Application of in vitro – in vivo correlation (ivivc) as a predictive tool for bio-equivalence studies for generic paracetamol immediate release tablets.

Abstract

xix ABSTRACT Medicines regulatory authorities among developing countries, particularly in Africa, are increasingly demanding that data on bioequivalence studies should be included when applying for marketing authorization for some generic products. Generic products for some of the drug substances for which BE data are demanded include common substances which have been in use for decades with good safety and efficacy profile. In addition, biowaiver monographs are available for some of the listed generic formulations, including Paracetamol immediate release tablets. Studies have been carried out to demonstrate that a simple mathematical model, the in vitro – in vivo correlation (IVIVC), can be used to predict bioavailability profile of a drug substance from in vitro dissolution data. The IVIVC tool has not been put into widespread use in some parts of the world especially the poorer countries where the greatest benefits would result, avoiding incurring the high cost of BE studies and reducing generic product development lead time. This study demonstrated how dissolution data are used to predict drug bioavailability by employing an IVIVC tool. Generic Paracetamol immediate release tablets were compared to a registered reference formulation using an IVIVC tool as a surrogate human bioequivalence studies. Three batches of a generic product, and one batch comparator product, were subjected to dissolution testing to generate a dissolution profile. The dissolution profile data were subjected to computation using an IVIVC tool to predict the blood drug concentration time profile, and specifically compute the AUC and Cmax values. The AUC and Cmax values obtained for the generic product and those obtained for the comparator product were subjected to statistical analysis to evaluate sameness. On this basis, the usefulness in the application of an IVIVC in generic product development was demonstrated with a possibility of wider application of this model by the drug regulatory authorities and marketing authorization (MA) applicants as a justification for biowaiver for generic formulations of candidate drug substances.