Formation of submicron poorly water-soluble drugs by rapid expansion of supercritical solution (RESS): Results for Naproxen

Numerous results of multitude investigations indicate that the particular properties of supercritical fluids can be conveniently exploited for the formation of submicron particles. In case of pharmaceutical substances the poor dissolution behaviour and therewith bioavailability of drugs in biological media can be enhanced dramatically by reduction of the particle size. In this paper we report the application of RESS (Rapid Expansion of Supercritical Solutions) and RESSAS (Rapid Expansion of Supercritical Solution into Aqueous Solution) to produce submicron particles of Naproxen, a poorly water-soluble drug. Thereby the effect of various process conditions on the obtained product properties was investigated. The experimental results show, that the RESS processing of Naproxen leads to particles in the range from 0.56 to 0.82 μm which is about 22 times smaller than the unprocessed powder. RESSAS experiments show, that stabilized Naproxen particles have an average diameter of 0.3 μm for drug concentrations up to 1 g/dm3 in 0.4 wt% PVP solution while expansion into a 0.4 wt% Tween® 80 solution produced particles 8 μm in diameter. Furthermore, it is shown that the improved dissolution behaviour of the processed powder depends on the particle size and hence increased surface area and on the pH-value of the dissolution media.