Many new pharmaceuticals in the pipeline are quite hydrophobic and thus suffer from poor aqueous solubility. This can lead to low bioavailability in oral administration applications. To improve the solubility of such molecules, amorphous solid dispersions (ASDs) consisting of the amorphous drug stabilized within a polymeric matrix are often utilized. The dissolution of ASDs have been found to result in the formation of drug-rich nanoparticles in solution, which can hinder drug crystallization and improve mass transport of the drug across membranes. However, little is known about how the polymer and drug form the nanoparticles and how they impact the dissolution profile. To address these questions, nilutamide, phenytoin, and itraconazole were utilized as drug models, and poly(N-isopropylacrylamide-<i>co</i>-N,N-dimethylacrylamide) and poly(vinyl pyrrolidone-<i>co</i>-vinyl acetate) were explored as model polymer excipients. Across a range of systems and dissolution profiles, we found that the formation of nanoparticles was a common feature and was associated with achieving and maintaining a high degree of drug supersaturation. Additionally, the degree of interaction between the polymer excipient and the drug rich nanoparticles appeared to control the dissolution profile by delaying drug crystallization and/or amorphous precipitation.

Role of nanostructures formed during polymer/drug dissolution

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.