Dissolution Testing of a Controlled-Release Capsule Formulation: Challenges and Solutions Using a Semi-Automated Dissolution System

A controlled-release formulation was developed using enteric-coated beads in a hard gelatin capsule shell. This formulation requires two-stage dissolution testing at low and neutral pH. Because of high toxicity and limited stability of the active pharmaceutical ingredient in aqueous solution at room temperature, it is preferable to limit the analyst's contact with the sample solutions during testing, and aliquots from the dissolution vessel need to be quickly filtered and refrigerated immediately after sampling. To meet these challenges, a semi-automated dissolution method was developed and validated. Dissolution samples are withdrawn and filtered into vials in the HPLC sample compartment where the temperature is controlled at 4 degrees C. A fast HPLC method was developed with a 3-min run per injection, enabling analysis of the samples within a very short time after collection, thereby decreasing the sample storage time and potential for degradation. An evaluation was also conducted for comparison of serial and parallel operation of two dissolution baths for the two-stage testing. Serial operation was chosen for this method and applied with a medium-exchange technique, which is safe, robust, easy to perform, compliant with USP, and gives enhanced productivity.