FORMULATION AND EVALUATION OF DARIFENACIN HBr …

www.wjpps.com Vol 7, Issue 5, 2018.

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Ashok et al. World Journal of Pharmacy and Pharmaceutical Sciences

FORMULATION AND EVALUATION OF DARIFENACIN HBr

EXTENDED RELEASE TABLETS

Vadiyala Ashok* and A. Seetha Devi

Department of Pharmaceutics, Hindu College of Pharmacy, Amaravathi Road, Guntur,

Andhra Pradesh, India-522002.

ABSTRACT

The objective of this study was to develop and evaluate Darifenacin

Hydro bromide Extended Release matrix tablet by using various grades

and ratios of hydroxy propyl methyl cellulose (HPMC), Xanthan gum,

Ethyl cellulose as rate controlling hydrophilic polymers and

bioequivalent testing with the innovator ENABLEX (prepared by

Novartis Pharma, Europe). The drug was compatible with the

formulation components. Hence Lactose Anhydrous, Di calcium

Phosphate (DC grade), Xanthan gum, Ethyl cellulose, HPMCK4M,

HPMCK100M, opadry orange were selected as excipients for the lab

scale development. Blends were evaluated for various parameters such

as bulk density, tapped density, Carr’s index, Hausner’s ratio and the

parameters evaluated for the matrix tablet are Drug content, hardness,

Friability, weight variation and Thickness and all physicochemical properties are within the

limits. Drug release from tablets complies with the prescribed limits. Formulation

development from F1 to F13 was executed to optimize the composition. At the final, the

dissolution profile of the batches F11 was closer with the reference product. The stability

studies were performed for the optimized formulation F11 at the accelerated conditions

(400C/75% RH) for two months and at stress conditions (60

0C/90% RH) for one month. The

results were indicated that all results were in limits after two months period. Hence the

optimized formulation F11 was stable. Finally the combinations of high viscous and low

viscous hydroxy propyl methyl cellulose polymers were used to develop a optimized formula

that was similar with the innovators product ENABLEX.

WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

SJIF Impact Factor 7.421

Volume 7, Issue 5, 1535-1554 Research Article ISSN 2278 – 4357

Article Received on

17 March 2018,

Revised on 07 April 2018,

Accepted on 28 April 2018

DOI: 10.20959/wjpps20185-11615

*Corresponding Author

Vadiyala Ashok

Department of

Pharmaceutics, Hindu

College of Pharmacy,

Amaravathi Road, Guntur,

Andhra Pradesh, India-

522002.


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KEYWORDS: Darifenacin Hydro bromide, Extended Release Tablets, Dissolution profile,

Controlled Release Polymers.

1. INTRODUCTION

ORAL DRUG DELIVERY

Oral drug delivery has been known for decades as the most widely utilized route of

administration among all the routes that has been explored for the systemic delivery of drugs

via various pharmaceutical products of different dosage form. Nowadays most of the

pharmaceutical scientists are involved in developing an ideal DDS. This ideal system should

have advantage of single dose for whole duration of the treatment and it should deliver the

drug directly at specific site. Scientists have succeeded to develop a system that can be as

near to an ideal system and it encourages the scientists to develop controlled release system[1-

3].

Extended Release Dosage Forms

It is defined as the one that allows at least a twofold reduction in dosing frequency as

compared to that of conventional dosage forms. Extended release (ER) dosage forms release

drug slowly, so that plasma concentrations are maintained at a therapeutic level for a

prolonged period of time (usually between 8 and 24 hours). Extended release oral drug

formulations have been used since the 1960s to enhance performance and increase patient

compliance. By incorporating the dose for 24hrs into one tablet from which the drug is slowly

released, peaks of high plasma concentration and troughs of low plasma concentrations can

be prevented. This helps to avoid the side effects associated with high concentration and lack

of activity associated with low plasma concentrations-giving better overall therapy. In

addition, in the treatment of diseases that is asymptomatic-such as hypertension-patients

generally remember morning and evening medication, but tend to forgot doses in between.

Once or twice daily dosing thus improves therapy through the constant presence of the drug[4-

6].

TYPES OF EXTENDED RELEASE PRODUCTS[6-9]

General approaches to manufacturing an extended-release drug product include the use of a

matrix structure in which the drug is suspended or dissolved, the use of a rate-controlling

membrane through which the drug diffuses, or a combination of both. Among the many types

of commercial preparations available, none works by a single drug-release mechanism. Most

extended-release products release drug by a combination of processes involving dissolution,


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permeation, and diffusion. The single most important factor is water permeation, without

which none of the product release mechanisms would operate. Controlling the rate of water

influx into the product generally dictates the rate at which the drug dissolves. Once the drug

is dissolved, the rate of drug diffusion may be further controlled to a desirable rate. Table

shows some common extended-release product examples and the mechanisms for controlling

drug release, and lists the compositions for some drugs.

Table-1: Examples of Oral Extended-Release Products.[10]

Type Trade Name Rationale

Erosion tablet

Constant-T Theophylline

Tenuate Dospan Diethylpropion HCl dispersed in hydrophilic matrix

Tedral SA

Combination product with a slow-erosion component

(theophylline, ephedrine HCl) and an initial-release

component theophylline, ephedrine HCl,

Phenobarbital)

Waxy matrix tablet Kaon Cl Slow release of potassium chloride to reduce GI

irritation

Coated pellets in

capsule Ornade spansule

Combination phenyl propanolamine HCl and

chlorpheniramine with initial- and extended-release

component

Pellets in tablet Theo-Dur Theophylline

Leaching

Ferro-Gradumet

(Abbott)

Ferrous sulfate in a porous plastic matrix that is

excreted in the stool; slow release of iron decreases GI

irritation

Desoxyn

gradumet tablet

(Abbott)

Methamphetamine methylacrylate methyl methacrylate

copolymer, povidone, magnesium stearate; the plastic

matrix is porous

Coated ion exchange Tussionex Cation ion-exchange resin complex of hydrocodone

and phenyltoloxamine

Flotation–diffusion Val release Diazepam

Osmotic delivery

Acutrim Phenyl propanolamine HCl (Oros delivery system)

Procardia-XL

GITS—gastrointestinal therapeutic system with NaCl-

driven (osmotic pressure) delivery system for

nifedipine

Microencapsulation

Bayer timed-

release Aspirin

Nitrospan Microencapsulated nitroglycerin

Micro-K

Extencaps Potassium chloride microencapsulated particles

2. MATERIALS AND METHODS USED

2.1. Materials used

Darifenacin HBr, Lactose anhydrous (DC Grade), Dicalcium phosphate, Xanthan gum, Ethyl

cellulose, Methocel K4M, Methocel K100M, Magnesium stearate, Opadry orange.


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2.2. Methods Used

CONSTRUCTION OF CALIBRATION CURVE

Analytical method by UV:Since, 0.1M HCl and pH 6.8 media both were used for

dissolution, method was developed in both the media for analysis and a calibration curve was

plotted for each media.

Preparation of 0.1M HCl: Accurately measured 0.85 ml of concentrated hydrochloric acid

was added to 1000 ml of distilled water.

Preparation of pH 6.8 phosphate buffer: Accurately measured 50 ml of 0.2 M potassium di

hydrogen orthophosphate was transferred to a 200ml volumetric flask and 22.4 mL of 0.2 M

sodium hydroxide was added to it. Volume was made up to 200 ml with distilled water,

mixed and pH was adjusted to 6.8 with 0.2 M sodium hydroxide.

0.2M potassium dihydrogen phosphate: Dissolve 27.218g potassium dihydrogen

phosphates in distilled water and dilute to 1000ml with distilled water.

0.2M sodium hydroxide solution: Dissolve 8g of sodium hydroxide in distilled water and

dilute to 1000ml with distilled water.

Determination of maximum wavelength

Concentrations 5-30 µg/ml were prepared using 0.1M Hcl media and pH 6.8 Phosphate

Buffer media. These concentrations were scanned between the wavelength 200nm to 400nm

and the wavelength at which maximum absorbance was observed for each concentration was

noted as maximum wavelength, & the λmax was found at 286nm.

Construction of calibration curve in 0.1M HCl & 6.8 pH phosphate buffer

Various concentrations of Darifenacin HBr were prepared using 0.1M HCl media and pH 6.8

Buffer media. The absorbance of these concentrations was noted at λ max and calibration

curve was plotted taking concentration on x-axis and Absorbance on y-axis. The equation for

the calibration curve was determined and used for calculation of concentration of unknown

samples.

Weighed accurately 100mg of Darifenacin HBr and transferred into a 100ml volumetric

flask. It was dissolved in 25ml of methanol and sonicated for 5 minutes. Volume was made

with 0.1M Hydrochloric acid and similarly in another volumetric flask with 6.8 pH Phosphate


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buffer. It was mixed well to get a concentration of 1000μg/ml. From the stock solution10 ml

was withdrawn & dilute to 100ml with respective Medias to get 100μg/ml. From this solution

withdraw 1,2,3,4,5,6 ml solutions and was further diluted to 20 ml to give 5,10,15,20,25 &

30μg/ml concentrations respectively, and the absorbance was noted at 286 nm against 0.1M

HCl as a blank. A plot of concentrations of drug versus absorbance was plotted42

.The linear

regression analysis was done on absorbance data points.

Preparation of Darifenacin HBr matrix tablets[11-14]

All the matrix Darifenacin tablets, each containing 200mg of Darifenacin, were prepared by

direct compression method

The steps involved:

Sieve the API and other ingredients individually through sieve no.40 except magnesium

Stearate which is passed through sieve no.60.

Uniformly blend the API and lactose anhydrous in a polythene bag for 5min.

Add DCP to above mixture and mix for 3min.

Add the polymer/s to above blend and total blend was loaded to a blender and mix for 15

min.

Lubricate the blend with Magnesium Stearate.

Compress the lubricated blend into tablets using 8 mm concave shaped punch in a single

rotary tablet press (8 stations).

Coating of Darifenacin HBr matrix tablets[15-17]

The tablets were film coated with the opadry orange to control the drug release. The %

weight build up of tablets was 3%.


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MANUFACTURING FLOW CHART

Collecting of all excipients & drug (Darifenacin)

↓

Sifting

↓

Drug mixing with excipients

↓

Sifting of Drug -Excipients

↓

Blending

↓

Tablet compression

↓

Film coating

Figure-8: Schematic representation of manufacturing procedure of darifenacin tablets.

EVALUATION STUDIES

Pre compression parameters[18-20]

Pre compression parameters like Angle of repose, bulk density, tapped density, Carr’s index

and Hausners ratio were determined for all the powder blends of formulations F1-F13 as for

the described procedures.

Post compression studies of the prepared formulations[20-22]

Weight variation, Hardness, Friability, Dissolution Studies, Disintegration Studies and Assay

procedures were determined as per described manner.

3. RESULTS

Table-2: Preliminary studies report.

COMPONENT

OBSERVATION

At 400

C/75% RH and 500

C/90%RH

INITIAL 15 days 30 days 15 days 30 days

Pure API White - - - -

API + Lactose White - - - -

API+DCP(Dc grade) White - - - -

API + Xanthan gum Light Yellow - - - -

API + Ethyl cellulose White - - - -

API+HPMC K 4M White - - - -

API+HPMC 100 M White - - - -

API + Mg Stearate White - - - -

API+ opadry orange Light orange - - - -


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Table-3: Flow properties of drug.

Table-4: Composition of Darifenacin oral extended-release tablets.

S.No Name of the

Ingredient

F1

(mg)

F2

(mg)

F3

(mg)

F4

(mg)

F5

(mg)

F6

(mg)

1 Darifenacin HBr 17.84 17.84 17.84 17.84 17.84 17.84

2

Lactose

anhydrous (DC

Grade) 100.16 90.16 60.16 100.16 90.16 100.16

3 DCP (DC Grade) 50 50 60 50 50 60

4 Xanthan gum 30

(15%) 40 (20%) 60 (30%) - - -

5 Ethyl cellulose - - - 30 (15%) 40 (20%) -

6 Methocel K4M - - - - - 20 (10%)

7 Methocel K100M - - - - - -

8 Magnesium

stearate 2 2 2 2 2 2

Total Weight 200 200 200 200 200 200

Film coating (%) 3.0 3.0 3.0 3.0 3.0 3.0

S.No Name of the

Ingredient

F7

(mg)

F8

(mg)

F9

(mg)

F10

(mg)

F11

(mg)

F12

(mg)

F13

(mg)

1 Darifenacin

HBr 17.84 17.84 17.84 17.84 17.84 17.84 17.84

2

Lactose

anhydrous

(DC Grade) 80.16 60.16 40.16 40.16 40.16 40.16 40.16

3 DCP (DC

Grade) 60 60 40 40 50 40 40

4 Xanthan gum - - 60

(30%)

50

(25%) - - -

5 Ethyl

cellulose - - - - - - -

6 Methocel

K4M 40

(20%)

60

(30%)

40

(20%)

50

(25%)

70

(35%)

80

(40%)

90

(45%)

7 Methocel

K100M - - - -

10

(5%)

10

(5%)

10

(5%)

8 Magnesium

stearate 2 2 2 2 2 2 2

Total Weight 200 200 200 200 200 200 200

Film coating

(%) 3.0 3.0 3.0 3.0 3.0 3.0 3.0

S.No Drug

Angle of

Repose

(degrees)

Bulk

density

(gm/ml)

Tapped

density

(gm/ml)

Carr’s index

(%)

Hausner

ratio

1 Darifenacin

HBr 32.90 0.424 0.587 27.76 1.38


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Table-5: Data for pre compression studies of the blends.

Formulation

Code

Angle of

Repose

(in degrees)

Bulk

density

(gm/ml)

Tapped

density

(gm/ml)

Compressibility

Index

Hausner’s

ratio

F1 29.37±0.98 0.418±0.006 0.530±0.003 21.08±0.71 1.26±0.01

F2 25.57±0.49 0.434±0.005 0.530±0.002 18.63±0.66 1.23±0.01

F3 23.26±1.33 O.486±0.006 0.590±0.001 17.56±0.94 1.26±0.11

F4 28.75±1.24 0.404±0.006 0.504±0.006 19.86±2.33 1.25±0.04

F5 24.92±0.85 0.427±0.004 0.530±0.004 19.47±0.23 1.25±0.01

F6 26.67±0.46 0.436±0.006 0.546±0.006 20.13±1.76 1.25±0.02

F7 25.64±0.89 0.508±0.01 0.636±0.005 19.98±1.17 1.25±0.02

F8 23.79±0.55 0.547±0.009 0.670±0.008 18.40±0.31 1.23±0.01

F9 24.97±1.14 0.476±0.005 0.574±0.005 16.91±0.30 1.20±0.01

F10 24.07±0.76 0.499±0.004 0.596±0.004 16.20±0.94 1.19±0.01

F11 25.13±0.72 0.457±0.004 0.547±0.005 17.50±2.21 1.19±0.01

F12 24.89±0.67 0.492±0.005 0.588±0.003 16.32±0.52 1.67±0.41

F13 24.48±0.77 0.525±0.003 0.644±0.001 18.48±0.35 1.23±0.01

Table-6: Data for post compression studies of the prepared tablets.

FORMULATION

CODE AVERAGE

Wt (mg)

AVERAGE

HARDNESS

(Kg/cm2)

AVERAGE

THICKNESS

(mm)

FRIABILITY

(%)

F1 200.15±1.78 8.50±0.33 3.60±0.09 0.20

F2 199.60±1.44 8.70±0.53 3.55±0.19 0.15

F3 199.56±1.94 8.30±0.58 3.69±0.02 0.18

F4 201.20±1.60 10.36±0.78 3.55±0.08 0.22

F5 202.35±1.53 10.55±0.50 3.56±0.11 0.24

F6 200.33±1.96 8.40±0.57 3.55±0.08 0.21

F7 200.15±1.48 8.35±0.03 3.68±0.05 0.16

F8 200.32±1.77 8.55±0.68 3.70±0.03 0.21

F9 199.62±2.09 8.60±0.77 3.73±0.02 0.21

F10 199.75±2.54 8.55±0.55 3.58±0.06 0.19

F11 198.45±2.13 8.40±0.56 3.61±0.06 0.20

F12 201.40±2.23 8.75±0.42 3.67±0.05 0.14

F13 199.75±2.97 8.45±0.64 3.62±0.04 0.12

Table-7: Assay data of the prepared tablets.

Formulation

code

Test

Absorbance

AVERAGE Wt

(mg)

DRUG

CONTENT

(ASSAY) mg/tab

ASSAY

(%)

F1 0.023 200.15±1.78 15.44 102.98

F2 0.022 199.60±1.44 14.73 98.23

F3 0.022 199.56±1.94 14.87 99.12

F4 0.021 201.20±1.60 14.17 94.52

F5 0.022 202.35±1.53 14.93 99.58


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Table-8: In-vitro drug release data of F1-F7 Formulations.

Table-9: In-vitro drug release data of F8-F13 Formulations.

TIME Hrs F8

(%) F9

(%) F10 (%)

F11 (%)

F12 (%)

F13 (%)

Innovator (%)

0 0 0 0 0 0 0 0

1 22.3±0.53 19±2.62 15.7±3.76 11±0.73 8.7±0.5 7.9±2.1 10.9±2.72

2 29.56±0.59 29±2.24 24.8±2.33 21±0.9 19±1.04 15±6.2 25±3.00

4 45.31±1.43 46.9±2.36 39.9±2.14 32.9±0.8 31.9±0.8 29±1.61 33.89±3.52

8 63.46±0.82 71.8±2.28 64.5±3.17 51.1±0.49 50±0.6 48.8±2.77 52.6±2.89

12 71.42±1.14 83.5±3.52 79.1±2.75 73.8±1.43 73±0.94 72.5±1.09 74.8±2.72

16 87.3±0.42 94.8±2.73 85.4±3.04 88.4±0.7 86.5±0.23 85.5±0.3 88.4±1.61

24

92.8±4.2 95.5±0.6 90±0.7 89±1.4 96.8±1.61

Figure-1: In-vitro drug release profile of Formulations F 1, F2 & Innovator.

F6 0.022 200.33±1.96 14.78 98.59

F7 0.022 200.15±1.48 14.77 98.5

F8 0.023 200.32±1.77 15.32 102.17

F9 0.022 199.62±2.09 14.73 98.24

F10 0.023 199.75±2.54 15.28 101.88

F11 0.0224 198.45±2.13 14.91 99.44

F12 0.0224 201.40±2.23 15.13 100.92

F13 0.0222 199.75±2.97 14.95 99.65

TIME

Hrs

F1

(%)

F2

(%)

F3

(%)

F4

(%)

F5

(%)

F6

(%)

F7

(%)

0 0 0 0 0 0 0 0

1. 45.5±0.8 43.6±0.82 25.23 ±0.98 29.15±0.76 26.13±0.52 29.16±1.1 26.13±1.16

2 69±0.89 63±0.98 41.84±1.2 35.89±0.9 33.72±0.9 45.14±0.6 33.72±1.2

4 92±0.5 89±1.03 59.04±1.4 57.13±0.8 47±1.04 62.19±0.89 50.67±0.55

8 98.5±0.7 96.5±0.89 85.9±0.57 79.1±1.3 68.37±0.57 87.11±1.1 78.74±1.10

12 91±1.6 89.93±0.98 91.39±0.5

16

24


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Figure-2: In-vitro drug release profile of Formulations F 3, F4, F5 & Innovator.

Figure -3: In-vitro drug release profile of Formulations F 6, F7, F8 & Innovator.

Figure-4: In-vitro drug release profile of Formulations F 9, F10 & Innovator.


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Figure-5: In-vitro drug release profile of Formulations F 11, F12, F13 & Innovator.

Figure-6: In-vitro drug release profile of Formulations F 10 & F 11.

Figure-7: In-vitro drug release profile of Formulations F 11 & Innovator.


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Table-10: The drug release kinetics of the prepared formulations.

Formulation

code

Zero order First order Higuchi Korsmeyer-peppas

r2 Slope r

2 Slope r

2 Slope r

2

Diffusion

exponent (n)

F-1 0.734 11.60 0.989 -0.236 0.934 36.71 0.681 0.43

F-2 0.734 10.53 0.954 -0.169 0.949 35.83 0.691 0.37

F-3 0.921 9.9 0.994 -0.104 0.995 30.93 0.749 0.36

F-4 0.891 6.874 0.994 -0.087 0.995 27.27 0.783 0.52

F-5 0.936 6.64 0.968 -0.073 0.993 25.69 0.809 0.52

F-6 0.894 9.85 0.956 -0.077 0.998 31.28 0.795 0.29

F-7 0.924 7.06 0.991 -0.088 0.994 27.51 0.810 0.23

F-8 0.922 7.06 0.961 -0.067 0.997 22.97 0.859 0.35

F-9 O.835 3.985 0.996 -0.071 0.973 22.47 0.631 0.29

F10 0.883 03.985 0.951 -0.064 0.984 21.97 0.680 0.29

F11 0.859 4.11 0.982 -0.056 0.966 22.11 0.988 0.694

F-12 0.902 3.974 0.967 -0.045 O.969 21.49 0.781 0.67

F-13 0.906 4.013 0.961 -0.04 0.988 21.57 0.812 0.79

F(I) 0.910 4.11 0.984 -0.062 0.981 22.13 0.733 0.6

Figure-8: The Zero order release kinetics of optimized formula F-11.

Figure-9: the first order release kinetics of optimized formula F-11.


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Figure-10: The Higuchi release kinetics of optimized formula F-11.

Figure-11: The korsmeyer-peppas model release kinetics of optimized Formula F-11.

Figure-12: Infra red spectra of pure drug Darifenacin Hydrobromide.


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Table-11: Characteristic peaks of pure Darifenacin HBr.

S.No Type of

bond

Type of

vibration

Actual

frequency

Observed

frequency Conformation

1 N-H Stretching 3500-3180 3465.29 Amide

2 C=O Stretching 1680-1630 1668.52 Amide

3 C=O-O-C Stretching 1270-1020 1097.87 Ether

4 C-H Stretching 3100-2900 2957.73 Aromatic

Figure-13: Infra red spectra of pure drug Darifenacin Hydrobromide + Lactose

Anhydrous.

Figure -14: Infra red spectra of pure drug Darifenacin HBr + Dicalcium phosphate (DC

grade).


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Figure-15: Infra red spectra of pure drug Darifenacin Hydrobromide + Xanthan gum.

Figure-16: Infra red spectra of pure drug Darifenacin Hydrobromide + Ethyl cellulose.

Figure-17: Infra red spectra of pure drug Darifenacin Hydrobromide + HPMC K4M.


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Figure-18: Infra red spectra of pure drug Darifenacin Hydrobromide + HPMC K100M.

Figure-19: Darifenacin HBr DSC report.

Table-12: Stability Summary data of Formulation-11.

Test Name Limits Initial 40°C/75% RH

50°C/90%

RH

1 month 2 months 1 month

Description

Orange colored,

round biconvex

film coated tablets

with plain surface

on both sides

Complies Complies Complies Complies

Dissolution by

UV Method

(%w/w) In Acid

Stage

NLT 25% in 1hr 12% 12.4% 13% 11.8%

Dissolution NLT 85% at 24th 99.2% 99.4% 99.2% 98.8%


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by UV Method

(%w/w) in pH

6.8 Buffer stage

hr

Identification by

HPLC

To match with

Standard Complies Complies Complies Complies

Average wt 206mg±2% 206.1 206.3 206.2 206.4

Water by KF (%

W/W) NMT 3.5% 2.2 2.7 2.4 2.7

Assay NLT 90.0 and

NMT 110.0 100.1 99.0 99.6 98.8

Related Substances (%w/w):

Known impurity

I (oxidized

impurity)

NMT 0.50 0.03 0.03 0.05 0.10

Known impurity

II NMT 0.30 0.08 0.07 0.11 0.11

Unknown

impurity NMT 0.50 0.06 0.06 0.08 0.11

Total impurities NMT 1.50 0.18 0.16 0.25 0.32

4. CONCLUSION

The project work entitled, ―Formulation Development and Evaluation of Darifenacin HBr

extended release Matrix Tablets‖ was carried out in the dissertation work. The objective of

this study was to develop and evaluate Darifenacin Hydro bromide Extended Release matrix

tablet by using various grades and ratios of hydroxy propyl methyl cellulose (HPMC),

Xanthan gum, Ethyl cellulose as rate controlling hydrophilic polymers and bioequivalent

testing with the innovator ENABLEX (prepared by Novartis Pharma, Europe).

The drug was compatible with the formulation components. Hence Lactose Anhydrous, Di

calcium Phosphate (DC grade), Xanthan gum, Ethyl cellulose, HPMCK4M, HPMCK100M,

Opadry orange were selected as excipients for the lab scale development.

Blends were evaluated for various parameters such as bulk density, tapped density, Carr’s

index, Hausner’s ratio and the parameters evaluated for the matrix tablet are Drug content,

hardness, Friability, weight variation and Thickness and all physicochemical properties are

within the limits. Drug release from tablets complies with the prescribed limits. Formulation

development from F1 to F13 was executed to optimize the composition. At the final, the

dissolution profile of the batches F11 was closer with the reference product.

The developed matrix tablets followed the first order release model and it was non- fickian

type of diffusion based on the korsmeyer-peppas model.


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Similarity factor value for optimized formulation F11 was above 50 indicates that the

dissolution profile of the batch matched with innovators Tablet.

The stability studies were performed for the optimized formulation F11 at the accelerated

conditions (400C/75% RH) for two months and at stress conditions (60

0C/90% RH) for one

month. The results were indicated that all results were in limits after two months period.

Hence the optimized formulation F11 was stable.

Finally the combinations of high viscous and low viscous hydroxy propyl methyl cellulose

polymers were used to develop a optimized formula that was similar with the innovators

product ENABLEX.

5. REFERENCES

1. Berner. B. and Dinh S. Fundamental concepts in controlled release In: A. Kydon ieus, ed.

Treatise on controlled drug delivery. Marcel Oekker, 1992; 1 – 36.

2. Chien. Y-W. Concepts and systems design for rate-controlled drug delivery. In: Chien

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