In vitro release tests for topical dermatological products (U01)

Background: Developing appropriate methods to determine bioequivalence of topical dermatological products has been a longstanding challenge to FDA. FDA has begun to identify situations when alternatives to clinical endpoint bioequivalence studies are possible. FDA will consider different bioequivalence approaches based on how similar formulations are to each other. If formulations contain the same inactive ingredients in the same amounts, then there is lower risk of in equivalence. For formulations that A differ in composition, FDA is interested in when in vitro release testing can predict that there will be no difference in drug delivery to and across the skin. Objectives: The goal is to identity in vitro release test conditions that are best correlated with in vivo performance. An in vitro release test could be used as part of the bioequivalence evaluation of topical products to evaluate whether a change in inactive ingredients would result in a change in drug delivery to and across the skin. Detailed Description: This project will investigate in vitro - in vivo correlations of topical dermatological products. The project has several phases as noted below: 1) Selection or manufacture of test formulations. The formulations should contain the same active ingredient and have different inactive ingredients. They may be currently marketed formulation. 2) Identification or generation of the in vivo data set. The in vivo data set may be obtained from the literature or generated as a part of this grant. In vivo performance could be assessed by either human PK data, human microdialysis data or any other proposed source. 3) In vitro in vivo correlation: The test formulations should be evaluated under a range of in vitro release test conditions. In vitro release tests could include using excised human skin or artificial membranes. 4) Optimization of the in vitro release testing protocol. The in vitro release test protocol with the best prediction of in vivo results should be identified. 5) A protocol for the external validation of the optimal method should be developed