Solubility determination and thermodynamic model analysis of nevirapine in different organic solvents from 278.15 K to 328.15 K

Nevirapine (NVP) is the first non-nucleoside reverse transcriptase inhibitor drug to be marketed for the treatment of HIV. The solubility of NVP under atmospheric pressure in eleven pure solvents and three mixtures was measured from 278.15 to 323.15 K. XRD and DSC were used to detect the crystal form and stability of NVP in this work. Overall, the solubility of NVP gradually increases as the temperature rises. In addition, under the same temperature conditions, the solubility of NVP increases with the ratio of the positive solvents in binary solvents. In the mixture (DMF + acetonitrile), when the proportion of DMF reaches 0.8, the solubility in the binary solvent is greater than that in pure DMF. The experimental data was fitted by five thermodynamic models (Buchowski-Ksiazaczak λh model, the Modified Apelblat model, Jouyban-Acree model, SUN model, and CNIBS/R-K model). Subsequently, the largest mean square deviation value (RMSD) is only 2.31E-04, which demonstrates that the correlation of the solubility data and the five models is relatively good. Additionally, KAT-LSER model was used to explore the effects of solute–solvent interactions on solubility at 298.15 K. The analysis results indicated that the dipolarity/polarizability (π^∗) of pure solvents plays a crucial role in the dissolution of NVP and its proportion of the total solvent effect reaches 30.92 %. This research was explored and developed the important systems (1-propyl alcohol and DMF + acetonitrile) for the industrial crystallization purification of NVP.