Development of controlled release tablet by optimizing HPMC: Consideration of theoretical release and RSM

• Development of controlled release tablet of nateglinide by optimizing HPMC through response surface methodology.
• Determination of theoretical release profile of the nateglinide controlled release formulations by considering its pharmacokinetic profile.
• In vitro dissolution data have fitted in both model independent and dependent factors.

The objective of the study was to develop controlled release tablets of nateglinide, a meglitinide derivative anti-diabetic drug, considering theoretical release profile and response surface methodology (RSM). 32 factorial design was utilized to optimize concentration of hydroxylpropylmethylcellulose (HPMC) K15M and K100M to obtain the desired responses (drug release at one and six hours). Theoretical release profile of drug for controlled release formulation was calculated and considered as reference for the determination of similarity factor (f2) and desimilarity factor (f1). RSM, f2 and f1 were used to select the optimum formulation. Formulation containing HPMC K15M (5%) and HPMC K100M (15%) was found optimum with desired responses with f2 = 86.05 and drug release profile followed zero order kinetics. Excipients used were compatible with drug, confirmed initially through DSC and IST study. The optimization of experiments was validated and optimum formulation was passed the stability study.