470461 Investigation of the Dfferences in Material Properties Between Amorphous Dispersions Created By Conventional Methods and High-Shear Co-Precipitation

Friday, November 18, 2016: 12:30 PM
Continental 5 (Hilton San Francisco Union Square)
Athanas Koynov1, Luke Schenck2, Narayan Variankaval3, Andrew Brunskill4, Amanda Mann5, Yongjun Li6, Dina Zhang6, Dirk Stueber4 and Paul Walsh5, (1)Merck, Rahway, NJ, (2)Chemical Process Development and Commercialization, Merck & Co, Inc., Rahway, NJ, (3)Process R&D, Merck & Co., Rahway, NJ, (4)MMC, Merck and Co., Rahway, NJ, (5)Preclinical Development, Analytical Sciences, Merck and Co., Rahway, NJ, (6)Preformulation, Merck and Co., Rahway, NJ

High-shear co-precipitation is a technique for the manufacturing of API-polymer amorphous solid dispersions, and is an alternative to the typical spray-drying and hot-melt extrusion processes. The technique relies on the rapid contacting of a solution of polymer and API with a common anti-solvent, resulting in a stable suspension where the precipitated amorphous solid dispersion is below its glass transition temperature.

In this work we present the characterization and analysis of a co-precipitated solid dispersion exhibiting significant differences in properties compared to equivalent dispersions, prepared via spray-drying and hot-melt extrusion. These differences extend across the full spectrum of “fundamental” characteristics, including morphology, true density, glass transition temperature and enthalpy, as well as indirect, “performance-based” properties, such as compactability and dissolution. A large collection of “orthogonal” techniques is brought to bear in the analysis of the material and the elucidation of the physical processes underlying these differences in properties.

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