Improvement of Some Pharmaceutical Properties of Thiopental by γ-Cyclodextrin Complexation

Abstract

To evaluate a possible utility of .gamma.-cyclodextrin (.gamma.-CyD) in an injecting agent, various pharmaceutical properties of inclusion complex such as dissolution, membrane permeation, chemical stability, protein binding and biological fate were investigated using thiopental (TP) as a test drug. Inclusion complex formation of TP with .gamma.-CyD in aqueous solution and in solid state was assessed by solubility method, spectroscopies, thermal analysis and X-ray diffractometry. The 1:1 TP-.gamma.-CyD complex exhibited a rapid dissolution in water, resulting in the net increase in the fraction of free TP available for membrane permeation. The TP in .gamma.-CyD complex was significantly stable compared with sodium salt of TP during the accelerated storage conditions (40.degree.C, RH 75%). The binding capacity of TP to rabbit serum albumin was reduced by CyD. Because of the small stability constant of TP-.gamma.-CyD complex, no significant effect of .gamma.-CyD was observed on the pharmacokinetic parameters of TP after the i.v. administration of rabbits. Many advantages obtained for TP-.gamma.-CyD complex suggested great utility of .gamma.-CyD in parenteral preparations without change in the biological fate of the drug.