Screening design of experiment applied to supercritical antisolvent precipitation of amoxicillin: Exploring new miscible conditions

Microparticles of amoxicillin (AMC) have been precipitated by supercritical antisolvent process (SAS) using carbon dioxide and N-methylpyrrolidone (NMP) as antisolvent and solvent, respectively. A fractional factorial design of experiment (DOE) with 27−4 experiments has been used. Mean particle size (PS) and particle size distribution (PSD) of the processed amoxicillin have been chosen as responses to evaluate the process performance. In a previous work, a DOE was applied too, but now, the range of operating conditions investigated has been changed to let the process take place in a single supercritical phase. Within this range, concentration is again the key factor having most effect on both PS and PSD and thus, the most important factor for controlling the formation of sub-microparticles of amoxicillin by the SAS technique. Moreover, all the experiments included in the new design matrix led to a successful precipitation of amoxicillin.