The role of dissolution test in a comparison of generic and branded controlled-release products

Abstract

The aim of the present work was to compare the in vitro drug release of marketed generic and branded immediate-release (IR) and controlled-release (CR) products of two drugs with different solubilities, namely diltiazem hydrochloride and ursodeoxycholic acid (UDCA). The objective was to assess whether their bioequivalence is reflected by the similarity of in vitro dissolution profiles, in particular when the products are not pharmaceutically equivalent. The IR dosage forms of the generic products did not appear to be critically different from the reference branded product. On the contrary, the CR generic products were less able to mimic the performance of the reference brand due to the different delivery systems adopted. The various release mechanisms significantly affected the in vitro behavior of the systems causing the release kinetics to differ. In the case of the sol. diltiazem products, where diffusion is the main mechanism of drug delivery, it seems reasonable to assume that the change in drug-release test conditions may lead to in vitro similarity. On the contrary, as regards the UDCA products, it is difficult to identify those test conditions that could be changed in order that the in vitro test reliably reflects the already established bioequivalence. This is due to the fact that the generic products did not mimic the specifically designed delivery kinetics of the brand