Improvement of dissolution and absorption characteristics of benzodiazepines by cyclodextrin complexation

Abstract

Inclusion complexes of 13 benzodiazepines with 3 cyclodextrins (α-, β-, γ-CyDs) in aqueous solution and in the solid phase were studied by solubility methods, spectroscopy (UV, CD, IR), thermal analysis, and X-ray diffractometry, and their modes of interaction were assessed. The importance of the hydrophobicity of the guest molecule and the spatial relationship between host and guest molecules were clearly reflected in the magnitude of the stability constant of the inclusion complexes. The solid complexes of some benzodiazepines with γ-CyD were obtained in a variety of molar ratios, and dissolution and membrane permeation behaviors were examined. The rates of dissolution and permeation of benzodiazepines through a cellophane membrane were significantly increased by γ-CyD complexation. As an example, the rapid dissolving form of diazepam-γ-CyD complex was found to significantly increase the serum levels of drug after oral administration to rabbits.