Photopolymerized Micelle-Laden Hydrogels Can Simultaneously Form and Encapsulate Nanocrystals to Improve Drug Substance Solubility and Expedite Drug Product Design.

Abstract

Formulation technologies are critical for increasing the efficacy of drug products containing poorly soluble hydrophobic drugs, which compose roughly 70% of small molecules in commercial pipelines. Nanomedicines, such as nanocrystal formulations and amorphous solid suspensions, are effective approaches to increasing solubility. However, existing techniques require additional processing into a final dosage form, which strongly influences drug delivery and clinical performance. To enhance hydrophobic drug product efficacy and clinical throughput, a hydrogel material is developed as a sacrificial template to simultaneously form and encapsulate nanocrystals. These hydrogels contain micelles chemically bound to the hydrogel matrix, where the surfactant structure dictates the crystal size and drug loading. Therefore, nanocrystals can be produced in high yield (up to 90% drug loading, by weight) with precisely controlled sizes as small as 4 nm independently of hydrogel composition. Nanocrystals and surfactant are then released together to increase the solubility up to 70 times above bulk crystalline material. By integrating nanocrystals into a final dosage form, micelle-laden hydrogels simplify hydrophobic drug product design.