquoEffect of the mode ofincorporation on the disintegrant properties of acid modifiedwater and white yam starchesrdquo Saudi Pharmaceutical Journalvol 20 no 2 pp 171ndash175 2012
[26] R Shangraw A Mitrevej and M Shah ldquoA new era of tabletdisintegrantsrdquo Pharmaceutical Technology vol 4 no 10 pp 49ndash57 1980
Journal of Drug Delivery 11
the dissolution media leading to swelling and wicking of theprepared conjugate creating hydrodynamic pressure insidethe tablets hence responsible for the quick and completedisintegration of tablets indicating the superdisintegrantactivity of conjugates prepared by physical chemical andmicrowave methods over the native corn starch
The results obtained from the in vitro dissolution studyare presented in Figures 7 8 9 and 10 ldquoMKTDrdquo representsthe standard marketed domperidone formulation to whichthe formulated FDTs were compared The similarity factor(1198912) is a logarithmic transformation of the sum-squared
error of differences between test and reference productsover all time points It was observed that the three differentapproaches used for the preparation of conjugate in thisstudy namely physical chemical and microwave methodsincreased the dissolution rate of the drug compared to thetablet prepared with the native corn starch and standardmarketed formulation of the drug The order of increaseddrug dissolution using the different approaches was asfollows microwave gt chemical gt physical In case of theFDTs prepared by using native corn starch (F1ndashF4) thepercentage cumulative drug release was found to be verypoor as compared to the standard marketed formulation ofdomperidone (MKTD)The119891
2value for formulation (F1ndashF4)
was below 50 depicting the dissimilarity between the drugreleases Formulations (F5ndashF8) (F9ndashF12) and (F13ndashF16)werecontaining corn starch-Neusilin UFL2 conjugate prepared byphysical chemical and microwave methods The percentagecumulative drug release for these formulations were found tobe comparable to the standardmarketed formulation of dom-peridone The 119891
2values for these formulations were found
to be over 50 evidencing the similarity between the drugreleases Results of various tablet evaluation tests as evidencedfrom Table 4 indicate that among the three methods usedfor the preparation of conjugates microwave was the mosteffectivemethod followed by chemical and physical methodsMoreover by increasing the concentration of conjugates thetablet did not show much effect on drug release from theformulated FDTs Hence from the commercial point of viewlowest concentration of superdisintegrant showing optimumtabletting results should be recommended
4 Conculsions
In present work an attempt was made to modify the cornstarch to develop corn starch-Neusilin UFL2 conjugatesusing different methods namely physical chemical andmicrowave The prepared conjugates and the corn starchwere characterised for powder flow pH viscosity swellingand effective pore radius Evaluation of precompressionparameter indicates good flow properties The preparedconjugates were also subjected to the compression studiesnamely Heckel and Kawakita function The Heckel plot isusually correlated with the speed of the tablet machine whilethe Kawakita plot is related to the crushing or tensile strengthof the tablet Fast disintegrating tablets of domperidone wereformulated by direct compression technique employing thecorn starch and the prepared conjugates The tablets were
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F1F2F3
F4MKTD
Figure 7 Dissolution rate profiles of FDTs (F1ndashF4) formulated byincorporating native corn starch as a superdisintegrant compared toa standard marketed formulation of domperidone (MKTD)
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F5F6F7
F8MKTD
Figure 8 Dissolution rate profiles of FDTs (F5ndashF8) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates preparedby physical method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
evaluated for physical parametric tests wetting time waterabsorption ratio porosity tablet packing fraction in vitrodisintegration time drug content in vitro dissolution andstability studies Extensive swelling porosity and wickingaction of the prepared corn Starch-Neusilin UFL2 conjugatesin the prepared fast disintegrating tablets were found to becontributing to its superdisintegrant action
In conclusion the prepared conjugates can be effectivelyused as superdisintegrant in order to develop a faster disin-tegrating tablet formulation Future challenges for many fastdisintegrating tablet manufacturers include reducing costsby finding ways to manufacture with conventional equip-ment using versatile packaging and improving mechanical
12 Journal of Drug Delivery
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F9F10F11
F12MKTD
Figure 9 Dissolution rate profiles of FDTs (F9ndashF12) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates preparedby chemical method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
F13F14F15
F16MKTD
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
Figure 10 Dissolution rate profiles of FDTs (F13ndashF16) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates prepared bymicrowave method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
strength Such products provide an opportunity for theproduct line extension in the market place and extensionof patent term of innovator Due to its wide significancethis drug delivery system may lead to better patient com-pliance and ultimate clinical output Future might witnessnovel technologies for development and utilization of themodified starches as tablet superdisintegrant for cost effectiveformulation of fast disintegrating tablets
Conflict of Interests
The authors declare that they have no conflict of interests
Acknowledgments
The authors gratefully acknowledge Dr Madhu ChitkaraVice Chancellor Chitkara University Rajpura Punjab IndiaDr Ashok Chitkara Chairman Chitkara Educational TrustChandigarh India and Dr Sandeep Arora Dean ChitkaraUniversity Rajpura Punjab India for support and institu-tional facilities
References
[1] I Rashid M Al-Remawi S A Leharne B Z Chowdhry andA Badwan ldquoA novel multifunctional pharmaceutical excipientmodification of the permeability of starch by processing withmagnesium silicaterdquo International Journal of Pharmaceutics vol411 no 1-2 pp 18ndash26 2011
[2] O A Odeku and K M Picker-Freyer ldquoAnalysis of the materialand tablet formation properties of four Dioscorea starchesrdquoStarchStarke vol 59 no 9 pp 430ndash444 2007
[3] N Visavarungroj and J P Remon ldquoAn evaluation of hydrox-ypropyl starch an disintegrant and binder in tablet formulationrdquoDrug Development and Industrial Pharmacy vol 17 no 10 pp1389ndash1396 1991
[4] M Nakano N Nakazono and N Inotsume ldquoPreparation andevaluation of sustained release tablets prepared with 120572-starchrdquoChemical and Pharmaceutical Bulletin vol 35 no 10 pp 4346ndash4350 1987
[5] O A Odeku and K M Picker-Freyer ldquoFreeze-dried prege-latinized Dioscorea starches as tablet matrix for sustainedreleaserdquo Journal of Excipients and Food Chemicals vol 1 no 2pp 21ndash32 2010
[6] H Staroszczyk ldquoMicrowave-assisted silication of potato starchrdquoCarbohydrate Polymers vol 77 no 3 pp 506ndash515 2009
[7] J Singh L Kaur and O J McCarthy ldquoFactors influencingthe physico-chemical morphological thermal and rheologicalproperties of some chemically modified starches for foodapplications a reviewrdquo Food Hydrocolloids vol 21 no 1 pp 1ndash22 2007
[8] I Rashid N Daraghmeh M Al-Remawi S A Leharne B ZChowdhry and A Badwan ldquoCharacterization of chitin-metalsilicates as binding superdisintegrantsrdquo Journal of Pharmaceuti-cal Sciences vol 98 no 12 pp 4887ndash4901 2009
[9] I Rashid N Daraghmeh M Al-Remawi S A Leharne B ZChowdhry and A Badwan ldquoCharacterization of the impactof magnesium stearate lubrication on the tableting propertiesof chitin-Mg silicate as a superdisintegrating binder whencompared to Avicel 200rdquo Powder Technology vol 203 no 3 pp609ndash619 2010
[10] Y Asai M Nohara S Fujioka K Isaji and S Nagira ldquoApplica-tion of Neusilin UFL2 on manufacturing of tablets using directcompression method Development of core tablets containingthe function of small degree of decrease of hardness at thehumid conditionsrdquoPharmaceutical Technical Newsletter vol 25pp 67ndash70 2009
[11] B G Prajapati and D V Patel ldquoFormulation and optimiza-tion of domperidone fast dissolving tablet by wet granulationtechniques using factorial designrdquo International Journal ofPharmTech Research vol 2 no 1 pp 292ndash299 2010
[12] J Cooper and C Gunn ldquoPowder flow and compactionrdquo inTutorial Pharmacy S J Carter Ed pp 211ndash233 CBS Publishersand Distributors New Delhi India 1986
Journal of Drug Delivery 13
[13] H Goel G Kaur A K Tiwary and V Rana ldquoFormulationdevelopment of stronger and quick disintegrating tablets acrucial effect of chitinrdquoYakugaku Zasshi vol 130 no 5 pp 729ndash735 2010
[14] J M Sonnergaard ldquoImpact of particle density and initial vol-ume on mathematical compression modelsrdquo European Journalof Pharmaceutical Sciences vol 11 no 4 pp 307ndash315 2000
[15] O A Odeku ldquoAssessment of Albizia zygia gum as a bindingagent in tablet formulationsrdquo Acta Pharmaceutica vol 55 no3 pp 263ndash276 2005
[16] F Kiekens A Debunne C Vervaet et al ldquoInfluence of thepunch diameter and curvature on the yield pressure of MCC-compacts duringHeckel analysisrdquo European Journal of Pharma-ceutical Sciences vol 22 no 2-3 pp 117ndash126 2004
[17] ldquoUnited States Pharmacopeia 24NF19rdquo inTheOfficial Compen-dia of Standards M D Asian Rockville Ed pp 1913ndash1914 USPharmacopeial Convention 2000
[18] T Y Puttewar M D Kshirsagar A V Chandewar and R VChikhale ldquoFormulation and evaluation of orodispersible tabletof tastemasked doxylamine succinate using ion exchange resinrdquoJournal of King Saud UniversitymdashScience vol 22 no 4 pp 229ndash240 2010
[19] A Fini V Bergamante G C Ceschel C Ronchi and C A Fde Moraes ldquoFast dispersibleslow releasing ibuprofen tabletsrdquoEuropean Journal of Pharmaceutics and Biopharmaceutics vol69 no 1 pp 335ndash341 2008
[20] M U Uhumwangho and R S Okor ldquoEffect of humidity on thedisintegrant property of 120572-cellulose Part II A technical noterdquoAAPS PharmSciTech vol 6 no 1 article no 7 pp E31ndashE342005
[21] T Sasaki and J Matsuki ldquoEffect of wheat starch structure onswelling powerrdquo Cereal Chemistry vol 75 no 4 pp 525ndash5291998
[22] O A Itiola and N Pilpel ldquoTableting characteristics of metron-idazole formulationsrdquo International Journal of Pharmaceuticsvol 31 no 1-2 pp 99ndash105 1986
[23] O A Odeku and O A Itiola ldquoEvaluation of khaya gum asa binder in a paracetamol tablet formulationrdquo Pharmacy andPharmacology Communications vol 4 no 4 pp 183ndash188 1998
[24] O A Odeku and J T Fell ldquoEffects of the method of preparationon the compression mechanical and release properties ofkhaya gum matricesrdquo Pharmaceutical Development and Tech-nology vol 11 no 4 pp 435ndash441 2006
[25] O A Odeku and B L Akinwande ldquoEffect of the mode ofincorporation on the disintegrant properties of acid modifiedwater and white yam starchesrdquo Saudi Pharmaceutical Journalvol 20 no 2 pp 171ndash175 2012
[26] R Shangraw A Mitrevej and M Shah ldquoA new era of tabletdisintegrantsrdquo Pharmaceutical Technology vol 4 no 10 pp 49ndash57 1980
12 Journal of Drug Delivery
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
F9F10F11
F12MKTD
Figure 9 Dissolution rate profiles of FDTs (F9ndashF12) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates preparedby chemical method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
F13F14F15
F16MKTD
0
10
20
30
40
50
60
70
80
90
100
0 10 20 30 40 50 60 70
Cum
ulat
ive d
rug
rele
ase (
)
Time (min)
Figure 10 Dissolution rate profiles of FDTs (F13ndashF16) formulatedby incorporating corn Starch-Neusilin UFL2 conjugates prepared bymicrowave method as a superdisintegrant compared to a standardmarketed formulation of domperidone (MKTD)
strength Such products provide an opportunity for theproduct line extension in the market place and extensionof patent term of innovator Due to its wide significancethis drug delivery system may lead to better patient com-pliance and ultimate clinical output Future might witnessnovel technologies for development and utilization of themodified starches as tablet superdisintegrant for cost effectiveformulation of fast disintegrating tablets
Conflict of Interests
The authors declare that they have no conflict of interests
Acknowledgments
The authors gratefully acknowledge Dr Madhu ChitkaraVice Chancellor Chitkara University Rajpura Punjab IndiaDr Ashok Chitkara Chairman Chitkara Educational TrustChandigarh India and Dr Sandeep Arora Dean ChitkaraUniversity Rajpura Punjab India for support and institu-tional facilities
References
[1] I Rashid M Al-Remawi S A Leharne B Z Chowdhry andA Badwan ldquoA novel multifunctional pharmaceutical excipientmodification of the permeability of starch by processing withmagnesium silicaterdquo International Journal of Pharmaceutics vol411 no 1-2 pp 18ndash26 2011
[2] O A Odeku and K M Picker-Freyer ldquoAnalysis of the materialand tablet formation properties of four Dioscorea starchesrdquoStarchStarke vol 59 no 9 pp 430ndash444 2007
[3] N Visavarungroj and J P Remon ldquoAn evaluation of hydrox-ypropyl starch an disintegrant and binder in tablet formulationrdquoDrug Development and Industrial Pharmacy vol 17 no 10 pp1389ndash1396 1991
[4] M Nakano N Nakazono and N Inotsume ldquoPreparation andevaluation of sustained release tablets prepared with 120572-starchrdquoChemical and Pharmaceutical Bulletin vol 35 no 10 pp 4346ndash4350 1987
[5] O A Odeku and K M Picker-Freyer ldquoFreeze-dried prege-latinized Dioscorea starches as tablet matrix for sustainedreleaserdquo Journal of Excipients and Food Chemicals vol 1 no 2pp 21ndash32 2010
[6] H Staroszczyk ldquoMicrowave-assisted silication of potato starchrdquoCarbohydrate Polymers vol 77 no 3 pp 506ndash515 2009
[7] J Singh L Kaur and O J McCarthy ldquoFactors influencingthe physico-chemical morphological thermal and rheologicalproperties of some chemically modified starches for foodapplications a reviewrdquo Food Hydrocolloids vol 21 no 1 pp 1ndash22 2007
[8] I Rashid N Daraghmeh M Al-Remawi S A Leharne B ZChowdhry and A Badwan ldquoCharacterization of chitin-metalsilicates as binding superdisintegrantsrdquo Journal of Pharmaceuti-cal Sciences vol 98 no 12 pp 4887ndash4901 2009
[9] I Rashid N Daraghmeh M Al-Remawi S A Leharne B ZChowdhry and A Badwan ldquoCharacterization of the impactof magnesium stearate lubrication on the tableting propertiesof chitin-Mg silicate as a superdisintegrating binder whencompared to Avicel 200rdquo Powder Technology vol 203 no 3 pp609ndash619 2010
[10] Y Asai M Nohara S Fujioka K Isaji and S Nagira ldquoApplica-tion of Neusilin UFL2 on manufacturing of tablets using directcompression method Development of core tablets containingthe function of small degree of decrease of hardness at thehumid conditionsrdquoPharmaceutical Technical Newsletter vol 25pp 67ndash70 2009
[11] B G Prajapati and D V Patel ldquoFormulation and optimiza-tion of domperidone fast dissolving tablet by wet granulationtechniques using factorial designrdquo International Journal ofPharmTech Research vol 2 no 1 pp 292ndash299 2010
[12] J Cooper and C Gunn ldquoPowder flow and compactionrdquo inTutorial Pharmacy S J Carter Ed pp 211ndash233 CBS Publishersand Distributors New Delhi India 1986
Journal of Drug Delivery 13
[13] H Goel G Kaur A K Tiwary and V Rana ldquoFormulationdevelopment of stronger and quick disintegrating tablets acrucial effect of chitinrdquoYakugaku Zasshi vol 130 no 5 pp 729ndash735 2010
[14] J M Sonnergaard ldquoImpact of particle density and initial vol-ume on mathematical compression modelsrdquo European Journalof Pharmaceutical Sciences vol 11 no 4 pp 307ndash315 2000
[15] O A Odeku ldquoAssessment of Albizia zygia gum as a bindingagent in tablet formulationsrdquo Acta Pharmaceutica vol 55 no3 pp 263ndash276 2005
[16] F Kiekens A Debunne C Vervaet et al ldquoInfluence of thepunch diameter and curvature on the yield pressure of MCC-compacts duringHeckel analysisrdquo European Journal of Pharma-ceutical Sciences vol 22 no 2-3 pp 117ndash126 2004
[17] ldquoUnited States Pharmacopeia 24NF19rdquo inTheOfficial Compen-dia of Standards M D Asian Rockville Ed pp 1913ndash1914 USPharmacopeial Convention 2000
[18] T Y Puttewar M D Kshirsagar A V Chandewar and R VChikhale ldquoFormulation and evaluation of orodispersible tabletof tastemasked doxylamine succinate using ion exchange resinrdquoJournal of King Saud UniversitymdashScience vol 22 no 4 pp 229ndash240 2010
[19] A Fini V Bergamante G C Ceschel C Ronchi and C A Fde Moraes ldquoFast dispersibleslow releasing ibuprofen tabletsrdquoEuropean Journal of Pharmaceutics and Biopharmaceutics vol69 no 1 pp 335ndash341 2008
[20] M U Uhumwangho and R S Okor ldquoEffect of humidity on thedisintegrant property of 120572-cellulose Part II A technical noterdquoAAPS PharmSciTech vol 6 no 1 article no 7 pp E31ndashE342005
[21] T Sasaki and J Matsuki ldquoEffect of wheat starch structure onswelling powerrdquo Cereal Chemistry vol 75 no 4 pp 525ndash5291998
[22] O A Itiola and N Pilpel ldquoTableting characteristics of metron-idazole formulationsrdquo International Journal of Pharmaceuticsvol 31 no 1-2 pp 99ndash105 1986
[23] O A Odeku and O A Itiola ldquoEvaluation of khaya gum asa binder in a paracetamol tablet formulationrdquo Pharmacy andPharmacology Communications vol 4 no 4 pp 183ndash188 1998
[24] O A Odeku and J T Fell ldquoEffects of the method of preparationon the compression mechanical and release properties ofkhaya gum matricesrdquo Pharmaceutical Development and Tech-nology vol 11 no 4 pp 435ndash441 2006
[25] O A Odeku and B L Akinwande ldquoEffect of the mode ofincorporation on the disintegrant properties of acid modifiedwater and white yam starchesrdquo Saudi Pharmaceutical Journalvol 20 no 2 pp 171ndash175 2012
[26] R Shangraw A Mitrevej and M Shah ldquoA new era of tabletdisintegrantsrdquo Pharmaceutical Technology vol 4 no 10 pp 49ndash57 1980
Journal of Drug Delivery 13
[13] H Goel G Kaur A K Tiwary and V Rana ldquoFormulationdevelopment of stronger and quick disintegrating tablets acrucial effect of chitinrdquoYakugaku Zasshi vol 130 no 5 pp 729ndash735 2010
[14] J M Sonnergaard ldquoImpact of particle density and initial vol-ume on mathematical compression modelsrdquo European Journalof Pharmaceutical Sciences vol 11 no 4 pp 307ndash315 2000
[15] O A Odeku ldquoAssessment of Albizia zygia gum as a bindingagent in tablet formulationsrdquo Acta Pharmaceutica vol 55 no3 pp 263ndash276 2005
[16] F Kiekens A Debunne C Vervaet et al ldquoInfluence of thepunch diameter and curvature on the yield pressure of MCC-compacts duringHeckel analysisrdquo European Journal of Pharma-ceutical Sciences vol 22 no 2-3 pp 117ndash126 2004
[17] ldquoUnited States Pharmacopeia 24NF19rdquo inTheOfficial Compen-dia of Standards M D Asian Rockville Ed pp 1913ndash1914 USPharmacopeial Convention 2000
[18] T Y Puttewar M D Kshirsagar A V Chandewar and R VChikhale ldquoFormulation and evaluation of orodispersible tabletof tastemasked doxylamine succinate using ion exchange resinrdquoJournal of King Saud UniversitymdashScience vol 22 no 4 pp 229ndash240 2010
[19] A Fini V Bergamante G C Ceschel C Ronchi and C A Fde Moraes ldquoFast dispersibleslow releasing ibuprofen tabletsrdquoEuropean Journal of Pharmaceutics and Biopharmaceutics vol69 no 1 pp 335ndash341 2008
[20] M U Uhumwangho and R S Okor ldquoEffect of humidity on thedisintegrant property of 120572-cellulose Part II A technical noterdquoAAPS PharmSciTech vol 6 no 1 article no 7 pp E31ndashE342005
[21] T Sasaki and J Matsuki ldquoEffect of wheat starch structure onswelling powerrdquo Cereal Chemistry vol 75 no 4 pp 525ndash5291998
[22] O A Itiola and N Pilpel ldquoTableting characteristics of metron-idazole formulationsrdquo International Journal of Pharmaceuticsvol 31 no 1-2 pp 99ndash105 1986
[23] O A Odeku and O A Itiola ldquoEvaluation of khaya gum asa binder in a paracetamol tablet formulationrdquo Pharmacy andPharmacology Communications vol 4 no 4 pp 183ndash188 1998
[24] O A Odeku and J T Fell ldquoEffects of the method of preparationon the compression mechanical and release properties ofkhaya gum matricesrdquo Pharmaceutical Development and Tech-nology vol 11 no 4 pp 435ndash441 2006
[25] O A Odeku and B L Akinwande ldquoEffect of the mode ofincorporation on the disintegrant properties of acid modifiedwater and white yam starchesrdquo Saudi Pharmaceutical Journalvol 20 no 2 pp 171ndash175 2012
[26] R Shangraw A Mitrevej and M Shah ldquoA new era of tabletdisintegrantsrdquo Pharmaceutical Technology vol 4 no 10 pp 49ndash57 1980
