Fine Drug Particles Prepared By Rapid Expansion Of Supercritical Solutions And The Main Influence Factors

Rapid Expansion of Supercritical Solutions (RESS) is a preferred particles micronization technology, developed in recent twenty years. Because of its advantages of non poisonous, non pollution, low solvent residue and low energy consumption, it attracts considerable attentions of the researchers.The solubility data of the substances in supercritical fluids is the foundation of RESS technology. In this paper, employed CO2as supercritical solvent, measured the solubility of chlorzoxazone,2-phenoxypropionic acid and carprofen in supercritical CO2, and correlated those data with several empirical equations. Micro-sized chlorzoxazone and carprofen and nanometre2-phenoxypropionic acid were prepared with RESS. The SEM photographs of the aforementioned microstructures were given to show the relationship between operation conditions and particle morphologys and sizes.Solubilities of chlorzoxazone,2-phenoxypropionic acid and carprofen in supercritical CO2were measured by a static method at pressure of9to30MPa and temperature of35to55℃. Their solubilities are at10-5,10-4and10-7mol·mol-1separately, and all increase with the increase of pressure. However, the relations between the solubility and temperature were different as the pressures and kinds of substances changed.Chrastil, modified Chrastil and Mendez-Santiago-Teja empirical equations were intruded to correlate those solubility data. Compared to Mendez-Santiago-Teja equations, Chrastil and its modified models have better correlation effects, especially the Adachi and Lu modified Chrastil model, provides nearly perfect average absolute relative deviations (AARD) of0.0170and0.0532for chlorzoxazone and2-phenoxypropionic acid respectively.In RESS process, the effects of the extraction temperature (308to328K), extraction pressure (10to30MPa), spray distance (10to30mm), nozzle temperature (343to383K), and nozzle diameter (0.1to0.4mm) on morphology and size of the microstructures were searched. When the RESS was applied to manufacture the2-phenoxypropionic, on the basis of different experimental conditions, filaments with the diameter of1to15nm were obtained, which entwine into a mesh pattern and even are accompanied with flakes or particles in some cases. When the chlorzoxazone was micronized, the short clavate particles with average length of0.5-5μm and diameter of0.1-1μm were obtained; the exact sizes varied with the different experimental conditions. The productions of carprofen after RESS were micro-size particles which having no apparent changes from the original morphologys.The microzation results showed that the aforementioned experimental critical parameters determining the size, morphology and state of aggregation the microstructures.