Dissolution Behavior of the Crystalline Inclusion Complex Formed by the Drug Diflunisal and Poly(ε-caprolactone)

Multicomponent crystals provide a promising strategy to modulate and optimize the dissolution behaviors of drugs, among which pharmaceutical cocrystals formed between drugs and small molecular coformers have received much attention. Recent studies have shown that certain drugs can also form crystalline inclusion complexes (ICs) with linear polymers, representing a new subcategory of multicomponent pharmaceutical crystals. In this study, we investigated in detail the dissolution behavior and the structure evolution of a crystalline inclusion complex formed by the drug diflunisal (DIF) and hydrophobic poly(e-caprolactone) (PCL). The dissolution profiles of DIF–PCL IC exhibited decreased solubility and dissolution rate compared with the pure DIF crystals at a low pH value. The PCL chains initially residing in the IC channels coalesced and formed crystalline but porous PCL shells on the IC particles during dissolution. These results demonstrated the possibility of using drug–PCL ICs to slow down the drug diss...