Micronization Of Drug Particles By The Rapid Expansion Of Supercritical Solutions

Not only chemical structures, but also the particle size and morphology decidethe effect of the pharmaceuticals. Higher bioavailability can be obtained with smallerparticle size and larger particle specific surface area, so the research of producing fineparticles is very profound. Rapid Expansion of Supercritical Solutions (RESS) is arapidly developing supercritical technology to micronize drug particles, due to a seriesof attractive advantages offered by the RESS process, such as without solvent residualproduct, nonhazardous, non-pollution, mild operating condition and low energyconsumption, the RESS process has attached more and more importance to researchon micronization of drug particles. The solubility of risocaine and phenacetin insupercritical carbon dioxide were measured by the static method at differentexperiment conditions, the empirical model and EOS model were applied to correlatethose solubility data and the results comparison was studied. Fine particles wereobtained by the RESS and the effect of important operating parameters wereevaluated by the analysis of SEM figures.The solubility of risocaine has been measured by the static method underdifferent operating conditions in this paper. It has been examined that the solubility ofrisocaine increases with the increase of pressure and decreases with the increase oftemperature, which was reached to10-4mol/mol. The results of pressure (9.0-30.0MPa) and temperature (308.0-328.0K) on solubility show that the solubility increasesmainly with increasing density. Results show that a reverse region where the solubilityof phenacetin decreases with the increase in temperature appears at a pressure of9.0MPa. The mole fraction solubility of phenacetin was reached to10–5.The empirical model and EOS model were applied to correlate the experimentaldata of risocaine. Agreement between experimental data and model predictions arebetter with Chrastil model and Adachi-Lu modified Chrastil model than that withMendez-Santiago-Teja model and the PR EOS model and the observed averageabsolute relative deviation (AARD) are0.0596and0.0345, respectively. Theexperimental data of risocaine were correlated by four empirical models. The particlessize of risocaine and phenacetin become smaller and the morphology become regularafter RESS process. The preparation of fine phenacetin particles by the RESS processunder different conditions of extraction temperatures (308.0–328.0K), extractionpressures (9.0–30.0MPa), nozzle temperatures (373.0–393.0K), nozzle diameters (0.1–0.8mm) and collection distance (20.0–40.0mm) was investigated. The resultsshow that the extraction temperatures, extraction pressures, nozzle diameters andcollection distance have important influence on particles size morphology except ofnozzle temperature. The key parameters play important role in supersaturation andsolubility of solutes, residence time, thereby effected the formation and growth of thefine particles.