Paper Title
Synthesis of Naproxen Molecular Clusters by RESS Processing

In pharmaceutical industry, poor water solubility and limited bioavailability has a major concern on new drug development. It is well established that the bioavailability of such drugs can be improved by reducing their particle size. A number of conventional strategies are available in literature for particle size reduction but they suffer with some disadvantages and handling concerns. Recently, supercritical CO2 based processes are found to be more promising for micronization of pharmaceuticals as they have successfully addressed the above concerns and offer additional advantages like economic, non-toxic, scalable, environmentally compatible and etc.In this paper, we report of synthesis of naproxen molecular clusters via supersonic jet expansion of the supercritical CO2 drug formulation. These molecular clusters were collected in a special designed a two-stage collection vessel, cooled to liquid N2 temperatures and resulted embedding of drug molecular clusters in ‘dry ice’, instantaneously. Gradual transferring of the ‘dry ice’ into deionized water, resulted in true solubilization of drug molecular clusters in water. Afterword’s, these solutions were drop-casted on silicon substrate and dried for overnight under ambient conditions, resulted in a stable, viscous films with liquid like behavior. Analytical characterizations showed that these water-solubilized naproxen solutions retained their chemical and structural identity after sc-CO2 processing. This is interesting to note that raw naproxen powder is solid powder under ambient conditions with melting points of 154o C. Our observations are expected to explore the sc-CO2 processing strategy for other existing drug formulations and would open up new drug delivery platforms. Keywords - Poor Water Solubility, Supercritical Processing, RESS Process, Naproxen, Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) and Drug Molecular Clusters.