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

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.