(440e) Encapsulated Quercetin Particles Using a Supercritical Antisolvent Process

Many drugs exhibit poor solubility in water and lead to an extremely low oral bioavailability in human. In the pharmaceutical industry, micronization techniques are used to improve dissolution rates of drugs into the biological environment. Several conventional techniques have been utilized for particle size reduction. These include mechanical processes (crushing, grinding, and milling), spray-drying, freeze-drying, and recrystallization of the solute particles from solutions using liquid anti-solvents. A novel technique, the supercritical anti-solvent (SAS), was developed for micronization of particles. In the SAS process, an active substance and a carrier dissolved or suspended in an organic solvent are sprayed together or separately in an anti-solvent. The anti-solvent expands the solvent(s) t]which leads to microparticle formation by instant precipitation. One advantage of the SAS process is the ability to produce solvent-free product without the need for additional solvents or surfactants to induce precipitation. Low critical temperature solvents such as CO2 (Tc=31.1 °C) can be used for the precipitation of thermally labile materials without the risk of degradation.

Quercetin belongs to the chemical class of flavonoid and is widely distributed in vegetables and plants. It has been demonstrated to possess a wide array of biological effects that are considered beneficial to health, including antioxidative, free radical scavenging and anticancer. However, quercetin is sparingly soluble in water, which has limited its absorption upon oral administration.

The effects of various process parameters including the co-solvent, temperature, pressure, and flow rates on the particle size and morphology of pure quercetin was studied. In most cases long needles of quercetin were formed, ranging from 1 to several microns long. With very low concentrations of quercetin rod like particles in the 500 nm range were formed. The anti-oxidative activity of quercetin is maintained following processing with the SAS system as shown using 2,2-diphenyl-1-picrylhydrazyl (DPPH) as a radical scavenger.

The particles were also encapsulated with a biodegradable polymer, poly(lactic acid), for controlled-release of drug and to maintain antioxidative activity during storage and delivery. The effect on encapsulation yield and release of quercetin was shown to vary with polymer concentration, choice of co-solvents, and flow rates. The SAS method proved to be a suitable process for encapsulating quercetin and these particles are now further studied in animal models to follow their fate in vivo.