Development and validation of an in vitro release test and use of Strat-M synthetic membrane as a predictor for the in vitro permeation test of topical gel formulations

The purpose of this research was to use the vertical diffusion cell method to produce an appropriate in vitro release test for topical gel formulations. In order to occur a topical drug product's pharmacological activity, the active pharmaceutical ingredient (API) must first be released from the vehicle and be available to penetrate the skin layers and reach the site of action. Formulation properties (characteristics / factors) have the greatest influence on drug release. Concepts presented in the EMA's draft guideline on topical product quality and equivalence were utilized to analyze critical qualification factors and validate in vitro release test (IVRT) methods. Factors that may influence the test, such as the receptor medium and membrane qualification, were appropriately evaluated, followed by an evaluation of method accuracy and method robustness. With 50% and 400% (200% for 2.32% gel) API formulations, the linearity of the IVRT technique as a function of drug concentration in the formulation was studied. Furthermore, the method's discriminatory power was proven using a formulation with variable viscosity as a significant quality parameter. A permeation study of API at 24 h and drug release rate was performed based on Strat-M membrane permeability parameters in order to predict the outcome of the in vitro permeation testing (IVPT). API release profile comparison fulfilled the applicable acceptance criteria for the 90% confidence interval (CI) for the ratio of means of the pairwise comparisons