Pilot scale micronization of amoxicillin by supercritical antisolvent precipitation

摘要

The supercritical antisolvent precipitation (SAS) process has been frequently applied to pharmaceutical compounds, due to its potential capacity to control particle size (PS) and distribution and the simple separation and recovery of the solvent and of the antisolvent. However until now, the SAS process has been performed preformed prevalently in laboratory scale apparatus; therefore, process limitations that are significant on the large scale, have not been studied yet. These limitations may even lead to the failure of translating the process to commercial dimensions. Herein we report the results of SAS precipitation of Amoxicillin from N-methylpyrrolidone performed in a semi-continuous pilot plant equipped with a 5 dm~3 precipitator, operated at 40 deg C and 150 bar. Non coalescing spherical microparticles were obtained with mode diameters ranging from 0.3 to 1.2 mum depending on the concentration of Amoxicillin in the liquid solution. The effect of the scale enalrgement and of the kind of injection device on the powder size and morphology has been investigated and a comparison with laboratory scale results is also presented. The change of nozzle arrangement and diameter from the laboratory to the pilot scale does not affect significantly the PS and distribution of Amoxicillin.