NASAL DRUG DELIVERY
M.pharm 1 yr.
Novel drug delivery is one of the
fastest growing healthcare sectors,
with sales of drugs incorporating
novel drug delivery systems
increasing @ an annual rate of 15%
DRUG DELIVERY STSTEM
GLOBAL DRUG DELIVERY MARKET BY
Nasal Drug Delivery
New Chemical Entity
DRUG DEVELOPMENT COST
Nasal drug Delivery2 – 5 years
10 – 14 years
DRUG DEVELOPMENT TIME
It is also a type of muco-adhesive drug delivery system.
Intranasal Medication administration offers a truly
“Needleless” solution to drug delivery.
Therapy through intranasal administration has been an
accepted as form of treatment in the Ayurvedic system
of Indian medicine
• Cytochrome p-450 dependent oxygenase , lactate
dehydrogenase , oxydoreductase , acid
hydrolases, esterases, lactic dehydrogenases, malic
enzymes, lysosomal proteinases, steroid hydroxylases
• Adult nasal secretion pH: 5.5-6.5
• Infants & children : 5-6.7.
• Lysosome in the nasal secretion helps as antibacterial &
its activity is diminished in alkaline pH.
ADVANTAGES OF NASAL DRUG DELIVERY
1 A noninvasive route.
2. Hepatic first – pass metabolism is absent.
3. Rapid drug absorption.
4. Quick onset of action.
5. The bioavailability of larger drug molecules can be improved by
means of absorption enhancer or other approach.
6. Better nasal bioavailability for smaller drug molecules.
7. Drugs which can not be absorbed orally may be delivered to the
systemic circulation through nasal drug delivery system.
8. Convenient route when compared with parenteral route for long
1. The absorption enhancers used to improve nasal drug delivery
system may have histological toxicity which is not yet
2. Absorption surface area is less when compared to GIT.
3. Once the drug administered can not be removed.
4. Nasal irritation.
NOSE BRAIN PATHWAY
The olfactory mucosa (smelling area in nose) is in direct
contact with the brain and CSF.
Medications absorbed across the olfactory mucosa directly
enter the brain.
This area is termed the nose brain pathway and offers a
rapid, direct route for drug delivery to the brain.
MECHANISM OF DRUG ABSORPTION
• Aq route of transport.
• Slow and passive.
• Transport through lipoidal membrane
• Active transport via carrier mediated
Factors affecting drug absorption
FACTORS AFFECTING DRUG ABSORPTION
Mucosal contact time
pH of the absorption site
Size of the drug particle
Relative lipid solubility
Molecular weight of the drug
PHYSIOCHEMICAL PROPERTIES OF
1. Effect of perfusion rate
2. Effect of perfusate volume
3. Effect of solution pH
4. Effect of drug lipophilicity
5. Effect of initial drug concentration.
6. Chemical form
8. Partition coefficient
9. Solubility and dissolution
10. Partical size
METHODS TO ENHANCE NASAL ABSORPTION
Salt or ester formation
Strategies for improving drug availability
in nasal administration:
1.Improve nasal residence time
• Apply drug anteriorly
• Formulation with polymers
• Use of biodegradable microspheres
2.Enhance nasal absorption
• Increase the rate at which drug passes through nasal
Zero order transdermal permeation kinetic=
First order transnasal permeation kinetic=
PHARMACOKINETICS OF NASAL
Delivery of non-peptide pharmaceuticals
Delivery of diagnostic drugs
Delivery of peptide-based pharmaceuticals
Cns delivery through nasal route
Drugs with extensive pre-systemic metabolism, such as
- sodium chromoglyate
can be rapidly absorbed through the nasal mucosa with a systemic
bioavailability of approximately 100%
1.Delivery of non-peptide pharmaceuticals:
Peptides & proteins - low oral bioavailability because of
their physico-chemical instability and susceptibility to hepato
gastrointestinal first-pass elimination
Eg. Insulin, Calcitonin, Pituitary hormones etc.
Nasal route is proving to be the best route for such
2.Delivery of peptide-based pharmaceuticals:
Diagnostic agents such as
Phenolsulfonphthalein – kidney function
Secretin – pancreatic disorders
Pentagastrin – secretory function of gastric acid
3. Delivery of diagnostic drugs
4.CNS delivery through nasal route :
The delivery of drugs to the CNS from the nasal route may
occur via olfactory neuroepithelium
Drug delivery through nasal route into CNS has been
i. Alzheimer’s disease
ii. brain tumours
iv. pain and sleep disorders. 29
Fast and extended drug absorption
Ex.- analgesics (morphine),
i. cardiovascular drugs(propranolol)
ii. hormones (levonorgestrel, progesterone)
iii. antiviral drugs
Marketed formulation- zolmitriptan and sumatriptan
Nasal mucosa is the first site of contact with inhaled
antigens and therefore, its use for
vaccination, especially against respiratory
infections, has been extensively evaluated.
Ex. Human efficacy of intranasal vaccines include
those against influenza A and B
virus, proteosoma‐influenza, adenovirus‐vectored
influenza, group B meningococcal native, attenuated
respiratory syncytial virus and parainfluenza 3 virus.
Most simple and convenient systems
developed for nasal delivery.
It has been reported that nasal drops
deposit human serum albumin in the
nostrils more efficiently than nasal sprays.
Disadvantage-lack of the dose precision .
Both solution and suspension
formulations can be formulated into
Deliver an exact dose from 25 to
Lincoln Pharma wins patent for a
novel nasal drug delivery system
Presently in India anti-vomiting treatments are available in
the conventional form of tablet and injection which take
longer time to bring relief.
LPL becomes the first company in India to introduce an
anti-vomiting treatment in the form of a Nasal spray
Nasal gels are high-viscosity thickened solutions or
Advantages of a nasal gel
Reduction of post-nasal drip due to high viscosity,
Reduction of taste impact due to reduced swallowing,
Reduction of anterior leakage of the formulation,
Reduction of irritation by using soothing/emollient
excipients and target to mucosa for better absorption.
Mucosal Atomization Device (MAD)
Device designed to
personnel to delivery
nasal medications as
an atomized spray.
Stem Cell Nasal Spray For Parkinson Disease
Significantly Improves Motor Function
Successful intranasal delivery of stem cells to the brains of
rats with Parkinson disease yielded significant improvement
in motor function and reversed the dopamine deficiency
characteristic of the disease.
This was reported as a Rejuvenation Research in journal
published by Mary Ann Liebert.
Nasal mucosa is first site of contact with inhaled antigens
and, therefore, its use for vaccination, especially against
Promising alternative to the classic parenteral
route, because it is able to enhance the systemic levels of
specific immunoglobulin G and nasal secretary
Examples of human efficacy of intranasal vaccines
include those against influenza A and B virus, proteosoma
Intra nasal H1N1 vaccine Nasovac by Serum Institute
Therapeutic class of drugs for nasal route
1. 2 adrenergic agonists
6. More recently, vaccines
An accessible alternative route for drug administration.
Provides future potential for several drugs through the development of
safe and efficacious formulations for simple, painless and long‐term
Drugs can be directly target to the brain in order to attain a good
therapeutic effect in CNS with reduced systemic side effects.
Much has been investigated and much more are to be investigated for
the recent advancement of nasal drug delivery system.
MATERIAL AND METHOD:
Zolmitriptan was a gift sample from Natco Labs,
Pluronic F-127 and pluronic F-68 by BASF Corporation,
Sodium alginate, sodium carboxy methyl cellulose and
polyvinyl pyrrolidone (K-25) of extra pure grade were
supplied by Emcure Research Center, Pune, India.
Benzalkonium chloride was procured from Loba
Chemicals, Mumbai, India. All other chemicals were of
Preparation of nasal gel formulations
Slow addition of polymer, drug and other additive in cold water with
continuous agitation. The formed mixtures were stored overnight at
Study revealed that the temperature sensitive
gelling system can be formulated using optimum
concentration of PF-127 and PF-68 that can gel at
the body temperature. Addition of bioadhesive
polymers can prolong the release of zolmitriptan
that may be helpful for migraine treatment.
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System, 2nd ed. Marcel Dekker, 1985, 189-195.
Pisal S.S., Paradkar A.R., Mahadik K.R., Kadam S.S., Pluronic gels for nasal
delivery of vitamin B12 Part I: Preformulation study, Int. J.
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Devi S.G., Udupa N., Niosomal sumatriptan succinate for nasal
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Alexandridis, P., Holzwarth
J.F., Hatton, T.A., Macromolecules, 1994,27,2414.
Alexandridis, P. & Hatton T.A., Colloids surface A., 1995, 96.
Singhare D.S., Khan S., Yeole P.G., Poloxamers: Promosing block co-
polymers in Drug delivery, Ind. J.Pharm. Sci. 2005, sept – oct., 523 – 531.