Furosemide:Triethanolamine Salt as a Strategy to Improve the Biopharmaceutical Properties and Photostability of the Drug

CHATTAH, ANA K.; LONGHI, MARCELA R.; CHATTAH, ANA K.; LONGHI, MARCELA R.; ABRAHAM MIRANDA, JULIETA; SANTIAGO DE OLIVEIRA, YARA; ABRAHAM MIRANDA, JULIETA; SANTIAGO DE OLIVEIRA, YARA; GARNERO, CLAUDIA; AYALA, ALEJANDRO P.; GARNERO, CLAUDIA; AYALA, ALEJANDRO P.

CRYSTAL GROWTH & DESIGN

AMER CHEMICAL SOC

Año: 2019 vol. 19 p. 2060 - 2068

1528-7483

With the purpose of enhancing the biopharmaceutical properties of the furosemide, a pharmaceutical salt was obtained and characterized by combining the drug and triethanolamine. The solid system was prepared using different techniques such as kneading, grinding, and slow evaporation. It was characterizated by X-ray powder diffraction, solid-state nuclear magnetic resonance, infrared and Raman spectroscopy, thermal analysis, and scanning electron microscopy. The results showed that the same pharmaceutical compound in solid state was obtained through the different preparation techniques. The crystalline structure was fully elucidated by single-crystal X-ray diffraction. The salt formation was confirmed by two-dimensional nuclear magnetic resonance experiments, which revealed the transference of the OH proton of the drug to triethanolamine. Besides, the solubility studies demonstrated an increase in the drug solubility attributed not only to a pH change but also to a soluble salt formation in solution. In addition, the combination of the drug with triethanolamine produces an enhancement of the chemical photostability, whereas the physical photostability and the hygroscopicity status were not modified. Finally, this new solid form of furosemide constitutes an interesting strategy to improve the biopharmaceutical properties and stability of furosemide, with potential application in pharmaceutical formulations.