Nasal drug delivery provides direct access to the systemic circulation while avoiding first-pass metabolism and potential degradation in the gastrointestinal tract. The nasal cavity has a large surface area and highly vascularized nasal mucosa that allows for rapid drug absorption. Various nasal drug formulations have been developed, including sprays, gels, and powders, to enhance drug retention and absorption in the nasal cavity. The nasal route is promising for local and systemic delivery of peptides, proteins, and central nervous system targeting of drugs.

1. NASAL DRUG DELIVERY SYSTEM
SARDAR BHAGWAN SINGH P.G. INSTITUTE OF BIO MEDICAL
SCIENCES AND RESEARCH, BALAWALA, DEHRADUN,
UTTARAKHAND
PRESENTED BY- GUIDED BY-
NAMAN PANT Mrs. GAUREE KUKRETI
M.Pharm. (Pharmaceutics) Assistant professor
SECOND SEMINAR (MPHR 120)
2016-17
1

2. ORGANIGATION-
 Introduction
 Anatomy & Physiology Of Nasal cavity
 Mechanism of drug absorption
 Advantages & Disadvantages
 Factors affecting drug absorption
 Components of nasal drug formulations
 Various drug delivery formulations
 Applications of nasal drug delivery systems
 Some marketed products
 Conclusion
2

3. 3

4. INTRODUCTION-
 Administration of drug through nasal route is referred as
Nasal drug delivery system.
 Nasal route is an alternative to invasive administrations
and provides a direct access to the systemic circulation.
 The nose offers easy access to a large mucosal surface
well suited for drug delivery.
 About 2% of the overall drug delivery is administered
via the nasal route.
 In recent years many drugs have been shown to achieve
better systemic bioavailability through nasal route than
by oral administration.
4(1) Singh AK, Singh A, Madhav NV, Nasal Cavity: A Promising
Transmucosal Plateform for Drug Delivery & Research, Journal of Drug
Delivery & Therapeutics, 2012, 2(3), Pp- 22-23

5. ANATOMY AND PHYSIOLOGY OF NASAL
CAVITY-
5
(2) Kaur H, Singh C, Gupta GD, Nasal Drug Delivery: Review, Indo
Anerican Journal of Pharmaceutical Research, 5(8), 2015, Pp. 2522-2530

6.  The nasal cavity is run from the nasal vestibule to the nasopharynx
which has depth of approximately 12-14cm.
 The nasal vestibule, the respiratory region and the olfactory region
are the three main regions of the nasal cavity.
 The sub mucosal zone of the nasal mucosa directly connects to the
systemic circulation, thus avoids first pass metabolism.
 Nasal cavity is about 60mm in length.
 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.
 Nasal blood flow external & internal carotid arteries.
 Nasal secretions :- Nasal secretions are secreted by goblet cells,
nasal glands and transudate from plasma.
 Composition:- 95% water, 1-2% salt, 2-3% mucin. in trace amount
Na, K, Ca, Albumin also present.
 Nasal enzymes:- Monooxygenase, lactate dehydrogenase,
oxidoreductase, phosphates , hydrolases, esterase's, etc.
 Nasal pH:- 5.5-6.5 (adults)
5.0-6.7 (infants & child)
6

7. FUNCTIONS OF NOSE-
OLFACTION
• Filtration
• Heating
• Humidification
RESPIRATION
• Smell Detection
7(3) Mygind N, Dahl R, Anatomy, Physiology & Function of the Nasal
Cavities in Health & Disease, Advance Drug Delivery Reviews, (29), 1998,
Pp. 3-12

8. MECHANISM OF DRUG ABSORPTION-
By paracellular process By transcellular process
8

9.  It involves an aqueous route of
transport.
 It refers to the transfer of drug
by passing through the
intracellular spaces between
the cells.
 The molecular weight greater
then 1000 Daltons having
drugs shows poor
bioavailability.
 It involves transport through a
lipoidal route.
 It responsible for the transport
of lipophilic drugs that show a
rate dependency on their
lipophilicity.
 Drugs cross the cell membrane
by an active transport route or
transport through the opening
of tight junctions.
Paracellular process Transcellular process
9(4) Laksitorini M, Vivitri D, Paul KK, Pathways and Progress in Improving
Drug Delivery Through the Intestinal Mucosa & Blood Brain Barriers,
AuthorManuscript,2014,5(10),Pp.1143-1163

10. PATHWAY OF DRUG ABSORPTION-
10
(5) Wen MM, Olfactory Targeting Through Intranasal Delivery of
Biopharmaceutical Drugs to Brain, Discovery Medicine, (6) ,2011.

11. NOSE BRAIN PATHWAY-
11
Olfactory
mucosa
Nerves Brain
CSF
Highly vascular
nasal mucosa
 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
CSF.
 This area is termed the nose brain
pathway and offers a rapid, direct route
for drug delivery to the brain
(6) Chen XQ, Fawcett JR, Delivery of Nerve Growth Factor to Brain via the
Olfactory Pathway, Journal of Alzheimer's Disease, (1), 1998, Pp.35-44

12. 12
ADVANTAGES-
o Drug degradation that is observed in the gastrointestinal tract is absent.
o Hepatic first pass metabolism is avoided.
o Rapid drug absorption and quick onset of action can be achieved.
o The bioavailability of larger drug molecules can be improved by means of absorption
enhancer or other approach.
o The nasal bioavailability for smaller drug molecules is good.
oDrugs that are orally not absorbed can be delivered to the systemic circulation by nasal
drug delivery.
oNasal route is an alternate to parental route, especially, for protein and peptide drugs.
oConvenient for the patients, especially for those on long term therapy, when compared
with parental medication.

13. DISADVANTAGES-
o The histological toxicity of absorption enhancers used in nasal drug
delivery system is not yet clearly established.
o Relatively inconvenient to patients when compared to oral delivery
systems since there is a possibility of nasal irritation.
o Nasal cavity provides smaller absorption surface area when
compared to GIT.
o There is a risk of local side effects and irreversible damage of the
cilia on the nasal mucosa, both from the substance and from
constituents added to the dosage form.
o Certain surfactants used as chemical enhancers may disrupt and
even dissolve the membrane in high concentration.
13
(7) Vyas SP, Khar RK, Controlled Drug Delivery, Vallabh Prakashan, ed(2),2012, Pp.
301-325

14. FACTORS AFFECTING ABSORPTION OF DRUG-
 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.
 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 μm size exhaled with air.
14
(8) Jadhav KR, Manoj N, Shaikh IM, Nasal Drug Delivery- Factors Affecting
& applications, Current Drug Therapy, (2), 2007, Pp.27-38

15. ENHANCEMENT OF DRUG ABSORPTION-
15
By using absorption
enhancers
By increasing the
retention time of drug
Microspheres
By using physiological
modifying agents.
Surfactants
Bile salts
Chelaters
Fatty acids
Phospholipids
Methyl cellulose,
CMC, Polyacrylic
acid
Starch,
Albumin,
Gelatin, Dextrin
Histamine,
Prostaglandin E1,
Terbutaline
(9) Merkus FWHM, Schiffer NGM, Hermens WAJJ, Absorption Enhancers
in Nasal Drug Delivery : Efficacy &Safety, Journal of Controlled Release,
24,1993, Pp. 201-208

16. COMPONENTS OF NASAL FORMULATIONS-
Osmotic
agents
• Sodium
chloride
• Sodium
sulfite
• Sodium
phosphate
Solubilizers
• Glycols
• Surfactants
• Cyclodextrin
Gelling
agents
• Carbopol
• Cellulose
• Starch
• Chitosan
Humectants
Glycerine
Sorbitol
Manitol
16(10) Turker S, Onur E, Ozer Y, Nasal Route & Drug Delivery System,
Pharma World Science, (26), 2004, Pp. 137-142

17. VARIOUS NASAL DRUG DELIVERY FORMULATIONS-
Nasal spray
Nose drops
Metered dose spray
Saturated cotton pledge
Mucosal atomizer device
Nasal gels
Nasal ointments
Mucosal atomization device
Nebulizer
Nasal powder
17(11) Djupesand GP, Nasal Drug Delivery devices: Characteristics &
Performance in a Clinical Perspective, Drug Delivery and Transl.
Research, 2013, (3), Pp. 42-62

18. NASAL SPRAYS-
 Larger surface area of coverage.
 Smaller liquid particle size
allowing thin layer to cover
mucosa.
 Less run-off out the nasal cavity.
 Types of spray pump devices-
Multidose & Unidose.
18
(12) Bommer R, Kern J, Hennes K, Nasal Drug Delivery System, Medical
Device Technology, (10), 2004, Pp. 2-5

19. SITE OF DRUG SPRAY & ABSORPTION-
Site of drug spray
Site of drug
absorption
19

20. NASAL DROPS-
•Nasal drop devices are the most
traditional dispensing systems.
•Nasal drops may be suitable for infants.
• In adults, drops into the nasal cavity mostly lead to a rapid
clearance of the drug from nasal cavity towards to the throat.
20
(13) Kaur H, Singh C, Gupta GD, Nasal Drug Delivery: Review, Indo
Anerican Journal of Pharmaceutical Research, 5(8), 2015, Pp. 2522-2530

21. METERED DOSE PUMP-
 Metered dose sprays include the container, the pump
with the valve and the actuator.
 The dose accuracy of metered dose pump spray is
depends upon the surface tension and viscosity of the
formulation.
 Propane, n-butane, isobutane, Dimethyl ether (DME)
and methyl ethyl ether are some examples of propellant.
21

22. SATURATED COTTON PLEDGETS-
• Cotton pledgets are soaked in the drug and
placed in the nasal cavity .
• Commonly used for local anesthetic’s
vasoconstrictors etc .
22

23. NASAL GELS-
 Nasal gels are high viscosity thickened solution or suspensions.
ADVANTAGES-
 Reduction of post-nasal drip due to high viscosity
 Reduction of taste impact due to reduce swelling.
 Reduction of irritation by using soothing/emollient excipients and
target to mucosa for better absorption.
23(14) Rathnam G, Narayanan, Carbopol Based Gels for Nasal Delivery of
Progestrone, AAPS Pharmaceutical Science Technology, 9(4), 2008, Pp-
1078-1082

24. NASAL OINTMENT-
 These are translucent, homogenous, viscous, semisolid
preparation intended to be instilled in the nose.
 Due to their viscosity they will not ooze out of the nose.
24(15) http://retailpharmaindia.com/product/bactroban-ointment-5-gm
accessed on 19/04/2017

25. MUCOSAL ATOMIZATION DEVICE (MAD)-
 This device designed to allow emergency personal to
delivery nasal medications as an atomized spray.
 Broad 30 micron spray ensure excellent mucosal
coverage.
 It is disposable and single use only.
25

26. NEBULIZER-
 Nebulizer is a drug delivery device used to administer medication
in the form of a mist inhaled into the lungs.
 The most commonly used nebulizers are Jet nebulizers, which are
also called "atomizers".
 Jet nebulizers are commonly used for patients in hospitals who have
difficulty using inhalers .
 The main advantage of the Jet nebulizer is related to its low
operational cost.
26
(16) Dahl R, Anatomy, Physiology & Function of the Nasal Cavities in
Health & Disease, Advance Drug Delivery Reviews, 29, 1998, Pp. 3-12

27. NASAL POWDER-
 This dosage form may be developed if solution and suspension
dosage forms cannot be developed due to lack of drug stability.
 The advantages to the nasal powder dosage form are the superior
stability of the formulation.
 Local application of drug is another advantage of this system.
27
(17) http://www.onzetrahcp.com accessed on 18/04/2017

28. APPLICATIONS OF NASAL DRUG DELIVERY SYSTEM-
 Delivery of non-peptide pharmaceuticals
Eg. Progesterone, estradiol, propranolol, nitroglycerin, sodium chromoglyate, etc.
 Delivery of peptide based pharmaceuticals
Eg. Insulin, Calcitonin, Pituitary hormones etc.
 Delivery of Diagnostic Drugs
 Phenol sulfo naphthalene- 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)
 Delivery of drugs to Brain:
 For Treatment of Parkinson’s disease, Alzheimer disease.
 For Delivery of Melanocyte stimulating hormone, ACTH, Insulin to brain
28
(18) Ozer YA, Alternative Applications for Drug Delivery: Nasal &
Pulmonary Routes, Nanometrials & Nanosystems for Biomedical
applications, Springer,2007, Pp. 99-112

29. EVALUATION OF NASAL DRUG DELIVERY-
 In the case of nasal powders-
Particle size, melting point, angle of repose, Carr's
comprexibility index etc.
 In the case of nasal gels-
Mucoadhessive strength, Flow property etc.
 In the case of nasal sprays-
Clearity of liquid, sterilization, content drug delivery
etc.
 In the case of nasal drops-
Clearity test, sterilization, closure system etc.
29
In-vitro studies-

30. In-vivo studies-
 Various animal compartment models are used for in-vivo evaluation
studies.
 The most convenient model is the anesthisized rat model.
 For most non-peptide drugs the results obtained in rats can
accurately reflect the absorption profiles in humans.
 Some other animal models are-
30
•Rabbit model
•Dog model
•Monkey model etc.
(19) Selcan T, Onur E, Ozer Y, Nasal route & Drug Delivery System,
Pharm. World Science, 2004, (26), Pp- 137-142

31. SOME MARKETED PRODUCTS-
31

32. SOME MARKETED PRODUCTS IN INDIA-
32
(20)http://www.zuventus.co.in/doctor_wise_products_se
lected.aspx?Medi_Id=146 accessed on 17/04/2017

33. CONCLUSION-
 NASAL DRUG DELIVERY OFFERS SUCH BENEFITS AS,
-Rapid onset of action with lower dose & minimal side effects.
-Has an advantages of site specific delivery with improved therapeutic
effect
-Attractive for delicate molecule allowing systemic circulation without
significant degradation.
 Nasal drug delivery offers flexibility for multiple formulation
ranging from nasal drop to nasal spray.
 Recent activities indicate a bright prospect for site specific delivery
of biotechnological product such as insulin & other hormones.
33

34. 34