Date of Award


Degree Type


Degree Name

Doctor of Pharmacy (PharmD)

First Advisor

Christopher T. Rhodes


The complexation of drugs with alpha, beta, gamma and hydroxyethyl beta cyclodextrins was investigated using the solubility method described by Higuchi and Connors . Beta cyclodextrin was shown to exhibit the most extensive complexation. The solubility isotherms of complexation were studied at different temperatures and at various pH conditions. The effect of ionization of drugs on complexation was thus evaluated for four drugs viz phenytoin, diazepam, ibuprofen and hydrochlothiazide. In the case of phenytoin and diazepam, both the non-ionized and the ionized species were shown to form a complex with cyclodextrins. The slope of complexation for ibuprofen and hydrochlorothiazide was found to be pH-independent. The thermodynamic parameters of complexation were determined using the temperature dependence method. In order to characterize more specifically the parameters of complexation, a novel computerized method was then developed. A non-linear regression software was used to evaluate the values of the complexation parameters as well as their standard deviation and 95% confidence limit. The complexation of drugs with hydroxyethyl beta cyclodextrin showed that the substitution of the natural cyclodextrin affected the solubility of the complexing agent without altering its solubilizing power. A rule of prediction was then proposed, allowing the calculation of potential drug concentration upon complexation with the cyclodextrin derivative. The ratio of solubility of the two kinds of cyclodextrins was shown to correlate very well with the ratio of the concentration of drug complexed. The rule might be applied to all drugs at various pH values. The potential use of beta cyclodextrin as an additive in tableting was also evaluated. The mechanism of dissolution rate enhancement was found to be related not only to the inclusion complex formation but also to mechanical changes during the mixing process.