Efficient and green production of pH-responsive composite hydrogels loaded with drug nanocrystals via oiling-out crystallization without organic solvent

Abstract

The combination of porous polymeric materials with nanodrugs is a promising approach for oral hydrophobic drug delivery. This study aims to establish a novel method for preparing composite hydrogels laden with drug nanocrystals using oiling-out crystallization, eliminating the need for organic solvents and overcoming limitations of traditional methods such as harsh operating conditions and high solvent residues. Using fenofibrate as model drug, a composite hydrogel with fenofibrate crystal size of 960 nm and drug loading of 58 % was prepared. Compared to commercial powders, the composite hydrogel reduced the dissolution time required for 70 % cumulative release by 89.17 % and exhibited excellent controlled-release performance across various pH environments. Unlike traditional organic solvent-based method, which leave anisole residues exceeding safety limits by over 3.5-fold, this method avoids the use of biohazardous solvents, saving at least 1.25 mL/g of fenofibrate produced. In addition, the method was successfully extended to nimodipine to demonstrate its universality.