Practical Considerations in Developing a Quality Control (In Vitro Release) Procedure for Topical Drug Products

Abstract

Topically applied drug products fall into two major categories: (1) transdermal patches, whose primary aim is to achieve optimal systemic exposure and (2) dermatological (topical) creams, ointments, gels, lotions, and so on, whose primary aim is to treat local skin disorders with minimal systemic exposure. The only known exception, to date, for the latter classification is nitroglycerin ointment, which is used for its systemic effect for the treatment of angina. At present, U.S. Food and Drug Administration (FDA) approval of these dosage forms requires in vivo and, where appropriate, in vitro data. In vivo studies include clinical safety and efficacy, local irritation, systemic toxicity, and bioavailability. In vitro studies, on the other hand, include quality control procedures such as assay, content uniformity, drug release characteristics (dissolution), and so on. Among all quality control in vitro tests, the dissolution or drug release test is the single most important test to assure quality, batch-to-batch uniformity, and bioequi-valence of the product, once the drug product’s bioavailability has been established. It should be emphasized that the in vitro aspects of the New Drug Application (NDA) or Abbreviated New Drug Application (ANDA) are evaluated only after the in vivo evaluation has been found to be satisfactory.