NMR study of the inclusion complexes of beta-cyclodextrin with diphenhydramine, clonidine and tolperisone

Abstract

Forming complexes with beta-cyclodextrin can enhance stability, dissolution rate, solubility, and bioavailability of an active pharmaceutical ingredient. In this study, the inclusion behavior between beta-cyclodextrin (beta-CD) and diphenhydramine, clonidine, and tolperisone in DMSO-d(6) was investigated using NMR spectroscopy. H-1, C-13, COSY, HMQC, and ROESY data were applied to determine the structure of inclusion complexes, and molecular docking analysis was engaged to identify the most favorable host-guest interactions in the inclusion complexes. Complexation of beta-CD with diphenhydramine, clonidine, and tolperisone is accompanied by the insertion of a molecular fragment of the guest molecule, one molecule of diphenhydramine and tolperisone, and two molecules of clonidine, into the inner sphere of one host molecule. The reported study provides useful information for the potential application of the complexation of beta-CD with diphenhy-dramine, clonidine, and tolperisone. This may be a good strategy for the development of solid pharmaceutical dosage forms based on beta-CDs as a drug delivery system.