A Modified PGSS Process: Encapsulation Of CoQ₁₀ And Menthol

PGSS (particles from gas-saturated solution) is a promising supercritical fluid (SCF)-assisted technique in preparing fine particles and microcapsules /microspheres. PGSS technique has some significant advantages over traditional methods in preparation of fine particles such as low energy comsumption, environment-friendly process, preferable particle morphology, and controllable particle size and particle size distribution. In the context of microcapsules /microspheres, the technique can also provide high encapsulation efficiency. This thesis focuses on the modification of conventional PGSS processes reported in literature and the applications of the modified process in pharmaceutics and flavors.A modifed PGSS apparatus was designed and built. In comparison to conventional PGSS processes, it has several advantages: N₂ and CO₂ can be independently used or mixed (CO₂ used as a solute and N₂ used as the atomizing gas); a two-way nozzle is used to prevent the noozle from blocking and improve the atomization; a circulation section is constructed to increase the contact of raw materials and supercritical fluids, shortening the time of formation of gas-saturated solution; a continuous pump is installed to control the fiowrate of the solution.The modified PGSS process with CO₂ (CO₂-assisted process) and N₂ (N₂-assisted process) was implemented for myristic acid, and nano- or/and microparticles were produced. The pre-expansion pressure shows obvious effect on the process: higher pressure produces smaller particles. The pre-expansion temperature shows no obvious effect on the produced particles' size, but agglomerated particles formed at relatively high temperatures. When the fiowrate increases, the average particle size increases slightly and particle size distribution broadens. DSC results show that the produced particles have small particle sizes. The produced particles from the CO₂-assisted process are flakes with a trimodal particle size distribution, indicating that the particles are from RESS process (solution crystallization), atomization (melt crystallization), and aggregation of fine particles. The produced particles from the N₂-assisted process are spherical with a unimodal particle size distribution, indicating only atomization occurs in the process.CoQ₁₀/myristic acid (lipid) microspheres and CoQ₁₀/PEG6000 (polymer) microspheres were produced from the CO₂-assisted process by using the modified apparatus. Results show that the produced microspheres of CoQ₁₀/myristic acid are flakes when the content of CoQ₁₀ is low. As the pre-expansion pressure increases, the produced particles' size decreases, while particle sise distribution broadens. The pre-expansion temperature and the flowrate show no obvious effect on the average particle size, but the particle size distribution broadens when the temperature increases. As the content of CoQ₁₀ reaches 70%, the produced microspheres become agglomerated. The dissolution test shows that myristic acid has no obvious effect on the release of CoQ₁₀ from the CoQ₁₀/myristic acid microspheres in aqueous solution (CoQ₁₀ release is less than 5% in 12h). The produced CoQ₁₀/PEG6000 microspheres with 10% CoQ₁₀ are irregular, and particles with an average particle size of 190nm were obtained when the microspheres were dispersed into water. The dissolution test shows that the CoQ₁₀ release from the CoQ₁₀/PEG6000 microspheres in aqueous solution is dramatically enhanced (release of 40% CoQ₁₀ in 10h). The study of light stability shows that both the CoQ₁₀/myristic acid and CoQ₁₀/PEG6000 microspheres have obvious protection of CoQ₁₀ from light.Menthol/wax microspheres were produced from the CO₂-assisted process by using the modified PGSS apparatus. Particle size decreases and particle size distribution becomes norrow as the pre-expansion pressure increases: the-particle size is in the range 2-30μm under 15 and 20MPa; agglomerated particles can be observed at low pressures. Particle size decreases and article size distribution becomes broad as the flowrate increases: the particle size is in the range 2-50μm under studied flowrates. Encapsulation efficicency and particle size decrease, particle size distribution becomes broad as the menthol content increases: the particle size is in the range 2-50μm under studied menthol contents. Pre-expansion pressure and flowrate show no effect on the encapsulation efficicency. Retention measurement shows that the microspheres have obvious protection of menthol from its volatilization loss.