Thermodynamics Research Center / ThermoML | Journal of Chemical and Engineering Data

Solubility Advantage of Pyrazine-2-carboxamide: Application of Alternative Solvents on the Way to the Future Pharmaceutical Development

Lourenco, C.[Catarina], Melo, C. I.[Catarina I.], Bogel-Lukasik, R.[Rafal], Bogel-Lukasik, E.[Ewa]
J. Chem. Eng. Data 2012, 57, 5, 1525-1533
ABSTRACT
The solubility of an antitubercular drug in alternative solvents can offer a potential application in pharmaceutical processing. Solid liquid equilibrium (SLE) measurements have been made using a dynamic (synthetic) method. The melting point, the enthalpy of fusion, temperature of the solid solid phase transition, and corresponding enthalpy of pyrazine-2-carboxamide were obtained using differential scanning calorimetry (DSC). The solubility of pyrazine-2-carboxamide in bis(trifluoromethylsulfonyl)amide ionic liquids is at least 1 order of magnitude lower than that in the studied trifluoromethanesulfonate ionic liquid. 1-Decyl-3-methylimidazolium trifluoromethanesulfonate ionic liquid was found to be the best solvent for a carboxamide drug. The solid liquid phase equilibria were described using six different correlation equations which revealed a relatively good description with an acceptable standard deviation temperature range. Nonvolatile ionic liquids, due to their safer aspects, can compete with other potentially flammable chemicals that are routinely used in the pharmaceutical development, given the data presented for the pyrazine derivative. Bis(trifluoromethylsulfonyl)amide and trifluoromethanesulfonate based ionic liquids showed sufficient solubilities toward a drug; thus, it makes them suitable for the future pharmaceutical processing.
Compounds
# Formula Name
1 C15H27F3N2O3S 1-decyl-3-methylimidazolium trifluoromethansulfate
2 C5H5N3O pyrazinecarboxamide
3 C8H11F6N3O4S2 1-ethyl-3-methylimidazolium bis((trifluoromethyl)sulfonyl)imide
4 C10H15F6N3O4S2 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide
5 C12H19F6N3O4S2 1-hexyl-3-methylimidazolium bis[(trifluoromethyl)sulfonyl]imide
6 C14H23F6N3O4S2 1-octyl-3-methylimidazolium bis[(trifluoromethyl)sulfonyl]imide
7 C16H27F6N3O4S2 1-decyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amide
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
  • 2
  • Molar enthalpy of transition or fusion, kJ/mol ; Crystal 1
  • Crystal 1
  • Liquid
  • Air at 1 atmosphere
  • DSC
  • 1
  • POMD
  • 2
  • Molar enthalpy of transition or fusion, kJ/mol ; Crystal 2
  • Crystal 2
  • Crystal 1
  • Air at 1 atmosphere
  • DSC
  • 1
  • POMD
  • 2
  • Triple point temperature, K ; Crystal 2
  • Crystal 2
  • Crystal 1
  • Air at 1 atmosphere
  • DTA
  • 1
  • POMD
  • 2
  • Normal melting temperature, K ; Crystal 1
  • Crystal 1
  • Liquid
  • Air at 1 atmosphere
  • DTA
  • 1
  • POMD
  • 3
  • Normal melting temperature, K ; Metastable crystal
  • Metastable crystal
  • Liquid
  • Air at 1 atmosphere
  • VISOBS
  • 1
  • POMD
  • 2
  • 3
  • Solid-liquid equilibrium temperature, K ; Liquid
  • Mole fraction - 2; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal - 3
  • VISOBS
  • 1
  • POMD
  • 2
  • 3
  • Solid-liquid equilibrium temperature, K ; Liquid
  • Mole fraction - 2; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal 2 - 2
  • VISOBS
  • 14
  • POMD
  • 2
  • 4
  • Solid-liquid equilibrium temperature, K ; Liquid
  • Mole fraction - 2; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal 2 - 2
  • VISOBS
  • 13
  • POMD
  • 2
  • 5
  • Solid-liquid equilibrium temperature, K ; Liquid
  • Mole fraction - 2; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal 1 - 5
  • VISOBS
  • 2
  • POMD
  • 2
  • 5
  • Solid-liquid equilibrium temperature, K ; Liquid
  • Mole fraction - 2; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal 2 - 2
  • VISOBS
  • 13
  • POMD
  • 2
  • 6
  • Solid-liquid equilibrium temperature, K ; Liquid
  • Mole fraction - 2; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal 2 - 2
  • VISOBS
  • 12
  • POMD
  • 2
  • 7
  • Solid-liquid equilibrium temperature, K ; Liquid
  • Mole fraction - 2; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal 2 - 2
  • VISOBS
  • 12
  • POMD
  • 2
  • 1
  • Solid-liquid equilibrium temperature, K ; Liquid
  • Mole fraction - 2; Liquid
  • Pressure, kPa; Liquid
  • Liquid
  • Crystal 2 - 2
  • VISOBS
  • 13