Preparation of drug nanoparticle-containing microparticles using a 4-fluid nozzle spray drier for oral, pulmonary,...

We prepared microparticles containing nanoparticles of water-insoluble pranlukast hemihydrate (PLH) using a 4-fluid nozzle spray drier. These particles were designed to improve the absorption of PLH and to allow delivery by oral, pulmonary, and injection routes. Mannitol (MAN) was used as a water-soluble carrier for the microparticles. We orally administered suspensions of PLH powder and PLH-MAN microparticles to rats. We also compared the in vitro aerosol performance of the PLH powder and PLH-MAN microparticles using a cascade impactor, and we compared the delivery of PLH by oral administration of PLH powder and pulmonary delivery of PLH-MAN microparticles at PLH/MAN ratios of 1:4 and 1:10. The absorption of PLH was markedly enhanced by pulmonary deliver of PLH-MAN composite microparticles. The area under the plasma concentration-time curve per dose for pulmonary administration of the 1:4 and 1:10 PLH-MAN microparticles was approximately 85- and 100-fold higher, respectively, than for oral administration of PLH powder. Also, we found that PLH rapidly disappeared from the plasma following injection of PLH aqueous solution or PLH-MAN microparticles dissolved in water. The PLH particles remaining after dissolution of MAN from the 1:10 PLH-MAN microparticles were 200 nm in diameter. Therefore, PLH particles may be captured immediately after injection by reticuloendothelial tissues such as the liver and spleen. This study demonstrated that it is possible to use the 4-fluid spray drier to prepare microparticles containing PLH nanoparticles that that improve drug absorption and can be administered by oral, pulmonary, and injection routes.