Precise tailoring of the crystal size distribution by controlled growth and continuous seeding from impinging jet crystallizers

Abstract

The desired bioavailability and the method of drug administration and delivery can require stringent control on the crystal size distribution. Optimal control strategies are proposed to manufacture crystals with a targeted size distribution by combining controlled seeding by impinging jet crystallization with a batch crystallizer operating at a controlled constant growth rate. The same strategies apply if the impinging jet crystallization is replaced by any process equipment that can continuously provide crystal seeds, typically through the application of high supersaturation, to the batch crystallizer. Limitations to the achievable crystal size distributions and sensitivity to process operations are analyzed. Simulation results indicate that one of the strategies has promise for manufacturing pharmaceutical crystals of a desired size distribution.