Metformin hydrochloride (MET•HCl) is one of the most widely used oral hypoglycemic drugs in the world. In addition to hypoglycemic effects, MET•HCl also has anti-inflammatory, anti-tumor, anti-aging, and other effects, showing good efficacy and safety of single and combined treatment. The solubility of MET•HCl in water, water + N,N-dimethylformamide, water + acetonitrile, and water + n-propanol was measured by the gravimetric method under atmospheric pressure at temperatures ranging from 283.15 to 323.15 K. The solubility of MET•HCl has a positive correlation with temperature and water content. The experimental solubility data in binary solvents was correlated by the modified Apelblat model, CNIBS/R-K model, Apelblat− Jouyban−Acree model, and λh model. By comparing the average ARD % values of the four models, it is found that the modified Apelblat model (ARD % = 1.26) provides better correlation. Hansen solubility parameters and apparent thermodynamic parameters were calculated to analyze the solubility behavior, indicating that the dissolution process is endothermic and entropically favorable.
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