Molecular Insights Into the Formation of Drug-Polymer Inclusion Complex
October 2023
TLDR The research shows how certain drugs can form stable structures with polymers, which is important for making new pharmaceuticals.
This study provides molecular insights into the formation of drug-polymer inclusion complexes (ICs), focusing on carbamazepine (CBZ) and griseofulvin (GSF) with guest polymers. Using microdroplet melt crystallization, single-crystal structures of these ICs were obtained, allowing for structural analysis, density functional theory calculations, and molecular dynamics simulations. The research found that CBZ can form stable channel structures on its own due to its mortise-tenon architecture and strong π...π interactions, while GSF channels require guest molecules for stability due to weaker Cl...O and C-H...π interactions. Channel size is influenced by the host molecules' size, shape, and intermolecular interactions, with observed channel sizes ranging from 3.86-5.18 Å, slightly larger than the guest polymers' radial diameter of 2.83-3.50 Å. The study suggests that the ability of host molecules to self-assemble into a porous structure with channels that can accommodate guest polymers is essential for IC formation. The successful use of microdroplet melt crystallization for rapid synthesis and high-quality single-crystal growth of drug-polymer ICs is highlighted, which is expected to advance research in this area and aid pharmaceutical development.
