Fuente: Molecules - Revista científica (MDPI) Molecules, Vol. 31, Pages 1855: Thermodynamics and Crystallization Behavior of Meropenem Influenced by Solvent Composition and pH
Molecules doi: 10.3390/molecules31111855
Authors:
Jinshen Ren
Sanli Yin
Yifu Zhang
Mingyu Chen
Na Wang
Ting Wang
Xin Huang
Hongxun Hao

To develop an improved crystallization process for meropenem trihydrate, an important carbapenem antibiotic, the pH-dependent solubility of meropenem trihydrate in different solvent systems was investigated using the laser monitoring dynamic method. The solubility data displayed a characteristic U-shaped profile. The solvent composition could also affect the solubility data and the isoelectric point of meropenem. The experimental solubility data were well correlated with the Tsuji model. Hirshfeld surface (HS) analysis highlighted the significance of O···H/H···O interactions in the crystal structure. Molecular electrostatic potential surfaces (MEPs) revealed complementary positive and negative regions on the meropenem molecule, enabling solute–solute aggregation through electrostatic interactions. Furthermore, molecular dynamics (MD) simulations provided deeper insights into the influence of ethanol and acetone on the solvation layer of meropenem. Additionally, the effects of pH value and solvent composition on the crystallization process of meropenem trihydrate were discussed. The crystal habit is affected by variations in solvent composition and pH. Finally, the combined effects of solvent polarity, dielectric constant, and solvation on both solubility and the crystallization process were comprehensively summarized.