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Abstract
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 β‐cyclodextrin (HPβCD) 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 HPβCD, and thus, no synergistic or additive effects were observed with the combined approach of complexation and cosolvency.