(625d) Fabrication of Curcumin-Loaded Microparticles from Oil-in-Water Emulsion By Supercritical Assisted Atomization

For oral administration of hydrophobic drugs, a novel oral drug delivery system based on emulsion has been widely implemented, where hydrophobic drug is encapsulated in the hydrophobic core. However, emulsion in liquid state is lack of long-term stability under the action of Ostwald ripening, coagulation, creaming and cracking. This can be avoided by the transformation from liquid emulsion to solid particles and an effective technology is necessary.

In this work, liquid emulsion was first prepared with ultrasound where ethylcellulose was as oil phase matrix and gum arabic (GA) as emulsifier and wall material. The oil-in-water emulsion formulation was then processed by an improved supercritical assisted atomization technique (SAA-HCM) and curcumin-loaded microparticles were successfully fabricated. Influences of operation conditions including mixer pressure, temperature, gas/liquid mass flow ratio on diameters and size distributions of microparticles were investigated in detail, and particle formation mechanism was discussed. It is verified that fast extraction of organic solvent from oil phase by supercritical CO₂ in mixer is favorable to entrap curcumin in the matrix of oil phase preventing drug leaching at stage of atomization, and high drug loading efficiency (53.91±1.6%) was obtained when the GA concentration was up to 20 g/L. CLSM indicated that the shell of curcumin-loaded microparticles was composed of GA and nanoparticles dried from emulsion droplets were enclosed in the inner. The chemical stability of curcumin loaded in microparticles was identified by FI-IR, and the amorphous form of curcumin attributed to fast formation of drug-loaded particles was confirmed by DSC and X-ray. In vitro drug release behavior of microparticles exhibited controlled release and enzyme trigger properties.

SAA-HCM is a green micronization technique, and this work will expand the application of SAA-HCM technique to emulsion, which will be of great progress in the design of drug-loaded microparticles with elaborate structures.