Micronization of pharmaceutical substances by the Rapid Expansion of Supercritical Solutions (RESS): a promising method to improve bioavailability of poorly soluble pharmaceutical agents

Abstract

A multitude of pharmaceutical substances are often insoluble or only slightly soluble in aqueous media and the application of oral or injectable drugs is often limited by its low bioavailability. A promising method to improve the bioavailability of pharmaceutical agents is the Rapid Expansion of Supercritical Solutions (RESS). The RESS-process enables the micronization of thermally labile materials and the formation of particles of less than 500 nm in diameter. Our current research is aimed towards an improved understanding of the relationship between process parameters and particle characteristics and to explore new areas of application for nanoscale particles. Therefore, experimental investigations and numerical simulations were performed. Measurements were carried out for Benzoic acid, the pharmaceuticals Griseofulvin and β-Sitosterol with the solvents CO 2 (Carbon dioxide) and CHF 3 (Trifluoromethane). These experiments led to particle sizes in the range of 200–500 nm depending on solvent and pre and postexpansion conditions. RESS-modelling is focused on the flow through the nozzle, the supersonic freejet, the Mach shock and particle growth in the expansion unit. From these calculations follows that particles are formed as small as 2–8 nm in the supersonic freejet. Hence, the conditions inside the expansion chamber are one key factor to control particle size. Furthermore, experiments show that the RESS processing of Griseofulvin leads to a significantly better dissolution rate of the drug resulting in an improved bioavailability. Moreover, stable suspensions of nanoscale particles of β-Sitosterol were produced by the rapid expansion of a supercritical mixture through a capillary nozzle into aqueous solutions. The particle sizes of β-Sitosterol in the aqueous solution were smaller or equal to those produced by RESS into air without the surfactant solution.