Many pharmaceutical substances are insoluble or only slightly soluble in aqueous media and the application of oral or injectable drugs is often limited by the low bioavailability. Due to the fact, that the bioavailability of drugs depends on the velocity of dissolution and absorption, nanoscale particles are needed in order to maximize the surface area, and to enhance the bioavailability. In recent years, we have used the RESS-process successfully to comminute water-insoluble drugs (Griseofulvin, Phytosterol, Ibuprofen). These experiments led to agglomerated particles in the range of 250±50 nm depending on solvent, pre- and post-expansion conditions. To minimize agglomeration of the particles due to coagulation during the expansion process and to suspend the particles, we utilized RESSAS (Rapid Expansion of Supercritical Solutions into Aqueous Solutions) to produce stable aqueous suspensions of water-insoluble drugs. In these experiments Tween 80, a nonionic surfactant and the anionic surfactant SDS was chosen to impede growth and agglomeration of the nanoscale drug particles. The concentration of the drug in the aqueous surfactant solution was measured by high performance liquid chromatography (HPLC) and the size of the stabilized particles was measured by dynamic light scattering (DLS). Independent of the pre-expansion conditions ultrafine Phytosterol particles (20 - 80 nm) were stabilized. Depending on surfactant and composition of the aqueous surfactant solution a bimodal particle size distribution was observed and suspensions with loadings up to 12 g/l could be achieved. Based on these promising results, the influence of various chemically different surfactants (Lutrol F68 and Solutol HS15, Tween 80 and SDS) on particle size distribution and on payloads was investigated.
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