Solubility Measurement, Model Correlation, and Solvent Effect Analysis of Spectinomycin Dihydrochloride Pentahydrate in Three Binary Solvents

The solubility data of spectinomycin dihydrochloride pentahydrate (SDP) in three binary solvents were determined over a temperature range of 278.15–318.15 K by the gravimetric method. Among the selected binary solvents, the solubility of SDP increased with the rise in temperature and initial methanol composition of binary solvents, and the general order of solubility of SDP under the same conditions was: (methanol + ethanol) > (methanol + n-propanol) > (methanol + i-propanol). Subsequently, solubility–temperature models including van’t Hoff equation, λh equation, Yaws equation, and Apelblat equation; solubility–solvent composition models including general single model; solubility–temperature and solvent composition models including NRTL equation and modified Jouyban–Acree model were used to correlate the solubility data. Regarding the application of the NRTL equation in binary solvent systems, the influence of solvent composition on model parameters was first taken into account by introducing a solvent composition correction factor, thereby exhibiting an enhancement in fitting accuracy. To gain deeper insights into the dissolving behavior of SDP, molecular electrostatic potential surface, Hirshfeld surface analysis and the KAT-LSER model were applied to analyze the molecular interactions between SDP molecules and the solvent effects. Meanwhile, entire solubility data in three binary solvent systems at 298.15 K were associated as a function of solvent properties on the basis of KAT-LSER model. The results revealed that SDP primarily acts as hydrogen bond acceptors in solution, and polar interactions between SDP and solvent molecules can play a crucial role in promoting the dissolution of SDP.