WORLD JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES

S. Bharath et al. World Journal of Pharmacy and Pharmaceutical Sciences Volume 2, Issue 1, 321-336. Research Article ISSN 2278 4357

DEVELOPMENT OF CHEMICALLY MODIFIED PECTIN BASED EXTENDED RELEASE TABLETS OF NIFEDIPINE

Murali Krishna Reddy. P1, S. Bharath*1, R. Deveswaran1 , B.V.Basavaraj1, V.Madhavan2
1

Department of Pharmaceutics, M. S. Ramaiah College of Pharmacy, M.S.R.Nagar, M.S.R.I.T. Post, Bangalore-54, India.

Department of Pharmacognosy, M. S. Ramaiah College of Pharmacy, M.S.R.Nagar, M.S.R.I.T. Post, Bangalore-54, India.

Article Received on 08 January 2013, Revised on 20 January 2013, Accepted on 28 January 2013

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

*Correspondence for Author: * S. Bharath Department of Pharmaceutics, M. S. Ramaiah College of Pharmacy, M.S.R.Nagar, M.S.R.I.T. Post, Bangalore-54, India. bharath1970in@yahoo.com,

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 www.wjpps.com 321

S. Bharath et al.

World Journal of Pharmacy and Pharmaceutical Sciences

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 available 1. 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 biodegradability properties . 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 frequency and 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.
2,3

favourable

www.wjpps.com

322

S. Bharath et al.

World Journal of Pharmacy and Pharmaceutical Sciences

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 twonecked 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.

www.wjpps.com

323

S. Bharath et al.

World Journal of Pharmacy and Pharmaceutical Sciences

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 phenolphthalein indicator. 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:

www.wjpps.com

324

S. Bharath et al.

World Journal of Pharmacy and Pharmaceutical Sciences

Ester value = Saponification value Acid 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 5 minutes. 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 P1 1 2 3 4 5 6 7 Nifedipine Pectin MP-20 MP-40 MP-60 Talc 30 30 6 4 130 200 P2 30 60 6 4 100 200 P3 30 90 6 4 70 200 Drug : Polymer ratio / Quantity in mg 2PA P1 30 30 6 4 130 200 2PA P2 30 60 6 4 100 200 2PA P3 30 90 6 4 70 200 4PA P1 30 30 6 4 130 200 4PA P2 30 60 6 4 100 200 4PA P3 30 90 6 4 70 200 6PA P1 30 30 6 4 130 200 6PA P2 30 60 6 4 100 200 6PA P3 30 90 6 4 70 200

Magnesium Stearate Micro 8 crystalline cellulose Tablet weight (mg)

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

www.wjpps.com

325

S. Bharath et al.

World Journal of Pharmacy and Pharmaceutical Sciences

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 studies
8

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 test The 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.

www.wjpps.com

326

S. Bharath et al.

World Journal of Pharmacy and Pharmaceutical Sciences

% 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 370.5 oC 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

www.wjpps.com

327

S. Bharath et al.

World Journal of Pharmacy and Pharmaceutical Sciences

increased as compared to pure pectin (Table 2 and 3). Table 2: Solubility parameters of the modified pectin in various solvents Quantity of polymer (mg) Solvent Pectin 80 44 52 Quantity of modified polymer dissolved (mg) MP-20 41 45 54 Modified pectin MP-40 37 49 62 MP-60 31 54 68

100

Distilled water Chloroform Methanol

Table 3: Swelling /gelling factor of the modified pectins Quantity of polymer (mg) Solvent Pectin 100 Distilled water 0.36 Quantity of water uptake Modified pectin (mg) MP-20 MP-40 0.27 0.21 MP-60 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 Pectin MP-20 MP-40 MP-60 Acid value 22.44 8.81 7.95 7.28 Saponification value 154.4 253.75 257.53 261.13 Ester value 131.96 244.94 249.58 253.85

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

www.wjpps.com

328

S. Bharath et al.

World Journal of Pharmacy and Pharmaceutical Sciences

IR spectra of modified pectins, confirming the chemical modification of pectin during acetylation process.

Fig. 1: IR spectrum of pure pectin

Fig. 2: IR spectrum of MP-20

Fig. 3: IR spectrum of MP-40

www.wjpps.com

329

S. Bharath et al.

World Journal of Pharmacy and Pharmaceutical Sciences

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 Formulation code P1 P2 P3 2PAP1 2PAP2 2PAP3 4PAP1 4PAP2 4PAP3 6PAP1 6PAP2 6PAP3 Bulk density* (g/cc) 0.392+0.008 0.414+0.004 0.424+0.01 0.382+0.008 0.390+0.006 0.408+0.004 0.380+0.002 0.386+0.014 0.392+0.008 0.412+0.003 0.388+0.006 0.398+0.007 Tap density* (g/cc) 0.432+0.004 0.444+0.002 0.468+0.004 0.436+0.002 0.432+0.008 0.456+0.012 0.426+0.006 0.432+0.004 0.434+0.008 0.454+0.003 0.436+0.004 0.444+0.008 Angle of repose* () 21018' 20030' 20 22' 22031' 20044' 19048' 23058' 20032' 18021' 21008' 22036' 19058'
0

Carrs index* (%) 9.25+0.08 6.75+0.092 9.40+0.084 12.38+0.068 9.72+0.104 10.5+0.089 10.7+0.068 10.6+0.044 9.67+0.076 9.25+0.054 11.0+0.092 10.36+0.044

Hausners ratio* 1.10+0.016 1.07+0.011 1.1+0.024 1.14+0.028 1.10+0.016 1.11+0.038 1.12+0.0088 1.11+0.072 1.10+0.026 1.10+0.0078 1.12+0.054 1.11+0.024

* Values represented as mean SD (n=3)

www.wjpps.com

330

S. Bharath et al.

World Journal of Pharmacy and Pharmaceutical Sciences

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 P1 P2 P3 2PAP1 2PAP2 2PAP3 4PAP1 4PAP2 4PAP3 6PAP1 6PAP2 6PAP3 Hardness* (kg/cm2) 5.8+0.18 6.8+0.22 6.0+0.14 6.6+0.24 7.2+0.18 7.6+0.38 6.4+0.41 7.0+0.27 7.2+0.22 6.8+0.26 7.2+0.32 7.6+0.41 Friability (%) 0.74 0.81 0.76 0.44 0.48 0.69 0.74 0.76 0.73 0.62 0.42 0.48 Weight variation* (mg) 194+6.32 201+2.3 200+3.2 200+8.4 193+6.2 197+8.6 203+8.4 204+8.2 196+6.8 198+5.9 202+6.2 201+6.8 Drug content* (%) 99.2+2.1 101.2+3.4 99.4+3.1 97.6+2.8 98.2+2.8 103.4+2.8 99.4+3.2 98.6+3.2 97.8+3.9 99.5+2.8 98.7+2.6 97.6+4.3 Thickness* (mm) 3.1+0.04 3.0+0.01 3.1+0.01 2.96+0.05 2.98+0.006 2.99+0.09 3.10+0.04 3.10+0.06 2.97+0.08 3.0+0.04 2.99+0.1 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.

www.wjpps.com

331

S. Bharath et al.

World Journal of Pharmacy and Pharmaceutical Sciences

Table 7: Cumulative percentage drug release data of nifedipine forrmulations at different time intervals Formulation code P1 P2 P3 2PAP1 2PAP2 2PAP3 4PAP1 4PAP2 4PAP3 6PAP1 6PAP2 6PAP3 Mktd. Product 1 53.47 51.0 33.89 56.4 51.1 34.3 48.3 47.5 38.2 52.5 45.4 30.7 26.24 Cumulative percentage drug release (%) 4 73.0 68.56 64.0 75.8 69.9 66.2 72.3 63.5 56.3 71.5 59.6 62.2 53.26 8 100.17 94.0 99.5 92.8 88.6 99.3 85.3 80.5 92.8 84.7 78.2 71.13 12 99.0 (6 h.) 100.17(8h.) 99.57(9h.) 99.5(8 h.) 99.2(9h.) 98.4(10h.) 99.3(8h.) 99.4(10h.) 99.6 99.1(10h.) 100.4 96.4 99.65

Fig. 5: Release profile of the nifedipine from different formulations along with the marketed product In-vitro drug 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.

www.wjpps.com

332

S. Bharath et al.

World Journal of Pharmacy and Pharmaceutical Sciences

Table 8: Curve fit data for the prepared formulations

FORMULATION CODE KORSMEYER-PEPPAS EQUATION R2 0.9279 0.9515 0.9939 0.9829 0.9784 0.9929 0.9895 0.9676 0.9921 0.9879 0.9688 0.9879 0.9933 N 0.3223 0.3299 0.5045 0.2628 0.2995 0.4587 0.3377 0.3145 0.4051 0.2851 0.3503 0.4692 0.5051 k 49.0252 45.9426 32.5201 52.4224 46.7929 34.2066 46.2328 42.5584 33.5097 49.1799 39.2758 28.9641 25.6231 Matrix Matrix Matrix Peppas Peppas Matrix Peppas Matrix Peppas Peppas Matrix Matrix Peppas Best fit Model

ZERO ORDER R2 K 18.1705 14.3501 12.8088 14.4661 12.7536 11.6814 14.5014 11.1816 9.4524 12.1106 9.8794 9.2040 8.8740

FIRST ORDER R2 0.8892 0.8938 0.9420 0.9477 0.9528 0.9473 0.9464 0.9222 0.9649 0.9709 0.9565 0.9828 0.8583 K -0.4663 -0.3947 -0.3413 -0.3447 -0.3037 -0.3036 -0.3753 -0.2594 -0.2246 -0.3172 -0.2626 -0.1964 -0.2084

MATRIX R2 0.9753 0.9765 0.9982 0.9512 0.9671 0.9960 0.9809 0.9711 0.9815 0.9551 0.9811 0.9933 0.9933 K 38.8659 35.1561 32.8403 35.8290 33.2323 31.6779 35.6304 30.5325 27.9189 33.3044 29.3355 27.2204 25.6231

HIX.CROW R2 0.9395 0.9521 0.9892 0.9125 0.9401 0.9816 0.9609 0.9371 0.9787 0.9405 0.9732 0.9704 0.9485 K -0.1049 -0.0856 -0.0759 -0.0816 -0.0718 -0.0685 -0.0849 -0.0618 -0.0531 -0.0718 -0.0587 -0.0490 -0.0487

P1 P2 P3 2PAP1 2PAP2 2PAP3 4PAP1 4PAP2 4PAP3 6PAP1 6PAP2 6PAP3 Mktd. Product

0.8135 0.7707 0.8873 0.5946 0.6648 0.8263 0.7455 0.6982 0.8202 0.5595 0.7384 0.8186 0.8938

333

S. Bharath et al.

World Journal of Pharmacy and Pharmaceutical Sciences

Stability studies The 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 storage conditions
Optimized formulation 4PAP3 Time (months) 0 2 4 6
*

Physical appearance ++ ++ ++ ++

Hardness* (kg/cm2 ) 7.0+0.22 7.20.18 6.80.14 6..80.32

Friability (%) 0.73 0.71 0.68 0.70

% drug content 100.81.9 99.165.2 98.014.3 98.122.6

Similarity factor (f2) 55.26 54.34 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 drug release profile of formulation 4PAP3 in accelerated storage conditions

www.wjpps.com

334

S. Bharath et al.

World Journal of Pharmacy and Pharmaceutical Sciences

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. REFERENCES 1. Carien BE, Alvaro VM, Josias H Polymeric Plant-derived Excipients in Drug Delivery. Molecules 2009; 14: 2602-20. 2. Hetangi R, Vishnu P, Dushyant S. Pectin based insitu gelling system of salbutamol for oral sustained drug delivery. Int J Pharm Res Dev 2011; 3(1).53-58. 3. Sungthongjeen S, Sriamornsak P, Pitaksuteepong T, Somsiri A, Puttipipatkhachorn S. Effect of degree of esterification of pectin and calcium amount on drug release from pectin-based matrix tablets. AAPS Pharm Sci Tech 2004; 5(1).1-8. 4. Varshosaz J, Dehghan Z. Development and characterization of buccoadhesive nifedipine tablets. Eur J Pharm and Bio pharma 2002; 54: 135141 5. Manish BS, Rameshwar D, Praffula C, Neela BM. Chemical modification of pectins, characterization and evaluation for drug delivery. Scientia Pharmaceutica 2008; 76: 775-84. 6. Harika Puppala SK, Bharath S, Basavaraj BV, Deveswaran R, Madhavan V. Chemical modification and characterization of pectin as a potential drug release retardant. Int J Res Ayu Pharm 2011; 2(2): 640-47.

www.wjpps.com

335

S. Bharath et al.

World Journal of Pharmacy and Pharmaceutical Sciences

7. Bharath S, Murali krishna reddy P, Deveswaran R, Basavaraj BV, Madhavan V. Extraction of polysaccharide polymer from dioscorea trifida and evaluation as a tablet binder. Int J Pharm Pharm Sci 2012; 4(3), 347-352. 8. Bharath Kumar N, Bharath S, Deveswaran R, Basavaraj BV, Madhavan V. Extended drug release retarding effect of aloe vera gel in the design of tablet dosage form. Int J Pharm Bio Sci 2012; 2(1):54-59. 9. Grzegorz G, Henning B, Werner W. Investigation of the Dissolution Characteristics of Nifedipine Extended-Release Formulations Using USP Apparatus 2 and a Novel Dissolution Apparatus. Dissolution Technologies 2009; 7-13. 10. Deveswaran R, Sindhu A, Bharath S, Basavaraj BV, Sharon F, Madhavan V. Design and characterization of diclofenac sodium tablets containing tamarind seed polysaccharide as release retardant. Int J Pharm Tech Res 2009, 1(2); 191-195.

www.wjpps.com

336