Formulation and Development of Bilayer Tablet for Antihypertensive Agents

Abstract

Ph.D Thesis Abstract newlineEnrollment No-15PS703001 Harsh J. Trivedi XII newlineABSTRACT newlineObjective: Aim of the present study was the optimization of the immediate release (IR) layer containing hydralazine hydrochloride (HHC) 25 mg and compressed with sustained-release (SR) layer of isosorbide dinitrate (ISDN) 40 mg to decrease the dosing frequency. Methods: In this study, Drug-excipients compatibility study was carried out by FT-IR and a preliminary trial was conducted for screening of super disintegrating agents. The amount of sodium starch glycolate (SSG) (X1) and the amount of ac-di-sol®(X2) was chosen as independent variables in 32 full factorial design while wetting time (WT) (Y1), disintegration time (DT) (Y2) and In-vitro drug release at 15 min (Q15) (Y3) were taken as dependent variables for immediate release layer. The amount of HPMC K100M (X1) and the amount of Polyoxtm WSR303 (X2) were chosen as independent variables in 32 full factorial designs. While % cumulative drug releases at 1 h (Q1) (Y1), % cumulative drug release at 2 h (Q2) (Y2), % cumulative drug release at 4 h (Q4) (Y3) and % cumulative drug release at 6 h (Q6) (Y4), were taken as dependent variables for sustained release layer and statistically evaluation both later by using sigma plot 13.0. Multiple linear regression analysis, ANOVA, and graphical representation of the influence of factor by 3D plots were performing. To validate the evolved mathematical models, a checkpoint batch was selected from its desirability value. Study was developed of In-vitro and In-vivo Correlation (IVIVC) of bilayer tablet. In-vitro dissolution of the bilayer tablets was performed using USP II apparatus and in-vivo pharmacokinetic data were obtained from bioavailability studies on Wister rats. Pharmacokinetic parameters were evaluated by using MS Excel 2007. Results: FT-IR spectra show that the drug and excipients were compatible with each other. For immediate release later the calculated F values found for WT, DT, and Q15 was 045.559, 077.100 and 278.760, respectively. Al