Design and optimization of Nicardipine hydrochloride push pull osmotic pump tablet using 32 full factorial design

Abstract

This paper deals with design, optimization and evaluation of Push Pull Osmotic Pump (PPOP) tablets of Nicardipine Hydrochloride (NH). A 32 full factorial design was employed to optimize the amount of osmotic agent (X1) and osmopolymer (X2) as independent variables that influence the drug release. PPOP tablets of NH were prepared by direct compression method and evaluated for % Cumulative Drug Release (% CDR) at 540min. as dependent variable. Fabricated PPOP tablets were evaluated for weight variation, thickness, diameter, hardness, friability, drug content and in vitro release studies. Amount of osmotic agent and osmopolymer had a pronounced effect on % CDR due to its osmotic property. The transformed values of the independent and dependent variables were subjected to multiple linear regression analysis to establish a full-model second-order polynomial equation. The computer optimization process, contour plots and response surface plots predicted at the concentration of independent variables X1, and X2 (60mg, and 75mg respectively), for maximized response. The drug release from developed formulation was found independent of pH and agitational intensity. The in vitro release kinetics studies reveal that optimized batch fits well with Korsmeyer Peppas model followed by zero order, Hixson Crowell, first order and then Higuchi’s model. Korsmeyer Peppas model analysis indicated that the mechanism of drug release is non-Fickian transport. The stability profiles indicate that the physico-chemical properties of the tablets are not affected on storage at 40 ± 2ºC & 75 ± 5% RH up to 6 months.