Polymer-Mediated Drug Supersaturation Controlled by Drug–Polymer Interactions Persisting in an Aqueous Environment

We investigated the drug–polymer interactions in nonaqueous and aqueous environments between a poorly water-soluble drug, BAY1161909 (909), and two commonly used polymers in amorphous solid dispersions, i.e., PVP and HPMC-AS. In an nonaqueous state, with a drug–polymer Flory–Huggins interaction parameter, solution NMR and FT-IR results revealed that strong specific interactions existed between 909 and PVP, while not between 909 and HPMC-AS. After prolonged moisture exposure under 95% RH, 909/PVP intermolecular interaction no longer existed, while hydrophobic interaction between 909 and HPMC-AS occurred and persisted. In an aqueous supersaturation study of 909, codissolved PVP significantly outperformed predissolved PVP in maintaining 909 supersaturation. We hypothesized that the codissolved PVP formed a specific interaction with 909, and thus, it was able to prolong 909 supersaturation before disruption of the interaction in aqueous medium, while predissolved PVP formed hydrogen bonds with water, and thus...