Solubility, thermodynamic properties, Hansen solubility parameter, and molecular simulation of amitriptyline hydrochloride (Form I) in fourteen organic pure solvents at different temperatures

The solubility of amitriptyline hydrochloride (AMT) (Form I) in fourteen mono-solvents, including {methanol, 2-methoxyethanol, ethanol, 2-ethoxyethanol, n-propanol, 2-propoxyethanol, n-butanol, 2-butoxyethanol, n-octanol, n-hexanol, n-heptanol, n-pentanol, N-Methyl pyrrolidone (NMP), N,N-Dimethylformamide (DMF)} was determined under 0.1 MPa from 278.15 K to 323.15 K by laser detection method. The experimental results showed that as the temperature increasing, the solubility of AMT (Form I) gradually increased. The order of solubility of AMT (Form I) in fourteen mono-solvents at 298.15 K was: methanol (0.1753) > 2-methoxyethanol (0.1488) > 2-ethoxyethanol (0.1082) > 2-propoxyethanol (0.08140) > ethanol (0.07940) > 2-butoxyethanol (0.06600) > n-propanol (0.05720) > NMP (0.04480) > DMF (0.04230) > n-butanol (0.04050) > n-pentanol (0.03210) > n-hexanol (0.02700) > n-heptanol (0.02250) > n-octanol (0.004700). In addition, the Hansen solubility parameter (HSP) was applied to further discuss the miscibility of AMT (Form I) in the studied solvents. Molecular dynamics simulation explored the intermolecular interaction between solute and solvents. And the solvent effect of AMT (Form I) in the tested pure solvents was explained by the KAT-LSER model. The basic data of experimental solubility of AMT (Form I) were correlated with five thermodynamic models, including NRTL, λh, modified Apelblat, NRTL-SAC and two-Suffix Margules. Furthermore, the van't Hoff equation was applied to calculate the dissolution thermodynamic properties of AMT (Form I) in all tested solvents, including Δ dis H o , Δ dis S o and Δ dis G o .