Optimization of sustained-release diltiazem formulations in man by use of an in-vitro/in-vivo correlation.

In-vitro/in-vivo correlations (IVIVC) are useful for predicting in-vivo results from in-vitro data. An IVIVC has been used to optimize a hydrocolloidal-based matrix tablet designed to be bioequivalent to an existing once-daily diltiazem HC1 product (Dilacor XR 240mg; Rhone-Poulenc Rorer). Data from a preliminary formulation dosed to fasted and fed subjects were used to establish the IVIVC. The correlation was then used during reformulation of the dosage forms to predict changes in the maximum plasma concentration (Cmax) and the area under the plasma-concentration-time curve (AUC) for fasted and fed subjects using in-vitro dissolution data. The IVIVC adequately predicted plasma profiles of two optimized formulations in studies with fasted and fed subjects.