(636f) Supercritical Fluid Precipitation, an Emerging "Jack of All Trades" Unit Operation in the Pharmaceutical Industry

Supercritical carbon dioxide (sc-CO₂) is a unique fluid which can be used as a supercritical antisolvent (SAS) to efficiently precipitate dissolved compounds from organic and organic/aqueous solutions relevant to pharmaceutical manufacturing. Despite sc-CO₂’s numerous advantages over common liquid solvents including high mass-diffusivity, low toxicity, non-flammability, and low cost, supercritical fluid-based processing has largely been relegated to niche applications in the pharmaceutical industry. In this work, we aim to demonstrate that supercritical fluid precipitation using sc-CO₂ provides an enabling and more efficient method to numerous common unit operations used in pharmaceutical manufacturing including precipitation, drying, solvent swaps, particle micronization, extraction, reactions, and crystal form screening.

Several case studies will be presented including a unique application in which a model compound, carbamazepine, can be crystallized from supercritical CO₂ in different polymorphs by varying the operating pressure and temperature of the SAS equipment. Furthermore, rapid drying of high boiling solvents such as DMSO at moderate temperatures (40°C) is demonstrated owing to the high mass diffusivity and miscibility of sc-CO₂ with organic solvents. Redissolution of dry precipitated solids in lower boiling solvents affords another advantage, allowing solvent swaps from high boiling solvents to lower boiling solvents without needing to chase distill. This greatly reduces process mass intensity and enables previously non-feasible solvent swaps. Finally, a sc-CO₂ intensified reactive precipitation of a piperidine fragment will be presented for one of AbbVie's pipeline assets. The transformation describes the carboxylation of an organolithiate intermediate to selectively form the desired carboxylate salt, isolated as a dry powder. Through the variety and wide applicability of sc-CO₂ based processing, we demonstrate an emerging, “jack of all trades” unit operation with the potential to have significant impact on common pharmaceutical unit operations.

Disclosures:

All authors except Bryan Erriah are employees of AbbVie and may own AbbVie stock. AbbVie sponsored and funded the study; contributed to the design; participated in the collection, analysis, and interpretation of data, and in writing, reviewing, and approval of the final publication.