Nasal administration
Encyclopedia
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.
. 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.
s 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.
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.
Advantages with nasal systemic drug delivery
The nasal cavity is covered by a thin mucosa which is well vascularised. Therefore, a drug molecule can be transferred quickly 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 moleculesSmall molecule
In the fields of pharmacology and biochemistry, a small molecule is a low molecular weight organic compound which is by definition not a polymer...
. 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 sprayNasal spray
Nasal sprays come in a variety of forms. Medicated such as Astelin, Afrin and Nasonex and natural such as Sinusoothe and Sterimar. Although delivery methods vary, most nasal sprays function by instilling a fine mist into the nostril by action of a hand-operated pump mechanism.-Antihistamine nasal...
s 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
Desmopressin
Desmopressin is a synthetic replacement for vasopressin, the hormone that reduces urine production. It may be taken nasally, intravenously, or as a tablet...
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
Summary of Product Characteristics
The Summary of Product Characteristics is a specific document required within the European Commission before any medicinal product is authorized for marketing. This summary is the definitive description of the product both in terms of its properties, chemical, pharmacological and pharmaceutical...
). 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 cavityNasal cavity
The nasal cavity is a large air filled space above and behind the nose in the middle of the face.- Function :The nasal cavity conditions the air to be received by the other areas of the respiratory tract...
is covered by respiratory epithelium, across which systemic drug absorption can be achieved. The olfactory epithelium
Olfaction
Olfaction is the sense of smell. This sense is mediated by specialized sensory cells of the nasal cavity of vertebrates, and, by analogy, sensory cells of the antennae of invertebrates...
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
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
(BBB), which is virtually impermeable to passive diffusion
Passive transport
Passive transport means moving biochemicals and other atomic or molecular substances across membranes. Unlike active transport, this process does not involve chemical energy, because, unlike in an active transport, the transport across membrane is always coupled with the growth of entropy of the...
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.