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 res ults from in-vitro data. An IVIVC has been used to optimize a hydrocolloida l-based matrix tablet designed to be bioequivalent to an existing once-dail y diltiazem HCl product (Dilacor XR 240 mg; Rhone-Poulenc Rorer). Data from a preliminary formulation dosed to fasted and fed subjects were u sed to establish the IVIVC. The correlation was then used during reformulat ion of the dosage forms to predict changes in the maximum plasma concentrat ion (C-max) and the area under the plasma-concentration-time curve (AUC) fo r fasted and fed subjects using in-vitro dissolution data. The IVIVC adequately predicted plasma profiles of two optimized formulation s in studies with fasted and fed subjects.