Pulmonary systemic drug delivery

BenJebria, A. Eskew, M.L. Edwards, D.A. Inhalation system for pulmonary aerosol drug delivery in rodents using large porous particles. Aerosol Sci. Technol. 2000, 52, 421 33. 

Although aerosols of various forms for treatment of respiratory disorders have been in use since the middle of the twentieth century, the interest in the use of pulmonary route for systemic drug delivery is recent. Interest in this approach has been further stimulated by the demonstration of potential utility of lung as a portal for entry of peptides and the feasibility of gene therapy for cystic fibrosis. It is important to understand the mechanism of macromolecule absorption by the lungs for an effective use of this route. 

As pharmaceutical scientists gain experience and tackle the primary challenges of developing stable parenteral formulations of proteins, the horizons continue to expand and novel delivery systems and alternative routes of administration are being sought. The interest in protein drug delivery is reflected by the wealth of literature that covers this topic [150-154]. Typically, protein therapeutics are prepared as sterile products for parenteral administration, but in the past several years, there has been increased interest in pulmonary, oral, transdermal, and controlled-release injectable formulations and many advances have been made. Some of the more promising recent developments are summarized in this section. 

J. S. Patton and R. M. Platz, Routes of drug delivery case studies (2) pulmonary delivery of peptides and proteins for systemic action, Adv. Drug Deliv. Rev, 8, 179 (1992). 

An ideal in vitro model for the characterization of aerosol formulations would incorporate cell types from various regions of the lung (tracheal, bronchial, and alveolar) and would facilitate simulation of deposition mechanisms by impaction, sedimentation, and diffusion of a high-metered singlebolus inhalation. In the future, such systems may reduce the need for animal studies and may offer to correlate in a predictive way the results from such in vitro tests to clinical bioavailability data after pulmonary drug delivery in vivo. 

The first commercially available DPI system appeared on the market in 1949, developed and marketed by Abbott under the name Aerohaler. Like all early pulmonary drug-delivery devices, it delivered small-molecule compoimds (bronchodilators or inhaled corticosteroids) to the airways (not necessarily the deep limg) for the treatment of asthma or chronic obstructive pulmonary disease. Table 6 lists some of the early DPI systems used for asthma and COPD the energy somces in these devices were mechanical and patient inspiration. 

Nebulizers and dry powder inhalers seem more appropriate systems to be used in the early stages of development of drug products for pulmonary drug delivery. However, it should not be concluded from this that the development of formulations for nebulizers or DPIs is easier and exhibits fewer theoretical and practical problems. 

Administration Iloprost is intended for inhalation administration only via the Prodose AAD system, a pulmonary drug delivery device. It has not been studied with any other nebulizers. 

---