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.

Bruni, G., Maietta, M., Berbenni, V., Mustarelli, P., Ferrara, C., Freccero, M., et al. (2014). Mechanochemical Synthesis of Bumetanide–4-Aminobenzoic Acid Molecular Cocrystals: A Facile and Green Approach to Drug Optimization. JOURNAL OF PHYSICAL CHEMISTRY. B, CONDENSED MATTER, MATERIALS, SURFACES, INTERFACES & BIOPHYSICAL, 118(31), 9180-9190 [10.1021/jp503256k].

Mechanochemical Synthesis of Bumetanide–4-Aminobenzoic Acid Molecular Cocrystals: A Facile and Green Approach to Drug Optimization

Mustarelli, P;Ferrara, C;
2014

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.
Articolo in rivista - Articolo scientifico
co-crystals; bumetanide; 4-amino benzoic acid; Mechanochemistry; DSC; FT-IR; NMR; SEM-EDS
English
2014
118
31
9180
9190
reserved
Bruni, G., Maietta, M., Berbenni, V., Mustarelli, P., Ferrara, C., Freccero, M., et al. (2014). Mechanochemical Synthesis of Bumetanide–4-Aminobenzoic Acid Molecular Cocrystals: A Facile and Green Approach to Drug Optimization. JOURNAL OF PHYSICAL CHEMISTRY. B, CONDENSED MATTER, MATERIALS, SURFACES, INTERFACES & BIOPHYSICAL, 118(31), 9180-9190 [10.1021/jp503256k].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/256843
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