Rapid Expansion from Supercritical to Aqueous Solution to Produce Submicron Suspensions of Water-Insoluble Drugs

Abstract

Stable suspensions of submicron particles of cyclosporine, a water-insoluble drug, have been produced by rapid expansion from supercritical to aqueous solution (RESAS). To minimize growth of the cyclosporine particles, which would otherwise occur in the free jet expansion, the solution was sprayed into an aqueous Tween-80 (Polysorbate-80) solution. Steric stabilization by the surfactant impedes particle growth and agglomeration. The particles were an order of magnitude smaller than those produced by RESS into air without the surfactant solution. Concentrations as high as 38 mg/mL for 400-700 nm particles were achieved in a 5.0% (w/w) Tween-80 solution.