Alternative solid-state forms of a potent antimalarial aminopyridine: X-ray crystallographic, thermal and solubility aspects

Graphical abstract: Alternative solid-state forms of a potent antimalarial aminopyridine: X-ray crystallographic, thermal and solubility aspects

Alternative solid-state forms of a potent antimalarial aminopyridine: X-ray crystallographic, thermal and solubility aspects

Dyanne L. Cruickshank, Yassir Younis, Nicholas M. Njuguna, Dennis S. B. Ongarora, Kelly Chibale and Mino R. Caira

CrystEngComm, 2014, 16, 5781 DOI:10.1039/C3CE41798K

http://pubs.rsc.org/en/Content/ArticleLanding/2014/CE/C3CE41798K?utm_medium=email&utm_campaign=pub-CE-vol-16-issue-26&utm_source=toc-alert#!divAbstract

3-(6-Methoxypyridin-3-yl)-5-(4-methylsulfonyl phenyl)-pyridin-2-amine (MMP) is a member of a novel class of orally active antimalarial drugs. This aminopyridine molecule has shown potent in vitro antiplasmodial activity and in vivo antimalarial activity in Plasmodium berghei-infected mice. The aqueous solubility of this molecule is, however, limited.

Thus investigations aimed at improving the physicochemical properties, including solubility, of MMP were accordingly conducted. Five salts of MMP were formed with co-former molecules saccharin, salicylic acid, fumaric acid, oxalic acid and suberic acid, but a cocrystal was obtained when the co-former adipic acid was employed.

All these new multi-component systems have been fully characterised using X-ray diffraction and thermal methods. Semi-quantitative, turbidimetric solubility tests in a phosphate-buffered saline solution at a pH of 7.4 were performed on the salts and the cocrystal of MMP. The saccharinate salt, fumarate salt and the cocrystal of MMP proved to have greater solubility than MMP itself. This work illustrates the importance of screening and modifying candidate drug compounds in their preliminary stages of development.
Alternative solid-state forms of a potent antimalarial aminopyridine: X-ray crystallographic, thermal and solubility aspects

Dyanne L. Cruickshank,a Yassir Younis,a Nicholas M. Njuguna,a Dennis S. B. Ongarora,a Kelly Chibalea and Mino R. Caira*a
*corresponding authors
aDepartment of Chemistry, University of Cape Town, Rondebosch 7701, South Africa
E-mail: mino.caira@uct.ac.za;
Fax: +27 21 650 5195 ;
Tel: +27 21 650 3071

CrystEngComm, 2014,16, 5781-5792

DOI: 10.1039/C3CE41798K