Coated Particles

A popular approach for tablets and granules is the application of coating materials [39]. These generally consist of natural or synthetic polymers, such as methacrylate, methylcellulose mixtures, and cellulose acetate phthalate (Aquacoat®), materials that would have dubious merits if employed for inhalation therapy. However, there have been a number of studies with aerosol powders demonstrating that release of probes can be markedly influenced after application of a coating agent. Notably, a study by Pillai et al. [40] using paraffin-coated particles was able to demonstrate a marked reduction in the absorption half-life of fluorescein and pentamidine. Related studies by Hickey et al. [7,41,42] have shown that the hygroscopic properties of aerosolized powders are altered when coated with fatty acids. It seems reasonable to expect that these materials would also influence the dissolution behavior in the lungs. The hydrophobic coatings constituted approximately 10% of the final particle mass, which is not substantive relative to the "drug" content when compared to the meager "payloads" offered by microspheres and liposomes, but there will always be the question of how much coating is necessary to achieve marked changes in dissolution and to what extent payload will be sacrificed. Fortunately, this may not be as much as first envisioned. Nanocoat Technologies Inc. (www.nano-sphere.com) is developing a technology that involves vapor deposition of minute quantities of biodegradable polymer (e.g., PLGA or PLA) using pulsed laser ablation. This approach has been used to efficiently coat the surface of hydrophobic drugs. Layer depths as small as 10 nm can have a profound effect on the dissolution of the "encapsulated" drug. Example data, using micronized particles of rifampicin, are shown in Fig. 2. This technology illustrates that of the various factors influencing dissolution, the thoroughness of the coverage can also play an important role.

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