(696a) Nanonization of Pharmaceutical Compounds By Solution-Enhanced Dispersion By Supercritical CO2

Supercritical CO₂ technologies have been shown to have great potential in pharmaceutical science; they are effective in producing microparticles or nanoparticles of pharmaceutical compounds due to the mild critical conditions (Tc = 304.1 K, Pc = 7.38 MPa), non-toxicity, non-flammability, and low price of supercritical CO₂.

In order to enhance the bioavailability of a poorly water-soluble drug by improving its solubility and dissolution rate, solution-enhanced dispersion by supercritical CO₂ (SEDS) was used to prepare the nanoparticles of pharmaceutical compounds, such as methotrexate (MTX) and puerarin. We designed a 2³ factorial experiment to investigate and identify the relative significance of the operating parameters on the surface morphology and mean size of drug particles. The effect of the nonsolvent/solvent (MTX: acetone/dimethyl sulfoxide, v/v; puerarin: dichloromethane/ethanol, v/v) ratio was found to exert a dominant influence on mean particle size. Increasing the nonsolvent/solvent ratio decreased the particle size significantly. The resulting MTX and puerarin nanoparticles exhibit a good spherical shape, a smooth surface, and a narrow particle size distribution, with a mean particle size of 81 and 188 nm, respectively. After supercritical processing, there was no change in the chemical composition of the pharmaceutical compounds. However, their physical states shifted from crystalline into amorphous due to the minor structural changes which occurred on a molecular level. Due to the reduced particle size and change of physical state, the solubility and dissolution rate of the MTX nanoparticles were much higher than those of the original MTX powder (5.9 µg×ml^-1 versus 3.7 µg×ml^-1 in 42 hours, and 12.6 µg×ml^-1 versus 10.8 µg×ml^-1 in 92 hours). Similar phenomena were also found for the puerarin after nanonization.

This study reveals that SEDS process may have a great potential in producing nanoparticles of poorly water-soluble pharmaceutical compounds with an improved dissolution rate.