DETERMINATION OF 3-COMPONENT PARTIAL SOLUBILITY PARAMETERS FOR TEMAZEPAM AND THE EFFECTS OF CHANGE IN PARTIAL MOLAL VOLUME ON THE THERMODYNAMICS OF DRUG SOLUBILITY

Three-component partial solubility parameters for temazepam were determined by the extended Hansen regression model. A high level of correlation was observed when the Flory-Huggins entropy correction was incorporated into the model. The partial molal volume of temazepam was determined in the saturated solutions and these experimental values further improved the correlation. The changes in molal volume are shown to affect both the entropy change and the enthalpy change, attributable to dispersion forces, occurring in the solution process. The dispersion forces operating between solute and solvent are corrected for changes in molal volume by the use of a derived equation. The final model for temazepam solubility showed a high degree of correlation, giving as values for the partial (Hansen) solubility parameters of temazepam: delta-D = 10.71, delta-P = 4.79, delta-H = 4.02 cal1/2 cm-3/2. The experimental partial solubility parameters predicted the solubility of temazepam in 29 solvents with an average error of 33.4%.