Synthesis of Composite Microparticles with a Mixing Cross
Abstract:Fine particles of pharmaceuticals and other materials can be rapidly made by a patented drying process known as CO 2 -Assisted Nebulization with a Bubble-Dryer ® (CAN-BD), by aerosolization from a low-volume mixing device (e.g., a tee or cross). The compounds of interest are dissolved in water or an appropriate organic solvent and mixed intimately with supercritical or near-critical CO 2 by pumping the fluids through a mixing device at room temperature and about 83 bar. The mixture is then decompressed through a capillary tube flow restrictor into a drying chamber maintained at near atmospheric pressure. The aerosol plume is mixed with preheated nitrogen in the drying chamber and is dried in less than 5 s at temperatures between 0 and 60°C. The dry powders (hollow, porous, or solid) collected from the chamber can usually be in the particle size range (1–5 µ m) optimum for pulmonary drug delivery. The use of a cross as a mixing device permits solutes or suspensions in two liquid streams and a nebulizing fluid (e.g., supercritical CO 2 ) to be mixed and desolvated to form heterogeneous microparticles. If one solid in the heterogeneous particles is a slowly dissolving coating material, the heterogeneous particles can release the second solid at a slower rate. If one solid is leached, a large porous particle with a high surface area can be obtained, yet its mean aerodynamic diameter is in the particle size optimum for pulmonary delivery. The primary advantages of this process are that (1) solids soluble in water and solids soluble in organic solvents can be micronized in a single-step process to generate heterogeneous particles, and (2) it facilitates drying of microbubbles and microdroplets at lower temperatures than those used in traditional spray drying processes.
Document Type: Research Article
Publication date: June 1, 2005