2. 2
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%
7. 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
7
INTRODUCTION
8. NASAL ENZYMES:
• Cytochrome p-450 dependent oxygenase , lactate
dehydrogenase , oxydoreductase , acid
hydrolases, esterases, lactic dehydrogenases, malic
enzymes, lysosomal proteinases, steroid hydroxylases
etc.
NASAL PH:
• 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.
8
9. ADVANTAGES OF NASAL DRUG DELIVERY
SYSTEM
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
term therapy.
9
10. LIMITATIONS
1. The absorption enhancers used to improve nasal drug delivery
system may have histological toxicity which is not yet
clearly established
2. Absorption surface area is less when compared to GIT.
3. Once the drug administered can not be removed.
4. Nasal irritation.
10
14. 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.
14
Olfactory
mucosa
Highly vascular
nasal mucosa
Brain
CSF
15. MECHANISM OF DRUG ABSORPTION
• Aq route of transport.
• Slow and passive.
Paracellular
transport
• Transport through lipoidal membrane
• Active transport via carrier mediated
means.
Transcellular
transport
15
18. 18
FACTORS AFFECTING DRUG ABSORPTION
Drug concentration
Mucosal contact time
pH of the absorption site
Size of the drug particle
Relative lipid solubility
Molecular weight of the drug
19. PHYSIOCHEMICAL PROPERTIES OF
DRUGS
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
7. Polymorphism
8. Partition coefficient
9. Solubility and dissolution
10. Partical size
19
21. 21
METHODS TO ENHANCE NASAL ABSORPTION
OF DRUGS
Structural modification
Formulation design
Salt or ester formation
22. 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
absorption.
22
24. 24
Zero order transdermal permeation kinetic=
Plasma concentration=
First order transnasal permeation kinetic=
Plasma concentration=
PHARMACOKINETICS OF NASAL
ABSORBTION
25. 25
APPLICATIONS
Delivery of non-peptide pharmaceuticals
Delivery of diagnostic drugs
Delivery of peptide-based pharmaceuticals
Cns delivery through nasal route
Nasal vaccination
26. 26
Drugs with extensive pre-systemic metabolism, such as
- progesterone
- estradiol
- propranolol
- nitroglycerin
- sodium chromoglyate
can be rapidly absorbed through the nasal mucosa with a systemic
bioavailability of approximately 100%
1.Delivery of non-peptide pharmaceuticals:
27. 27
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
biotechnological products
2.Delivery of peptide-based pharmaceuticals:
28. 28
Diagnostic agents such as
Phenolsulfonphthalein – kidney function
Secretin – pancreatic disorders
Pentagastrin – secretory function of gastric acid
3. Delivery of diagnostic drugs
29. 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
reported for
i. Alzheimer’s disease
ii. brain tumours
iii. epilepsy
iv. pain and sleep disorders. 29
30. 5.Systemic delivery:
Fast and extended drug absorption
Ex.- analgesics (morphine),
i. cardiovascular drugs(propranolol)
ii. hormones (levonorgestrel, progesterone)
iii. antiviral drugs
Marketed formulation- zolmitriptan and sumatriptan
30
31. 6.Nasal vaccines
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.
31
34. Nasal drops
34
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 .
35. Nasal sprays
35
Both solution and suspension
formulations can be formulated into
nasal sprays.
Deliver an exact dose from 25 to
200 μm.
36. 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
pump.
36
37. 37
Nasal Gels
Nasal gels are high-viscosity thickened solutions or
suspensions.
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.
38. Mucosal Atomization Device (MAD)
Device designed to
allow emergency
personnel to delivery
nasal medications as
an atomized spray.
Broad 30-micron
spray ensure
excellent mucosal
coverage.
38
39. 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.
39
40. Nasal vaccines
40
Nasal mucosa is first site of contact with inhaled antigens
and, therefore, its use for vaccination, especially against
respiratory infections
Promising alternative to the classic parenteral
route, because it is able to enhance the systemic levels of
specific immunoglobulin G and nasal secretary
immunoglobulin A.
Examples of human efficacy of intranasal vaccines
include those against influenza A and B virus, proteosoma
influenza
Intra nasal H1N1 vaccine Nasovac by Serum Institute
41. Therapeutic class of drugs for nasal route
41
1. 2 adrenergic agonists
2. Corticosteroids
3. Antiviral
4. Antibiotics
6. More recently, vaccines
5. Antifungal
42. CONCLISION
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
therapy.
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.
42
44. MATERIAL AND METHOD:
Zolmitriptan was a gift sample from Natco Labs,
Hyderabad, India.
Pluronic F-127 and pluronic F-68 by BASF Corporation,
Mumbai, India.
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
research grade.
44
45. METHOD:
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
4oC.
45
52. CONCLUSION
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.
52
53. REFERENCES
.Chien, Y.W., Nasal drug delivery. In: chien, W. (Ed.) Novel Drug Delivery
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.
Pharm., 2004, 270, 37-45.
Devi S.G., Udupa N., Niosomal sumatriptan succinate for nasal
administration, Ind. J.Pharm. Sci., 2000, Nov – Dec., 479 – 481.
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.
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