UK Journal of Pharmaceutical and Biosciences Vol. 3(6),...

UK Journal of Pharmaceutical and Biosciences Vol. 3(6), 30-41, 2015 RESEARCH ARTICLE

Design and In-Vitro Evaluation of Colon Targeted Prednisolone Solid Dispersion

Tablets

Sura Zuhair Mahmood Alkazzaz*, Wedad Kamal Ali

Department of Pharmaceutics, College of Pharmacy, University of Al-Mustansiriya, Baghdad-Iraq

Article Information

Received 19 September 2015

Received in revised form 26 Sep 2015

Accepted 28 Sep 2015

Abstract

In the present investigation an attempt was made to prepare colon targeted enteric coated tablet

containing different prednisolone solid dispersion formulations, to prevent ulcerative colitis,

improve the patient compliance and reduce the side effects of drug in the gastro intestinal tract

(GIT). Solid dispersion is one of the most widely used approaches to enhance the solubility as

well as dissolution rate of poorly water soluble drugs. Solid dispersions (SDs) of Prednisolone

with D-mannitol, PEG 4000 and Kollicoat IR were prepared and evaluated to deliver Prednisolone

to the colon in a pre-solubilized form. The selected formula using drug compatible excipients was

compressed into fast disintegrating tablets and then coated with Eudragit S100 (pH-responsive

polymer), several variables related to both solid dispersion preparation (carrier type and drug to

the carrier ratio) and tablet coating (coat level) were studied to show their effects on drug

solubility and dissolution. Different analytical techniques like differential scanning caloremitry

(DSC), powder x-ray diffraction (PXRD) and scanning electron microscopy (SEM) were studied to

prove the change of drug particle from crystal to amorphous form in SDs. The 1:3

Prednisolone/Kollicoat IR SDs showed the greatest improvement in the dissolution rate. The

coating level was critical for determining the duration of the lag phase. Best result was given by

the 16% coat (Eudragit S100/ Dibutyl phthalate/ talc). This coating level showed an acceptable

lag time for the proposed colonic targeting (5 h) as the selected tablet resisted pre-colonic pH

values, followed by an immediate release stage in pH 7.4. The suggested covered (coated)

tablets may provide a colonic delivery system for prednisolone with enhanced solubility and

bioavailability.

Keywords:

Prednisolone,

Colon Targeted,

Solid dispersions

*Corresponding Author:

E-mail: [email protected]

Mob.: 07901325199

1 Introduction

In the last few years, the development of the site specific drug

delivery system has been introduced to be studied with great deal of

research work which compromises numerous benefits over the

traditional drug treatments. The principle goal of the site specific

delivery is to deliver the drug in the specific organs of the body1.

Targeted drug delivery to the colon is highly required for local

treatment of a variety of bowel diseases such as ulcerative colitis,

Crohn’s disease, amebiosis, and colonic cancer2. The most critical

challenge in such drug delivery approaches is to protect the

formulation during its passage through the stomach and about first

six meters of the small intestine arriving to colon with no loss of

active ingredient by preventing the dissolution and the release till it

reached the colon3. Among the various pharmaceutical approaches

used to target drugs to the colon are pH-dependent, time-dependent

and bacterially degradable polymers4.

Prednisolone (a potent synthetic corticosteroid that available for

clinical use in 1955) making it useful for the treatment of a wide

range of inflammatory and auto-immune conditions such as Crohn’s

disease, Ulcerative colitis and Rheumatoid arthritis and others5.

Peak plasma concentrations of prednisolone are obtained after 1-2

hours of an oral dose administration, and it has a usual plasma half-

life of 2 to 4 hours6.

UK Journal of Pharmaceutical and Biosciences

Available at www.ukjpb.com ISSN: 2347-9442

Alkazzaz et al. Design and In-Vitro Evaluation of Colon Targeted Prednisolone

UK J Pharm & Biosci, 2015: 3(6); 31

Improvement of the dissolution rates of class II water-insoluble drugs

is one of the most challenging issues of drug development, because

the enhanced dissolution rates can enhance drug oral

bioavailability7. For water-insoluble drugs the solid dispersion

technique established by Chiou and Reigelman supplies an effective

way to increase the dissolution rates of drugs8.

In the present study, efforts were made to improve the dissolution

behavior and consequently, absorption, of Prednisolone by applying

the solid dispersion technique using three different hydrophilic

carriers (PEG 4000, D- mannitol and Kollicoat IR) the solid

dispersion formulations were compressed into tablets and further

coated to deliver the drug to colon.

2 Materials and Methods

2.1 Materials

Prednisolone, D-mannitol, Crospovidone, Croscarmellose sodium,

magnesium stearate were obtained from Samara drug industry, Iraq;

Kollicoat IR was obtained from Sigma-Aldrich Co., USA; Poly

ethylene glycol (PEG4000) from Sinopharm chemical reagent Co.,

China, Eudragit S100 was purchased from Evonik Company,

Germany and Dibutyl phthalate was manufactured by Fluka

Company, UK. All other chemicals, reagents and solutions used

were of analytical grade. Marketed tablet Deltacortril® (Pfizer,

Turkey) was purchased from local pharmacy.

2.2 Methods

2.2.1 Solubility determination of Prednisolone

For the determination of solubility of Prednisolone, an excess

amount of the drug about 50 mg was added to 25 ml phosphate

buffers pH7.4. The flask was stirred for 24 hours using magnetic

stirrer and maintained at 25oC. The sample was then filtered through

0.45 μm membrane filters, suitably diluted, and analyzed by UV-

spectrophotometer at 247 for prednisolone. The study was

performed in triplicate9-11

.

2.2.2 Preparation of Prednisolone solid dispersions

Solid dispersions of prednisolone in three hydrophilic carriers at

three different weight ratios were prepared by solvent evaporation

method by using ethanol as common solvent. The calculated amount

of polymer and drug was dissolved separately in the required amount

of solvent ethanol and mixed under mechanical agitation. The

solvent was eliminated using a rotary evaporator under reduced

pressure. The solid dispersions when dried were grinded using a

mortar and pestle then passed through 0.36 mm sieve and stored in

desiccators till use12

, and the optimum one for each carrier was

compared with the physical mixture and pure Prednisolone. Solid

dispersion and physical mixture of different weight ratios are listed in

table 1.

2.2.3 Evaluation of the prepared solid dispersion

2.2.3.1 Determination of saturated solubility of Prednisolone in solid

dispersions

Similar procedure mentioned in (2.2.1) was used to determine the

saturation solubility of different solid dispersions in phosphate buffer

pH7.4 and compared to that of pure drug13,14

.

Table 1: Formulation code of Prednisolone solid dispersions

and physical mixtures prepared with different carriers

Formulation

Codes

Carrier

Drug:

Carrier

ratio

Method of

preparation

SD1 PEG4000 1:1 Solvent Evaporation

SD2 1:2 Solvent Evaporation


PM1 1:3 Physical Mixture

SD4 D- Mannitol 1:1 Solvent Evaporation




SD7 Kollicoat IR 1:1 Solvent Evaporation




2.2.3.2 In-vitro dissolution study:

The in vitro dissolution study was carried out by using USP type II

(paddle type) dissolution test apparatus (Cosmo Lab). Using 900 ml

dissolution medium (pH 7.4) at 37◦C and rotation speed of 50 rpm.

Accurately weighted amount (5mg) of pure drug and equivalent

amount from solid dispersions and physical mixtures to 5mg

prednisolone were placed in the dissolution vessel for 90min and at

appropriate time intervals (2, 5, 10, 15, 20, 30, 45, 60 and 90 min), 5

ml samples were withdrawn and replenished with the same volume

of fresh medium to keep the sink condition constant, samples then

filtered and analyzed spectrophotometrically at (247 nm for

Prednisolone). The procedure was performed in triplicate for each

run test and the mean and standard deviation were calculated15-17

.



2.2.3.3 Determination of drug content

The drug content in each solid dispersion formulation was

determined by placing the weighted amount of solid dispersion

samples equivalent to 2mg of Prednisolone in 100ml volumetric flask

containing phosphate buffer (pH 7.4), the samples were continuously

shaking until completely dissolve them then filtered. The absorbance

of the samples was determined at λmax 247 nm, using UV-visible

spectrophotometer. Three readings were taken, and then mean and

standard deviation was calculated18

.

2.2.3.4 Selection of the best formula

The phase solubility and in vitro dissolution test were used for

selecting the best solid dispersion formula which will be subjected to

further analysis.

2.2.4 Characterization of the selected solid dispersion formula

2.2.4.1 Fourier transforms infrared spectroscopy (FTIR):

Samples of pure drug, Kollicoat IR and SD9 (equivalent to about 5

mg of Prednisolone) were ground, mixed with dry potassium bromide

and pressed in the form of discs using hydraulic press. The discs

were analyzed by FTIR spectroscopy (4000-400 cm-1)19, 20

.

2.2.4.2 Differential scanning calorimetry (DSC)

DSC was used to determine thermal behavior of Prednisolone,

Kollicoat IR, and SD9 formulations. The pure drug, polymer and solid

dispersions were examined by DSC 60 (Shimadzu, Japan), where 5-

6 mg sample was placed in aluminum pan and scan at a heating rate

of 10oC/min (in range of 0-350

oC ) with purging of dry nitrogen at a

constant rate; an empty aluminium pan was used as a reference.

Indium/Zinc standards were used to calibrate the DSC temperature

and enthalpy scale21, 22

.

2.2.4.3 Powder x-ray diffraction (PXRD)

The extent of crystallinity was determined for pure drug and prepared

solid dispersion using X-ray (Shimadzu, Japan) powder diffraction

system equipped with Cu radiation (λ=1.54060 A◦) at a voltage of (40

Kv) and a current of (30 mA).The instrument was operated in the

continuous scan mode and sample were analyzed in the range (5-

80oC) with a step size of (0.05

oC) at scanning speed of (5

oC /min)

and (2θ) axis23

.

2.2.4.4 Scanning electron microscopy (SEM):

The SEM analysis was carried out using a scanning electron

microscope (SEM Tescan Vega lll Czech). Before to examination,

mounted the sample on an aluminum stub using a double sided

adhesive tape, then coating with a thin layer of gold (approximately

20 nm) in the vacuum to make it electrically conductive. SEM

provides a high resolution images that show details of a sample

surface since a high energy beam of electrons typically from 0.5 kV

to 40 kV is used to scan the surface of sample to give image in a

raster scan pattern24

.

2.2.5 Manufacturing of colon targeted tablet of Prednisolone by direct

compression method

Tablets of pure drug and solid dispersion formulations were prepared

to evaluate the impact of solid dispersion on the release of the drug.

Tablets ingredients used in tablet formulation (Table 2) were

accurately weighed then passed through 0.36 mm sieve to get

uniform particle size. The drug and all the ingredients except

lubricants were mixed and blended for 5 min. Finally, magnesium

stearate was added, mixed for 2 min to coat the particle surface by

lubricant evenly. The blend was compressed using 6mm punch and

die on a single punch tablet machine. The formulated tablets were

stored in a tightly closed container until evaluated. Based on the

results of dissolution study the best formulation was selected among

the six formulations for further study25

.

Table 2: Formulation ingredient of pure and solid dispersions

tablet of Prednisolone

Ingredient F1

F2

SD3

F3

SD3

F4

SD3

F5

SD6

F6

SD18

Prednisolone 5 - - - - -

Solid Dispersion - 20 20 20 20 20

Cros-carmellose Na 2 2 - - 2 2

Cros-povidone - - 2 - - -

Magnesium stearate 1 1 1 1 1 1

Avicel pH302 92 77 77 79 77 77

Total weight 100 100 100 100 100 100

2.2.5.1 Pre-compression parameters evaluation

Various micromeritic parameters like angle of repose, bulk density,

tap density, Carr’s (Compressibility) Index (CI), and Hausner’s ratio

were measured for solid dispersions powders26

.

2.2.5.2 Post-compression parameters evaluation

Thickness of tablets prepared was calculated using Vernier caliper27

,

the hardness of the tablets was determined using electrical hardness

tester. It is expressed in Kg/cm2. The hardness test was performed in

which five tablets from each formula were tested randomly and the

average reading ± sd was recorded28

. The friability test was done by



placing 20 pre-weighed tablets in the friabilator which was then

operated for 25 rpm for 4 minutes; the tablets were then dusted and

reweighed. Tablets that lose a maximum of not more than 1% of their

weight are generally considered acceptable29

. In addition, weight

variation was performed according to the USP specifications.

2.2.5.3 Content Uniformity test

Content uniformity was done by weighing and powdering 20 tablets.

Weigh accurately a quantity of the powder equivalent to (5 mg of

Prednisolone) and transferred to 100 mL volumetric flasks containing

50 mL of phosphate buffer pH 7.4. The flasks were shaken to

solubilize the drug. The volume was completed to 100 mL with the

buffer, allowed to stand for 24 h to make sure complete solubility of

the drug. The solution was filtered, and 1 mL of the filtrate liquid was

suitably diluted and analyzed for prednisolone content

spectrophotometrically at 247 nm30-32

.

2.2.5.4 In-vitro disintegration study

The in-vitro disintegration study of the uncoated tablets was

determined using the disintegration test apparatus as per USP

specifications. One tablet was placed in each of the six tubes of the

basket, the disc was add to each tube and running the apparatus

using 900 ml of phosphate buffer pH 7.4 maintained at 37ºC. The

time in seconds for complete disintegration of the tablets with no

palpable mass remaining in the apparatus was measured and

recorded33

.

2.2.5.5 In-vitro dissolution study

The in vitro dissolution study was carried out as mentioned

previously in section (2.2.3.2) except that one tablet of each

prepared formula was placed in the dissolution vessel instead of

powdered sample for 90min

2.2.5.5.1 Effect of different superdisintegrants addition on uncoated

tablet release profile

Formulas F2SD3 and F3SD3 were designed to study the effect of

different superdisintegrants addition on drug release of uncoated

tablet compared with one without the addition of superdisintegrant

(F4SD3), where 2% Croscarmellose, 2%Crospovidone and no

superdisintegrant were used respectively.

2.2.6 Eudragit S100 coating of tablets for pH dependent release

For minimizing the drug release in upper GIT (stomach and small

intestine) Eudragit S100 was selected as the pH dependent coating

polymer. A 6% w/v Eudragit S100 coating solution was prepared

using the mixture of isopropyl alcohol and acetone with the addition

of 1% plasticizer- Dibutyl phthalate and used to coat tablet of

optimized formula using dip coating method34

.

2.2.6.1 Evaluation of the prepared coated tablets

Tablet of optimum formula was coated and around the selected core

tablet formula and the resulted coated tablets evaluated for

thickness, hardness and friability in the same way for uncoated

tablets.

2.2.6.2 Disintegration test for enteric coated tablets

The disintegration test was carried out for all the formulations

according to British Pharmacopeia method for enteric-coated tablets.

0.1N HCL and 7.4 pH phosphate buffer was used as disintegrating

media. Six tablets were used in each case35

.

2.2.6.3 In-vitro drug release study of coated tablets of Prednisolone

Similar dissolution conditions mentioned for powder, and uncoated

tablets were used. For simulating the gastric fluid in stomach, the

dissolution was accomplished in 0.1 N HCl (pH 1.2) for 2hr, in the

phosphate buffer (pH 6.8) to simulate the small intestinal fluid for

three hours and for another two hours in phosphate buffer (pH 7.4),

simulating the colonic environment. Sample aliquots withdrawn at

specific time intervals, were analyzed at 247 nm using UV-Vis

Spectrophotometer34,36

.

2.2.6.4 Drug-excipient interactions

The physicochemical compatibilities of the drug and the used

excipients were tested by FTIR. Pure Prednisolone, selected core

and press coated tablets (which were previously grinded); were

mixed thoroughly with potassium bromide. The potassium bromide

discs were prepared by compressing the powder at a pressure in a

hydraulic press and analyse in the ranges (4000- 400 cm-1)37

.

2.2.6.5 Statistical analysis

The results of the experiments are given as a mean values ±

standard deviation (SD) and were analyzed according to one-way

analysis of variance (ANOVA) at which significant results (p<0.05)

and non-significant (p>0.05).

3 Results and Discussions

The measured solubility of Prednisolone in phosphate buffer pH7.4

(215±0.005 μg/ml) indicates that the drug is a very slightly soluble

compound in this buffer. Solubility studies revealed a linear increase

in drug solubility in the presence of an increasing carrier

concentration this is because hydrophilic carriers are known to

interact with drug molecules, mainly by electrostatic forces and

occasionally by other types of forces like intermolecular hydrogen

bonds38,39

. The solubility enhancement of the various carriers was in

the order of Kollicoat IR > PEG4000> D-Mannitol. The markedly

higher solubility of Prednisolone in Kollicoat IR may be attributed to

the higher solubilizing capacity as it is non-ionic polymer and its



solubility is pH-independent40

. The content of Prednisolone was

determined in all the prepared formulas and was found to range from

98-101% of the theoretical calculated content which is within the

limits of the official monographs of Prednisolone preparations of the

British Pharmacopeia. The dissolution results of pure and solid

dispersion of Prednisolone in the different carrier are presented in

Figure1. It is evident that all Prednisolone solid dispersions exhibit

fast dissolution rate than pure drug. However, the rate of dissolution

was varying among different Prednisolone solid dispersions

(prepared using different types of carrier and ratios). The significant

higher dissolution rate (p<0.05) obtained from solid dispersion

formulations is a result of particle size reduction of the drug41

,

formation of higher energy metastable state with higher degree of

amorphization of the drug, improved drugʼs wetting properties, local

solubilization of the carrier at the diffusion layer42

, increased porosity,

and the formation of intermolecular hydrogen bonding between the

drug and the carrier43

.

Formula SD9 was chosen as the best formula since it showed higher

drug solubility and percent drug release at the short period of time

among other solid dispersion formulations; therefore, further

characterization on this formula was done.

The FTIR spectrum (Figure2) of Kollicoat IR showed a characteristic

band at 3421 cm-1, which is assigned for OH stretching. No

appearance of new bands in SD9 FTIR spectrum suggesting no

chemical interaction between the drug and the carrier. Reduction in

the sharpness and smoothing of the peaks means a reduction of

Prednisolone crystallinity which is further can be confirmed by DSC

and PXRD analysis studies.

0

20

40

60

80

100

120

0 20 40 60 80

cum

ula

tive

%o

f d

rug

rele

ase

Time (min)

pure

SD1

SD2

SD3

SD4

SD5

SD6

SD7

SD8

SD9

Figure 1: Effect of using different carrier ratio and type on drug release in phosphate buffer pH7.4 at 37 oC

In general, there is a reduction in the intensity and sharpness of the

absorption bands of SD9 compared to Prednisolone alone as a result

of formation of intermolecular hydrogen bonding.

Thermal analysis using DSC showed the presence of single

endothermic peak in the thermogram of SD9 (Figure 3) around the

polymer melting point related to polymer fusion with the absence of a

peak corresponding to melting endotherm of Prednisolone can be

attributed to the possible dissolution of the drug in the molten carrier

during heating cycle in DSC analysis44

, and PXRD result shown in

figure 4 reveals the decrease in the intensity of prednisolone SD9

peak compared to pure drug which indicate decrease in crystallinity

of the drug in SD9.

The results of SEM are shown in figure 5 SEM micrographs indicate

that the pure drug is in the crystalline form whereas physical mixture

contains both amorphous particles and some crystals of the drug. In

the case of the solid dispersion, the drug particles reduced in size,

some have spherical shape; which is might be one of the factors that

are responsible for enhancing drug dissolution and solubility45

.

The values of angle of repose, bulk density, tapped density, Carr's

index, and Hausner ratio for the prepared uncoated powder blends of

each formula was illustrated in table 3. These results estimated

according to USP33

. The results show that the prepared uncoated

mixtures have acceptable flow properties and compressibility.

The results of thickness, hardness and friability of all the prepared

uncoated tablets are shown in table 4.

In vitro disintegration time for all prepared Prednisolone uncoated

tablet was found to be in the range of (43-420 seconds).This short

disintegration time is desirable since it facilitates the dissolution and



releases of the drug from the tablet. In general disintegration of

tablets achieved through overcoming the cohesive strength of tablets

using different types and amount of Disintegrants in tablet

formulation.

A

B

C

Figure 2: FTIR spectra of A- Prednisolone, B- Kollicoat IR and C - SD9

Figure 6 shows dissolution profiles of Prednisolone from 4 different

SD tablets in the phosphate buffer (pH 7.4) compared to marketed

one. These results are similar to those obtained from powdered

Prednisolone, which indicates that the enhancement in the

dissolution of drug from solid dispersion samples is maintained after

manufacturing these samples into tablets.

The result of in vitro dissolution (F2, F3 and F4) uncoated tablet

formula which was designed to show the effect of Croscarmellose

sodium, Crospovidone and without addition of any disintegrants

respectively on the drug release from the uncoated tablet shown in

figure7. There was significant difference (p<0.05) in the initial release

of drug from these formulation among these formulas the F2 give the

best result of 100% release due to the rapid increase in dissolution of

Prednisolone with the use of Croscarmellose sodium may be

attributed to rapid swelling and disintegration of tablet into apparently

primary small particles while Crospovidone disintegrates the tablets

quickly but into larger masses of accumulated particles. It exhibits

high capillary activity and marked hydration with a little tendency to

gel formation46, 47

.

The developed formulation of coated tablet F6 was studied for its

physical properties like thickness, hardness, friability and weight

variation and the result was as follow thickness (3.66±0.002 mm),

hardness (7±0.005 Kg/cm2), friability (0.18%) and weight variation

(116±0.5 mg). The content uniformity test was done for the selected

coated tablet formula and the result was 99.95%. This result agrees

with the requirements of the United States pharmacopeia.

The coated tablet met pharmacopeial (BP/USP) requirements for the

enteric performance test in the 0.1N HCl for 2hr. tablet disintegrate in

phosphate buffer solution pH7.4 after 20±0.02 min. Also we found

that tablet coated at higher levels had longer disintegration times

than that coated at lower levels at the same medium as for 16% and

19% coat level was 20 and 60min respectively48

.



Figure3: DSC thermograms of A - pure Prednisolone, B - Kollicoat IR and C - SD9 (1:3 Kollicoat IR)

Prednisolone

SD9

Figure 4: X-ray diffraction (XRD) patterns of Pure Prednisolone and SD9

The requirement for in vitro release pattern selected for the colon

targeting was no drug release up to the end of 5hrs to achieve this

different Eudragit S100 coating level was examined, and the best

result was using 16% coating level.

The concentration of polymer in solution and the % coating level was

related to the drug release directly. Percent of drug release versus

time plot illustrations that the dissolution rate was in reverse



proportional to the coating level applied. The percentage of drug released for different coating level showed significant differences36

.

Figure 5: SEM of A-pure drug, B- physical mixture and C-SD9

Table 3: Pre-compression physical parameters for core powder blend

Formula

Angle of

repose

(Degree)

Bulk density

(g/cm3)

Tapped density

(g/cm3)

Carr's

Index

Hausner

ratio

Type of flow

F1 33.78±0.66 0.323±0.04 0.37±0.01 12.7 1.15 Good

F2 31.21±0.51 0.323±0.01 0.364±0.06 11.26 1.13 Good

F3 31.21±0.51 0.323±0.01 0.364±0.06 11.26 1.13 Good

F4 31.15±0.63 0.364±0.04 0.408±0.01 10.78 1.12 Good

F5 24.52±0.62 0.385±0.02 0.417±0.03 7.67 1.08 Excellent

F6 33.17±0.64 0.345±0.03 0.408±0.04 15.44 1.18 Good

The selected tablet formula was used to study the effect of coat level

(thickness) on lag time of colon targeted coated tablet. The lag time

of coated tablet which have tablet thickness 3.66mm was 5 hours

and 20 min while for the same tablet formula which have tablet

thickness 3.75mm was 7 hours as shown in figure 8. These results

showed that as the thickness of the coat increased, the lag time

increased since the time required to complete the erosion of the

outer shell would be longer. The same results were reported with

other related studies49

. The FTIR spectra results showed that the

drug bands didn't change significantly in the FTIR spectra of the

grinded uncoated, and selected coated tablets as shown in figure 9

and the small shifting in the absorption bands was listed in table 5.

These results indicating that there is no significance evidence of

chemical interaction between drug and polymer, which confirm the

stability of drug.

4 Conclusion

Amorphous solid dispersions of prednisolone were successfully

prepared by solvent evaporation method. The presence of

amorphous form in SDs was confirmed by DSC, PXRD and SEM,

and was reflected in the significant improvement in rate as well as

the extent of in vitro drug dissolution. Proper selection of the



Eudragit®S100 coat level is essential to deliver prednisolone to the

colon. The optimized prednisolone colon targeted tablets could be

promising in reducing the drug dose and improving its bioavailability

based on the protection from the intestinal metabolism. Such a

delivery system could be applied for similar water insoluble drugs

liable to intestinal enzymatic degradation. Additional studies are

needed to assess its performance in vivo.

Table 4: Post compression parameter of Prednisolone tablets

Formula Thickness

(mm)

Hardness

(kg/ cm2)

Friability

(%)

Weight

variation

(mg)

F1 3.19± 0.01 4.5± 0.02 0.46±0.04 99±0.04

F2 3.19±0.03 5.02±0.04 0.1±0.05 99.5±0.01

F3 3.19±0.02 5.8±0.01 0.2±0.03 100±0.02

F4 3.21±0.01 5.5±0.02 0.25±0.05 98.5±0.01

F5 3.19±0.01 4±0.03 0.51±0.02 98±0.02

F10 3.20±0.01 4±0.03 0.6±0.01 99.7±0.01

Figure 6: Dissolution profiles of Prednisolone from 4 different

uncoated tablets in phosphate buffer (pH 7.4) compared to

marketed one

5 Acknowledgements

We are grateful for the cooperation of Iraqi Ministry of Science and

Technology for doing the required analytical measurements and Ibn-

Sena center for drug research (Baghdad/Iraq) for providing

chemicals from Samara drug industry.

6 Competing interests

Authors have no competing interests.

Figure 7: Effect of different superdisintegrant addition on

uncoated tablet for F2, F3 and F4 in phosphate buffer pH 7.4

Figure 8: In- vitro release of uncoated tablet and Effect of coat

thickness on percent of drug release in different dissolution

media

Table 5: Characteristic absorption bands of Prednisolone

Characteristic

Group

Pure

Prednisolone

cm-1

Prednisolone

core tablet

cm-1

Prednisolone

coat tablet

cm-1

-OH 3454 cm-1 3379.4 cm

-1 3354 cm

-1

Sp3 C-H 2982 cm-1 2910 cm

-1 2910 cm

-1

-C=O 1654 cm-1 1654 cm

-1 1654 cm

-1

Aromatic C=C 1610 cm-1 1612 cm

-1 1610 cm

-1

C-H bend 1446 cm-1 1437 cm

-1 1431 cm

-1

OH bend 1348 cm-1 1371 cm

-1 1371 cm

-1

-C-O 1236 cm-1 1240 cm

-1 1242 cm

-1

Aromatic C=C bend 893 cm-1 893 cm

-1 895 cm

-1



Figure 9: The FTIR spectra of the grinded uncoated, and coated Prednisolone tablets

7 Author’s contributions

The study was conceived, planned, performed and written in the

form of manuscript by SZM, WKA participated in literature review

and manuscript editing. Both authors read and approved on the final

manuscript.

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