(766d) 'designer' Hydrogel Particles for Controlled Crystallization and Release of Hydrophobic Active Pharmaceutical Ingredients

Badruddoza, A. Z. M., Massachusetts Institute of Technology
Godfrin, P. D., University of Delaware
Myerson, A. S., Massachusetts Institute of Technology
Trout, B. L., Massachusetts Institute of Technology
Doyle, P. S., Massachusetts Institute of Technology
Nearly 40% or more of drugs currently in the pipeline of the pharmaceutical companies are poorly water soluble, which introduces a significant hurdle for formulating such major class of drugs with an effective dosage. Utilization of innovative biocompatible materials in formulations of hydrophobic drugs to enhance their solubility-limited oral bioavailability and absorption is a rapidly growing area in pharmaceutical materials research. In this work, we develop a novel bottom-up approach for producing and formulating nanocrystals of poorly water-soluble active pharmaceutical ingredients (APIs) using core-shell composite hydrogel beads. Organic phase nanoemulsion droplets stabilized by polyvinyl alcohol (PVA) and containing a model hydrophobic API (fenofibrate) are embedded in the alginate hydrogel matrix and subsequently act as crystallization reactors. Controlled evaporation of this composite material produces core-shell structured alginate-PVA hydrogels with drug nanocrystals (500 - 650 nm) embedded within the porous confinement environment of the core. Adjustable loading of API nanocrystals up to 83% by weight is achieved with improved dissolution behavior. We also develop a quantitative model and experimentally validate that the drug release patterns of the fenofibrate nanocrystals can be modulated by controlling the thickness of the PVA shell and drug loading. In summary, our composite hydrogel enabled encapsulation system allows for controlled crystallization, adjustable drug loading, and customizable dissolution profiles ranging from fast to delayed release by utilizing the unique microstructures of coreâ??shell hydrogels, thus provides a versatile oral delivery system.