Pharmalytical Summit 2021 - Technical/Others 3. New Molecular Insights into the Solid-State Variability of Warfarin Sodium 2-Propanol Solvate Using a Multivariate and Multi-technique Approach

A primary anti-coagulant narrow therapeutic index drug, warfarin sodium, poses a high risk of thrombosis or excessive bleeding with sudden death. The root cause for these risks is not well established. It has been hypothesized that a freely soluble crystalline warfarin sodium (WARC) transforms to non-crystalline warfarin sodium (WARNC) under stress conditions and that the WARNC can later transform to the poorly soluble un-ionized form. This transformation could directly lead to dissolution failure in-vivo and could be responsible for the increased clinical risks. The study presented here focused on systematically characterizing solid form changes and 2-propanol (IPA) content under different environmental conditions followed by a low volume 2-stage dissolution method to mimic in vivo GIT behavior.