No abstract

This work presents systematic investigations on sonocrystallization to elucidate the effects of key variables on sonocrystallization product properties. A novel continuous flow sonocrystallization apparatus was used to prepare NaCl microparticles from a NaCl-ethanol-water antisolvent system. By implementing a full factorial experimental design, we investigated the effects of ultrasonic power (75-225 W), antisolvent feed rate (0.5-6.5 l/h), system flow rate (2.8-4.1 l/min) and sonication time (5-30 min) on product crystal size. Data from these experiments were regressed to develop an empirical model that was found to be in agreement with experiments. The model identified the interaction between sonication power and system flow to be rather significant. Model simulations found that particle size decreases when antisolvent feed rate or ultrasonic power increases. This was found to be in contrast to increasing the system flow which resulted in larger particle sizes. The regression model was subsequently used to determine optimal operating conditions that minimize mean size, as smaller sizes are commonly required for pharmaceuticals such as for inhalation particles. These optimal values were found to be as follows: antisolvent flow rate = 6.5 l/h, power ultrasound = 225 W, system flow = 2.8 l/min and sampling time = 15 min. The optimal mean size predicted at these conditions was 28.6 ± 5.7 µm which is very close to the observed value of 27.6 µm. A high-speed camera was used to visualize the ultrasonic irradiation in the sonoreactor and was crucial in explaining the significant interactive effect of sonication power and system flow on crystal size. 