Nasal administration

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Main article: Drug administration methods

Nasal administration can be used to deliver drugs for either local or systemic effect. Locally acting drugs are for example decongestants and allergy treatments. Examples of systemically active drugs available as nasal sprays are migraine drugs, nicotine replacement and hormone treatments.

Advantages with nasal systemic drug delivery

The nasal cavity is covered by a thin mucosa which is well vascularised . A drug molecule can therefore quickly be transferred across the single epithelial cell layer directly to the systemic blood circulation without first-pass hepatic and intestinal metabolism. The effect is often reached within 5 min for smaller drug molecules . Nasal administration can therefore be used as an alternative to oral administration of for example tablets and capsules if a fast effect is desired or if the drug is extensively degraded in the gut or liver.

Limitations with nasal systemic drug delivery

Nasal administration is primarily suitable for potent drugs since only a limited volume can be sprayed into the nasal cavity. Drugs for continuous and frequent administration may be less suitable because of the risk of harmful long term effects on the nasal epithelium. Nasal administration has also been associated with a high variability in the amount of drug absorbed. Upper airway infections may increase the variability as may the extent of sensory irritation of the nasal mucosa, differences in the amount of liquid spray that is swallowed and not kept in the nasal cavity and differences in the spray actuation process . However, the variability in the amount absorbed after nasal administration should be comparable to that after oral administration .

Drugs for nasal administration

Nasal sprays for local effect are quite common. Several antimigraine drugs are also currently administered by nasal administration because a fast effect is desired and oral administration can be prohibited by nausea. Peptide drugs (hormone treatments) are also available as nasal sprays, in this case to avoid drug degradation after oral administration. The peptide analogue desmopressin is, for example, available for both nasal and oral administration. The bioavailability of the commercial tablet is 0.1% while that of the nasal spray is 3-5% according to the SPC (summary of product characteristics) . Other potential drug candidates for nasal administration include anaesthetics, antiemetics and sedatives that all benefit from a fast onset of effect.

Olfactory transfer

The major part of the approximately 150 cm² surface in the human nasal cavity is covered by respiratory epithelium, across which systemic drug absorption can be achieved. The olfactory epithelium is situated in the upper posterior part and covers approximately 10 cm² of the human nasal cavity. The nerve cells of the olfactory epithelium project into the olfactory bulb of the brain, which provides a direct connection between the brain and the external environment. The transfer of drugs to the brain from the blood circulation is normally hindered by the blood-brain barrier (BBB), which is virtually impermeable to passive diffusion of all but small, lipophilic substances. However, if drug substances can be transferred along the olfactory nerve cells, they can bypass the BBB and enter the brain directly. ,

The olfactory transfer of drugs into the brain is thought to occur by either slow transport inside the olfactory nerve cells to the olfactory bulb or by faster transfer along the perineural space surrounding the olfactory nerve cells into the cerebrospinal fluid surrounding the olfactory bulbs and the brain (8, 9)

Olfactory transfer could theoretically be used to deliver drugs that have a required effect in the central nervous system such as those for Parkinson’s or Alzheimer’s diseases. Studies have been presented that show that direct transfer of drugs is achievable but the possibility of olfactory delivery of therapeutically relevant doses to humans remains to be demonstrated.

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