Solubility Behavior of Pimozide in Polar and Nonpolar Solvents: Partial Solubility Parameters Approach

The solubility behavior of pimozide in individual solvents ranging from nonpolar to highly polar was studied. For understanding the solute-solvent interactions, the partial solubility parameters concept was utilized. Solutions containing excess drug were shaken in a water bath for 72 hours at 25 °C. After the solutions attained equilibrium, they were filtered and analyzed for drug content. A multiple regression method, using extended Hansen’s partial solubility parameters, was applied to verify the solubilities of pimozide in pure polar and nonpolar solvents and to predict its solubility in untested solvents. The three-parameter approach and the Flory-Huggins size correction term ‘B’ give predictions of solubilities with correlations up to 97%. The four-parameter approach involving proton-donor and proton-acceptor parameters was also used in fitting the solubility data. The correlations are appreciable (94%). Further, the ‘B’ term coupled with four-parameter approach was examined in order to improve the data representation, and resulted in a 1% improvement (98%) in the correlation when compared to the Flory-Huggins size-correction method. The solubility parameter obtained by this method is 10.43 H which is closer to the values obtained by theoretical methods, such as Fedors’ and Hoy’s. The resulting partial solubility parameters are δ2d=8.85 H, δ2p=2.17 H, δ2a=3.15 H, and δ2b=4.08 H, which give insights into the interaction capability of pimozide and are consistent with its chemical structure. Pimozide is a Lewis base as its δ2b>δ2a. The total solubility parameter of pimozide is assigned at 10.43 H. This work demonstrates for the first time the validity of the four-parameter approach coupled with the Flory-Huggins size-correction term and therefore the result is interesting.