Before discussing the three categories of delivery device, the nature of the emitted aerosol will be considered. Droplet formation may be characterized in terms of the nature of the propulsive force and the liquid being dispersed, and this topic is dealt with for specific situations in the following sections. However, dry particles, which are delivered from suspension in pMDIs or from dry powder inhalers (DPIs) alone or from a blend, must be prepared in respirable sizes. The production of respirable aerosol particles has traditionally been achieved by micronization of the drug (26). This is commonly achieved through air-jet milling (27,28). This involves the introduction of bulk particles on a gas stream into the path of an opposing gas stream under high pressure. Particles impact on each other and are thereby ground into small particles, which ultimately pass through a cyclone separator and are collected in a vessel or a bag filter. These particles can be produced in size ranges less than 5 |im, which is suitable for lung deposition.
A variety of technologies (27,29) exist for creating respirable colloidal particles in the solid state. In recent years, spray drying has been employed as an alternative method of production (27,30-33). This method has the advantage that particles produced are frequently spherical. In addition, it may be the case that the particles are not subject to such high-energy input as in the case of jet milling, and consequently, this may be more suitable for thermolabile materials. As more sophisticated techniques are being developed for the production of particles, they are finding applications in the production of aerosol particles. One of the more successful of these approaches is the supercritical fluid method of manufacture, which involves controlled crystallization of drugs from dispersion in supercritical fluids, notably carbon dioxide (27,32,34,35). Many supercritical fluid technologies exist and have found demonstrated utility in generating respirable solid-state particles for a variety of pulmonary materials and emulsion systems (27,33,35-43).
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