(600b) Combining Liquid-Liquid Phase Separation and Mesoporous Carrier to Deliver Drug Product Intermediate

Moussa Boukerche, Sean Garner, and Nandkishor K. Nere

Center of Excellence for Isolation and Separation Technologies (CoExIST), Process Research and Development, AbbVie Inc

Liquid-Liquid Phase Separation (LLPS), typically known as oiling out is an undesired phenomenon when developing a robust and scaleable antisolvent crystallization process. LLPS can occur in ternary phase system composed of the molecule, a solvent and an anti-solvent. The solvent and anti-solvent alone are fully miscible but the presence of the solute can force the system to phase split and deliver a binary solution made of a continuous (solute rich) and a dispersed phase (solute lean). This phenomenon will impact the purity and physical properties of the molecule of interest and typically delivers a sticky amorphous phase not suitable for drug product development. In order to circumvent this issue and take advantage of LLPS, a phase diagram determination combined with the use of Mesoporous carrier (Neusilin US2 in this case) allows the preparation of Drug Product Intermediates (DPI) with tunable drug load from 0.1 to 65wt%. The DPI has the physical properties of the carrier and is not impacted by the physical properties of the Drug Substance (DS). This DPI has the potential to be readily suitable for direct compression, reduce the risk of variability of content uniformity, sticking behavior, polymorphic phase transition during DP processing. This approach is different than the Incipient Wetness Impregnation technique that is traditionally used to load mesoporous carrier. This presentation will describe the workflow of this new approach to quickly enable DPI by triggering LLPS purposefully to load mesoporous carrier with a defined drug load.

All authors 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.