Relative importance of the operating conditions involved in the formation of nanoparticles of ampicillin by supercritical antisolvent precipitation

A screening design of experiments has been applied to the supercritical antisolvent precipitation of ampicillin (APC) using carbon dioxide (CO2) and N-methylpyrrolidone (NMP) as antisolvent and solvent, respectively. The proposed design of experiment (DOE) is useful for identifying the key factors involved in the SAS process in just a few runs at an early stage of experimentation. Seven factors were studied, and two levels were assigned to each. A fractional factorial design with 2(7-4) experiments plus two additional runs to calculate the accuracy of the estimates was used. The mean particle size (PS) and particle size distribution (PSD) of the processed ampicillin were chosen as responses to evaluate the process performance. Within the range of operating conditions investigated, concentration, temperature, and nozzle diameter proved to be the key factors having the greatest effect on both PS and PSD and, thus, the most important factors for controlling the formation of submicrometer particles of ampicillin by the SAS technique.