The administration of topical pharmaceuticals to the respiratory tract is well proven, and the inhalation route of administration is gaining increased attention for further indications. By comparison, oral and parenteral administration of drugs may require much higher doses than topical administration to the lung, and can lead to significant unwanted systemic exposure and side effects. However, the lung also presents unique challenges because of the complex structure of the airways.
The main advantage of delivering by inhalation directly to the lung (topical) is that the actual site of action is targeted, allowing for localized treatment and minimizing the dose needed and therefore any systemic side effects, with an order of magnitude improvement in lung dose reported.
An inhaled particle or droplet must negotiate the mouth, throat and upper airways, in order to avoid unintended deposition before reaching the specific disease targets or receptor locations. Mucociliary and macrophageal clearance also present physical barriers. Macrophages ingest and destroy invading pathogens, including drug particles in the range 0.5 – 6 µm. Consequently, it is advantageous to deliver particles of less than 500 nm to avoid this form of clearance.
Advantages of formulated nanoformed API for lung delivery:
- Smaller particle size increases surface area and therefore improves dissolution, solubility and bioavailability
- Better ensures dispersion of particles on inhalation, improving respirable fraction
- Improvement of drug adhesion and penetration
- Increased local delivery and reduction of absorption over systemic routes of delivery
- Higher drug load possible in dry powders minimizes patient’s inhalation burden of multiple inhalations
- Improved lung dose delivery
- Increase of delivered dose output using liquid nebulizers