Kinetics modeling of ampicillin nanoparticles synthesis via supercritical gas antisolvent process

Modeling of supercritical gas antisolvent (GAS) process was carried out for ampicillin nanoparticles synthesis. The particle size distribution of ampicillin limits bioavailability. Therefore, the kinetic data are essential for the control of particle size. Volume expansion and phase equilibrium modeling was studied to determine optimal operating conditions for experimental ampicillin production. Experimental ampicillin precipitations with GAS process at various antisolvent addition flow rates were investigated. The process model was then studied for the determination of nucleation and growth rate parameters. Equation of state, material and population balance equations were used for this modeling. A combination of the Crank-Nicholson and Lax-Wendroff methods was utilized to solve the population balance equation. Comparison of the experimental and modeling data showed that the model successfully predicted the particle size distribution. The effect of antisolvent addition rate on nucleation indicated that nucleation was enhanced via higher antisolvent addition rate and consequently smaller particle size was obtained. The mean particle sizes of ampicillin were obtained to be 357.09, 337.04 and 356.68 nm at antisolvent flow rates of 1.6, 2 and 2.4 mL/min, respectively.