Beta-cyclodextrin/steroid complexation: effect of steroid structure on association equilibria.
Molecular associations of beta-cyclodextrin (beta-CyD) with four steroids (cortisone, hydrocortisone, progesterone, and testosterone) have been studied using phase-solubility and spectroscopic techniques. Phase solubility diagrams could be categorized as B type. The complexes are formed at the stoichiometric ratios of 1:2 (drug:beta-CyD). A mathematical model has been proposed to calculate the apparent stability constants. The results suggest that the inclusion of a steroid molecule into the first beta-CyD cavity is thermodynamically more favorable over the association of 1:1 complex with the second beta-CyD molecule except for cortisone, which exhibits anomalous behavior. A mechanism of complexation has been proposed based on the apparent stability constants and chemical structures of the steroids and beta-CyD. It suggests that complexation is first brought about by inclusion of the five-member cyclopentane ring of the steroid molecule into the first beta-CyD cavity. The 1:1 complex subsequently binds with the second beta-CyD to form the 1:2 complex. The association constants of steroid/beta-CyD complexes are of the following order: progesterone greater than cortisone greater than testosterone greater than hydrocortisone. The order of aqueous solubilities of the complexes is hydrocortisone greater than cortisone greater than testosterone greater than progesterone.
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Department of Industrial and Physical Pharmacy, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47907.
Kildsig
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Mitra
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D003348:Cortisone / Q000737:chemistry; D003505:Cyclodextrins / Q000737:chemistry*; D004355:Drug Stability; D006854:Hydrocortisone / Q000737:chemistry; D011374:Progesterone / Q000737:chemistry; D012995:Solubility; D013256:Steroids / Q000737:chemistry*; D013739:Testosterone / Q000737:chemistry; D047392:beta-Cyclodextrins
D003505:Cyclodextrins; D013256:Steroids; D047392:beta-Cyclodextrins; D013739:Testosterone; D011374:Progesterone; C031215:betadex; D003348:Cortisone; D006854:Hydrocortisone