CFD simulation and experimental study of antisolvent precipitation through impinging jets for synthesis of nanodrug particles

Abstract

The nucleation and growth kinetics of loratadine, one of the primary antihistamines among drugs, are determined experimentally in confined liquid impinging jet channels, followed by simulating the anti-solvent precipitation process to obtain ultrafine loratadine nanoparticles. The effect of supersaturation is assessed as the essential factor on the nucleation and growth rates. Based on classical nucleation theory, induction time and nucleation rate showed homogeneous and heterogeneous nucleation regions in high and low supersaturations, respectively. The interfacial free energy measured from the induction time is obtained at about 18.99 mJ/m2. The size-dependent particle growth and growth dispersion effects are assessed through the experimental data. The nonlinear curve fitting with the experimental data in log population density plot at residence time of 7.69 s reveals that the four-parameter model has a better fit, with no growth dispersion. The microchannel mixing performance is assessed by analyzing the Damkohler number under different Reynolds numbers. The loratadine particle size distribution (CSD) is obtained by combining the population balance equation with the computational fluid dynamics in following the discretization method with and without turbulence aggregation kernel. The simulated CSD with turbulence aggregation kernel are 7 % more consistent with experimental results. The effects of collision angle, outlet nozzle length, Reynolds number, and solution concentration on the average particle size are assessed. An increase in the collision angle from 60 to 180°decreases the average particle size. The ultrafine loratadine nanoparticles of 49 nm are obtained with a narrow distribution, related to the angle of 180⁰, outlet nozzle length of 0.5 cm, Reynolds number of 4875, and the solution concentration of 35 mg/ml.