Thermodynamics Research Center, ThermoML : Journal of Chemical Thermodynamics

Solubility of clopidogrel hydrogen sulfate polymorphs in ethyl acetate + 2-butanol mixtures at 283.15-313.15 K

Li, Lu, Zhao, Shicheng, Xin, Zhong
J. Chem. Thermodyn. 2019, 139, 105846
ABSTRACT
Aimed at exploring the influence of solvent on crystallization thermodynamics of clopidogrel hydrogen sulfate (CHS), the solubility of CHS polymorphs (Form I and II) in 2-butanol + ethyl acetate mixtures was measured over temperatures from 283.15 to 313.15 K with a static equilibrium method. It was found that the solubility of Form I & II increases first and then decreases with the mole fraction of 2-butanol (x1) increasing, reaching maximum value when x1 = 0.7. The experimental results were well-fitted with the modified Apelblat equation, van't Hoff equation, CNIBS/R-K model, combined version of the Jouyban-Acree model and NRTL model, respectively. Furthermore, the thermodynamic quantities of dissolution and mixing process were calculated. The results indicate that the dissolution process of CHS polymorphs is endothermic and entropy-driven, and thermodynamic quantities of mixing processes is clearly dependent on the mixture's composition.
Compounds
# Formula Name
1 C16H18ClNO6S2 (S)-(+)-Clopidogrel hydrogen sulfate
2 C4H10O butan-2-ol
3 C4H8O2 ethyl acetate
Datasets
The table above is generated from the ThermoML associated json file (link above). POMD and RXND refer to PureOrMixture and Reaction Datasets. The compound numbers are included in properties, variables, and phases, if specificied; the numbers refer to the table of compounds on the left.
Type Compound-# Property Variable Constraint Phase Method #Points
  • POMD
  • 1
  • Triple point temperature, K ; Crystal 2
  • Crystal 2
  • Liquid
  • Air at 1 atmosphere
  • DSC
  • 1
  • POMD
  • 1
  • Molar enthalpy of transition or fusion, kJ/mol ; Crystal 2
  • Crystal 2
  • Liquid
  • Air at 1 atmosphere
  • DSC
  • 1
  • POMD
  • 1
  • Triple point temperature, K ; Crystal 1
  • Crystal 1
  • Liquid
  • Air at 1 atmosphere
  • DSC
  • 1
  • POMD
  • 1
  • Molar enthalpy of transition or fusion, kJ/mol ; Crystal 1
  • Crystal 1
  • Liquid
  • Air at 1 atmosphere
  • DSC
  • 1
  • POMD
  • 1
  • 2
  • 3
  • Mole fraction - 1 ; Liquid
  • Temperature, K; Liquid
  • Solvent: Mole fraction - 2; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal 1 - 1
  • gravimetric method
  • 55
  • POMD
  • 1
  • 2
  • 3
  • Mole fraction - 1 ; Liquid
  • Temperature, K; Liquid
  • Solvent: Mole fraction - 2; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal 2 - 1
  • gravimetric method
  • 55
  • POMD
  • 1
  • 3
  • Mole fraction - 1 ; Liquid
  • Temperature, K; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal 1 - 1
  • gravimetric method
  • 5
  • POMD
  • 1
  • 3
  • Mole fraction - 1 ; Liquid
  • Temperature, K; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal 2 - 1
  • gravimetric method
  • 5
  • POMD
  • 1
  • 2
  • Mole fraction - 1 ; Liquid
  • Temperature, K; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal 1 - 1
  • gravimetric method
  • 5
  • POMD
  • 1
  • 2
  • Mole fraction - 1 ; Liquid
  • Temperature, K; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal 2 - 1
  • gravimetric method
  • 5