Biopharmaceutical characterization of oral controlled/modified-release drug products. In vitro/in vivo correlation of roxatidine

Abstract From the marketed drug product Roxane® 75 mg C/MR capsules (roxatidine controlled/modified-release capsules), an in vitro/in vivo comparison was performed to demonstrate a 1:1 correlation between in vitro and in vivo dissolution, and, furthermore, to ensure bioequivalence of the roxatidine controlled/modified-release (C/MR) capsules exhibiting dissolution profiles within the defined acceptance criteria. This 1:1 in vitro/in vivo comparison was calculated using a model independent numerical deconvolution method. The high degree of correlation is extremely rare, nevertheless it allows to omit the testing of clinical side batches for the setting of acceptance criteria for the in vitro dissolution of roxatidine controlled/modified-release (C/MR) capsules. The 1:1 in vitro/in vivo correlation can be explained by the biopharmaceutical characteristics of the drug substance as well as the drug product, that is, pH-independent high solubility of the drug substance as well as dissolution which is independent of pH and agitation. These facts lead to a controlled/modified-release formulation. Therefore, it is important to keep in mind that in most cases in which a pH-dependent solubility/dissolution as well as permeability characteristics can be found, a 1:1 in vitro/in vivo correlation could not be expected.