Solubility prediction for furosemide in water-cosolvent mixtures using theminimum number of experiments

The mole fraction solubility of a poorly water soluble loop diuretic, furos emide, was determined in aqueous binary mixtures of ethanol, propylene glyc ol, and glycerol from 0% to 100% cosolvent concentrations at 25 degreesC. S olubility predictions based on the minimum number of experimental data poin ts were performed using the commonly used accurate cosolvency models: the t hree-suffix excess free energy (3xEFE), the mixture response surface (MRS), the combined nearly ideal binary solvent/Redlich-Kister (CNIBS/R-K), and t he general single model (GSM). This prediction method was tested using thre e sets of solubility data for furosemide generated in this study and I I da ta sets collected from the literature. The average percentage deviations (A PDs) were 8.4 +/- 3.8, 13.6 +/- 7.3, 7.4 +/- 2.8, and 7.6 +/- 2.9, respecti vely, for 3xEFE, MRS, CNIBS/R-K, and GSM models. Using 3xEFE, CNIBSIR-K, an d GSM models, which are theoretically related, a mean predicted solubility, (MPS) approach was also proposed. The APD for this method was 7.3 +/- 2. 3 . The mean differences between MRS and the others were statistically signif icant (p < .001). The results showed that one can employ solubility predict ion based on a minimum of five experimental data points, and the expected A PD is less than 10%.