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The objective of the present work is extraction of pectin from waste of orange fruit peel and further characterization for useful alternative pharmaceutical excipient. The pectin was subjected to phytochemical and physicochemical characterization of its safety and suitability to use as binding and suspending agent. FT-IR spectroscopy, DSC studies were performed for drug, orange peel pectin powder, prepared tablet and suspension formulations. Aceclofenac tablets were prepared by wet granulation method containing mannitol as diluent; using 2.5, 5, 7.5 and 10 %w/w of orange peel pectin powder and 7.5 %w/w of PVP (reference) as binding agents in the tablet formulation. Aceclofenac suspensions were prepared with orange peel pectin powder at 0.5, 1, 1.5 and 2 %w/v as suspending agent and 1.5 %w/v of sodium CMC as reference suspending agent. Pharmaceutical properties of granules and tablets such as carr’s index, Haunser’s ratio and angle of repose and post compression parameters like friability, hardness, and disintegration time studies were determine and found satisfactory. The evaluation test of suspension like sedimentation volume, redispersibility, pH, degree of flocculation were found satisfactory. In vitro release studies shows that release rate of drug is decreased with increase in the orange peel pectin powder percentage in the formulation. Orange peel pectin powder showed good binding and suspending properties at 10 %w/w and 2 %w/v, respectively. *Corresponding author, Mailing address: Kopparam Manjunath Department of Pharmaceutics, Sree Siddaganga College of Pharmacy, Tumkur-572102, Karnataka, India. Email: [email protected] Article History:-----------------------Date of Submission: 27-03-2013 Date of Acceptance: 07-04-2013 Conflict of Interest: NIL Source of Support: NONE F u ll L e n g t h R e s e a r c h M a n u s c r ip t Int. J. Drug Dev. & Res., April-June 2013, 5 (2): 283-294 Covered in Scopus & Embase, Elsevier 283 suspending, stabilizing agents in pharmaceutical industries and used as matrices for sustained release of drugs [2-3]. Pectin, a multifunctional constituent contained in the cell wall of terrestrial plants. Pectin is a non-starch linear polysaccharide consists of 1, 4 D-galacturonic acid [4]. Galacturonic acid of pectin may or may not be esterified with methanol or acetic acid, in which case percentage esterified groups are expressed as degree of methoxylation (DM) and degree of acetylation (DA) respectively. Low degree of methoxyl pectins (< 50 % esterified) form thermo reversible gels in the presence of calcium ions and at low pH (3 4.5) whereas high degree of methoxyl pectins (>50 % esterified) rapidly form thermally irreversible gels in the presence of sufficient (for example, 65 % by weight) sugars such as sucrose and at low pH (< 3.5)[5]. Pectins are mainly used as gelling agent and also act as thickener. In view of above interesting aspects, pectin still remains a promising excipient for oral drug delivery. In the present study, we have extracted pectin for orange peel and verified its potentials for using as binding and suspending agent in the aceclofenac tablet and suspension dosage forms. MATERIALS AND METHODS Materials Aceclofenac is purchased from Yerrow Chem, Pvt. Ltd and orange peel pectin powder was extracted in the lab. Mannitol, sodium starch glycolate, magnesium stearate, talc, sodium CMC, methyl paraben, propyl paraben and vanillin flavor are of analytical grade. Methods Extraction of orange peel pectin powder Ripped orange peel was obtained from local fruit shop. Peel was carefully washed and dried under shade for 24 h, further dried at 60 °C in a hot air oven. Dried fruit peel was cut into pieces and powdered by electric grater. Powdered peel was further passed from sieve No. 20. Peel powder, 200 g of was dissolved in 1 L of water and 1 g of citric acid was added to maintain acidic pH 2. This solution was subjected to reflux condensation at 70 oC for 6 h to extract pectin. The extractor thimble was a whatman cellulose thimble with 33 mm internal and 80 mm external length. Hot acid extract was pressed in a cheese cloth bag and the concentrated juice was cooled to 4 oC. Pectin was precipitated by ethanol: water (2:1 v/v) treatment followed by continuous stirring for 15 min and allowed to stand for 2 h. Pectin coagulate was filtered through cheese cloth, washed with 95 % alcohol and pressed. Pressed pectin was further dried to constant weight at 35 – 45 oC. Hard pectin cake was ground and passed through sieve No.60, stored in desiccators for further use [6]. Preliminary phytochemical screening of orange peel pectin powder The phytochemical properties such as presence of alkaloids, carbohydrate, glycosides, tannins, proteins and amino acids were determined [7] as shown in Table 1. Physicochemical characterization of orange peel pectin powder The physico chemical characterization of orange peel pectin powder such as solubility, pH, loss on drying, viscosity and ash values were determined as shown in Table 2. FT-IR Studies Pure drug aceclofenac, orange peel pectin powder, prepared tablet formulations and suspension formulation are studied for FT-IR spectra. Aceclofenac suspension formulation was filtered using Whatman filter paper and the residue was used for the FT-IR study [8]. Scanning Electron Microscopy Extracted orange peel pectin powder is subjected for SEM studies to understand its surface morphological characters. Differential Scanning Calorimetry DSC studies were carried out for pure aceclofenac, orange peel pectin powder and tablet formulation F4 to find out any chemical interactions among them. F u ll L e n g t h R e s e a r c h M a n u s c r ip t Kopparam Manjunath et al: Evaluation of Pectin derived from Orange peel as a Pharmaceutical Excipient Int. J. Drug Dev. & Res., April-June 2013, 5 (2): 283-294 Covered in Scopus & Embase, Elsevier 284 Preparation of Aceclofenac Tablets Aceclofenac was used as model drug, wet granulation method was used for preparation of the aceclofenac tablets. Drug and excipients are passed through the sieve no.60 individually. Aceclofenac, orange peel pectin powder, mannitol and sodium starch glycolate were added and mixed uniformly. Distilled water in a sufficient quantity was added to form a wet mass and it was passed through the sieve no. 12. Distilled water was added as granulating fluid. The same procedure was followed to prepare the granules with different concentrations of orange peel pectin powder (2.5, 5, 7.5 and 10 %w/w) and 7.5 %w/w concentration of PVP as synthetic binding agent for comparison shown in Table 3. The prepared granules were subjected to evaluate pre compression parameters. Granules were lubricated with magnesium stearate, talc and were compressed into the tablets of 200 mg, using 10 station rotary tablet compression machine (Shakti Pharma Tech, Ahmadabad) [9]. Evaluation of Aceclofenac Granules Angle of repose15 The angle of repose was calculated using the formula, θ = tan-1(h/r) Where θ = angle of repose h = height of pile, r = radius of the base of the pile. Compressibility Index Tapped bulk density and untapped bulk density was measured using measuring cylinder. The compressibility index was calculated using formula: Evaluation of the Tablets16 Weight Variation Test Randomly selected twenty tablets were weighed individually and together in a single pan balance. The average weight was noted and percentage deviation was calculated. Hardness, Thickness Six tablets were taken randomly and hardness was measured by the Monsanto hardness tester. Hardness was expressed in Kg/cm2. The thickness and diameter of the tablet was measured using Vernier calipers. Friability Twenty tablets selected randomly from each batch were tested at a time. Tablets collective weight was determined before (W1 g) and after (W2 g) the test. The percentage friability was then calculated by formula, Drug content Five tablets were weighed individually and powdered collectively. The powder equivalent to average weight of tablets was weighed and drug was extracted in phosphate buffer pH 6.8, the drug content was determined spectrophotometrically. In case of suspension, 5 ml was subjected to extraction with phosphate buffer pH 6.8 and measured the absorbance after suitable dilution using a UV spectrophotometer at 274 nm. Disintegration Test Disintegration test was carried out according to I.P. method. Six tablets were placed in glass tubes of disintegration apparatus. Disintegration fluid temperature was maintained at 37 ± 2 °C and time required for disintegration was noted. In vitro Dissolution Studies The dissolution of aceclofenac tablets & suspension was carried out using phosphate buffer pH 6.8 at 37 ± 1 °C & rotation speed of the paddle was maintained at 50 rpm for tablets and 25 rpm for suspension. Samples were withdrawn at every 10 min until 120 min in case of tablets, whereas in case of suspension samples were withdrawn at every 2 min until 24 min in case of suspensions. Dissolution media was replaced each time to maintain 900 ml volume constant. Samples were analyzed using UV Spectrophotometer at 274 nm. Similarly a marketed F u ll L e n g t h R e s e a r c h M a n u s c r ip t Kopparam Manjunath et al: Evaluation of Pectin derived from Orange peel as a Pharmaceutical Excipient Int. J. Drug Dev. & Res., April-June 2013, 5 (2): 283-294 Covered in Scopus & Embase, Elsevier 285 tablet, Acenac also studied for dissolution studies for comparison purpose [10]. Preparation of Aceclofenac Suspension Aceclofenac (1 g) and orange peel pectin powder (0.25 g) are triturated to get a fine powder, little quantity of distilled water was added and continued trituration. Methyl paraben, propyl paraben and vanillin are added in sufficient quantities and volume was made up to 50 ml using distilled water and stored in a well closed dispensing bottle (Table 4). Similarly aceclofenac suspensions were prepared with different concentrations of orange peel pectin powder (1, 1.5 and 2 %w/v). A reference aceclofenac suspension was prepared using 1.5 %w/v sodium CMC as synthetic suspending agent for comparison purpose [11]. Evaluation of Aceclofenac Suspension pH Measurements The pH measurements of the suspensions were done weekly for three weeks using a digital pH meter. Sedimentation Volume [12] Each suspension (50 ml) was placed in a 100 ml measuring cylinder and stored for 7 days at room temperature. The volume of the sediment at every hour for 7 hr and then every 24 hr for 7 days was noted. Marketed product IMOL was selected for comparison. The sedimentation volume of different suspensions was calculated by the equation