A Plackett–Burman design for screening of the operation variables in the formation of salbutamol sulphate particles by supercritical antisolvent

A Plackett–Burman experimental design was applied for screening of the influence of various processing parameters in micronization of salbutamol sulphate using the supercritical antisolvent process. Methanolic solutions of the drug were injected into supercritical carbon dioxide and process parameters, such as pressure, temperature, concentration of drug solution, nozzle internal diameter, drug solution flow rate and injection interval were changed at two levels. Morphology, size characteristics and density of produced particles were evaluated as the response. In all conditions, some needle-like particles with different size and bulk densities were obtained. Analysis of the results showed that the nozzle internal diameter and the flow rate of drug solution were the main effective parameters on the particles size. In the case of bulk density of powders, none of the parameters had pronounced effect; however the flow rate was more effective than others.