Hydrodynamic Cavitation-induced Breakage of Carbamazepine Dihydrate Crystals: Experimental Insights and Modeling.

Downstream milling is often employed to control the particle size distribution (PSD) of crystalline products. Recently, hydrodynamic cavitation (HC) was shown to be quite effective for particle breakage compared to traditional wet milling and acoustic cavitation. In this work, we investigated the use of HC for tailoring the size and shape of carbamazepine dihydrate (CBZ-DH) crystals. A vortex-based HC device (VD) was used. An endoscopic optical probe (SOPAT GmbH, Germany) was used to measure the PSD during the breakage experiments. The variation in mean length, width, and aspect ratio (AR) of CBZ-DH crystals as a function of the number of passes through the VD was quantified. The breakage of CBZ-DH crystals exhibited two regimesinitially fast breakage up to a certain number of passes, followed by a significantly slower breakage. An empirical correlation for estimating the reduction in the mean length and width of the crystals was developed. The HC-induced breakage was modeled using the population balance model (PBM). The model successfully simulated the experimental PSD across all operating conditions with an appropriate selection of breakage model parameters. The data and models presented in this work provide a useful basis for tailoring pharmaceutical crystals by using VD.