Cyclodextrin complexation and pH adjustments have been reported as useful tools to increase the solubility of drug. The aim of this study was to investigate the influence of both cyclodextrin and pH on the overall solubility of ketoprofen. β-cyclodextrin (β-CD) and hydroxypropyl β-cyclodextrin (HP-β-CD) were used for the preparation of inclusion complex by shaking method in aqueous solution at pH 2, 5, 7 and 10. It was found that the solubility of ketoprofen significantly increased with increasing pH and cyclodextrin concentration, showing AL type phase solubility diagram. However, the apparent stability constant of complex (KC) was found to decrease with increasing pH due to the decreased affinity of ionized drug to cyclodextrin cavity. The ionization of ketoprofen increased when the pH was raised, corresponding with its higher zeta potential. The result indicated that the solubility of ketoprofen could be improved by using a combined approach of pH adjustments and complexation with cyclodextrin. Moreover, the unionized drug that was formed by pH adjustments interacted with cyclodextrin more strongly than the ionized drug.
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