- 12:55 PM

Rapid Expansion of Supercritical Solution with Solid Cosolvent (Ress-Sc) Process for Pharmaceutical Nanoparticles Formation

Ram B. Gupta and Ranjit Thakur. Chemical Engineering, Auburn University, 0322 Haley Center, Auburn, AL 36849-5127

In conventional RESS process, a solute dissolved in supercritical fluid is rapidly expanded through a nozzle to precipitate the solute as microparticles. The modeling of RESS has shown that the precipitated solute at the nozzle tip is of the order of 5-25 nm in size. However the final particles experimentally obtained are in the order of 800-3000 nm in size, due to growth by coagulation in the expansion chamber. Another difficulty is that most of the pharmaceutical compounds have poor solubility in supercritical carbon dioxide (a fluid of choice). In this work, both challenges are addressed by utilizing a cosolvent that is solid at the nozzle exit conditions. The solid cosolvent (SC), menthol, enhances the solubility and provides barrier for coagulation in the expansion chamber. The new process is termed as RESS-SC. RESS-SC concept is demonstrated by producing nanoparticles of griseofulvin, 2-amino benzoic acid, and phenytoin. RESS-SC produces about 10 fold small nanoparticles than conventional RESS process. In addition, for all three compounds, solubility in supercritical carbon dioxide is significantly enhanced providing a much higher (as high as 500 fold!) production rate of the nanoparticles. Menthol solid co-solvent is conveniently removed from the final powder by sublimation.