Solubility and Micronization of Griseofulvin in Subcritical Water

The technology developed in this work takes advantage of the temperature-sensitive dielectric constant of water to micronize hydrophobic compounds. At elevated temperatures subcritical water (SBCW) is a good solvent for nonpolar compounds, while at ordinary temperatures it behaves as an antisolvent. The solubility of the model compound griseofulvin in SBCW was determined at 70 bar and temperatures between 130 and 170 degrees C. In this work griseofulvin was dissolved in subcritical water. The resulting subcritical solution was then injected into water at room temperature to rapidly quench the temperature and trigger precipitation of the solute. The resulting particle morphology was markedly dependent on operating conditions such as temperature and concentration of the subcritical solution. It was possible to generate microparticles of griseofulvin with controllable morphologies. The process is rapid and does not involve the use of organic solvents.