title: Mechanochemical synthesis of bumetanide-4-aminobenzoic acid molecular cocrystals: a facile and green approach to drug optimization.
abstract: Molecular cocrystals are of growing interest in pharmaceutics for their improved physicochemical properties. Their mechanochemical synthesis is very promising, being easy, cheap, and "green". Here, for the first time, we report on cocrystallization of bumetanide, a diuretic and natriuretic active principle, and 4-aminobenzoic acid. The synthesis is performed both by wet and dry grinding. The cocrystal formation was investigated with a wide range of techniques, including solid-state NMR, IR, XRD, microscopy, and thermal analysis. Wet and dry grinding procedures led to different cocrystal polymorphs. In particular, the dry method gave a cocrystal by powder amorphization and subsequent crystallization. DFT calculations at the B3LYP/6-31+G(d,p) level of theory shed light on the H-bond scheme at the basis of cocrystal formation. The cocrystals showed improved solubility and dissolution rate with respect to the drug alone. This could guarantee a faster absorption and a better bioavailability of the active principle.
authors: C.S.G.I. - Department of Chemistry, Physical-Chemistry Section, University of Pavia , Viale Taramelli 16, 27100 Pavia, Italy.
authors: Giovanna
authors: G
authors: Bruni
authors: Mariarosa
authors: M
authors: Maietta
authors: Vittorio
authors: V
authors: Berbenni
authors: Piercarlo
authors: P
authors: Mustarelli
authors: Chiara
authors: C
authors: Ferrara
authors: Mauro
authors: M
authors: Freccero
authors: Vincenzo
authors: V
authors: Grande
authors: Lauretta
authors: L
authors: Maggi
authors: Chiara
authors: C
authors: Milanese
authors: Alessandro
authors: A
authors: Girella
authors: Amedeo
authors: A
authors: Marini
mesh_terms: D010129:4-Aminobenzoic Acid / Q000138:chemical synthesis* / Q000737:chemistry; D002034:Bumetanide / Q000138:chemical synthesis* / Q000737:chemistry; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D055595:Mechanical Phenomena; D008855:Microscopy, Electron, Scanning; D008956:Models, Chemical; D015394:Molecular Structure; D010784:Photomicrography; D012995:Solubility; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D014732:Vibration; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D012996:Solutions; D014867:Water; D002034:Bumetanide; D010129:4-Aminobenzoic Acid