High Loading Capacity Nanoencapsulation and Release of Hydrophobic Drug Nanocrystals from Microgel Particles

摘要

Nanosizing of active pharmaceutical ingredients (APIs) is a key approach to improve their bioavailability, particularly in the case of water-insoluble compounds. Moreover, enabling the high load encapsulation of stable API nanocrystals is desirable for their tunable dosing in final products, as well as for further pharmaceutical formulation steps where the active compounds are often diluted with excipients or other additives. Yet, these remain challenging goals due to the lack of a simple and scalable approach. Using nanoemulsion templating in microgel particles, we demonstrate that stable API nanocrystal-loaded particles can be easily synthesized up to high drug loads (>70) via a scalable, low-energy process. Our study shows that the drug release kinetics has a nonlinear dependence on the drug load of the microgel particles, where internal packing of the nanocrystals influences their release from the microgel matrix as the drug load increases. Despite the wide range of dissolution time scales, all of the dissolution profiles can be rescaled using only two adjustable parameters. The effect of particle size can also be used to tune the release rate, and significant dissolution enhancement is observed (up to 70X) compared to bulk API crystals, including at the highest drug load.