Comparison of Clobetasol Propionate Generics Using Simplified In vitro Bioequivalence Method for Topical Drug Products

Abstract

Background: The aim of this paper is to evaluate a simple in vitro skin penetration experiment in which the drug is extracted from the whole skin piece as a test valid for formulation screening and optimization during development process, equivalence assessment during quality control or postapproval after changes to the product.

Methods: Twelve clobetasol propionate (CP) formulations (six creams and six ointments, being five generics and one reference from each formulation type) from the local market were used as a model to challenge the evaluated methodology in comparison to in vitro skin penetration following tape-stripping for drug extraction. To support the results, physicochemical tests for pH, viscosity, density and assay, as well as in vitro release were performed.

Results: Both protocols, extracting the drug from the skin using the tape-stripping technique or extracting from the full skin were capable of differentiating CP formulations. Only one formulation did not present statistical difference from the reference drug product in penetration tests and only other two oitments presented equivalent release to the reference. The protocol is straightforward and reproducible.

Conclusion: Results suggest the bioinequavalence of tested CP formulations reinforcing the necessity of such evaluations.

Keywords: Clobetasol propionate; in vitro release; in vitro skin penetration; pharmaceutical equivalence; topical bioequivalence..