Micronization of Pharmaceutical Substances by Rapid Expansion of Supercritical Solutions (RESS): Experiments and Modeling

An increasing number of newly developed pharmaceutical substances are poorly soluble in both aqueous and organic media. Thus, the application of oral or injectable drugs is often limited by its low bioavailability. An alternative and promising method to improve the bioavailability of pharmaceutical agents is the production of nanoscale particles by the rapid expansion of supercritical solutions (RESS). Our research is aimed towards an improved understanding of the underlying physical phenomena of the relationship between the process conditions and the particle characteristics. Therefore, experimental investigations and numerical simulations were performed. RESS experiments with the pharmaceutical substances β-sitosterol, griseofulvin, and ibuprofen led to particle sizes in the range of 240±80 nm. In addition, as one step towards intravenous application of poorly soluble drugs, β-sitosterol was used to produce aqueous suspensions of a water-insoluble drug with a particle size smaller than or equal to those produced by RESS into air. RESS modeling is focused on the flow through the nozzle, the supersonic free jet, the mach shock, and particle growth in the expansion unit. The comparison with experimental results shows a good agreement in the general trends but does not match exactly the measured mean particle sizes.