Combined effect of cosolvent and cyclodextrin on solubilization of nonpolar drugs

Solubility enhancement has broad implications in parenteral formulation des ign. A simple mathematical model has been developed to describe the combine d effect of cosolvency and complexation on nonpolar drug solubilization. Th e total drug solubility is determined by the summation of three drug specie s present in the solution: free drug [D], drug-ligand binary complex [DL], and drug-ligand-cosolvent ternary complex [DLC]. The proposed model establi shed the dependencies of these three species upon the intrinsic drug solubi lity, [D-u], the cosolvent solubilizing power, sigma, the binary and ternar y intrinsic complexation constants, K-b(int) and K-t(int), and the cosolven t destabilizing powers for the binary and the ternary complexes, rho(b) and rho(t). A nonpolar solute, Fluasterone, is used to evaluate the newly gene rated equation. The model explains the decline in drug solubility produced by low cosolvent concentrations as well as the increase in the solubility p roduced by high cosolvent concentrations that are observed at all cyclodext rin concentrations.