BM635 is a small molecule endowed with outstanding anti-mycobacterial activity (minimum inhibitory concentration of 0.12 μM against M. tuberculosis H37Rv) identified during a hit-to-lead campaign. Its poor aqueous solubility together with its high lipophilicity led to low exposure in vivo. Indeed, the half-life in vivo of BM635 was 1 h, allowing a reasonable maximum concentration (Cmax = 1.62 μM) and a moderate bioavailability (46%). The present study aimed to develop salt forms of BM635 with pharmaceutically accepted hydrochloric, methanesulphonic, phosphoric, tartaric, and citric acids to overcome these drawbacks. BM635 salts (BM635-HCl, BM635-Mes, BM635-PA, BM635-TA and BM635-CA) were evaluated for physicochemical as well as biopharmaceutical attributes.
Pharmaceutical salt of BM635 with improved bioavailability / Poce, Giovanna; Consalvi, Sara; Cocozza, Martina; Fernandez Menendez, Raquel; Bates, Robert H.; Ortega Muro, Fátima; Barros Aguirre, David; Ballell, Lluis; Biava, Mariangela. - In: EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES. - ISSN 0928-0987. - STAMPA. - 99:(2017), pp. 17-23. [10.1016/j.ejps.2016.12.003]
Pharmaceutical salt of BM635 with improved bioavailability
POCE, Giovanna;CONSALVI, SARA;COCOZZA, MARTINA;BIAVA, Mariangela
2017
Abstract
BM635 is a small molecule endowed with outstanding anti-mycobacterial activity (minimum inhibitory concentration of 0.12 μM against M. tuberculosis H37Rv) identified during a hit-to-lead campaign. Its poor aqueous solubility together with its high lipophilicity led to low exposure in vivo. Indeed, the half-life in vivo of BM635 was 1 h, allowing a reasonable maximum concentration (Cmax = 1.62 μM) and a moderate bioavailability (46%). The present study aimed to develop salt forms of BM635 with pharmaceutically accepted hydrochloric, methanesulphonic, phosphoric, tartaric, and citric acids to overcome these drawbacks. BM635 salts (BM635-HCl, BM635-Mes, BM635-PA, BM635-TA and BM635-CA) were evaluated for physicochemical as well as biopharmaceutical attributes.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
