Crystal structure of Minoxidil at low temperature and polymorph prediction

An experimental and theoretical investigation on crystal forms of the popular and ubiquitous pharmaceutical Minoxidil is presented here. A new crystallization method is presented for Minoxidil (6-(1-piperidinyl)-2,4-pyrimidinediamide 3-oxide) in ethanol-poly(ethylene glycol), yielding crystals with good quality. The crystal structure is determined at low temperature, with a final R value of 0.035, corresponding to space group P2(1) (monoclinic) with cell dimensions a=9.357(1) angstrom, b=8.231(1) angstrom, c = 12.931(2) angstrom, and P = 90.353(4)degrees. Theoretical calculations of the molecular structure of Minoxidil are set forward using empirical force fields and quantum-mechanical methods. A theoretical prediction for Minoxidil crystal structure shows many possible polymorphs. The predicted crystal structures are compared with X-ray experimental data obtained in our laboratory, and the experimental crystal form is found to be one of the lowest energy polymorphs. (C) 2007 Wiley-Liss, Inc. and the American Pharmacists Association.