Pharmaceutical salt of BM635 with improved bioavailability

  • Eur J Pharm Sci. 2017 Mar 1;99:17-23. doi: 10.1016/j.ejps.2016.12.003.
Giovanna Poce  1 ,  Sara Consalvi  2 ,  Martina Cocozza  2 ,  Raquel Fernandez-Menendez  3 ,  Robert H Bates  3 ,  Fátima Ortega Muro  3 ,  David Barros Aguirre  3 ,  Lluis Ballell  3 ,  Mariangela Biava  2
Affiliations
  • 1. Dipartimento di Chimica e Tecnologie del Farmaco, "Sapienza" Università di Roma, Rome, Italy. Electronic address: [email protected].
  • 2. Dipartimento di Chimica e Tecnologie del Farmaco, "Sapienza" Università di Roma, Rome, Italy.
  • 3. Diseases of the Developing World, Tres Cantos Medicines Development Campus, GSK, Tres Cantos, Madrid, Spain.
PMID: 27939618 DOI: 10.1016/j.ejps.2016.12.003
Abstract

BM635 is a small molecule endowed with outstanding anti-mycobacterial activity (minimum inhibitory concentration of 0.12μM 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 1h, allowing a reasonable maximum concentration (Cmax=1.62μM) 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.

Keywords
BM635; Drug development; MmpL3; Pharmaceutical salts; Tuberculosis.
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