Chapter 3.3 - Formation of nanoscale drugs by Rapid Expansion of Supercritical Solutions (RESS): — Experimental and theoretical investigations —

Abstract

This chapter elaborates experimental and theoretical investigations of the formation of nanoscale drugs by rapid expansion of supercritical solutions (RESS). The particle size of the pharmaceutical substances (3-sitosterol, griseofulvin, and ibuprofen precipitated by RESS was in the range of 160 to 320 nm. The improvement of the bioavailability of the RESS-produced griseofulvin has been verified by dissolution experiments according to the Strieker model. As a first step toward intravenous application of poorly soluble drugs, stable suspensions of nanoscale particles of β-sitosterol were produced. In these experiments, the supercritical mixture was sprayed directly into an aqueous surfactant solution. The particle sizes of β-sitosterol in the aqueous solution were smaller or equal to those produced by RESS into air. These experiments show that the RESS technique is a promising method for the formulation of water-insoluble drugs. The modeling results show that particle growth is not completed in the supersonic free jet, and the post-expansion conditions are an important factor to control particles size. The comparison between experimental and calculated particle size shows a good agreement in the general trends, but does not match exactly the measured mean particle sizes.