Formation of particles for dry powder inhalers

• We analyze a particle deposition and retention in the respiratory system.
• It is shown that particles with tapped density below 0.4 g/cm3 and MMAD below 5 μm are effective for inhalation therapy.
• Methods of formation of hollow and porous therapeutic particles are discussed.
• We report characteristics of dry powder inhalers for systemic and lung treatments.

Inhalation therapy is widely employed to deliver drugs to the respiratory epithelium, predominantly for the treatment of local disorders. Recently aerosol therapy has become an attractive non-invasive way for systemic administration of biologically active components, because of the unique features of the lung, namely its large surface area, high permeability and wide blood supply. Success of a therapy depends on the effectiveness of particle delivery to a targeting site of the lungs. The paper explains mechanisms of particle transport, deposition and retention in the respiratory system coupled with the efficiency of the powder aerosolization with a dry powder inhaler (DPI) leading to the definition of the required particle structure. The most promising hollow or porous nanostructured particles have tapped density below 0.4 g/cm3 and mass medium aerodynamic diameter (MMAD) below 5 μm. Key features of the process leading to the formation of particles with the required structure are explained. Spray-drying, spray-freeze-drying and supercritical antisolvent precipitation are shown to be the most promising methods for efficient production of particles for inhalation. Examples of the production of therapeutic particles for delivery of peptides, antibiotics, anticancer drugs, and the structures of particles obtained with the above mentioned and other methods are presented. The paper concludes with brief information about a recent construction of DPIs for aerosolization of therapeutic particles.

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