Formulation and Evaluation of a Pulsatile Delivery System of Losartan Potassium by Factorial Design

Abstract

The present study was aimed to prepare a time-dependent pulsed release system for the programmed release of losartan potassium for the treatment of hypertension. The core tablets of losartan potassium were prepared using wet granulation containing a superdisintegrant. The design was based on 32 full factorial design containing 2 factors evaluated at 3 levels and the experimental trials were performed on coating of the core tablets. Eudragit S100 and Eudragit L100 were used as pH dependent polymers for coating of the tablets. Factors influenced the lag time and In-vitro drug release of formulations, called as dependent factors. Dissolution studies of coated tablets in media with pH (1.2 and 6.8) showed that drug release could be modulated by optimizing the concentration of Eudragit L100: Eudragit S100. Polynomial mathematical model generated for various response variable using multiple linear regression analysis, were found to be statistically significant. Contour plots and response surface plots were drawn and optimum formulation were selected by feasibility and desirability function. The experimental values obtained from the optimized formulation highly agreed with the predicted values. The results of in vitro dissolution studies indicated that formulation P5 is the most successful formulation of the study and exhibited lag time 5.5 h and drug release 95.23 % in 12 h. The total release pattern was very close to the theoretical release profile of pulsed release system. The study showed that lag time prior to drug release was highly affected by the coating level. The dissolution data revealed that the level of coating and the ratio of polymers are very important to achieve an optimum formulation. Stability study of the optimized formulation indicates no significant difference in release profile after a period of one month.