DEVELOPMENT AND IN-VIVO EVALUATION OF REPAGLINIDE OSMOTIC DRUG DELIVERY SYSTEM USING TWO DIFFERENT TECHNIQUES

Objective: The aim was to formulate elementary osmotic pump (EOP) and push-pull osmotic pump (PPOP) based drug delivery system for controlled release of an anti-diabetic agent, repaglinide.

Method: Repaglinide tablets were prepared by EOP and PPOP method by wet granulation technique. 15 formulations F1-F15 were designed by EOP and 14 formulations were done by PPOP method. All the formulations were evaluated for various physicochemical parameters and in-vitro dissolution studies. Further the optimised formulations from both the method were characterized by FTIR, stability studies and pharmacokinetic studies.

Results: Repaglinide osmotic tablets were prepared by EOP and PPOP method and exhibited satisfactory results for all evaluated parameters. The highest drug release was exhibited from F15 prepared by EOP method with 99.76% and FF14 with 15% coating prepared by PPOP method with drug release of 99.73%. The study by FTIR indicated no significant interactions between drug and excipients. The formulations were stable after 3 months of accelerated stability studies. In-vivo studies in rabbits showed that osmotic tablet of repaglinide (F15) Cmax of 22.56±0.08 ng/ml and the marketed 's Cmax of 30.73±0.063 ng/ml. Both the osmotic tablet formulation and the commercial product had Tmax values of 6.0 ±0.06 and 1.0 ±0.03 hours, respectively. The osmotic tablet formulation had a greater AUC_0-infinity (184.21±1.37 ng. h/ml) than the marketed (153.8 ±0.42 ng. h/ml). In comparison to the marketed, the osmotic tablet formulation had a considerably greater AUC0-t (p<0.05).

Conclusion: The bioavailability and in-vitro dissolution characteristics of the osmotic tablets of repaglinide were significantly improved in comparison to the commercial product.

Keywords: Repaglinide, Hyperglycemia, Osmotic drug delivery system, HPLC, pharmacokinetics