Study On The Technology Of Supercritical Process

With the development of modern science and technology, there is an increasing strict ofrequirement on the applications of the micro-particles. Numerous researchers aim at to obtainthe particles with small particles size and narrow particle size distribution. The SupercriticalAntisolvent(SAS) process has been proposed to produce micro-particles recently as a newtechnique and a lot of studies have been conducted at home and abroad. However, most ofstudies have still been in the laboratory plant because of the complicated system of SAS andthe conclusions from these experiments are incompatible, which make it difficult to achieve apilot scale and further industrialization. In this work, experiments of SAS process on pilotscale, based on laboratory scale, were performed and the effect results of operation parameteron the process were obtained. Tetracycline, rifampicin and ampicillin sodium were selected asmodel material to perform the single factor and orthometric experiments on two scales.During the single factor experiments, several factors, such as pressure,temperature,solutionconcentration,solution flow rate and the ratio of antisolvent flow and solution flow rate, wereinvestigated. During the orthometric experiments, the significance levels of all factors and theoptimal operation conditions were obtained.In single factor experiments, for three drugs, on two experiment scales, the same resultswere obtained as follows: with the pressure increasing the particle size decreased, with thesolution flow rate increasing the particles size increased and there were no obvious effects onthe particle size resulting from temperatures but the higher temperature easily led tocoagulation of particles. At lower solution concentration, no obvious changes were found withthe solution concentration increasing while at higher solution concentration, the particle sizeincreased and the size distribution became broad with the solution concentration increasing.The washing time should be increased with the solution concentration and the quantity ofsolution increasing; The different morphology were precipitated from different solvents. Themicroparticles could be prepared successfully only with the ratio of antisolvent flow rate tosolvent flow rate in a certain range.In orthometric experiments, on two experiment scales, for tetracycline, the same optimaloperation parameters, particle size and size distribution were obtained. For rifampicin, thereare some different results of the effect of the pressure and the solution concentration fromlaboratory and pilot scale. For Ampicillin sodium, the particle sizes obtained from pilot scale are larger than those from laboratory scale and different effect rule of the pressure and thesolution concentration on particle size, were represented on the two scales.In this paper, by studying SAS process on pilot and laboratory scale, the furtherinformation of the effect rule of the operation parameters on the particles were obtained,which provided some essential data for the theoretical research on SAS process and contributeto the study on the scale-up experiments.