title: A new way of stabilization of furosemide upon cryogenic grinding by using acylated saccharides matrices. The role of hydrogen bonds in decomposition mechanism.
abstract: Recently it was reported that upon mechanical milling of pure furosemide significant chemical degradation occurs (Adrjanowicz et al. Pharm. Res.2011, 28, 3220-3236). In this paper, we present a novel way of chemical stabilization amorphous furosemide against decomposing that occur during mechanical treatment by preparing binary mixtures with acylated saccharides. To get some insight into the mechanism of chemical degradation of furosemide induced by cryomilling, experimental investigations supported by density functional theory (DFT) computations were carried out. This included detailed studies on molecular dynamics and physical properties of cryoground samples. The main thrust of our paper is that we have shown that furosemide cryomilled with acylated saccharides forms chemically and physically stable homogeneous mixtures with only one glass transition temperature, Tg. Finally, solubility measurements have demonstrated that furosemide cryomilled with acylated saccharides (glucose, maltose and sucrose) is much more soluble with respect to the crystalline form of this active pharmaceutical ingredient (API).
authors.affiliation: Department of Pharmacognosy and Phytochemistry, Medical University of Silesia, ul. Jagiellonska 4, 41-200 Sosnowiec, Poland. ekaminska@sum.edu.pl
authors.forename: E
authors.initials: E
authors.lastname: Kaminska
authors.forename: K
authors.initials: K
authors.lastname: Adrjanowicz
authors.forename: K
authors.initials: K
authors.lastname: Kaminski
authors.forename: P
authors.initials: P
authors.lastname: Wlodarczyk
authors.forename: L
authors.initials: L
authors.lastname: Hawelek
authors.forename: K
authors.initials: K
authors.lastname: Kolodziejczyk
authors.forename: M
authors.initials: M
authors.lastname: Tarnacka
authors.forename: D
authors.initials: D
authors.lastname: Zakowiecki
authors.forename: I
authors.initials: I
authors.lastname: Kaczmarczyk-Sedlak
authors.forename: J
authors.initials: J
authors.lastname: Pilch
authors.forename: M
authors.initials: M
authors.lastname: Paluch
mesh_terms: D000215:Acylation; D002152:Calorimetry, Differential Scanning; D002241:Carbohydrates / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D004232:Diuretics / Q000737:chemistry; D004355:Drug Stability; D005615:Freezing; D005665:Furosemide / Q000737:chemistry*; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D015394:Molecular Structure; D012995:Solubility; D014961:X-Ray Diffraction
chemical_list: D002241:Carbohydrates; D004232:Diuretics; D005665:Furosemide