Enabling isolation of an intrinsically amorphous API using a mesoporous carrier-assisted particle engineering...

In this study, we have developed a mesoporous silica-assisted isolation approach to enable the efficient isolation of an intrinsically amorphous active pharmaceutical ingredient (API), Compound X, with enhanced physicochemical properties, including improved flowability and bulk density. Advanced in-situ process analytical tools (PAT) were applied to systematically investigate the effects of carrier type, solvent composition, API-to-carrier ratio, and anti-solvent addition time on the isolation process, leading to an optimized and scalable methodology. An API-to-carrier ratio of 1:1 (w/w) was achieved, with uniform and complete deposition of the API onto the carrier surface. Building upon gram-scale process understanding, the approach was successfully scaled up to 200 g in a 5 L reactor, demonstrating its feasibility for larger-scale production. The isolated solids exhibited excellent flow properties, high bulk density, and favorable compressibility, tabletability, and compatibility (CTC), enabling a streamlined drug product manufacturing process via direct compression into tablets. Drug release performance was evaluated using FaSSIF-V1 biorelevant medium and full drug release was observed for the Drug substance (DS)/carrier co-processed material. This study highlights the advantages of carrier-assisted API isolation, demonstrating how the integration of PAT can accelerate development timelines and how co-processed APIs can simplify downstream drug product manufacturing. These findings pave the way for more efficient API isolation strategies, addressing the challenges posed by intrinsic amorphous APIs in pharmaceutical development.