THE INFLUENCE OF COMPENDIAL CELLS DESIGN AND EXPERIMENTAL SETUP ON THE IN-VITRO SIMILARITY OF KETOCONAZOLE TOPICAL CREAMS

Two cream dosage forms containing 2% ketoconazole with significant similarity of their qualitative composition were comparatively analyzed by compendial tests using vertical diffusion cells and immersion adaption for the standard dissolution equipment. The mean in-vitro release profiles displayed marked differences between reference listed drug and the generic formulation, independent on the design of the cell and implemented operational parameters. These results corresponded to a marked non-similarity in terms of microstructure, as revealed by the hysteresis loop test. Considering that both topical semisolid formulations are approved by the regulatory authorities, probably based on clinical endpoint studies, the in-vitro data can be regarded as proofs of the overly discriminatory character of the methodology.