Crystalline inclusion complexes formed between the drug diflunisal and block copolymers

The solid form of drugs plays a central role in optimizing the physicochemical properties of drugs, and new solid forms will provide more options to achieve the desirable pharmaceutical profiles of drugs. Recently, certain drugs have been found to form crystalline inclusion complexes (ICs) with multiple types of linear polymers, representing a new subcategory of pharmaceutical solids. In this study, we used diflunisal (DIF) as the model drug host and extended the guest of drug/polymer ICs from homopolymers to block copolymers of poly(ethylene glycol) (PEG) and poly(epsilon-caprolactone) (PCL). The block length in the guest copolymers showed a significant influence on the formation, thermal stability and dissolution behavior of the DIF ICs. Though the PEG block could hardly be included alone, it could indeed be included in the DIF ICs when the PCL block was long enough. The increase of the PCL block length produced IC crystals with improved thermal stability. The dissolution profiles of DIF/block copolymer ICs exhibited gradually decreased aqueous solubility and dissolution rate with the increasing PCL block length. These results demonstrate the possibility of using drug/polymer ICs to modulate the desired pharmaceutical profiles of drugs in a predictable and controllable manner. (C) 2017 Chinese Chemical Society and Institute of Materia Medica, Chinese Academy of Medical Sciences. Published by Elsevier B.V. All rights reserved.