Formation of Tubular Crystals of Pharmaceutical Compounds

Tubular crystals of the pharmaceutical compounds caffeine, carbamazepine, carbamazepine dihydrate, and theophylline monohydrate have been prepared by evaporative crystallization. These novel, rod-shaped, hollow crystals have hexagonal or rectangular cross sections, and pore diameters ranging from 0.1 to 25 μm. Crystallization is believed to occur under conditions where crystal growth was more rapid than diffusion of molecules to the most rapidly growing face of the crystal, leading to formation of a central cavity within the crystal. The two key factors in this mechanism of tubule formation are highly anisotropic crystal growth, where the growth rate of one of the crystal faces is several times greater than that of the others, and high supersaturation levels, giving high crystallization rates and diffusion limited growth. This mechanism of tubular crystal formation is likely to be applicable to a wide range of chemical species, as both of these factors can be achieved for a given compound through selection of appropriate crystallization conditions. On the basis of this mechanism, conditions suitable for the growth of tubular crystals of aspirin were identified systematically through selection of solvent and control of crystallization rate.