Computer-aided design of crystalline drugs

A method to predict crystal structures of crystalline drugs by systematic searching for minimum-energy packings is outlined. It bases on the use of the observed space-group occurrence factors to postulate crystal symmetry. The search region is chosen within the fundamental unit of multi-dimensional crystal-structure parameter space, including the cell parameters and rigid-body molecular parameters. A version of the accelerated convergence method for lattice energy, and a multi-step structure optimization technique realized in the PMC (Packing of Molecules in Crystal) program are used in practical calculations. The calculated packings are tested for their similarity and occurrence of implicit symmetry with the CRYCOM (CRYstal COMparison) program. As a numerical example, the computational study of crystal structure polymorphism piracetam, aimed at the structure prediction of its metastable form, is reported