Effect of hydroxypropyl beta-cyclodextrin on drug solubility in water-propylene glycol mixtures

Combined effects of cosolvency and inclusion complexation on drug solubility were studied using a model hydrophobic compound (carbamazepine) and a model hydrophilic compound (Compound S). Propylene glycol (PG) was used as the nonaqueous solvent, and deionized water was employed for the aqueous systems. Hydroxypropyl beta-cyclodextrin (HPbetaCD) was chosen as the complexing agent and studied at concentrations up to 28% (w/v). Complex formation constants (Kc) and solubility enhancement ratios were determined for the respective compounds in various water/PG vehicles. The data suggested that the inclusion of the compounds was most favorable when water alone was used as the vehicle. However, the combined approach of cosolvency and complexation resulted in a significant increase in the total apparent solubility of carbamazepine (the hydrophobic compound). The same was not observed with Compound S (the hydrophilic model), since PG weakened the interactions between the molecule and HPbetaCD, and thus, no synergistic or additive effects were observed with the combined approach of complexation and cosolvency.