In ancient time Ayurvedic system of medicine used nasal route for administration of drugs and the process is called as “Nasya”. Nasal route has been used for local effects of decongestants but, in recent time it is being considered as a preferred route of drug delivery for systemic bioavailability. Various proteins & peptides have shown a good bioavailability through this route.

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Mr. Sagar Kishor savale
Department of Pharmaceutics
avengersagar16@gmail.com
2015-2016
Mr. Sagar Kishor savale
Department of Pharmaceutics
avengersagar16@gmail.com
2015-2016
Department of Pharmacy (Pharmaceutics) | Sagar savale

2. CONTENTS
 INTRODUCTION
 ANATOMY AND PHYSIOLOGY OF NOSE
 MERITS AND LIMITATIONS
 NASAL BLOOD FLOW AND NERVE SUPPLY
 FACTORS AFFECTING NASAL ABSORPTION
 MUCOCILLIARY CLEARANCE
 DRUG DISTRIBUTION AND DEPOSITION IN NASAL
CAVITY
 MECHANISM OF DRUG ABSORPTION
 ABSORPTION PATHWAYS
 APPLICATIONS
 REFERENCES
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3. INTRODUCTION
 In ancient time Ayurvedic system of medicine used nasal route for administration
of drugs and the process is called as “Nasya”.
 Nasal route has been used for local effects of decongestants but, in recent time it is
being considered as a preferred route of drug delivery for systemic bioavailability.
 Various proteins & peptides have shown a good bioavailability through this
route.
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a – nasal vestibule d – middle turbinate
b – palate e – superior turbinate (olfactory mucosa)
c – inferior turbinate f – nasopharynx

6. Site of drug
spray &
absorption
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7. The nasal cavity is divided into two symmetrical halves by the nasal septum, a central
partition of bone and cartilage; each side opens at the face via the nostrils and connects
with the mouth at the nasopharynx.
The nasal vestibule, the respiratory region and the olfactory region are the three main
regions of the nasal cavity.
The lateral walls of the nasal cavity includes a folded structure which enlarges the surface
area in the nose to about 150cm2
.
This folded structure includes three turbinates: the superior, the median and the inferior.
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8. During inspiration, the air comes into close contact with the nasal mucosa and
particles such as dust and bacteria are trapped in the mucous. Additionally, the
inhaled air is warmed and moistened as it passes over the mucosa (high blood
supply in the nasal epithelium.)
The submucosal zone of the nasal mucosa directly connects to the systemic
circulation, thus avoids first pass metabolism.
The nasal cavity is covered with a mucous membrane which can be divided into
nonolfactory and olfactory epithelium areas. The nonolfactory area includes the
nasal vestibule and respiratory region.
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9. The olfactory region
In human, the olfactory region is located on the roof of the nasal cavities, just
below the cribriform plate of the ethmoid bone(which separates the nasal
cavities from the cranial Cavity).
Humans have relatively simple noses(the primary function is breathing) while
other mammals have more complex noses( primary function is olfaction).
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10. 10
Physiology of olfaction

11. Odorant molecules reacts with olfactory receptors
Adenyl cyclase
ATP C-AMP
Opening of sodium channel
Influx of sodium ion
Depolarisation
Generation of nerve impulse
Propagation 11

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The Respiratory region:
The nasal respiratory epithelium is generally described as a pseudostratified
ciliated columnar epithelium (PSCCE).
The four main types of cells have seen in this region:
ciliated columnar cells
non ciliated columnar cells,
goblet cells
Basal cells

13. The proportions of the different cell types vary in different
regions of the nasal cavity. In the lower turbinate area, about 15-20% of
the total numbers of cells are ciliated and 60-70% is non-ciliated .
The numbers of ciliated cells increase towards the nasopharynx with
a corresponding decrease in non-ciliated cells. The high number of nonciliated
cells indicates their importance for absorption across the nasal epithelium.
Both columnar cell types have numerous (about 300-400 per cell)microvilli.The
large number of microvilli increases the surface area and this is one of the
main reasons for the relatively high absorptive capacity of the nasal cavity.
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14. MERITS
 Drugs Can be easily administered to the unconscious patients.
• Compared to oral medications, intranasal medication delivery results in:
▫ Faster delivery to the blood stream
▫ Avoid Metabolism by stomach acid and intestinal enzymes
▫ Avoid hepatic first pass metabolism
• Compared to IV medications, intranasal medication delivery results in:
▫ Comparable blood levels depending on the drug and dose.
▫ Convenient for patients of long term therapy.
• The nasal route is an alternate to parenteral route, especially for protein and peptide
drugs.
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15. LIMITATIONS
1) The histological toxicity of absorption enhancers used in nasal drug delivery
system.
2) There is a possibility of nasal irritation.
3) Nasal cavity provides smaller absorption surface area when compared to GIT.
4) Once administered, rapid removal of the therapeutic agent from the site of
absorption is difficult.
5) Pathologic conditions such as cold or allergies may alter significantly the nasal
bioavailability
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16. Nasal Blood Flow
 Nasal mucosa is highly vascular.
 Arterial supply to nose derived from both external and internal carotid arteries.
 Terminal branch of the maxillary artery (Branch of external carotid Artery)
supplies blood to lateral and medial wall of nasal cavity.
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17. Nasal Nerve Supply
 Nasal blood vessels and Glands have supplied both autonomic and somatic system.
 Autonomic in nasal mucosa reaches via vidian nerve and follows distribution of
trigeminal nerve to nose.
 Vidian nerve may consists parasympathetic and sympathetic cholinergic fibers.
 Cappilary vessels receive primary alpha adrenergic sympathetic fibers(constrictor)
and may receive small beta adrenergic(Dialators).
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18. FACTORS AFFECTING ABSORPTION
 Chemical form:
The form of a drug can be important in determining absorption.
Example : Nasal absorption of carboxylic acid esters of L-Tyrosine
significantly greater than that of L-Tyrosine.
 Polymorphism:
Polymorphism is known to affect the dissolution rate, solubility of drug
and thus their absorption through biological membranes.
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19.  Molecular Weight:
 A linear correlation has been reported between the absorption of drugs and
molecular Weight up to 300 Daltons.
Absorptions decreases significantly if the molecular weight is greater than
1000 Daltons (except with the use of absorption enhancers).
 Particle Size:
It has been reported that particle sizes 10 -20 μm are deposited in the nasal cavity.
Particles Which are less than 2 μm can be retained in the lungs, and particles of
greater than 20 um size exhaled whith air.
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20.  Solubility and Dissolution Rate:
Drug solubility and dissolution rates are important factors in determining
nasal absorption from powders and suspensions. The particles deposited in
the nasal cavity need to be dissolved prior to absorption.
 Nasal pH:
 5.5-6.5(adult)
 5.0-6.7(infants)
pH Depends on:
rhinitis and sinusitis
Cold air and Hot air
Lysozyme (Maintain Antiseptic Nostril)
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HOW
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21.  Nasal Enzymes:
Cytocrome P-450 –Dependent Mono-oxygenase
Leucine Aminopeptidase
15-hydroxy PG dehydrogenases
 Nasal secretions:
 It is the mixture of secretory Materials From Goblet cells,Nasal glands,Lacrimal
glands.
 Transudate from plasma.
Composition:
Sodium, potasium, calcium, prostaglandins, albumin, protease-inhibitor,
IgG, IgA, Lysozyme
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E-Sol layer
F-Basal cells
G-Basement membrane
A-Ciliated cells
B-Nonciliated cells
C-Goblet cells
D-Mucus layer

23.  Clearance of mucus and adsorbed substances into GIT called MCC.
 It is the function of upper respiratory tract to prevent entry of noxious substance
into lungs.
 It is a co-ordinated interaction between mucus layer and wave like movement of
cilia.
 Ciliary beat frequency is 20 hz.
Mechanism for Mucus secretion:
 Mast cell derived mediators induced secretion of GP.
 Neuroharmons may in crease nasal blood flow and transudation of fluid and plasma
proteins.
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24. Factors Affecting MCC
 Viscosity of mucus
 Environmental factors like Temperature
 Pathological conditions:
Kartagener’s syndrome
Sjorgens syndrome
Rhinitis
Sinusitis
 Calcium ion concentration:If it is decreased than CBF will decreased.
• It is more important in nasal muco adhesive drug delivery.
Example: Muco adhesive polymer like poly acrylic acid form chelates with calcium
ion and increase residence time of drug.
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Functions of Mucus:
Retainer for the substance
Adhesive
Protects the Mucosa
Water holding capacity
Surface electrical activity

26.  Delivery effect factors:
 Formulation
Concentration pH Osmolarity
 Drug distribution and deposition
 Viscosity
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27. Drug Distribution In Nasal Cavity
 It depends on mode of drug administration like nose drops, Nebulizer,Meter dose
inhalers.
 Atomized pump is the best nasal delivery system because it gives a constant dose
and very good mucosal distribution so use of large volume of a weak solution is
preferable to a small volume of a concentrated solution.
Example: A simulated Nasal Cavity made of acryl Resin was developed for studing
the Distribution of Beclomethasone Dipropionate Aerosol particals in nasal cavity
no signficance difference is found among gas,liquid and powder prepertation.
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28.  Depends upon :
• Particle size of drug
• Shape
• Density
• Hygroscopicity of particles
• Pathological conditions
 Change in particle size in Aerosol depends upon RH.if RH is inreased,particle size
of Aerosol increases that will determine efficacy and toxicity of Aerosol.
 Example: In metered dose Flunisolide Solution ,particle size is greater than 10 um
for local effects in nasal cavity.
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29. MECHANISM
Inertia Sedimentation Diffusion
 Deposition in nasal cavity depends on:
• Types of dosage form
• Mode of administration
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30. Deposition of drug in nasal cavity by using Gas spray and Powder spray:
 3 types of nasal cavities were designed by using Dental compound and Celluloid
plate
• Straight Septum with Normal Turbinates
• Concave septum with Hypertrophic Turbinates.
• Convex Septum with Atrophic Turbinates
 Inner surface of nasal cavity covered with moistened filter paper (Except vestibular
portion)
 Delivered Beclomethasone Dipropionate particles and obsered that shape of nasal
cavity produce greater effect gas spray than powder spray.
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31.  Powder spray is preffered than gas spray because in gas spray particle deposition
depends upon Spray angle,size of particles,speed.
 Nasal spray preferred than Nose drops .
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Why?

32. MECHANISM OF DRUG ABSORPTION
 Two mechanisms are found:
 Transcellular process: Transport of lipophillic drugs through cell membrane by
active transport or transport through opening of tight junction.
Example: Levodopa,Carbidopa
 Paracellular process: It involves aqueous route of transport. it is slow and
passive.Water soluble drugs which have moleculer weight greater than 1000
daltons shows poor bioavailability.
Example: Insulin,MSH,ACTH
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33. Low Bioavailability:
 It is due to Low membrane permeability (limiting factor for high mol.weight polar
drugs like protein and peptides )
Low Membrane Transport:
 Rapid clearance of administered formulation due to MCC.
 Ex: Liquid and powder formulation shows rapid clearance
Enzymatic Degradation:
 Degradation of protein and peptides by Exopeptidase and Endopeptidase.
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35.  Drugs which have poor oral absorption like Insulin and drugs which have extensive
first pass metabolism like propanolol can be better absorbed through Nasal mucosa.
 Olfactory Epithelium is a portal for substances to enter in CNS and Peripheral
circulation.
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36. Strategies To Improve Nasal Absorption
1.Ester Formation:
2.Formulation Design:
3. Modifying drug structure:
 Here modificationof physiochemical properties such as molecular size,
molecular weight, Pka and solubility, are favourable for nasal drug absorption.
Ex: Salmon calcitonin (C-N bond) to Ecatonin(S-S bond)
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37. 4.Prodrug approach:
 Enamine derivatives of Angiotensin-2,bradykinin acts as a prodrug.
5.Particulate drug delivery:
 Microspheres
 Liposomes (Cationic liposome)
 Nanoparticles
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38. 6.Absorption Enhancers:
• Ideal Properties:
1. It should increase in the absorption of the drug
2. It should not cause permanent damage or alteration to the tissue
3. It should be non irritant and nontoxic.
4. It should be effective in small quantity.
5. The enhancing effect should occur when absorption is required .
6. The effect should be temporary and reversible .
7. It should be compatible with other excipients.
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39.  Classification of penetration enhancer:
1) Glycols:N-ethylene glycols
2) Fatty acid salts:Caprylate,laurate
3) Surfactants: Saponin,
4) Chelators: Salicylates,EDTA
5) Bile Salts:
 Gentamycin with 1℅ Sodium glycocholate.
 Nasal absorption of Insulin increases with increase hydrophobicity of bile salts
 Deoxycholate>Cholate>Ursodeoxycholate
6) Cyclodextrins
7) Glycyrrhetinic acid derivates: Carbenozolone,glycyrrhizinate
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How ?

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Mechanism of Penetration Enhancers:
 Inhibit enzymetic activity
 Reduce mucus viscosity
 Reduce MCC
 Open tight junctions
 Solubilize the drug

41. APPLICATIONS
 1. Delivery of non-peptide pharmaceuticals
Drugs with extensive pre-systemic metabolism, such as :
- progesterone
- estradiol
- propranolol
- nitroglycerin
- sodium chromoglyate
 It can be rapidly absorbed through the nasal mucosa with a systemic
bioavailability of approximately 100%
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42.  2. Delivery of peptide-based pharmaceuticals
 Peptides & proteins have a generally 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 products.
 Britannia Pharmaceuticals, London, U.K., plans to begin a clinical study on its
nasal powder dihydroergotamine (DHE ) (anti-migraine drug).
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43.  3.Delivery of Diagnostic Drugs
 Phenol red-For diagnosis of kidney functions
 Secretin-For diagnosis of pancreatic disorders
 Pentagastrin-For diagnosis of secretory functions of gastric acid.
 Cerulin-For diagnosis of Gallbladder function
 Vital dyes-Trypan blue and Evans blue (it can not enter in cranium because they
can not pass through sheath)
 4.Delivery of drugs to Brain:4.Delivery of drugs to Brain:
 For Treatment of Parkinson’sdisease,Alzheimer disease.
 For Delivery of MSH,ACTH,Insulin to brain
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46. 5.Delivery of Vaccines :
 Nasal mucosa is the first site of contacts with inhaled pathogens
 Nasal passages are rich in lymphoid tissue
 Creation of both mucosal and systemic immune responses
 Non injectable
Examples:
Nasal Vaccines are Prepared for Measels,pertussis,meningitis and
Influenza virus because these pathogens enter into the body through nasal
mucosa.
 Nasal delivery of vaccines produces both local and systemic immune
response.
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47.  Y.W.Chien, K.S.E. Su and S.F.Chang. “Nasal systemic drug delivery” Dekker,
1989,vol-39,Marcel Dekker,inc.New york,p.n.1-6,16-18,39-53,90-100,200-205
 J.Tortora,Derrickson,2009, “ Pinciples of anatomy and physiology”,12th
edi.,vol-
1,john wiley and sons (Asia) pvt.ltd,p.n.600-601
 www.britannia-pharma.co.uk
 www.sciencedirect.com
 M.Alagusundara et al. “ Nasal drug delivery system - an overview” Int. J. Res.
Pharm. Sci. Vol-1, Issue-4, 454-465, 2010.
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