Introduction of new method for prediction of solubility parameter using aripiprazole as a model drug

Aripiprazole, a typical antipsychotic medication used in the treatment of schizophrenia, is a poorly water-soluble drug. The solubility of aripiprazole can be better understood through its solubility parameter. Hence an attempt is made to determine the solubility parameter (SP) and partial solubility parameters (PSP) for aripiprazole using the methods reported in the literature. SP has been determined by various theoretical group contribution methods, such as Hoy's, Fedors’, Small's and van Krevelen's, using molar attraction constants and molar volumes given for various groups. Partial solubility parameters of aripiprazole were determined using the constants given by van Krevelen. Further, the SP was also determined by experimental method using the saturation solubility data determined in 19 solvent blends namely hexane- ethyl acetate, ethyl acetate- ethanol, and ethanol- water, which cover least polarity to highest polarity at 25 °C using cryostatic constant temperature shaker bath. In addition to this, an attempt was made using 7 more solvent blends of dioxane-water to determine the saturation solubility. The SP values for Aripiprazole obtained were 10.26 H and 10.97 H by Hoy's method. Fedors’ method revealed the values as 11.19 H and 10.63 H. However, Small's method gave the value as 13.72 H. In addition, van Krevelen's method was useful in obtaining total solubility parameter (11.61 H) and partial solubility parameters (δd 10.63 H, δp = 2.91 H, and δh= 3.66 H). Apart from this, experimentally determined mole fraction saturated solubility values in 19 solvent blends were used to obtain the solubility parameter as 9.72 H. The accuracy of the total solubility parameter (TSP) was improved to 10.03 H, when solubility data were analyzed by incorporating 7 more solvent blends of dioxane-water systems. The TSP of aripiprazole was found to be 10.03 H. Hence the obtained value can be used to select the most appropriate solvent or solvent blends with the solubility parameter values near to it (10 ± 1 H). The new method adopted in this investigation is successful and can be applied for other drugs also.