Dose calculation, design and development of nateglinide matrix tablets using quality by design approach and its pharmacokinetic evaluation in animal model

Abstract

The present work deals with design of zero order sustained release nateglinide matrix tablets by application of statistical design using response surface methodology as a tool. Central composite design was used to investigate the effect of two independent formulation variables (at three levels) such as Kollidon SR (X1), PVP K 30 (X2) on dependent variables viz. time required to release 30 % (T30, Y1), percentage drug released at 6th hour (DR6, Y2) and time required to release 90 % (T90, Y3) of drug. Wet granulation technique was employed for tablets preparation. The result showed that release pattern of the optimized formulation was almost equal to the statistically predicted values. There was no chemical interaction observed between drug and polymer based up on FTIR and DSC results. In vitro release studies were performed in 0.1 N HCl containing 0.5 % SLS for first 2 h followed by pH 6.8 phosphate buffer containing 0.5 % SLS. Stability studies were performed to statistically optimized formulation. The release pattern from statistically optimized formulation was followed zero order kinetics with non-Fickian process as drug release mechanism. Pharmacokinetic studies were performed to optimized formulation in comparison with nateglinide suspension in rabbit as animal model. The results of in vivo studies revealed the % relative bioavailability of statistically optimized formulation was found to be 68.87 %.