A New Approach for Quantitative Determination of γ-Cyclodextrin in Aqueous Solutions: Application in Aggregate Determinations and Solubility in Hydrocortisone/γ-Cyclodextrin Inclusion Complex

Fast and simple high-pressure liquid chromatographic (HPLC) method with charged aerosol detector (CAD) was developed for quantitation of γ-Cyclodextrin (γCD) in aqueous solutions. The chromatographic system consisted of a C18 column (i.e., the stationary phase) and an aqueous mobile phase containing 7% (v/v) methanol. Calibration curve was obtained over the γCD concentration range of 0.005%-1% (w/v). The limit of detection and quantitation of γCD were 0.0001% and 0.0002% (w/v), respectively. Formation of γCD aggregates in aqueous solution and their critical aggregation concentration (cac) were determined by both conventional dynamic light scattering method and permeation method using HPLC-CAD for quantitative determination of γCD. The cac of γCD was determined to be 0.95% (w/v) and the amount of γCD self-aggregates increased with increasing γCD concentrations. Also, the developed HPLC-CAD method was used to determine the γCD phase-solubility profile in an aqueous hydrocortisone (HQ/γCD complexation medium. The maximum concentration of dissolved γCD and HC was determined to be 1.47% and 0.31% (w/v), respectively. The membrane permeation method was shown to be a reliable method for determination of metastable γCD aggregates. The HPLC-CAD method was successfully applied for quantitative determination of γCD in aqueous solutions during permeation and phase-solubility studies.