development of chemically modified pectin based extended release tablets of nifedipine

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S. Bharath et al. World Journal of Pharmacy and Pharmaceutical Sciences

DEVELOPMENT OF CHEMICALLY MODIFIED PECTIN BASED

EXTENDED RELEASE TABLETS OF NIFEDIPINE

Murali Krishna Reddy. P1, S. Bharath

*1, R. Deveswaran

1, B.V.Basavaraj

1,

V.Madhavan2

1Department of Pharmaceutics, M. S. Ramaiah College of Pharmacy, M.S.R.Nagar,

M.S.R.I.T. Post, Bangalore-54, India.

2Department of Pharmacognosy, M. S. Ramaiah College of Pharmacy, M.S.R.Nagar,

M.S.R.I.T. Post, Bangalore-54, India.

ABSTRACT

The main aim of the present research was to work on established

natural polymer and further improvement of its efficacy by

overcoming its limitations. Pectin, a naturally occurring polysaccharide

is a potential polymeric material used in the extended drug delivery

systems. But its aqueous solubility leads to undesirable and abrupt

drug release over a period of time. Hence, pectin was chemically

modified by acetylation process using 20%, 40% and 60% w/v phenyl

acetyl chloride to reduce its polarity, the obtained modified pectins

were examined for various physico-chemical properties and FTIR

studies to prove the hydrophobicity of the semisynthetic modified

polymer and the results revealed that the chemical modification of the

polymer has occurred. The drug-excipient compatibility studies were

carried out and the results showed that there was no interaction

between the drug and excipients and found to be compatible. The extended release tablets of

nifedipine were developed by wet granulation technique using various fractions of chemically

modified pectins and compared with pure pectin in varied polymer ratios and evaluated for

official and unofficial quality control tests. All the tablet formulations complied with the

pharmacopieal specifications. In-vitro dissolution studies were carried out for all the

formulated tablets in pH 1.2 buffer and the release profile compared with the pharmacopoeial

standard limits . Based on the experimental results , 4PAP3 was selected as the optimized

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Article Received on

08 January 2013,

Revised on 20 January 2013,

Accepted on 28 January 2013

*Correspondence forAuthor:

* S. Bharath

Department of Pharmaceutics,

M. S. Ramaiah College of

Pharmacy, M.S.R.Nagar,

M.S.R.I.T. Post, Bangalore-54,

India.

[email protected],
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formulation and compared with the marketed product showed similarity factor (f2) value

above 50, the stability studies showed that the optimized formulation was physically and

chemically stable when studied carried out at the accelerated conditions according to ICH

guidelines assuring modified pectin as an effective drug release retardant polymer. Thus

modified pectin served as an effective polymer when compared to pure pectin in extending

the drug release from the formulated dosage form.

Key words: modified pectin, nifedipine, extended release tablets, in-vitro release.

INTRODUCTION

Plant and their products have always been a source of various drugs and excipients used in

pharmaceutical formulations because they are non-toxic, less expensive and freely available.Furthermore, they can be modified to obtain tailor made materials for drug delivery systems

allowing them to compete with the synthetic products that are commercially available1.

Pectin, a naturally occurring polysaccharide obtained from citrus peels, has high potential as

a hydrophilic polymeric material for controlled release matrix drug delivery systems, but its

aqueous solubility contributes to undesirable, premature and fast release of the drug from

these polysaccharide matrices. One of the options to reduce the high solubility of pectin in

aqueous medium is through chemical modification without affecting favourable

biodegradability properties2,3.

Patients with chronic diseases are increasing day by day. This situation necessitates the use of

drugs for a longer period and taking a lot of medicines simultaneously, which may lead to

patient non- compliance. This problem is serious for drugs with short biological half- lives

like nifedipine a cardio-vascular drug because they must be taken more frequently. In this

condition controlled release formulation becomes beneficial for reducing dosing frequencyand thus increase patient compliance4.

The present study aims at reducing the aqueous solubility of pectin by chemical modification

process and to evaluate its drug release retarding efficiency from the tablet dosage form using

nifedipine as the model drug.
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MATERIALS AND METHODS

Nifedipine was kindly gifted by Srushti pharmaceuticals, Bangalore; Pectin, (Himedia

laboratories Pvt. Ltd, Mumbai), Thionyl chloride, Ethanol (Rankem RFCL Ltd, New Delhi),

Phenyl acetic acid (NR Chem. products, Mumbai.), Micro crystalline cellulose (Yarrow chem

Pvt. Ltd., Mumbai), All other ingredients used were of analytical grade.

SYNTHESIS OF MODIFIED PECTIN BY CHEMICAL METHOD

The pure pectin was chemically modified by acetylation process using phenyl acetyl chloride

as the reagent5.

Preparation of phenyl acetyl chloride

1.636 g (0.9772 ml, 0.00136 mol) of redistilled Thionyl chloride was placed in a 100 ml two-

necked flask equipped with a dropping funnel and a reflux condenser connected at the top to

the gas absorption trap and gently heated on water bath. 1 g of phenyl acetic acid (1.004 ml,

0.01136 mol) was slowly added over a period of 30 40 min. The solid phenyl acetyl

chloride was collected.

Chemical modification of pectins

The different fractions of chemically modified pectins were synthesised using varied

concentrations of phenyl acetyl chloride. Weighed quantity of 10 g pectin was gradually

added into a flask containing 20 ml of 20 % w/ v, 40 % w/v and 60 % w/v phenyl acetyl

chloride in ethanol and stirred over a period of 90 min. in a closed condition over magnetic

stirrer at 50 rpm . The product was filtered, and dried in a hot air oven at 50C. The dried

product was triturated and passed through sieve no. 60.

CHARACTERIZATION OF MODIFIED PECTINS

Solubility studies

The solubility studies were performed in various solvents like distilled water, methanol and

chloroform. Accurately weighed quantity of 100 mg pure and modified pectins was added to

10 ml of particular solvent in a small conical flask and was shaken for 24 hrs. in a closed

condition on a water bath shaker. Then the solution was filtered through pre weighed

whatman filter paper No. 41 and the paper was re-weighed after complete drying. The

solubility of the samples in a particular solvent was determined by the difference between the

final weight and initial weight of paper6.


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Gelling or swelling factor

A watch glass was taken containing a weighed quantity of 100mg of modified pectin and to

which distilled water was added dropwise gradually till no further absorption could be visibly

observed. The swelling index/gelling capacity of the samples was determined by the

difference in the weight of watch glass before and after addition and absorption of water.

Determination of acid value

The acid value is the number which expresses in milligrams the amount of potassium

hydroxide necessary to neutralize the free acid present in 1 gram of the substance. 10.0 g of

modified pectin was dissolved in 50 ml of a mixture of equal volumes of ethanol (95%) and

ether, previously neutralized with 0.1 M potassium hydroxide using phenolphthaleinindicator. If the sample does not dissolve in cold solvent then flask was connected with reflux

condenser and warmed slowly with frequent shaking. 1 ml of phenolphthalein solution was

added and titrated with 0.1 M potassium hydroxide until the solution remained faintly pink

after shaking for 30 sec. The acid value was calculated from the equation:

Acid value = 5.61 n/w

where n is the number of ml of 0.1 M potassium hydroxide required and w is the weight in g

of the substance.

Saponification value

The saponification value is the number of milligrams of potassium hydroxide necessary to

neutralize the free acid and to saponify the esters present in 1 g of the sample. In this, 2 g

polymer sample was taken into a 200 ml flask of borosilicate glass fitted with a reflux

condenser. 25 ml 0.5 M ethanolic potassium hydroxide solution and a little pumice powder

was added and refluxed on a water-bath for 30 minutes. 1ml of phenolphthalein solution was

added and titrated immediately with 0.5 M hydrochloric acid (a ml). For the blank, the

experiment was repeated in absence of polymer (b ml). The saponification value was

calculated from the equation:

Saponification value = 28.05 (b-a)/w

where w is the weight of the polymer (g)

Ester value

Ester value is the amount of potassium hydroxide (mg) required to saponify the esters present

in 1 g of the sample. The ester value was calculated from the equation:


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Ester value = Saponification valueAcid value.

FTIR studies of the modified pectin

Samples of modified pectins and pure pectin were mixed with KBr powder and then

subjected to hydrostatic pressure at a pressure of 5 ton/cm2 for 5minutes. The scanning range

of infrared spectra was 500 4000 cm-1

using computer mediated Fourier transformed

infrared spectroscopy (FTIR) (model-8400S, Shimadzu).

FORMULATION OF NIFEDIPINE TABLETS

Table 1: Formulation of nifedipine tablets

Sl.No.

Ingredients Drug : Polymer ratio/Quantity in mg

P1 P2 P32PAP1

2PAP2

2PAP3

4PAP1

4PAP2

4PAP3

6PAP1

6PAP2

6PAP3

1 Nifedipine 30 30 30 30 30 30 30 30 30 30 30 30

2 Pectin 30 60 90 - - - - - - - - -

3 MP-20 - - - 30 60 90 - - - - - -

4 MP-40 - - - - - - 30 60 90 - - -

5 MP-60 - - - - - - - - - 30 60 90

6 Talc 6 6 6 6 6 6 6 6 6 6 6 6

7Magnesium

Stearate4 4 4 4 4 4 4 4 4 4 4 4

8Microcrystalline

cellulose

130 100 70 130 100 70 130 100 70 130 100 70

Tablet weight

(mg)200 200 200 200 200 200 200 200 200 200 200 200

Here MP-20, MP-40, MP-60 indicates pectin modified with 20%, 40%, 60% w/v of phenyl

acetyl chloride in ethanol respectively.

The tablets formulations were prepared by wet granulation technique using varying

concentrations of pectin, modified pectins MP- 20%, MP- 40%, MP- 60% as a drug release

retardant employing microcrystalline cellulose as a diluent, purified talc and magnesium

stearate as glidant and lubricant. Weighed quantity of drug, polymer and micro crystalline

cellulose (previously passed through sieve no. 85) were added, mixed and granulated using

distilled water as granulating agent. The wet mass was passed through sieve no. 16 and the


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granules obtained were dried at 60oC for 45 min. The dried granules were subjected to dry

screening by passing through sieve no. 20 and blended with the mixture of talc and

magnesium stearate. The lubricated blend was compressed into tablets using 6 mm round

shaped punches in a single rotary tablet press (Rimek RSB-4 minipress, Cadmach).

EVALUATION STUDIES

Pre-compression studies

The prepared granular blend was evaluated for various parameters like bulk density, tapped

density, angle of repose, compressibility index and Hausner ratio 7.

Post-compression studies8

All the batches of formulated tablets were evaluated for various quality control tests like

hardness, friability, weight variation, drug content, and in-vitro dissolution studies.

Weight variation

Randomly selected 20 tablets of each formulation batch were weighed using an electronic

digital balance and the test was performed according to the Indian Pharmacopeia.

Hardness testThe tablet crushing strength was tested by using Monsanto tablet hardness tester. A tablet

was placed between the anvils and the crushing strength which causes the tablet to break was

recorded. Three tablets from each formulation batch were tested randomly and the average

readings were expressed as mean values of triplicates.

Drug content

Twenty tablets from each batch were weighed and crushed to powder with mortar and pestle.

Powder triturate equivalent to 30mg of the drug was accurately weighed, suitably diluted with

pH 1.2 buffer and analysed for drug content at 238nm using UV-Visible spectro photometer

(UV-1601, Shimadzu).

Friability

Randomly selected dedusted tablets of weight equivalent to 6.5g were placed in a Roche

friability test apparatus and rotated 100 times at 25 1 rpm. Then the tablets were removed,

dedusted and re-weighed.


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% Friability = Initial weight-Final weight 100

Initial weight

In-vitro drug release studies9

Drug release studies were carried out using USP XXIII dissolution test apparatus, rotating

paddle method (Lab India, Mumbai, India). The study was conducted at 370.5oC and 100

rpm using 900 ml of 1.2 pH buffer. Aliquots of sample were withdrawn from the dissolution

apparatus at regular pre-determined time intervals and fresh medium was replaced in order to

maintain sink condition. The withdrawn samples were diluted suitably and drug content was

measured spectrophotometrically at 238 nm, against pH 1.2 buffer as blank.

In-vitro dissolution mechanism and similarity factor analysis10

The in-vitro dissolution data of the formulations were studied for drug release kinetics using

PCP DISSO V2 software. Depending upon highest R2 and k values obtained from different

models, the best-fit model was selected.

The similarity factor (f2) is a logarithm transformation of the sum-squared error of differences

between the test and reference product over all time points. It represents closeness of two

comparative formulations. Generally similarity factor in the range of 50-100 is acceptable

according to USFDA.

Stability studies

The accelerated stability studies were carried out for the best suited formulations as per the

ICH guidelines. The tablet formulations were aluminium foiled and were placed in the

stability test chamber and subjected to stability studies at accelerated testing conditions (40

2C/ 75 5 % RH) for 6 months. At specified intervals of time, the samples were withdrawn

and evaluated for their physical and chemical parameters.

RESULTS AND DISCUSSION

The hydrophilicity of the natural pectin was reduced by chemical modification using

acetylation process with varied concentrations of 20%, 40%, and 60% w/v phenyl acetyl

chloride in ethanol and evaluated for physico-chemical properties.

Evaluation studies of modified pectin

The aqueous solubility and swelling behaviour of modified pectins decreased with the

increase in the degree of acetylation process whereas the solubility in organic solvents


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increased as compared to pure pectin (Table 2 and 3).

Table 2: Solubility parameters of the modified pectin in various solvents

Quantity ofpolymer (mg)

Solvent Quantity of modified polymer dissolved (mg)

Modified pectin

Pectin MP-20 MP-40 MP-60

100 Distilled water 80 41 37 31

Chloroform 44 45 49 54

Methanol 52 54 62 68

Table 3: Swelling /gelling factor of the modified pectins

Quantity of polymer

(mg) Solvent Quantity of water uptake

Modified pectin (mg)

Pectin MP-20 MP-40 MP-60

100Distilled

water0.36 0.27 0.21 0.18

The decreased results of acid value and increased saponification and ester values of modified

pectins as compared to pure pectin showed that acetylation has occurred with the free acid

groups of the pectin (Table 4). It was confirmed that degree of acetylation with the pectin was

based on the strength of the acetylating agent used during the reaction process.

Table 4: Acid value, Saponification value, Ester value of modified pectins in comparison

with pure pectin

Polymer Acid value Saponification value Ester value

Pectin 22.44 154.4 131.96

MP-20 8.81 253.75 244.94

MP-40 7.95 257.53 249.58

MP-60 7.28 261.13 253.85

FTIR studies

The IR spectra of all the modified pectins (Fig.2-4) remained almost similar but when

compared with the pure pectin (Fig.1), it was found that pure pectin having the OH stretch

of alcohol (3200-3500 cm-1) shown by strong broad band were found to be absent in all the


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Fig. 4: IR spectrum of MP-60

Pre compression studies of granules

The results of preformulation studies are represented in Table 5. The mean bulk densities of

the formulations were found to be in the range from 0.382 to 0.424 g/ml. The mean tapped

densities of powders were recorded to be in the range between 0.426 to 0.468 g/ml and the

results of Carrs index and Hausners ratio values showed that the granules of formulations

P1 to 6PAP3 had acceptable flow properties. Finally the of angle of repose values 18021'

to 23058' proved excellent flowability of the granules formulated.

Table 5: Data for pre-compression studies of the formulated granules

Formulationcode

Bulk density*(g/cc)

Tap density*(g/cc)

Angle ofrepose* ()

Carrsindex* (%)

Hausnersratio*

P1 0.392+0.008 0.432+0.004 21 18' 9.25+0.08 1.10+0.016

P2 0.414+0.004 0.444+0.002 20 30' 6.75+0.092 1.07+0.011

P3 0.424+0.01 0.468+0.004 20 22' 9.40+0.084 1.1+0.024

2PAP1 0.382+0.008 0.436+0.002 22 31' 12.38+0.068 1.14+0.028

2PAP2 0.390+0.006 0.432+0.008 20 44' 9.72+0.104 1.10+0.016

2PAP3 0.408+0.004 0.456+0.012 19 48' 10.5+0.089 1.11+0.0384PAP1 0.380+0.002 0.426+0.006 23 58' 10.7+0.068 1.12+0.0088

4PAP2 0.386+0.014 0.432+0.004 20 32' 10.6+0.044 1.11+0.072

4PAP3 0.392+0.008 0.434+0.008 18 21' 9.67+0.076 1.10+0.026

6PAP1 0.412+0.003 0.454+0.003 21 08' 9.25+0.054 1.10+0.0078

6PAP2 0.388+0.006 0.436+0.004 22 36' 11.0+0.092 1.12+0.054

6PAP3 0.398+0.007 0.444+0.008 19 58' 10.36+0.044 1.11+0.024

* Values represented as mean SD (n=3)


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Post compression studies of the prepared formulations

Weight variation test was carried out for all the designed formulations and was found to be

within the standard limits. The hardness of all the formulations P1 to 6PAP3 ranged from

5.8+0.18 to 7.6+0.41 kg/cm2 with good mechanical strength and friability values of 0.42 to

0.81 % showed that the formulations were physically stable to mechanical shocks during

handling and transportation. The uniformity of drug distribution with in the batch tablets was

confirmed by the assay values of 97.6to103.4 % for all the formulations.

Table 6: Post compression studies data of the formulated tablets

Formulation

code

Hardness*

(kg/cm2

)

Friability

(%)

Weight variation*

(mg)

Drug content*

(%)

Thickness*

(mm)

P1 5.8+0.18 0.74 194+6.32 99.2+2.1 3.1+0.04

P2 6.8+0.22 0.81 201+2.3 101.2+3.4 3.0+0.01

P3 6.0+0.14 0.76 200+3.2 99.4+3.1 3.1+0.01

2PAP1 6.6+0.24 0.44 200+8.4 97.6+2.8 2.96+0.05

2PAP2 7.2+0.18 0.48 193+6.2 98.2+2.8 2.98+0.006

2PAP3 7.6+0.38 0.69 197+8.6 103.4+2.8 2.99+0.09

4PAP1 6.4+0.41 0.74 203+8.4 99.4+3.2 3.10+0.04

4PAP2 7.0+0.27 0.76 204+8.2 98.6+3.2 3.10+0.06

4PAP3 7.2+0.22 0.73 196+6.8 97.8+3.9 2.97+0.08

6PAP1 6.8+0.26 0.62 198+5.9 99.5+2.8 3.0+0.04

6PAP2 7.2+0.32 0.42 202+6.2 98.7+2.6 2.99+0.1

6PAP3 7.6+0.41 0.48 201+6.8 97.6+4.3 2.98+0.12

* Values are represented as mean SD (n=3)

In-vitro drug release studies

The release profile of the drug nifedipine from different formulations along with the

marketed product are represented in the Fig. 5 and the cumulative percentage drug release of

various formulations at the end of 1, 4, 8 and 12 hour intervals were depicted in Table 7.

Based on the comparative drug release profile of all the formulations, 4PAP3 was concordant

to the standard specified limits as per the USP with a controlled release upto 12 h. and found

to be comparable to the drug release of the marketed formulation. Thus the formulation

4PAP3 was selected for further studies.


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Table 7: Cumulative percentage drug release data of nifedipine forrmulations at

different time intervals

Fig. 5: Release profile of the nifedipine from different formulations along with the

marketed product

In-vitrodrug

release kinetics and similarity factor analysis

The dissolution data of all the formulations obtained were processed with the software PCP

Disso. V3 to predict the best fit model.The selected formulation 4PAP3 with highest R2 value

and n value less than 0.5 showed Fickian type of drug diffusion mechanism with peppas as

the best fit model. The dissolution data of the formulation 4PAP3 was compared with the

marketed product as the reference standard and the calculated similarity factor (f2) value was

found to be 66.03. As the value was above 50, as per USFDA specifications the formulation

4PAP3 found to comparable with the marketed product.

Formulation code Cumulative percentage drug release (%)

1 4 8 12

P1 53.47 73.0 - 99.0 (6 h.)

P2 51.0 68.56 100.17 100.17(8h.)

P3 33.89 64.0 94.0 99.57(9h.)

2PAP1 56.4 75.8 99.5 99.5(8 h.)

2PAP2 51.1 69.9 92.8 99.2(9h.)

2PAP3 34.3 66.2 88.6 98.4(10h.)

4PAP1 48.3 72.3 99.3 99.3(8h.)

4PAP2 47.5 63.5 85.3 99.4(10h.)

4PAP3 38.2 56.3 80.5 99.6

6PAP1 52.5 71.5 92.8 99.1(10h.)

6PAP2 45.4 59.6 84.7 100.4

6PAP3 30.7 62.2 78.2 96.4

Mktd. Product 26.24 53.26 71.13 99.65


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Table 8: Curve fit data for the prepared formulations

FORMULATION

CODEZERO ORDER FIRST ORDER MATRIX HIX.CROW

KORSMEYER-PEPPAS

EQUATION

Best fit

Model

R2 K R2 K R2 K R2 K R2 N k

P1 0.8135 18.1705 0.8892 -0.4663 0.9753 38.8659 0.9395 -0.1049 0.9279 0.3223 49.0252 Matrix

P2 0.7707 14.3501 0.8938 -0.3947 0.9765 35.1561 0.9521 -0.0856 0.9515 0.3299 45.9426 Matrix

P3 0.8873 12.8088 0.9420 -0.3413 0.9982 32.8403 0.9892 -0.0759 0.9939 0.5045 32.5201 Matrix

2PAP1 0.5946 14.4661 0.9477 -0.3447 0.9512 35.8290 0.9125 -0.0816 0.9829 0.2628 52.4224 Peppas

2PAP2 0.6648 12.7536 0.9528 -0.3037 0.9671 33.2323 0.9401 -0.0718 0.9784 0.2995 46.7929 Peppas

2PAP3 0.8263 11.6814 0.9473 -0.3036 0.9960 31.6779 0.9816 -0.0685 0.9929 0.4587 34.2066 Matrix

4PAP1 0.7455 14.5014 0.9464 -0.3753 0.9809 35.6304 0.9609 -0.0849 0.9895 0.3377 46.2328 Peppas

4PAP2 0.6982 11.1816 0.9222 -0.2594 0.9711 30.5325 0.9371 -0.0618 0.9676 0.3145 42.5584 Matrix

4PAP3 0.8202 9.4524 0.9649 -0.2246 0.9815 27.9189 0.9787 -0.0531 0.9921 0.4051 33.5097 Peppas

6PAP1 0.5595 12.1106 0.9709 -0.3172 0.9551 33.3044 0.9405 -0.0718 0.9879 0.2851 49.1799 Peppas

6PAP2 0.7384 9.8794 0.9565 -0.2626 0.9811 29.3355 0.9732 -0.0587 0.9688 0.3503 39.2758 Matrix

6PAP3 0.8186 9.2040 0.9828 -0.1964 0.9933 27.2204 0.9704 -0.0490 0.9879 0.4692 28.9641 Matrix

Mktd. Product 0.8938 8.8740 0.8583 -0.2084 0.9933 25.6231 0.9485 -0.0487 0.9933 0.5051 25.6231 Peppas


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Stability studiesThe accelerated stability studies for the selected formulation 4PAP3 were performed as per

the ICH guidelines for a period of 6 months and the results (table 10) showed that there were

no significant differences between the initial and final test nifedipine tablets. Also Fig. 6

showed similar dissolution profile between the initial and aged tablets. This indicated that the

physico-chemical parameters and drug dissolution of tablets was not affected by aging.

The similarity factor (f2) calculated from the in-vitro drug release profile of the samples at

the end of 2, 4 and 6 months with initial sample as the reference standard showed all the

values above 50 representing closeness of the two comparative formulations.

Table 9: Stability studies of optimized formulation 4PAP3 at accelerated storageconditions

Optimized

formulation

Time

(months)

Physical

appearance

Hardness*

(kg/cm2)

Friability

(%)

% drug

content

Similarity

factor (f2)

4PAP3 0 ++ 7.0+0.22 0.73 100.81.9 -2 ++ 7.20.18 0.71 99.165.2 55.26

4 ++ 6.80.14 0.68 98.014.3 54.34

6 ++ 6..80.32 0.70 98.122.6 53.48

*Average of three determinations

+: Slight change in appearance ++: Same as on 0 day

f2: Similarity factor was calculated with initial sample (0 months) as reference values

Fig. 6: Stability studies in-vitro drugrelease profile of formulation 4PAP3 in

accelerated storage conditions


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CONCLUSION

The pure pectin was chemically modified by acetylation with phenyl acetyl chloride. The

obtained modified pectins of different fractions were evaluated for various physico-chemical

properties and the results ascertained the hydrophobicity of the modified pectin. The tablet

formulations of nifedipine prepared using different fractions of modified pectins as a polymer

in varied ratios complied with unofficial and official quality control tests.

The in-vitro drug release studies indicated the drug release retarding efficiency with the

linear increase in the polymer concentration of the formulations. Thus the semi synthesized

pectin polymer proved to be a promosing drug release retardant in the formulation of oral

controlled drug delivery systems.

ACKNOWLEDGEMENT

The authors wish to thank Gokula Education Foundation (Medical) for providing necessary

facilities to carry out the research work. The authors are also thankful to Srushti

Pharmaceuticals Pvt. Ltd. Bangalore, for providing a gift sample of nifedipine.

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