Determination and Correlation of Solubility of Metformin Hydrochloride in Aqueous Binary Solvents from 283.15 to 323.15 K

Chuanping Yu; Xinyuan Sun; Yan Wang; Shichao Du; Liang Shu; Qilei Sun; Fumin Xue

doi:10.1021/acsomega.1c06468

Determination and Correlation of Solubility of Metformin Hydrochloride in Aqueous Binary Solvents from 283.15 to 323.15 K

ACS Omega. 2022 Mar 1;7(10):8591-8600. doi: 10.1021/acsomega.1c06468. eCollection 2022 Mar 15.

Authors

Chuanping Yu¹, Xinyuan Sun², Yan Wang², Shichao Du², Liang Shu³, Qilei Sun¹, Fumin Xue²

Affiliations

¹ School of Material Science and Engineering, Shandong Jianzhu University, Jinan 250101, PR China.
² School of Pharmaceutical Sciences, Shandong Analysis and Testing Center, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250014, PR China.
³ Suzhou Lixin Pharmaceutical Company Ltd., Suzhou 215000, PR China.

Abstract

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.