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

Abstract

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.

Influence of Aqueous Solubility-Enhancing Excipients on the Microstructural Characteristics of Furosemide-Loaded Electrospun Nanofibers

“…However, it can also be observed at 1610 cm −1 in the physical mixture of composition-TEA, where the liquid triethanolamine was added to the powder excipients, and the mixing of the compositions in a mortar led to partial salt formation. Similar results were found by Abraham et al They observed a new band at 1612 cm −1 , corresponding to the COO − group, while furosemide and triethanolamine were used for salt formation [31].…”

Furosemide/Non-Steroidal Anti-Inflammatory Drug–Drug Pharmaceutical Solids: Novel Opportunities in Drug Formulation

“…Several authors have reported pharmaceutical salts and cocrystals of FUR. A search of this dataset for drug-drug multi-component crystals revealed a total of 11 systems [8,[10][11][12][13][29][30][31]. A common structural feature observed is the key role of the carboxylic group in the interaction with the coformer or counterion and the formation of other synthons involving the sulfonamide group that participates in stabilizing the crystal structure packing.…”

“…When the two APIs are joined together in the solid form, the reported IR bands with diagnostic values are expected to be shifted, thus indicating the presence of intermolecular forces between functional groups-i.e., hydrogen bonds-which build the cocrystal structures [44]. Band assignments (Table 3) were performed based on the crystallographic analysis (Section 3.1) and considering the spectroscopic data available for related FUR compounds found in the literature [13]. FUR exhibits stretching frequencies at 3400 and 3351 cm −1 (sulfonamide primary amine), 3285 cm −1 (sulfonamide secondary amine), 1670 cm −1 (carboxyl stretch), and 1328 and 1139 cm −1 (sulfonamide S=O stretching modes).…”

“…The development of this novel strategy is rather interesting because allows industry to save money compared to the traditional drug development scheme, still guarantying the possibility of generating intellectual property rights [7]. In this context, there has been reported several studies devoted to studying pharmaceutical cocrystals and salts of furosemide [8][9][10][11][12][13].…”

Structurally Unique Salts of Cyamemazine and Their Pharmaceutical Implications

“…), sometimes along with solubility enhancement. The triethanolamine salt of furosemide not only increased the aqueous solubility of the drug but also improved its chemical photostability …”