Core-Shell Composite Hydrogels for Controlled Nanocrystal Formation and Release of Hydrophobic Drugs


Abu Zayed Md Badruddoza, P. Douglas Godfrin


Abu Zayed Md Badruddoza, P. Douglas Godfrin, Allan S. Myrson, Bernhardt L. Trout, Patrick S. Doyle

Author Affiliation: 

Department of Chemical Engineering, Massachusetts Institute of Technology


Although roughly 40% of pharmaceuticals being developed are poorly water-soluble, this major class of drugs still lacks a formulation strategy capable of producing high loads, fast dissolution kinetics, and low energy input. Utilization of innovative biocompatible materials in formulations of such drugs to enhance their dissolution and bioavailability 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 ranging from 500 nm to 650 nm embedded within the core. Adjustable loading of API nanocrystals up to 83% by weight is achieved with dissolution (of 80% of the drug) occurring in as little as 30 minutes. 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. Thus, these composite materials offer a ÔdesignerÕ drug delivery system. Overall, our approach enables a novel means of simultaneous controlled crystallization and formulation of poorly soluble drugs that circumvents energy intensive top-down processes in traditional manufacturing.