FORMULATION AND EVALUATION OF FAST DISSOLVING TABLET DOMPERIDONE
Transcript
FORMULATION AND EVALUATION OF FAST DISSOLVING TABLET
SEMINAR REPORT ON FAST DISSOLVING TABLET DOMPERIDONE BY
PAVULURI RAJA RAJESWARA RAO MOHAMMED SUFIYAN AHMED MOHAMMED
MUDASSIR KHAJA FAHEEMUDDIN MOHAMMED ALTAF ALI UNDER THE GUIDANCE OF
Mrs. K GOUTHAMI (Assit. Proff in department of pharmaceutics)
DEPARTMENT OF PHARMACEUTICS SHADAN COLLEGE OF PHARMACY
CONTENTS INTRODUCTION LITERATURE OBJECTIVE PLAN OF WORK DRUG
PROFILE EXCIPIENT PROFILE MATERIALS METHODOLOGY RESULTS AND
DISCUSSION CONCLUSION REFERENCES
INTRODUCTION
DEFINATION OF FAST DISSOLVING TABLETS : A fast disintegrating
tablet can be defined as a solid dosage form that can disintegrate
or dissolve within 30 seconds, in the oral cavity resulting in a
solution or suspension without administration of water.
REQUIREMENTS OF FAST DISINTEGRATING TABLET: Require no water for
oral administration Have a pleasing mouth feel. Have an acceptable
taste masking property. Be optimum harder and less friable
ADVANTAGES : Ease of administration to patients who refuse to
swallow a tablet, such as pediatric and geriatric patients and
psychiatric patients. No need of water to swallow the dosage form.
Rapid dissolution and absorption of drug Convenience of
administration and accurate dosing as compared to liquids. Good
mouth feel property helps to change the basic view of medication as
"bitter pill", particularly for pediatric patients. DISADVANTAGES:
The disadvantage of most ODT is that they are fragile and brittle.
It needs special package for protection during storage and
transportation.
CHARACTERISTICS OF FAST DISINTEGRATING SYSTEMS a) Ease of
administration b) Taste of the medicament c) Hygroscopicity d)
Friability e) Mouth feel PREPARATION METHODS OF FAST DISSOLVING
TABLETS Freeze drying Molding Sublimation Spray Drying Direct
Compression Melt granulation Phase transition process ETC.
S. NO. TRADE NAME ACTIVE DRUG MANUFACTURER 1. Felden fast melt
Piroxicam Pfiser Inc., NY, USA 2. Claritin redi Tab Loratidine
Schering plough Corp., USA 3. Maxalt MLT Rizatriptan Merck and Co.,
NJ, USA 4. Zyprexia Olanzapine Eli lilly, Indianapolis, USA 5.
Pepcid RPD Famotidine Merck and Co., NJ, USA 6. Zofran ODT
Ondansetron Glaxo Wellcome, Middlesex, UK 7. Zoming-ZMT
Zolmitriptan AstraZeneca, Wilmington, USA 8. Zeplar TM Selegilline
Amarin Corp., London, UK 9. Tempra Quiclets Acetaminoph en Bristol
myers Squibb, NY, USA 10. Febrectol Paracetamol Prographarm,
Chateauneuf, France List of Marketed Fast Dissolving Tablets
Mechanism of tablet disintegration: Capillary action (Wicking).
Swelling. Due to disintegrating particle/particle repulsive forces.
Due to deformation. Due to release of gases.
LITERATURE SURVEY
LITERATURE REVIEW Sharma Shailesh*, Singh Gurjeet and Gupta
GD., developed mouth dissolve tablets of domperidone. Tablet
containing domperidone, camphor and crospovidone were prepared by
direct compression technique. Baria A.H et. al develop a
formulation for this drug which overcomes problems such as
difficulty in swallowing, inconvenience in administration while
traveling and better compliance. Vikas Sharma, vandana aurora,
Chandra ray developed the fast disintegrating tablets with improved
patient compliance and convenience.
Himanshu Deshmkh et. al development of numerous formulations
with improved performance and acceptability. SHAILESH SHARMA et.
al., (2011) prepared and evaluated the co processed
superdisintegrant in promoting tablet disintegration and having low
friability. BIRAJU PATEL et. al., (2009) fast dissolving tablets of
glipizide were prepared by direct compression method with a view to
enhance patient compliance. Two superdisintegrants via,
crospovidone and croscarmellose sodium (4%, 5%, 6%) with different
binders viz, pvp k-30 and pregelatinized starch (3%) were used.
P.S.Kawtikwaret et al., (2009) formulated, evaluated and optimized
the fast dissolving tablets containing tizanidine hydrochloride by
using different superdisintegrants like sodium starch glycolate,
croscarmellose sodium and crospovidone.
OBJECTIVE
OBJECTIVE OF THE STUDY The concept of Fast dissolving drug
delivery system is to provide patient with conventional means of
taking their medication In some cases such as motion sickness,
sudden episodes of allergic attacks or coughing and unavailability
of water, swallowing conventional tablets may be difficult. Such
problems can be resolved by means of Fast dissolving tablets when
put on tongue these tablets disintegrate and dissolve rapidly in
saliva without need of drinking water. Some drugs are absorbed from
the mouth, pharynx and esophagus as saliva passes down into the
stomach. In such cases, bioavailability of drug is significantly
greater than those observed from conventional tablets dosage
form.
PLAN OF WORK
1. Literature survey 2. Selection of drug and
superdisintegrants 3. Determination of analytical methodology for
Domperidone a. Standard graph of Domperidone in 6.8 pH buffer 4.
Preformulation studies 5. Preparation of Domperidone fast
disintegrating tablets using direct compression method 6.
Evaluation of prepared tablets a.Weight variation b.Thickness c.
Hardness d. Friability e.Wetting time f.Water absorption ratio g.
In-vitro disintegration test h. Content uniformity i. In-vitro
release studies 8. Selection of optimized formulation based on
evaluation parameters.
DRUG PROFILE
Name: Domperidone Description: A specific blocker of dopamine
receptors. It speeds gastrointestinal peristalsis, causes prolactin
release, and is used as antiemetic and tool in the study of
dopaminergic mechanisms. Structure: IUPAC Name:
5-chloro-1-{1-[3-(2-oxo-2,3-dihydro-1H-1,3-
benzodiazol-1-yl)propyl]piperidin-4-yl}-2,3-dihydro-1H-1,3-
benzodiazol-2-one
Chemical Formula: C22H24ClN5O2 Molecular weight: 425.911
CLINICAL PHARMACOLOGY: Domperidone is a D2 dopamine receptor
antagonist that blocks the agonistic action of fescue alkaloids at
the cellular level does not readily cross the blood-brain barrier
In humans, domperidone is 91-93% bound to plasma proteins.
undergoes rapid and extensive hepatic metabolism by hydroxylation
and N-dealkylation. Urinary and feacal excretions of domperidone in
humans amount 31 and 66% of the oral dose, plasma half-life of
domperidone administered orally is 6 hours with low oral
bioavailability Pharmacodynamics: a specific blocker of dopamine
receptors. speeds gastrointestinal peristalsis, causes prolactin
release, used as antiemetic
Mechanism of Action Domperidone acts as a gastrointestinal
emptying (delayed) adjunct and peristaltic stimulant. decreases
small bowel transit time by increasing esophageal and gastric
peristalsis and by lowering esophageal sphincter pressure.
generally related to its dopamine receptor blocking activity. It
has strong affinities for the D2 and D3 dopamine receptors, located
just outside the blood brain barrier, that regulates nausea &
vomiting Indications management of dyspepsia, heartburn, epigastric
pain, nausea, and vomiting. For oral dosage form (tablets):
Treatment of GI motility disorder Adults10 mg three to four times
daily. Some patients may require higher doses up to 20 mg three or
four times daily. Nausea and vomiting: Adults20 (mg) three to four
times daily.
Uses of Domperidone : increases the contractions of stomach
& bowel treat nausea and vomiting given only by or under the
immediate supervision of your doctor. Storage conditions: Store the
medicine in a closed container at room temperature, away from heat,
moisture, and direct light. Keep from freezing. keep away from
children dont keep outdated medicine.
EXCIPIENTS PROFI
Croscarmellose sodium (CCS) Chemical name: Cellulose,
carboxymethyl ether, sodium salt, cross linked. Functional
category: Tablet and capsule disintegrants Structural formula:
Molecular weight: 90,000-700,000 Applications in pharmaceutical
formulation or technology: used in oral pharmaceutical formulations
as a disintegrant used in both direct-compression and
wet-granulation processes. Description: odourless, white or grayish
white powder. Solubility: Insoluble in water,soluble in acetone,
ethanol , toulene Uses: used in oral pharmaceutical formulation as
a disintegrants
Crospovidone Chemical Name and CAS Registry Number
1-Ethenyl-2-pyrrolidinone homopolymer [9003-39-8] Structural
Formula Functional Category : Tablet disintegrant. Applications in
Pharmaceutical Formulation or Technology water-insoluble tablet
disintegrant and dissolution agent solubility enhancer for poorly
soluble drugs Description: white to creamy-white, finely divided,
free-flowing, tasteless, odorless or nearly odorless, hygroscopic
powder. Stability and Storage Conditions: crospovidone is
hygroscopic, it should be stored in an airtight container in a
cool, dry place.
Magnesium stearate Chemical name: Octadecanoic acid magnesium
salt. Structural formula: [CH3 (CH2)16COO] 2Mg. Functional
category: Tablet and capsule lubricant. Applications in
pharmaceutical formulation or technology: used in cosmetics, foods,
and pharmaceutical formulations. primarily used as lubricant in
tablets and capsule formation. Description: very fine, light white,
precipitated , faint odour of steric acid & characteristic in
taste. Melting range: 1171500C (commercial samples), 1261300C (high
purity magnesium stearate). Solubility: insoluble in ethanol, ether
& slight soluble in warm benzene
MATERIALS AND EQUIPMENTS SISCO
S. NO EQUIPMENT NAME SOURCE 1 DIGITAL WEIGHING MACHINE SHIMADZU
ATY 244 2 TABLET COMPRESSION MACHINE KARNAVATHI MINI PRESS-I 3
MONSANTO HARDNESS TESTER CINTEX IND. CORPORATION, MUMBAI 4
FRIABILITY TESTER ELECTROLAB PVT LTD. INDIA 5 USP DISSOLUTION
APPARATUS LAB INDIA DS 8000 6 DISINTEGRATION APPARATUS LAB INDIA DT
1000 7 TRAY DRYER SISCO 8 UV-VIS DOUBLE BEAM SPECTROPHOTOMETER
ELICO SL 164DOUBLE BEAM SPECTROPHOTOMETER INSTRUMENTS DETAILS
S.NO DRUG/EXCIPIENTS NAME OF SUPPLIER 1 DOMPERIDONE TORRENT
PHARMA 2 LACTOSE MONO HYDRATE SD FINE CHEM PVT, MUMBAI 3 MANNITOL
SD-200 SD FINE CHEM PVT, MUMBAI 4 CROSCARMELLOSE SODIUM SD FINE
CHEM PVT, MUMBAI 5 CROSPOVIDON SD FINE CHEM PVT, MUMBAI 6 ASPERTAME
SD FINE CHEM PVT, MUMBAI 7 MAGNESIUM STEARATE SD FINE CHEM PVT,
MUMBAI 8 TALC SD FINE CHEM PVT, MUMBAI INGREDIENT DETAILS
Colour, odour, taste and appearance: The above terms were
recorded by using descriptive terminology Melting point
determination: determined by capillary method by using melting
point apparatus Determination of solubility: determined by adding
excess amount of drug in the solvent and equilibrium solubility was
determined by taking supernatant and analyzing it on Lab India,
double beam spectrophotometer. % solubility = sample absorbance
/standard absorbance dilution factor 100 Fourier Transformation
Infra-red (FTIR) analysis: Infra-red spectroscopy analysis was
performed by Fourier Transformation Infrared Spectrophotometer
Alpha Brooker FTIR (Tokyo, Japan).The instrument was calibrated by
using polystyrene film.
Ultraviolet Visible (UV-visible) spectroscopy: Construction of
Calibration Curve: Preparation of Stock Solution: 100 mg of
Domperidone was taken in a 100 ml volumetric flask. 5 ml of
methanol was added and shaken to dissolve the drug. Add 7.4 ph
phosphate to make upto level. From the above solution 1 ml is
diluted to 10 ml with, 7.4 pH phosphate buffer solutions to give
100 g /ml concentration. The prepared solution i.e., 10 g/ml
concentration was scanned for max from 200-400 nm in UV/Visible
spectrophotometer. Evaluation of API and Blend (Pre-compression
Parameters): Angle of Repose: Flow property was determined by
measuring the Angle of Repose. Angle of repose= tan- (h/r) Where, h
= height r = radius
Procedure: 20gms of the sample was taken The sample was passed
through the funnel slowly to form a heap. The height of the powder
heap formed was measured. The circumference formed was drawn with a
pencil on the graph paper . The radius was measured and the angle
of repose was determined. This was repeated three times for a
sample. Bulk density: Bulk density is ratio of given mass of powder
and its bulk volume. Bulk density = M / V0 Where M= mass of the
powder; V0=bulk volume of the powder. Tapped density: It is
generally given by an equation Tap density = M / Vr Where M = mass
of the powder, Vr = final tapping volume of the powder.
Compressibility index and Hausner ratio: to measure the
unsettled apparent volume,(VO), and the final tapped volume, (Vf),
of the powder after tapping the material until no further volume
changes occur. Given by an expression as follows Compressibility
index = 100 1-( bulk density /tapped density) Hausner ratio =
tapped density / bulk density Flow properties determination: S.No
Flow properties Angleof repose() Compressibility Index (%)or Carrs
index Hausner ratio 1 Excellent 25-30 66 >38 >1.6
EVALUATION OF TABLETS (Post Compression Parameters): Evaluation
include the diameter, size, shape, thickness, weight, hardness,
disintegration & dissolution characters. Physical Appearance:
The general appearance of a tablet. Size & Shape: It can be
dimensionally described & controlled. Tablet thickness should
be controlled within a 5% variation of standard value. Weight
variation test: comparison of the weight of the individual tablets
(xi) of a sample of tablets with an upper and lower percentage
limit of the observed sample average (x-mean). Limits for Tablet
Weight variation test: Average weight of tablet (mg) % Difference
allowed 130 or less 10 % From 130 to 324 7.5 % > 324 5 % Content
Uniformity: used to ensure that every tablet contains the amount of
drug substance intended with little variation among tablets within
a batch.
Friability: The friability test is closely related to tablet
hardness & designed to evaluate the ability of the tablet to
withstand abrasion in packaging, handling & shipping. The
percentage friability was determined by the formula: % friability =
(W1-W2) / W1 X 100 W1 = Weight of tablets before test andW2 =
Weight of tablets after test Wetting time: time required for water
to reach the upper surface of the tablets was noted as the wetting
time. Water absorption ratio: A tablet was put on the paper &
the time required for complete wetting was measured. R = Wa W b
/Wb100 Where Wa = weight of tablet after absorption Wb = weight of
tablet before absorption Disintegration time: time required for a
tablet to disintegrate. Disintegration test : The disintegration
test is a measure of the time required under a given set of
conditions for a group of tablets to disintegrate into
particles
Dissolution study of Domperidone of fast disintegrating
tablets: Bath temperature : 37 0.5oC Dissolution media : 7.4 pH
buffer Volume of dissolution media : 900 ml Aliquot withdrawn : 5
ml Dissolution apparatus : USP type II (paddle) Revolutions per
minute (Speed) : 50 FORMULATION DEVELOPMENT List of used Excipients
in the formulation: Ingredients Purpose Croscarmellose Sodium,
Crospovidone Super disintegrants Lactose monohydrate and Mannitol
Diluents Aspartame Sweetener Magnesium stearate and Talc Glidant
& Lubricant
Procedure for Formulation: Weigh all the ingredients (except
Mg.Stearate) and sifted through # 44 mesh separately. The
ingredients after sifting through sieve no. 44 were thoroughly
mixed by geometrical order and mixed for 10 min. And finally add
the Glidant (Magnesium Stearate) to the above blend mix it for
2min. Compressed the above lubricated blend by using 6mm round
punches. S.NO. Ingredients (mg) F1 F2 F3 F4 F5 1 Domperidone 20 20
20 20 20 2 Croscarmellose sodium 10 20 10 3 Crospovidon --- --- 10
20 10 4 Lactose anhydrous 122 112 122 112 112 5 Mannitol 40 40 40
40 40 6 Aspertame 3 3 3 3 3 7 Magnesium stearate 3 3 3 3 3 8 Talc 2
2 2 2 2 Total weight(mg) 200 200 200 200 200 Composition of
Domperidone Tablets:
PREFORMULATION: S.N O API CHARACTERISATIO N RESULTS 1 Physical
Appearance Domperidone is a white powder 2 Melting point 242 C 3
solubility It is freely soluble in water, soluble in alcohols, and
slightly soluble in common organic solvents, such as acetonitrile
and methyl ethyl ketone. 4 Bulk density 1.11 gm/ml 5 Tapped Density
1.42 gm/ml 6 Carrs index/Compressibility index 27.92 7 Hausners
Ratio 1.27 Conclusion: The value of compressibility index above
25%, 15-25%, less than 15% indicates poor flowability, optimum
flowability & high flowability respectively.
PREPARATION OF STANDARD GRAPH FOR DOMPERIDONE S. No
Concentration (/ml) Absorbance (284nm) 1 0 0 2 2 0.072 3 4 0.162 4
6 0.249 5 8 0.329 6 10 0.422 Table for standard graph of
domperidone Standard graph Domperidone
Preformulation studies of blend of all formulation Formulation
Bulk density (gm/cm3) Tapped density(gm/cm 3) Angle of repose()
Carrs Index(%) Hausners ratio F1 0.40 0.47 21.5 14.8 1.17 F2 0.41
0.46 20.1 10.86 1.12 F3 0.41 0.47 19.6 12.7 1.14 F4 0.42 0.45 18.8
12.4 1.13 F5 0.43 0.48 17.8 10.4 1.11 FORMULATIO N CODE WEIGHT
VARIATIO N HARDNES S Kg/Cm2 THICKNESS (mm) FRIABILIT Y (%) CONTENT
UNIFORMIT Y (%) F1 Passes 4.5 2.08 0.15% 99.2 F2 Passes 5 1.98
0.12% 99.3 F3 Passes 4.3 1.99 0.13% 98.3 F4 Passes 4.4 2.02 0.14%
98.1 F5 Passes 4.8 2.01 0.12% 99.5 EVALUATION STUDIES OF
TABLETS:
Disintegration time , Wetting time & Water absorption ratio
of all formulations Formulation Disintegration time (sec) Wetting
time (sec) Water Absorption Ratio F1 21 16 22.95 F2 18 15 24.29 F3
22 18 22.5 F4 20 17 21.5 F5 15 12 24.92 Invitro-Dissolution
profiles: Dissolution media pH 7.4 Phosphate buffer Volume 900 ml
Apparatus Paddle Speed 50 rpm Time 2,4,6,8,10 min
Time (Min) F1 F2 F3 F4 F5 0 0 0 0 0 0 2 20.69 22.58 28.14 30.41
36.14 4 27.74 37.11 40.85 44.82 52.95 6 51.01 61.55 65.66 70.41
67.75 8 74.32 80.63 82.17 87.21 91.43 10 85.76 92.58 91.38 94.72
99.80 Dissolution profile of prepared formulations: Conclusion:
Above graph indicates that %Drug release of F5 formulation shows
better drug release when compared with other formulations.
The objective of the present study is to develop a Domperidone
Fast dissolving tablets. Finally it was concluded that: Formulation
1&3: Drug and super disintegrant (i.e. Croscarmellose sodium
and Crospovidon) in the ratio of 1:1 which was prepared by direct
compression method have poor wetting property as it consist of less
concentration of super disintegrant. Formulation 2, 4: consists
Drug and superdisintegrants in the ratio of 1:2. Formulation 5:
consists Drug and combination of superdisintegrants in the ratio of
1:2. Formulation-5, has shown better dissolution profile and has
shown maximum %drug release within 10 minutes. Among the all
formulations (F1-F5), it was observed that formulation-5 has shown
better dissolution profile with sufficient wetting capability. So
Formulation-5 was found to be the best formulation among others.
CONCLUSION
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Indurwade , et al., Novel approach Fast dissolving tablets , Indian
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