Effect of Plasticizer on Release Kinetics of Diclofenac Sodium Pellets Coated with Eudragit RS 30 D
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The present study was designed to investigate the effect of two plasticizers, i.e., triethyl citrate (TEC) and polyethylene glycol 6000 (PEG 6000) on the in vitro release kinetics of diclofenac sodium from sustained-release pellets. Ammonio methacrylate copolymer type B (Eudragit RS 30 D) is used as the release-retarding polymer. Both plasticizers were used at 10% and 15% (w/w) of Eudragit RS 30 D. Pellets were prepared by powder layering technology and coated with Eudragit RS 30 D by air suspension technique. Thermal properties of drug and drug-loaded beads were studied using differential scanning calorimeter (DSC). DSC thermogram represented the identity of raw materials and exhibited no interaction or complexation between the active and excipients used in the pelletization process. Dissolution study was performed by using USP apparatus 1. No significant difference was observed among the physical properties of the coated pellets of different batches. When dissolution was performed as pure drug, about 8.22% and 90% drug was dissolved at 2 h in 0.1 N HCl and at 30 min in buffer (pH 6.8), respectively. From all formulations, the release of drug in acid media was very negligible (maximum 1.8 ± 0.08% at 2 h) but in buffer only 12% and 30% drug was released at 10 h from coated pellets containing TEC and PEG 6000, respectively, indicating that Eudragit RS 30 D significantly retards the drug release rate and that drug release was varied according to the type and amount of plasticizers used. The amount of TEC in coating formulation significantly effected drug release (p < 0.001), but the effect of PEG 6000 was not significant. Formulations containing PEG 6000 released more drug (98.35 ± 2.35%) than TEC (68.01 ± 1.04%) after 24 h. Different kinetic models like zero order, first order, and Higuchi were used for fitting drug release pattern. Zero order model fitted best for diclofenac release in all formulations. Drug release mechanism was derived with Korsmeyer equation.
Key wordsaqueous coating diclofenac sodium Eudragit RS 30 D plasticizer thermal analysis
The authors would like to thank Eskayef Bangladesh Ltd. (formerly, SmithKline & French, UK) for providing the raw materials as well as manufacturing facilities, Bangladesh Council of Scientific and Industrial Research (BCSIR), and Renata Ltd. Bangladesh (formerly, Pfizer, USA) for providing the scanning electron micrograph and the DSC thermogram, respectively.
- 1.B. C. Andrew, and L. Shargel. Applied Biopharmaceutics and Pharmacokinetics, Appleton & Lange, Connecticut, 1941, pp. 225–264.Google Scholar
- 6.W. Chuanbin, and W. M. James. Influence of ibuprofen as a solid-state plasticizer in Eudragit® RS 30 D on the physicochemical properties of coated beads. AAPS PharmSciTech. 2(4) article 24 (2001).Google Scholar
- 7.L. L. Augsburger, A. Lin, N. A. Muhammad, and D. Pope. Effect of curing and storage conditions on drug release from pellets coated with Eudragit NE30D. AAPS Annual Meeting Supplement 2(4) (2000).Google Scholar
- 8.D. Dreher, and K. Lehmann. The use of aqueous synthetic polymer dispersions for coating pharmaceutical dosage forms. Drugs Made Ger. 16:126–136 (1973).Google Scholar
- 10.G. Cole (eds.), Pharmaceutical Coating Technology, Taylor & Francis Ltd., London, 2001, pp. 27–31.Google Scholar
- 11.J. W. McGinity (eds.), Aqueous Polymeric Coating for Pharmaceutical Dosage Forms, Marcel Decker Inc., New York, 1996, pp. 101–174.Google Scholar
- 12.K. Lehmann. Practical Course in Film Coating of Pharmaceutical Dosage Forms with Eudragit, Pharma Polymers, Darmstadt, 2001, pp. 8–15.Google Scholar
- 13.Pharmaceutical Coatings Bulletin. Influence of Citrate Ester Plasticizers on the Properties of Acrylic Resin Polymers, Morflex, Inc., 1993, p. 102.Google Scholar
- 14.Pharmaceutical Coatings Bulletin. Physical and Mechanical Properties of Acrylic and Cellulosic Polymers Plasticized with Citrate Esters. Morflex, Inc., 1994, p. 102.Google Scholar
- 15.USP 23/NF 18. Triethyl Citrate-Official Monograph, 1995, p. 2316.Google Scholar
- 17.A. G. Gilman, T. W. Rail, A. S. Nies, and P. Taylor. The Pharmacological Basis of Therapeutics, Pergamon Press, New York, 1990.Google Scholar