Comparison of Efavirenz Release in Biorelevant Dissolution Media Using Manual Sampling and In Situ UV Fiber Optic System

Abstract

There has been a growing interest in the use of biorelevant dissolution media in drug formulations research and development. Biorelevant media mimic the physiological conditions of the human gastrointestinal tract, which allows for a more discriminating dissolution test. That is even more important for poorly soluble drugs, like efavirenz and other class II (Biopharmaceutical Classification System) drugs. Traditionally, these media were used in the compendial standard dissolution apparatus; however, reduced automation of the conventional tests could be, in general, costly, high-labor, and error-prone. Thus, the use of in situ ultraviolet (UV) fiber optic probes has been applied in research and development and in quality control routines for drug manufacturing. The present study aims to assess the suitability of an in situ UV dynamic monitoring system for characterization of dissolution behavior of 600-mg efavirenz immediate-release coated tablets in different biorelevant media by comparison with traditional manual sampling. The biorelevant media used were fasted and fed state simulated intestinal fluid (FaSSIF, FaSSIF-V2, FeSSIF, FeSSIF-V2) and SLS (0.5%). Both sampling methods were similar for FaSSIF, FaSSIF-V2, and SLS. For FeSSIF and FeSSIF-V2, the results were statistically different due to high concentration of oxidation phospholipids and degradation lipids in these media. These results support the use of dynamic monitoring of dissolution in FaSSIF, FaSSIF-V2, and SLS, and inform understanding of the rate-limiting steps, which may improve quality and accuracy in data acquisition for dissolution tests with biorelevant media.