Measurement and correlation of solubility, Hansen solubility parameters and thermodynamic behavior of Clozapine in eleven mono-solvents

Abstract

Mole-fraction solubility of Clozapine (CLZ) in eleven mono-solvents (methanol, ethanol, n-propanol, isopropanol, acetone, 1,2-dichloroethane, benzene, toluene, N,N-Dimethylformamide (DMF), n-Methyl-2-pyrrolidone (NMP) and dimethyl sulfoxide (DMSO)) at varied temperatures (from 283.15 K to 333.15 K at 5 K intervals) was experimentally determined by a classic gravimetric method under an atmosphere pressure of 0.101 MPa. The mole solubility of CLZ in the selected mono-solvents exhibited a positive relation with temperature. In addition, the solubility sequence of CLZ at 298.15 K is: DMF > DMSO > NMP > 1,2-dichloroethane > acetone > methanol > benzene > n-propanol > ethanol > toluene > isopropanol. The Hansen solubility parameters (HSPs) and solvents polarity were applied to explore this solubility behavior. The KAT-LSER model was calculated to investigate the solvent effect based on linear solvation energy relationships concept. Four thermodynamic models including the modified Apelblat model, Wilson model, NRTL model and UNIQUAC model were employed to correlate the experimental solubility, which indicated that both modified Apelblat model and NRTL model were more suitable in correlation with the measured solubility data. Furthermore, the solution thermodynamic properties (ΔdisGo, ΔdisHoand ΔdisSo) of CLZ in the selected eleven solvents were calculated by van't Hoff equation, and the positive values of ΔdisHo and ΔdisSo indicated that the dissolution process of CLZ in the measured mono-solvents was endothermic and entropy-driven.