A new solvate of furosemide with dimethylacetamide

Abstract

The loop diuretic furosemide is used widely in the treatment of congestive heart failure and edema, and is practically insoluble in water. The physicochemical and pharmacokinetic properties of drugs can be modified by preparing the drug in an appropriate solid-state form. A new solvate of furosemide with dimethylacetamide (DMA) {systematic name: 4-chloro-2-[(furan-2-yl)methylamino]-5-sulfamoylbenzoic acid N,N-dimethylacetamide disolvate}, CHClNOS·2CHNO, (I), is reported. The channeled structure formed on slow crystallization contains DMA solvent molecules in its channels. This structure adds to the evidence of varied conformations observed across all known structures, so supporting the idea that this flexible molecule has conformational lability. The current structure also differs from those of other previously known furosemide solvates in the number of solvent molecules per furosemide molecule, viz. 2:1 instead of 1:1. Desolvation of (I) gives the most stable form of furosemide, i.e. Form I.

First Evidence of Polymorphism in Furosemide Solvates

“…Formal analysis based on the geometric parameters, interatomic distances and angles, can suggest the existence of various possible intermolecular contacts and interactions − ,− (Schemes S1 and S2, Tables S2–S4, Figure S2 and S3, SI). However, not all of these “contacts” necessarily correspond to real hydrogen bonds and attractive interactions.…”

“…With a vast diversity of conformational energy minima, furosemide is prone to crystallization as different polymorphs (ref , CSD version 5.38, November 2016). A systematic study of polymorphism of furosemide , and its capacity to form different salts, , solvates, , and cocrystals ,− was started only in the past few years. To date, the crystal structures of three polymorphs have been reported, with the structure of the fourth high-temperature phase remaining unknown .…”

Triamterene–furosemide salt: structural aspects and physicochemical evaluation

“…As one of the BCS (biopharmaceutical classification system) class IV drugs (Ghadi & Dand, 2017), its aqueous solubility (0.01825 mg ml À1 ) (Shin & Kim, 2003) and membrane permeability (0.5) (Rege et al, 2001) are poor and, hence, has low bioavailability. Fur has three polymorphs (Lamotte et al, 1978;Babu et al, 2010) and several solvates (Minkov et al, 2014;Beloborodova et al, 2016Beloborodova et al, , 2017 with poor solubility. Several strategies have been used to improve its physicochemical properties, such as improving the solubility by cocrystallization techniques (Goud et al, 2012;Banik et al, 2016), enhancing the bioavailability by loading into chitosancoated liposomes (Vural et al, 2011), improving its oral absorption by a using silica-lipid hybrid microparticles system (Sambaraj et al, 2015).…”