Biopharmaceutical characterization of sotalol-containing oral immediate release drug products.

The objective of this study was replacing an in vivo bioequivalence study by generating suitable in vitro data in order to get generic marketing authorisation. Solubility and permeability of sotalol hydrochloride were determined thereby achieving classification of this compound according to the biopharmaceutical classification system. In addition comparative investigation of in vitro dissolution properties of different Sota-saar formulations and the reference product provided satisfying justification to waive in vivo bioavailability (BA)/bioequivalence (BE) studies. The investigations on solubility were performed considering the highest dose strength in aqueous media (250 ml) with pH conditions between pH 1.0 and 7.5. Permeability was studied using the human colorectal carcinoma cell line Caco-2. In vitro as well as in vivo data suggest high permeability of the drug compound through the intestinal membrane. Thus, evaluation of solubility and permeability allow sotalol hydrochloride to be classified as biopharmaceutics classification system class I drug. In vitro dissolution profiles demonstrate comparable rapid dissolution (more than 85% in 15 min) for test and reference products. Summarizing, relevant prerequisites are fulfilled to waive BA/BE studies. Copyright 2004 Elsevier B.V.