(355a) Particle Engineering of Amorphous API Via Co-Processing for Enhanced Physical Properties

Co-processing, an emerging technology that can optimize the physical properties of various active pharmaceutical ingredients (API) and integrate drug substance and drug product manufacturing, is gaining increasing attention widely. This technique has been demonstrated to effectively modify the e.g., bulk density, particle size distribution, morphology, and flowability of crystalline APIs. It has also been applied to directly generate amorphous solid dispersion (ASDs) using various polymers in a drug substance manufacturing facility to improve or control the dissolution profiles and enhance the bioavailability compared to their crystalline counterparts. Such ASDs prepared by co-processing has shown comparable properties compared the ones made from spray drying or hot melt extrusion.

Recently, more APIs has been found to be inherently amorphous due to their flexible or bulky structures that prevent them to form crystalline structures and render them with poor physical properties such as particle size uniformity, flowability and processibility. It also poses significant challenges in terms of drug substance isolation and formulation.

In this presentation, various co-processing strategies have been explored and compared to improve the physical property of an inherently amorphous API. The co-processed API gives uniform particle size distribution, enhanced flowability, which ultimately simplify the drug product manufacturing. The dissolution profile is also compared with the ones prepared from conventional spray drying. In addition, the process feasibility and scalability have also been studied. Various process analytical tools (PAT), such as in situ IR, in situ Raman, and real time imaging tools, are also applied during the co-processing to gain process understandings and used for process optimization.