Computer-aided design of crystalline drugs

A method to predict crystal structures of crystaline 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 rigidbody mlecular parameters. A version of the accelerated convergence method for lattice energy, and a multi-step structure optimization technique realized in the PM: (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 CRYCOA4(CRYstal COMparison) program. As a numerical example, the computational study of crystalstructure polymorphism in piracetam, aimed at the structure prediction of its metastable form, is reported.