Experimental Investigation On Preparation Of Drug Micro-particles By Supercritical Assisted Atomization

Micro-particle preparation techniques, especialy those based on supercritical fluid technology are one of the most important research fields of material science and chemical engineering. The efforts have been taken to obtain micro-particles with small particle size and narrow particle size distribution. Supercritical assisted atomization (SAA) process, which has been developed very recently, is a new micro-particle preparation technique based on supercritical fluid technology. The object of this study is to conduct SAA process experiments and investigate the effects of the process parameters on particle morphology (PM), particle size (PS) and particle size distribution (PSD) respectively.An experimental apparatus for SAA process was designed and set up. Systematic experiments were conducted for both water soluble and non-water soluble drugs on this apparatus. Paracetamol, cefadroxil, tetracycline hydrochloride and compound preparation for hepatitis were selected for water soluble drugs while erythromycin and griseofulvin were selected for non-water soluble drugs. The effects of solvent properties and process parameters including saturator pressure and temperature, concentration of solution, inlet flow rate and precipitator temperature on PM, PS and PSD were studied experimentally.The results show that water soluble and non-water soluble drugs were micronized successfully using SAA process. Well-defined spherical particles with controlled PS and PSD in the range of inhalation delivery were formed from these experiments. PM, PS and PSD of the particles after treatment were changed distinctly. In all cases, particles with diameters smaller than 5 μm were obtained. Non-coalescing particles were also gained at the most favourable operating conditions.It is found that there are various influence factors of SAA process such as solute and solvent properties and process parameters. The different influence factors have different effects on PM, PS and PSD and, in some experiments, they interact to each other and make the effects more complicated. PM, PS and PSD can be controlled by adjusting process parameters. For different solute-solvent-supercritical CO₂ systems, there are some generalities of the effects of the process parameters, for example, PS decreases with the increase of saturator pressure. But the effects of the process parameters are not same relating to the characteristics of the solutes and solvents. Adding a few of co-solvent properly is favorable to SAA process in the experiments of water soluble drugs, and better results will be obtained.Considering solvent has significant effects on phase equilibrium in the saturator, ethanol is more suitable for the experiments of non-water soluble drugs.SAA process can be used for the micronization of water and non-water soluble drugs and is high efficient, rapid and energy-saving. It can be concluded that SAA process has promising potentials in pharmaceutical micronization.