Experimental Investigation On Micro-particle Production By Supercritical Assisted Atomization

In recent years Supercritical assisted atomization (SAA) has been proposed as a newmicronization technique based on supercritical technology. It can be used to produce micro-and nano-particles of aqueous and thermo-liable compounds. SAA is a very promisingprocess to produce micronic particles of drugs, polymers and pigments and so on. Particularly,polymer microsphere can be largely used in medical applications. It can be used for drugdelivery system to controll release of the drug. It also can be used for Artificial Cells,Artificial Organs and immobilization of proteins and DNA.SAA was used to micronize poly(methyl methacrylate) (PMMA), polyethylene glycoland polylactic acid (PLLA) which were selected as model polymers, to verify SAAprocessability of polymers and the performance of this process. The effect of processparameters such as pressure and temperature in the saturator, solute concentration in the liquidsolution, inlet flow rate and precipitation temperature were studied to evaluate their influenceon morphology and size of precipitated particles. Successful micronization of the polymerswas obtained with spherical micrometric particles and a narrow controlled particle sizedistribution at temperature conditions far from the glass transition temperature and meltingpoint. The effects of saturator pressure and solute concentration are more remarkable thanother process parameters and they are the key steps controlling the efficiency of the SAAprocess. At the same time, the feasibility of SAA process to prepare the particles ofthermosensitive compounds was proved.An impinging-stream reactor was designed as a precipitation chamber instead of theinitial precipitation chamber of the SAA apparatus. Then this process was used to micronizerifampicin and cephadroxil, selected as model materials, to verify its feasibility and theperformance. The effect of process parameters such as pressure and temperature in thesaturator, solute concentration in the liquid solution, inlet flow rate, precipitation temperatureand impinging distance were studied to evaluate their influence on morphology and size ofprecipitated particles. Microparticles of the drugs were obtained successfully with a narrowcontrolled particle size distribution. The particles prepared in the impinging-stream reactorwere smaller than those prepared in the initial precipitation chamber. The transfer coefficientswere also enhanced and the particles were dried very well in the impinging-stream reactorwhere the number of coalescing particles reduced very obviously. The impinging distance between two nozzles is one of the key steps controlling the efficiency of the SAA process.In this work, the micronization technique based on supercritical technology and theeffect of process parameters on particles' morphologies and size are understood more deeply.This study also contributes to a foundation of theoretical study on this process.