Intranasal Drug Delivery
Medically Edited and Reviewed by Dr. Erin Zinkhan MD, BSBE
Intranasal Transmucosal Drug Delivery
Intranasal medications are medications that can be given through the nasal passages through a process known as transmucosal administration or nasal drug delivery. Devices used to give intranasal medications employ an atomization device that fragments the medication into fine particles as it is being sprayed into the nose. This atomization helps the medication absorb into the body more easily. This method of administration offers several advantages. This article will examine these advantages, as well as what medications are commonly dispensed using this method.
The use of nasal administrated medications offers several key advantages. Nasal administration avoids gastrointestinal break down of the medication and hepatic first pass metabolism. Nasal administration may decrease the time it takes for the medication to start working, is easy to use, and is safe. We will explore these advantages in more detail below.
Gastrointestinal Breakdown and Hepatic First-Pass Metabolism Medications taken by mouth are absorbed through the gastrointestinal tract. Some medications can be significantly degraded by gastric acidity, enzymes in the intestinal lining, combination with food, or enzymes found in normal intestinal bacteria. After absorption into the blood, the medication is first delivered to the liver where further modification and partial elimination of the medication occurs. This modification and elimination of the medication is called hepatic first-pass metabolism. Drug manufacturers know about the specific ways that the liver metabolizes each medication and modify their medications so that the correct dose reaches your body. Nasally administered medication bypasses first pass metabolism while orally administered medication does not.
Bioavailability refers to the amount of medication taken compared with the amount of the medication circulating around the body in the bloodstream. For instance, medications given through an IV are immediately and fully available for the body's use, and thus have 100% bioavailability. Most oral medications have only about 5 to 10% bioavailability because of gastrointestinal breakdown and hepatic first-pass metabolism.
The bioavailability of nasal medications is dependent upon molecule size and the pH of the medication. For instance, Naloxone, a common intranasal medication, has more than 90% bioavailability, while midazolam has 75% bioavailability, and both Naloxone and Fentanyl have 80% bioavailability.
Time of Onset
Giving a medication through the intranasal route usually results in a shorter time between giving the medication and producing an effect on the patient. Intranasal administration of a medication usually has an onset time between only 2 to 10 minutes.
Ease of Use
Nasally administered medications are convenient and easy. The administration in the nose does not expose the patient or caregiver to accidental needle sticks. Waste is reduced without the need for sharps containers and hazardous disposal. Nasally administered medications are safe to use in violent patients or in patients with seizures. Medications may be delivered to the patient in any position, whether they are sitting, lying down, lying on their side, or standing upside-down. Because nasal administration takes only a second to administer, the patient may not need to be restrained.
Types of Nasal Mucosa Administrations
There are several ways to give a nasally administered medication to a patient. These ways include spray bottles, nose droppers, pressurized aerosols, and atomized unit dose sprays. Atomized unit dose sprays are the most effective method. Spray bottles do not always provide a consistent dose and can result in large amounts of the drug draining into the throat. Large particles of the medication can also form deposits on the nasal mucosa. Nose droppers may produce the same unwanted results as spray bottles with some of the medication draining into the throat. Pressurized aerosol devices may break the medication droplets into smaller droplets that can be inhaled into the lungs and can result in respiratory complications.
Atomization of the medication breaks down the particles into sizes ranging from 2 to 10 micrometers and provides for optimal absorption through the nasal mucosa.
Nasal Medication Delivery Devices
There are several manufacturers that make nasal medication devices. Below is a list of the bestselling devices listed alphabetically.
- Accuspray by Becton Dickenson. Designed for use by both doctors and patients, Accuspray is easy to use with no pre-activation or loading required. The medication to be administered is clearly visible in the Accuspray tubing, which allows for visual inspection of the medication before administration. Accuspray allows for the administration to be easily divided, allowing the drug to be delivered to each nostril to increase the size of the mucosa exposed to the medication.
- Carpuject by Pfizer. Carpuject has a compact design that is needleless and prevents injuries. The Carpuject syringe system can dispense a wide variety of medications with easy-loading cartridges. Caregivers enjoy the easy one-handed operation and disposal.
- OptiNose - The OptiNose nasal device is designed to treat chronic nasal inflammatory diseases, migraines, and autism spectrum disorder. OptiNose provides two separate delivery devices designed to administer either powder or liquid medications. The device minimizes local irritation and allows patients to give themselves their own medications.
- MAD Intranasal Mucosal Atomization Device by Teleflex. This nasal atomization device is designed to be used with drugs approved for intranasal delivery. It requires no sterile procedures and is quick and easy to use.
- CPD by Kurve Technology. This nasal atomization device is non-invasive and provides controlled particle dispersion to deliver medications directly to the nasal mucosa. The CPD nasal medication delivery system can control the size of the liquid droplets down to 1 micron regardless of the viscosity of the formulation.
- DirectHaler by Acerus Pharma. The DirectHaler is also known as the Direct-Haler and is a nasal drug delivery device designed to use a patient's breath inwards to disperse dry powered medications. Recently, the Acerus Pharmaceutical Corporation has acquired this award-winning intranasal drug delivery device from a company in Denmark.
- VeriDoser by Mystic Pharmaceuticals. The VeriDoser offers nasal drug delivery with precise, calibrated dosing. Mystic's VeriDoser requires no priming and has a dose counter. The spray plume is configurable into steam, spray, or aerosolized spray. The design accommodates proteins, peptides, and stem cells formulations to treat neurodegenerative disorders, brain tumors, HIV encephalopathy, epilepsy, Huntington's, Alzheimer's, and Parkinson's.
Common Medications Dispensed Using Nasal Atomization
Nasal atomization delivery is being developed for many applications, including for Alzheimer's dementia, Parkinson's disease, brain tumors, diabetes, multiple sclerosis, schizophrenia, pain control, and migraine. Below is a list of the most popular drugs currently dispensed by intranasal administration. They are grouped by treatment type.
Pain Control - Opiates
Sedation - ά-2 Agonists
Seizure Therapy – Benzodiazepines
Reversal of Conscious Sedation
Angina (Chest Pain)
Specific Nasal Drug Delivery Administrations
Fentanyl is an opiate used for pain control and is an ideal medication to be given by intranasal administration. A prescription is required for this medication. Fentanyl has a rapid onset and short duration and is one of the strongest opiate medications sold on the market. Intranasal fentanyl is rapidly absorbed and reaches maximum concentration in 4 to 11 minutes. Bioavailability is around 71% but appears to be pH dependent with increased bioavailability associated with higher pH. 1 Opiate medications like Fentanyl are addictive and should be used as infrequently and for as short a duration as possible. 1
Ketamine is a dissociative anesthetic opiate that is recently being used in select patients for treatment-resistant depression. Ketamine usually is given only in a hospital through an IV, but it can be given intranasally. Many patients report that IV infusion of ketamine offers more relief and lasts longer, while intranasal administration of ketamine is less expensive and more convenient. 2
Midazolam produces sleepiness or drowsiness and helps relieve anxiety. It also produces amnesia so that the patient will forget discomfort or pain that may occur during surgery. This drug is also used to treat seizures. Midazolam requires a prescription and close doctor supervision. Intranasal midazolam was found in a study to have the same efficacy as IV administration of midazolam. 3
Narcan is an FDA-approved drug with the generic name of naloxone. This drug is an opioid antagonist used for the emergency treatment of individuals with respiratory or central nervous system failure due to opioid overdose. Administration of naloxone by nasal spray atomization is easy and convenient. Commercially available Narcan nasal spray is designed to provide a singe 4 mg dose. Administration of the medication using a Narcan MAD Syringe allows the medication to be atomized for quick metabolism.4 The LMA MAD Nasal Intranasal Mucosal Atomization Device from Teleflex is specifically designed for administering this lifesaving medication.
First Responders Use of Intranasal Naloxone
Emergency medical technicians (EMTs) and ambulance crews have found the use of Narcan nasal spray restores spontaneous breathing in patients with a drug overdose in just a matter of seconds. The ease of use and lack of risk of a needlestick injury are cited as primary benefits. The minimal training needed to effectively use Narcan also has been cited as a benefit. Narcan is now available to the public in many states. Some police departments are now equipping officers with Narcan because the police are often the first on the scene of a drug overdose.6 The U.S. Attorney General, Eric Holder, advocated that the police and fire departments equip first responders with naloxone to save the lives of people with a drug overdose.7
Parental Use of Nasal Nacan
Some states are allowing naloxone to be sold at drug stores without a prescription in an effort to curb teenage overdose deaths. 8
Nasal Narcan Studies
- Barton, Erik D., et al. " Efficacy of intranasal naloxone as a needleless alternative for treatment of opioid overdose in the prehospital setting ." The Journal of emergency medicine 29.3 (2005): 265-271
- Kerr, Debra, et al. "Randomized controlled trial comparing the effectiveness and safety of intranasal and intramuscular naloxone for the treatment of suspected heroin overdose ." Addiction 104.12 (2009): 2067-2074.
- Kelly, A., and Z. Koutsogiannis. " Intranasal naloxone for life threatening opioid toxicity." Emergency medicine journal: EMJ 19.4 (2002): 375.
1Foster, David, et al. "Pharmacokinetics and pharmacodynamics of intranasal versus intravenous fentanyl in patients with pain after oral surgery." Annals of Pharmacotherapy 42.10 (2008): 1380-1387.
2"Route of Administration: Critical to Achieving Relief." Ketamine Advocacy Network. N.p., 2015. Web. 30 Aug. 2016.
3"Therapeutic Intranasal Drug Delivery." Treating Seizures with Intranasal Medications. N.p., n.d. Web. 30 Aug. 2016.
5Strang, John, et al. "Clinical provision of improvised nasal naloxone without experimental testing and without regulatory approval: imaginative shortcut or dangerous bypass of essential safety procedures?." Addiction (2016).
6Fuller, Steve. "City police make first Narcan save." The Ellsworth American. August 24, 2016.
7Sledge, Matt. "Eric Holder Calls On First Responders To Carry Naloxone, Anti-Overdose Drug." The Huffington Post. April 16, 2014.
8Fiangan, Katlin. "Narcan to Be Sold at Pharmacies Without Prescription in Vermont." NECN.com. August 25, 2016..
Other Applicable Studies of Using Intranasal Administration
- Barton, Erik D., et al. " Efficacy of intranasal naloxone as a needleless alternative for treatment of opioid overdose in the prehospital setting ." The Journal of emergency medicine 29.3 (2005): 265-271.
- Jain, Kewal K. "Drug delivery systems-an overview." Drug delivery systems (2008): 1-50.
- Hussain, Anwar A. "Intranasal drug delivery." Advanced drug delivery reviews 29.1 (1998): 39-49.
- Pires, Anaísa, et al. " Intranasal drug delivery: how, why and what for?." (2009).
- Reger, M. A., et al. "Effects of intranasal insulin on cognition in memory-impaired older adults: modulation by APOE genotype ." Neurobiology of aging27.3 (2006): 451-458.
- Wermeling, Daniel P., and Jodi L. Miller. " Intranasal drug delivery." DRUGS AND THE PHARMACEUTICAL SCIENCES 126 (2003): 727-748.
- Wolfe, Timothy R., and Tony Bernstone. " Intranasal drug delivery: an alternative to intravenous administration in selected emergency cases ."Journal of Emergency Nursing 30.2 (2004): 141-147.
- Zia, H., P. Dondeti, and T. E. Needham. " Intranasal drug delivery." Clinical Research and Regulatory Affairs (2008).