55. Thakur, Ranjit; Gupta, Ram B.  Rapid Expansion of Supercritical Solution with Solid Cosolvent (RESS-SC) Process: Formation of Griseofulvin Nanoparticles.    Industrial & Engineering Chemistry Research (2005), 44(19), 7380-7387.


In the conventional RESS process, a supercrit. soln. is rapidly expanded through a nozzle to ppt. the solute as microparticles.  The modeling of RESS has shown that the pptd. particles at the nozzle tip are on the order of 5-25 nm in size.  However, for most solutes, the final particles exptl. obtained are on 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 compds. have poor soly. in supercrit. 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) enhances the soly. and provides a barrier for coagulation in the expansion chamber.  The solid cosolvent is later remove from the solute particles by lyophilization (sublimation).  The new process is termed as RESS-SC.  A suitable solid cosolvent is menthol, which is solid below 35 (the typical nozzle exit temp. is 5-30) and can be easily sublimed.  The RESS-SC concept is demonstrated by producing nanoparticles of griseofulvin, an antifungal drug which has very low soly. in supercrit. CO2.  With the use of the menthol cosolvent, griseofulvin soly. in supercrit. CO2 is increased by about 28-fold.  With the use of a simple capillary nozzle, griseofulvin particles in the range of 50-250 nm were obtained, which is a 10-fold redn. from the conventional RESS process.  The final powder is pure griseofulvin, free of any stabilizing agents.  Particles are characterized by SEM, XRD, and DSC analyses.  In addn., data and modeling of the soly. enhancement are presented.


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