The pulmonary or inhalational route of administration has been traditionally used for drug administration to the respiratory tract, in pathologies like chronic obstructive pulmonary disease or COPD, asthma, cystic fibrosis, etc.
The main advantages of administering medications by inhalation include the rapid absorption and rapid onset of action (e.g. very important for bronchodilator and anti-inflammatory drugs) as well as the localization of drug activity in the lung with minimal systemic toxicity, which is particularly important in the case of anti-inflammatory corticosteroids such as beclomethasone, budesonide, fluticasone, etc. But it would be a mistake to consider the lungs as an administration site only suitable for the local effect of drugs.
Indeed, the respiratory tract may also be regarded as a systemic administration route, as in the case of inhalable insulin. The lungs have a large surface area available for the systemic absorption of drugs: the alveolar-capillary barrier. This is a highly permeable and highly irrigated membrane, less than 0.5 μm thick, with a surface area of around 100 m2.
Human lungs, however, also have effective means for the elimination of deposited particles. In the upper airways, the ciliated epithelium contributes to mucociliary sweeping, by which the particles are drawn from the airways to the mouth. Already in the lungs, alveolar macrophages are able to phagocyte particles shortly after their deposition. Thus, effective inhalation therapy, and especially when a prolonged action of the drug is desired, requires bypassing the lungs’ clearance mechanisms for the drug to be completely absorbed.
As for the pre-systemic losses of the drug, it is generally accepted that they are smaller by respiratory route than orally, but this is an aspect that must be addressed on a case-by-case basis. Although to a lesser extent, most metabolizing enzyme systems of the liver are also present in the lung. Bearing in mind that blood flow normalized to tissue weight is almost ten times greater in the lung, this organ may play a significant role in the overall systemic clearance of a drug.
To be able to reach the lungs, through the bronchial tree, a drug must be in aerosol form, generated by an appropriate device. Aerosols are relatively stable two-phase systems consisting of condensed and finely divided matter suspended into a continuous gaseous phase. Due to the size restrictions imposed by this route, dispersion must be colloidal, and the dispersed phase may be a liquid (mist), solid (suspension), or a combination of both.
There are three main devices for administering medications by inhalation
In addition to rapid absorption and rapid onset of action, other advantages of pulmonary route of drug administration include:
1. Fewer systemic side effects
2. Dose can be removed without the risk of contaminating the remaining material in the container.
3. There is greater protection against drug degradation by oxygen and moisture, so stability is increased for labile substances.
4. Direct delivery of the medication to the affected area in the desired form is possible.
5. As compared to topical application, irritation produced by mechanical application is reduced or eliminated.
6. It is easy and convenient to apply the formulation.
7. The medication can be applied in a thin layer.
8. Protein-containing solutions can be nebulized.
9. Drug solubility issues can be solved by using lipid, water, or lipid/water emulsions as drug carriers. Thereby, viscous drug formulations can also be nebulized.
10. Effective for patients with respiratory problems.
11. Dose can be titrated.
1. The transport of drug to the site of action is not guaranteed.
2. There may be drug irritation and toxicity.
3. Drug retention and drug clearance may be a problem.
4. Drug may not be stable in vivo.
5. Targeting specificity is questionable.
6. Most addictive route (drug can enter the brain quickly).
7. Patient may have difficulty regulating dose.
8. Some patients may have difficulty using inhalers.