Nateglinide Modified Release Dosage Form Using Elementary Osmotic Pump and Push Pull Osmotic Pump Methods: Formulation and in-vivo evaluation

Abstract

Objective: The aim was to develop osmotic tablets of nateglinide by two methods namely elementary osmotic pump (EOP) and push-pull osmotic pump (PPOP) method for controlled drug release. Methods: The tablets were prepared by the wet granulation and were evaluated for various physicochemical parameters, in-vitro dissolution and in-vitro dissolution. The optimised formulation obtained in both methods was further characterised for FTIR, stability studies and pharmacokinetic studies. Results: In EOP method coated tablet F14 showing highest drug release of 98.82%. In PPOP formulation FF14 was optimized with highest drug release of 99.97% and also its granules were having better flow property. Both F14 and FF14 were further characterized for FTIR, which showed no significant interaction and the accelerated studies indicated formulations were stable for 3months. The in-vivo studies in rabbits revealead Cmax of the optimised formulation (FF14) was 469.67±0.034 ng/ml, and the Cmax of the marketed product was 401.27±0.08 ng/ml. The Tmax of the formulation and the pure drug were 6.0±0.07 h and 1.5±0.04 h, respectively. The AUC0-infinity of the FF14 was higher ((2829.83±1.47 ng.h/ml) than the marketed suspension (1310.62±0.82 ng.h/ml). The AUC0-t of the FF14 formulation was significantly higher than that of the marketed product (p<0.05). Conclusion: A better improvement in-vitro dissolution profile and bioavailability of the osmotic tablet of nateglinide was observed using PPOP method.