Transmucosal Nasal Drug Delivery: Systemic Bioavailability of ...

1. Nasal drug delivery
1 Nasal drug delivery
1.1 Topical and systemic bioavailability of nasally applied drugs
The rate and extend to which an active substance or active moiety is absorbed from the
pharmaceutical preparation and becomes available at the site of action, is defined as
bioavailability by the European Agency for the Evaluation of Medical Products [EMEA 26. July
2001].
In general, drug administration is characterized by the systemic bioavailability (the rate and
extend the active substance is absorbed into the systemic blood circulation, not taking in
consideration the site of action). The reasons are ease of blood sampling contrary to the difficulties
to assess the drug concentration directly at the site of action (e.g., central nervous system).
Topical drug delivery describes the application of a drug directly on the target organ (e.g.,
application of glucocorticosteroides for dermatological therapies). To study vehicle effects of topical
drug delivery, both the assessment of topical bioavailability and systemic bioavailability are
performed. Whereas topical bioavailability allows predicting the therapeutic effect and
systemic bioavailability reflects the systemic exposure meaning the risk for systemic adverse
drug reactions.
The term nasal drug delivery refers to topical and systemic nasal drug delivery. For diseases
of the nasal mucosa, such as infectious rhinitis, allergic rhinitis, and nasal polyposis, the topical
nasal administration delivers drug directly to the target organ [Salib and Howarth 2003]. Nasal
applications of topical decongestants or anti-inflammatory drugs are therefore the most popular
topical nasal drug deliveries.
Whereas nasal drug delivery for systemic effect means transmucosal drug delivery, and
provides, for some compounds, direct access to the systemic circulation. Transmucosal
absorption describes the uptake of a compound into the systemic circulation after application on a
mucosa (e.g., nasal, buccal, or rectal mucosa). Transmucosal absorption subsumes following
subsequent processes: drug release, penetration (entry into a layer), permeation (transition of a
layer), and absorption (uptake into the vascular system).
The common term nasal bioavailability usually refers to the systemic bioavailability after nasal
drug delivery and not to the topical bioavailability in the nasal mucosa.
Katja Suter-Zimmermann Page 11 of 188 University of Basel, 2008