Inhalation drug delivery methods

Relenza ) in 1999. The polar nature of Relenza precluded significant oral absorption, and therefore an infraoral inhalation drug delivery method was developed that delivered the drug to the primary site of infection. 

Markert M, Klumpp A, Trautmann T, Guth BD (2004) A novel propellant-free inhalation drug delivery system for cardiovascular safety pharmacology evaluations in dogs. Journal of Pharmacological and toxicological Methods 50 109-119... 

The first commercially available DPI system appeared on the market in 1949, developed and marketed by Abbott under the name Aerohaler. Like all pulmonary drug-delivery methods that existed before now, it delivered small molecule compounds (brochodilators or inhaled corticosteroids) to the airway (not necessarily to the deep lung) for the treatment of asthma or chronic obstructive pulmonary disease. Table 6 lists some of the early DPI systems and their basic characteristics. 

In 1974, the Sugarloaf Conference [3] underscored the empiric nature of many applications of inhalation therapy, as it was called at that time. The scientific basis for many treatments was very weak. Although there has been considerable progress since the early 1980s, there are today still many uncertainties about inhaled drug delivery and many variations of delivery equipment and methods. A more recent consensus statement reviews some advances and describes continuing needs for investigation [4]. 

Low-dose regimens frequently result in very low corticosteroid concentrations in body fluids (e.g., low pg/mL range in plasma). PK analysis that is often necessary to manage these therapies is hindered by the inadequate sensitivity by most established analytical methods. In addition, certain drug delivery strategies, such as inhalation or intraocular injection, result in systemic levels too low to be detected by current methods. Furthermore, administration of some corticosteroid prodrugs, such as these in the forms of acetates/propionate, often results in sustained, low concentrations in plasma. Therefore, a highly sensitive and selective analytical approach is necessary for cases in which sustained low concentration of corticosteroids may be present systemically or in tissues. 

Although the oral route is the most common route of drug delivery, investigation into the prediction of uptake by other routes is also important. Dermal penetration and inhalation are not only relevant as methods of drug delivery, but in terms of toxicology they represent important routes of exposure. 

Selection of the appropriate route of administration and delivery device is critical for the commercial success of a drug product. Although injections are the most efficient delivery method for proteins, they are not always the most suitable from the patient s perspective. Few routes of administration (IV, IM, SC, pulmonary, and topical for local delivery) have been successful to date with protein therapeutics because of the size and complexity of the protein structure. Consideration of the bioavailability via a given route must be made when determining the dose required. Use of a delivery device such as an implantable pump, needle-free injector, or dry-powder inhaler may yield a product with a commercial advantage over a competitor s product. 

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