Controlling the Product Crystal Size Distribution by Strategic Application of Ultrasonication

In this work, different strategies of ultrasonication (continuous, single pulse, and multiple pulse) are compared for control of the product crystal size distribution of three model API compounds: piracetam, paracetamol, and ibuprofen. Experiments have been performed on 0.5 and 3 L scales continuously recorded by FTIR and FBRM. Irrespective of the sonication operating mode, sonication in general produced smaller sized crystals with a more narrow size distribution in comparison to those for a normal cooling crystallization process. A multiple-pulse sonication mode, in particular, was capable of delivering more narrow size distributions. Sonication power per unit mass of solution does not appear to be a relevant scaling-up parameter.