Determination and Correlation of Solubility of Quetiapine Fumarate in Nine Pure Solvents and Two Aqueous Binary Solvents

A gravimetric method was used to determine the solubility of quetiapine fumarate (QF) in nine pure solvents and two aqueous binary solvents (water + methanol/ethanol) at different temperatures from 283.15 to 323.15 K. The solubility of QF increases with the increase of temperature in nine pure solvents, and it is in the order DMF > methanol > ethanol >1-butanol > isopropyl alcohol > (acetone > ethyl acetate > isobutyl alcohol) > water at low temperature, and in the order DMF > methanol > ethanol >1-butanol > isopropyl alcohol > (acetone > isobutyl alcohol > ethyl acetate) > water at relatively high temperature at a given temperature. The solubility of QF in the binary solvents also shows temperature dependence, while at a given temperature the solubility is mainly influenced by the solvent composition with the presence of maximum, reflecting cosolvency. Also the solubility of QF increases with the increase of temperature in binary solvents in a given composition. The Hansen solubility parameters were used to explain the cosolvency and maxima shift, confirming that for large values (>25 MPa1/2) of solute, the solubility shows a peak in the range of 35 to 31 MPa1/2 of solubility parameters of alcohol mixtures. The experimental solubility of QF in pure and binary solvents is well correlated by modified Apelblat equation, the nonrandom two-liquid model, and the CNIBS/R-K equation, respectively.