Semi-Solid In Vitro Release Testing (IVRT) – Are You Ready?


In the pharmaceutical industry, in vitro release testing has played an important role in both formulation design and quality control of finished products. Used primarily for solid oral dosage forms, this test has expanded to a variety of “novel” or “complex” dosage forms as drug delivery becomes more complex. Because these formulations, including semi-solids, have become more prevalent, there has been an increase in development of this testing method to determine the release performance of various dosage forms.

For orally administered solid drug products, this test is commonly referred to as a “dissolution” test, since the intention is that the drug dissolves rapidly in a test medium. For non-oral dosage forms such as topical and transdermal delivery systems, the test is commonly referred to as an in vitro release test, since the drug, in the vehicle, must diffuse and be released by the vehicle, becoming available to penetrate into skin.

Because novel or complex dosage forms exhibit significant variability in formulation design, it has been difficult to devise a single test system that can be used to study the drug release properties of each dosage form. Different apparatus, procedures, and techniques have been employed on a case-by-case basis, and the methods are often specific to the dosage form category, formulation type, or even an individual product.

Recent updates to the US Pharmacopeia now provide guidance for in vitro testing of semi-solid dosage forms. These published guidelines create a change in regulatory perspective – a change that will likely result in requests for in vitro test results. The good news is that in vitro release testing is an alternative that can save both time and cost compared to bioequivalence studies.

This paper examines in vitro release testing for semisolid topical dosage forms, discusses the recent changes in published testing standards, subsequent increase in interest by regulators, and how to navigate this new environment to give your drug development project the best chance to clear regulatory scrutiny.