The objective of this study was to develop and validate the in vitro-in vivo correlations (IVIVCs) of three commercially available immediate-release solid dosage forms of indapamide using drug dissolution/absorption simulating system (DDASS). The in vitro dissolution profiles of three brands of immediate-release tablets were obtained using the USP I basket method and DDASS. A single-dose, three-way, crossover pharmacokinetic study for the tablets was carried out in six beagle dogs. Correlation models were developed for each immediate release formulation using cumulative percentage dissolved/eluted (Fd) versus cumulative percentage absorbed (Fa) and cumulative percentage permeated (Fp) versus cumulative percentage absorbed (Fa). Prediction errors were estimated for the Cmax and AUC to determine the validity of the correlation. Level A IVIVCs were established for the three brands between in vitro (dissolution and permeation) data from DDASS and in vivo data from dogs. Predicted plasma concentrations of each commercial brand were obtained from the dissolution and permeation profile data using the correlation models. A percent prediction error of <15% for the Cmax and AUC was found for all of the formulations, which validates the internal predictability of the IVIVC models obtained. However, the IVIVC models from the permeation data failed to predict the AUC. The results support the use of in vitro dissolution and permeation data as a surrogate for bioequivalent study and suggest that DDASS can be applied as an in vitro system for the validated-IVIVC development of BCS II solid drug formulations.
Keywords: Dissolution; Wagner–Nelson equation; drug dissolution/absorption simulating system (DDASS); in vitro–in vivo correlation (IVIVC) validation; permeation; pharmacokinetics.