Convolution and validation of in vitro-in vivo correlation of water-insoluble sustained-release drug (domperidone) by first-order pharmacokinetic one-compartmental model fitting equation

The experimental study presents a brief and comprehensive perspective on the methods of developing a Level A in vitro-in vivo correlation (IVIVC) for extended oral dosage forms of water-insoluble drug domperidone. The study also evaluates the validity and predictability of in vitro-in vivo correlation using the convolution technique by one-compartmental first-order kinetic equation. The IVIVC can be substituted as a surrogate for in vivo bioavailability study for the documentation of bioequivalence studies as mandatory from any regulatory authorities. The in vitro drug release studies for different formulations (fast, moderate, slow) were conducted in different dissolution mediums. The f (2) metric (similarity factor) was used to analyze the dissolution data for determination of the most discriminating dissolution method. The in vivo pharmacokinetics parameters of all the formulations were determined by using liquid chromatography mass spectrometry (LC/MS) methods. The absorption rate constant and percentage of absorption of drugs at different time intervals were calculated by using data convolution. In vitro drug release and in vivo absorption correlation were found to be a linear correlation model, which was developed by using percent absorbed drug release versus percent drug dissolved from the three formulations. Internal and external validation was performed to validate the IVIVC. Predicted domperidone concentrations were obtained by convolution technique using first-order one-compartmental fitting equation. Prediction errors estimated for C (max) and AUC (0-infinity) were found to be within the limit.