Experimental and Computational Evaluation of Sonofragmentation: Toward Enhanced Understanding of Sonocrystallization for Pharmaceuticals

Sonocrystallizationis a promising technology for the design ofcrystalline materials across many industries. In this work, controlledsingle-pass experiments are used to investigate and quantify the effectof sonication parameters on the breakage rate of carbamazepine dihydrate.The particle size distribution was measured after each of the fivepasses through the sonication zone. A population balance model isused to quantify the breakage mechanism and shows that the breakagerate in the sonication vessel can be assumed to be proportional tothe sonication power across the flow rates and powers investigated.This was validated by fitting the population balance model breakageparameters to one of five experimental conditions and the good predictionof breakage rates at other experimental conditions in the validationset. This finding suggests that the scale-up and design of sonicationprocesses could be carried out with a limited number of milling-curveexperiments and that particle size can be tuned by both power inputor number of passes through the sonication zone, without having torely on terminal milling conditions to reach a target particle size.Practical scale-up considerations are also discussed as a part ofthis work, and findings from extensive vendor communications and industrybenchmarking are reported here. Overall, ultrasound (sonocrystallization)proves to be a promising technology for particle design in the pharmaceuticalindustry, and this work demonstrates that breakage rate at the laboratoryscale is consistently predicted under a range of experimental conditions.