Conventional dry powder inhalation systems are based on the preconception that the inhalant formulation is suitably pre-micronized during the manufacturing process. Here, I report Otsuka Dry Powder Inhalation;ODPI) system in which a freeze-dried cake breaks down into fine particles upon inhalation.
The ODPI system is characterized by the utilization of a freeze-dried cake with a unique porous network structure resembling a spider web that differs from the conventional freeze-dried cake at the micro-level.

View full abstract

Various nanotechnologies have been utilized in recent researches on pulmonary drug delivery. Notably, pulmonary administration of nanoparticulate formulation is regarded as promising in terms of effective deposition and prolonged retention of the drugs.
In this review, recent development of the nanotechnology-driven particle engineering for pulmonary drug delivery, with emphasis on control of surface characteristics of the particles using nanofabrication technique. Also noticed is the electrospray method, which is a novel technology to prepare nanoparticles. The advantage of this method is that it can be operated in ambient temperature and pressure conditions.

View full abstract

The lung is an attractive route for drug delivery because it has a large surface area, because the thickness of the air-blood barrier in the alveolar epithelium is less than 1 μm and because the blood capillaries are packed around the alveoli. Nano-particles are expected to apply in the new drug delivery systems. However, the surface energy of the particles is extremely high for nanoscale particles. Therefore, it is difficult to for them to exist in a solid state because of extremely high adhesion and cohesion forces, and when the particles adhere, it is difficult to disperse them again, resulting in their loss of function as nanoparticles. In the inhalation therapy, the particles are efficiently delivered to the bronchi and alveoli when their aerodynamic diameter is from approximately 0.4 to 5.8 μm. 4-fluid nozzle spray drier has a unique nozzle with two liquid and two gas passages, which allows drug and carrier to be dissolved in separate solvents, thereby avoiding the need for a common solvent. We have developed new technology to prepare mannitol microspheres containing nano-sized drug in one-step using the 4-fluid nozzle and succeeded in improving the absorption of water-insoluble drug by pulmonary administration of the particles. We also developed the particles for inhalation therapy of tuberculosis and studied the delivery to the lung, retention in the lung and uptake to the alveolar microphages.

View full abstract

Drug particles used for dry powder inhalation (DPI) are required to have good flowability in handling and dispersibility in delivering the drug into lung in order to effectively treat the pulmonary and systemic diseases. In this study, design of drug particles for DPI by using a supercritical carbon dioxide (SC-CO₂) has been presented. First of all, micronization process of water insoluble drug by a SC-CO₂ and its improved drug dissolution property were shown. Secondly, a novel agglomeration method of micronized drug, so called "Freeze Granulation by Supercritical Fluid:FG-SCF" has been developed and its application to DPI was discussed.

View full abstract

Recent progress of micronization technique has greatly contributed to the development of several functional medicines based on the arrangement of their shape in μ∼nm order. For optimized inhalable dry powders, their aerodynamic particle diameters should be 1∼5 μm to achieve effective pulmonary delivery, while micronization process may generates stronger cohesive force between them, thereby leading to lower dispersion. To overcome these problems, hollow porous microparticles with low density have been developed.
In this topic, we review the development of hollow porous microparticles for inhalable dry powder formulation, and introduce novel sea-urchin like microparticles that we have developed.

View full abstract

The clinical efficacy of inhalation therapy has been established against patients with bronchial asthma. Recently the inhalation of antimicrobial agents for respiratory infection is needed because few newer antibiotics have been developed.
The administration of inhaled of aminoglycoside antibiotic in patients with chronic respiratory pseudomonas aeruginosa infection indicated clinical efficacy. The usefulness of aerolized liposomal amphotericin B against patients with invasive pulmonary aspergillosis is expected.

View full abstract