Formation of Submicron Drug Particles with Enhanced Dissolution Behaviour by Rapid Expansion of Supercritical Solution (RESS)

The poor dissolution behaviour and therewith bioavailability of poorly soluble drugs in biological media can be enhanced dramatically by reduction of the particle size. The disadvantages of the conventional micronization techniques such as milling and grinding, spray-drying, freeze-drying, high-pressure homogenization, ball and air jet milling are often degradation of the product, a broad particle size distribution, change of crystallinity  and cumbersome solids handling. To overcome this, supercritical fluid based particle size reduction processes are gaining in importance in material science and pharmaceutical technology. Experimental results confirm that the RESS-process (Rapid Expansion of Supercritical Solutions) is a promising technique for the formation of submicron particles. In the talk, typical results obtained from RESS-experiments performed in our lab with poorly water soluble drugs such as S-(+)-Naproxen, RS-(±)-Ibuprofen, Phytosterol, Carbamazepine and Salicylic acid are presented. In addition, it is shown that the improved dissolution behaviour of these particles depends on: a) reduced particle size and hence increased surface area of the processed powders and b) pH-value of the dissolution