Preparation, Characterization and Optimization of Sustained Release Matrix Tablets of Repaglinide using Box–Behnken Design

Abstract

The aim of this investigation was to develop and optimize the Sustained release Matrix formulations of Repaglinide (RLD) using response surface methodology by employing a 3-factor, 3-level Box–Behnken statistical design. The independent variables studied were the amount of hydroxypropyl methylcellulose (HPMC K4M), Ethyl cellulose (EC) and PVP K30. The Swelling index (Y1), drug release at 8 hr and 12hr were the target responses. The response surface methodology and multiple response optimizations utilizing a polynomial equation were used to search for the optimal formulation with a specific release rate at different time intervals. The results showed that the effect of combination of HPMC K4M and EC was the most influencing factor on the drug release from ER matrix tablets. The mechanism of drug release from RLD Matrix tablets was dependent on the added amount of EC. Validation of the optimization technique demonstrated the reliability of the model. The optimized formulation containing 50mg of HPMC K4, 35mg of EC, and 30mg of PVP K30 was prepared according to the software determined levels. DSC and FTIR studies combined with the stability study of the optimized formulation proved the integrity of the developed formulation. The Box–Behnken experimental design facilitated the formulation and optimization of extended release hydrophilic matrix systems of RLD in a short period of time and with the fewest number of experiments. The optimized Matrix tablet of Repaglinide showed good pharmacokinetic result over conventional formulation.