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 P21 (monoclinic) with cell dimensions a = 9.357(1) Å, b = 8.231(1) Å, c = 12.931(2) Å, and β = 90.353(4)°. 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. © 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:815-830, 2008