Therapeutic
Intranasal Drug DeliveryNasal drug delivery techniques
How should one deliver medications to the nose?
Snorting
The method of intranasal medication delivery likely impacts the success of the procedure. Elicit drug users employ a technique called “snorting” whereby they take a highly concentrated powder form of a drug such as cocaine or heroin and rapidly sniff the drug into the nostril. This causes deposition of the powder onto the nasal mucosa and rapid transfer of the drug into the circulation and brain. This technique requires an experienced and cooperative user and is unlikely to be effective in medical therapeutic situations.
Drug delivery as drops using a syringe or dropper
A second method of intranasal drug delivery is to take a solubilized medication (liquid form) and drip it into the nose a few drops at a time, allowing it to run down onto the nasal mucosa. This can be done using a syringe or in some instances using the packaged form of the medication to drip it directly into the nose. To use this technique, most generic medications will need to be removed from within their storage bottle using a syringe. The syringe can then act as the measuring/dosing device as well as the dropper. The efficacy of the nasal dropper techniques varies depending on which author you read. Some authors find drops to be an effective method of delivery,[1-3] while others note poor surface area coverage and rapid removal of the medication into the throat via runoff and ciliary movement.[1, 4-10] Never the less it is this method has been used in many research studies and found to be an effective method of delivering adequate doses of medication to patients.
Usability problems with drops
Unfortunately, outside the research arena there are some issues regarding the “usability” of the nasal dropper technique. Usability is a term that evaluates the human-technological interface to assess how easy a technology is to master and use. Usability also includes an evaluation of efficacy (did it work) and satisfaction (did I like using it or was it very difficult to use). A good idea that is difficult to apply will rarely be adopted outside the research setting. While mastering the concept of using a syringe as a dropper is very simple, the actual application in a clinical environment is less straight forward and can lead to delivery failure, drug failure and clinician/patient abandonment of the technique due to low satisfaction. Unfortunately, nasal dropper delivery of medications requires a fairly cooperative patient or actual physical restraint of the patient to position them in a semi-recumbent position (usually requiring at least two adults to hold in position) so the medicine will run back into the nose and not out onto their lip. Drops delivered too rapidly cause the drug to run straight through into their throat leading to coughing, gagging and poor absorption. Drops delivered slowly often require prolonged restraint in any but the most cooperative patient. It is also very common for the uncooperative patient to violently blow their nose at the time of delivery – expelling the drug externally into the environment and onto the clinician. It is possible that these usability issues have contributed to the delayed adoption of intranasal drug delivery in the medical community despite over 20 years of research demonstrating how effective intranasal medications can be in selected situations.
Syringe dropper "technique"
Sprayed or atomized medication delivery
Sprayed or atomized intranasal medication delivery is a more recent technique adopted by the pharmaceutical industry due to improved usability issues as well as improved bioavailability data. This delivery technique combines a method of measuring a unit dose of medication – either via a syringe or unit dose pump – with a spray tip that fragments the medication into fine particles as it is being sprayed into the nose. It appears that this method of delivery results in a broader distribution of the medication across the nasal mucosa and an increased bioavailability of the drug. [1, 4-7, 9-12] Furthermore, the usability issue makes this nasal spraying of medications far easier to employ – the patient can have the medication delivered from any position (sitting, lying down, prone, on side) and since it only takes a second to administer the dose they do not need to be restrained. Finally, because the medication is sprayed/atomized as a mist, less is likely to be blown back out the nose into the external environment. For all these reasons, most pharmaceutical nasal medications are now packaged with a spray applicator rather than a dropper. In addition, syringe driven and pump driven spraying devices (atomizers) now exist for delivery of a variety of generic nasal medications.
Atomized mist demonstrating small diffuse particles:
Types of Delivery Devices available for intranasal medication delivery:
Accuspray Nasal Atomizer:
Direct-Haler powdered drug nasal delivery:
Go-Pump:
MAD (Mucosal Atomization Device) nasal:
Optinose:
ViaNase Electronic atomizer
Regardless of the method chosen to deliver a nasal medication, several suggestions are worth mentioning:
· Use a highly concentrated form of the medication to reduce volume and therefore reduce runoff. ¼ to 1/3 ml per nostril would be preferred. 1/2 to 1 ml per nostril is tolerable but there will be some loss as the volume increases. More than one ml per nostril per dose should likely be split and delivered over several cycles separated by 10-20 minutes.
· Always use a method that allows the delivery of a measured dose (syringe or unit dose pump)
· Be knowledgeable of the “dead space” within the delivery device and account for this dead space when calculating the volume you will deliver to the patient
· Deliver half the medication up each nostril to double the surface area for absorption
Bibliography (Click here for abstracts)
1. Hardy, J.G., S.W. Lee, and C.G. Wilson, Intranasal drug delivery by spray and drops. J Pharm Pharmacol, 1985. 37(5): p. 294-7.
2. Aoki, F.Y. and J.C. Crowley, Distribution and removal of human serum albumin-technetium 99m instilled intranasally. Br J Clin Pharmacol, 1976. 3(5): p. 869-78.
3. Tsikoudas, A. and J.J. Homer, The delivery of topical nasal sprays and drops to the middle meatus: a semiquantitative analysis. Clin Otolaryngol, 2001. 26(4): p. 294-7.
4. Chien, Y.W., K.S.E. Su, and S.F. Chang, Chapeter 3: Physicochemical, biopharmaceutical, and toxicophysiological considerations. Nasal Systemic Drug Delivery,, 1989. Dekker, New York: p. 39-90.
5. Mygind, N., Nasal Allergy, 2nd edition. Blackwell, Oxford, England, 1979: p. 257-270.
6. Mygind, N. and S. Vesterhauge, Aerosol distribution in the nose. Rhinology, 1978. 16(2): p. 79-88.
7. Bryant, M.L., et al., Comparison of the clearance of radiolabelled nose drops and nasal spray as mucosally delivered vaccine. Nucl Med Commun, 1999. 20(2): p. 171-4.
8. Daley-Yates, P.T. and R.C. Baker, Systemic bioavailability of fluticasone propionate administered as nasal drops and aqueous nasal spray formulations. Br J Clin Pharmacol, 2001. 51(1): p. 103-5.
9. David, G.F., C.P. Puri, and T.C. Anand Kumar, Bioavailability of progesterone enhanced by intranasal spraying. Experientia, 1981. 37(5): p. 533-4.
10. Henry, R.J., et al., A pharmacokinetic study of midazolam in dogs: nasal drop vs. atomizer administration. Pediatr Dent, 1998. 20(5): p. 321-6.
11. Harris, A.S., et al., Effect of viscosity on particle size, deposition, and clearance of nasal delivery systems containing desmopressin. J Pharm Sci, 1988. 77(5): p. 405-8.
12. Bjorkman, S., G. Rigemar, and J. Idvall, Pharmacokinetics of midazolam given as an intranasal spray to adult surgical patients. Br J Anaesth, 1997. 79(5): p. 575-80.