(536d) Morphology Control Through Cycles of Particle Breakage, Dissolution and Growth

Needles and plates are commonly observed morphologies in pharmaceutical crystallization which lead to difficulties in downstream processing causing higher cake resistance in filtration, resistance to free flow, and poor compressibility. The processibility of such ill-behaved crystals can be improved by reducing their aspect ratios through cycles of sequential processes involving particle breakage, dissolution and growth. These cycles are widely used in pharmaceutical industries to improve aspect ratio of crystals. The dissolution-growth cycles can improve the aspect ratios of 2D crystals only if the relative dissolution rate of the slowest face is greater than its corresponding relative growth rate. Particle breakage has the additional advantage of providing flexibility in attaining target morphologies within the feasible operating regimes. The particle breakage using either a Rotor-Stator or a Sonicator usually affects the longer dimension of the crystal, resulting in the production of fines and reduction in the aspect ratio. Successively, the dissolution of crystals will redistribute fines into the solution and may further improve the aspect ratio of crystals. Finally, the crystals are allowed to grow to increase their mass without much increase in their aspect ratio. In this work, we develop optimal cycles of particle breakage, dissolution and growth for shape control of Cholesterol crystals in a batch slurry which has the potential for considerable improvement in productivity.