Solubility and pseudopolymorphic transitions in mixed solvent: Meropenem in methanol–water solution

• Solubility of meropenem in mixed methanol–water solvent was first measured.
• Novel solvate form of methylate MERO was first characterized.
• Pseudopolymorphic transitions of meropenem were first observed.
• The equilibrium constant Kh at different temperatures was calculated.
• The transformation enthalpy and entropy were calculated using van’t Hoff equation.

Meropenem exists in the solid state as trihydrate and methylate. In the present work, the solubility data of meropenem in mixed methanol–water solvent ranging from 273.15 K to 288.15 K were measured and pseudopolymorphic transitions of meropenem were first observed. The transition points were determined at various temperatures. The corresponding water/methanol activities at transition points were calculated using Wilson equation, and correlated by van’t Hoff equation. The results show that the ratio of water activity to methanol activity plays a crucial role in determining the thermodynamic stability of trihydrate and methylate of meropenem at a specific temperature. The result can be extended to the application of other pseudopolymorphic systems.