Nasal drug delivery systems

1. Presentation on
Nasal Drug Delivery System
Submitted to – Presented by -
Dr. Rekha Rao Anusha
Assistant Professor M.Pharmacy
(Pharmaceutics) 2nd sem
Roll no.220121220014
GURU JAMBHESHWAR UNIVERSITY OF SCIENCE AND TECHNOLOGY
HISAR -125001

2. 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.
➢ Intranasal Medication administration offers a truly “Needleless ” solution
delivery.
➢ In recent years many drugs have been shown to achieve better systemic
bioavailability through nasal route than by oral administration.
➢ Nasal therapy, has been recognized form of treatment in the Ayurvedic
systems of Indian medicine, it is also called “NASAYA KARMA”.
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3. • Drugs are administered to the nasal cavity for
a) localized
b) systemic action
c) vaccine delivery
d) possible direct nose brain delivery
ADVANTAGES
1. A non invasive 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.
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4. 6. The nasal bioavailability for smaller drug molecules is good.
7. Conventional route when compared with parenteral route for long term
therapy.
DISADVANTAGES
1. The absorption enhancers used to improve nasal drug delivery systems may
have histological toxicity which is not yet clearly established.
2. Absorption surface area is less when compared to GIT.
3. Once the drug is administered can not be removed.
4. Nasal irritation
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5. ANATOMY & PHYSIOLOGY OF NASAL CAVITY
• The nasal cavity is divided into two halves by the nasal septum and
extends posterior to the nasopharynx, while the most anterior part of
the nasal cavity, the nasal vestibule, opens to the face through the
nostril.
• The nasal cavity consists of three main regions:
1) Nasal vestibule
2) Olfactory region
3) Respiratory region
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6. Anatomy of Nose
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7. The respiratory region contain three nasal turbinates the superior,
middle and the inferior, which project from the lateral wall of each half
of the nasal cavity.
In non-olfactory area includes-the nasal vestibule, covered with skin –
like stratified squamous epithelium cells.
In respiratory region, it has typical airways in the epithelium covered
with numerous microvilli, resulting in a large surface area available for
drug absorption and transport.
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8. Mucus layer is propelled in a direction from the anterior towards the
posterior part of the nasal cavity.
The goblet cells are present in the mucus membrane which covers the
nasal turbinate and the atrium. It secretes mucus as mucus granules
which swell in the nasal fluid to contribute to the mucus layer.
Composition-
95% water, 2% mucin, 1% salts, 1% of proteins such as albumin,
immunoglobulins, lysozyme and lactoferrin and 1% lipids.
The mucus secretions give immune protection against inhaled bacteria
and viruses.
The pH of nasal secretion is 5.5-6.5 in adults and 5.0-6.7 in infants.
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9. The respiratory tract, which includes
❑nasal
❑mucosa
❑Hypo pharynx
❑ large airways
❑small airways
provides a relatively large mucosal
surface area of approx. 100 m2
(in normal adult) for drug
absorption
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10. TYPES OF NASAL DRUG DELIVERY
LOCAL DRUG DELIVERY
NOSE TO BRAIN DRUG DELIVERY
SYSTEMIC DRUG DELIVERY
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11. Local Drug Delivery
➢It is a logical delivery choice for local (or topical) treatment.
➢Prominent examples are decongestants for nasal cold symptoms and
antihistamines and corticosteroids for allergic rhinitis.
➢Examples of nasal products with widespread use in this area include
the histamine, the anti-cholinergic agent Ipratropium bromide and
steroidal anti inflammatory agents.
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12. Local absorption of the drug through the mucus
layer
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13. Nose to Brain Drug delivery
➢Nose to brain drug delivery presents a promising alternative enabling
the delivery of therapeutic drugs to the CNS, while bypassing the
blood-brain barrier (BBB).
➢It is a non-invasive method , to access the CNS directly through the
olfactory or trigeminal nerves.
➢Improve therapy outcomes and to reduce side effects.
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14. Nose to brain drug delivery pathway
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15. Systemic Drug delivery
❖Positive attributes of systemic delivery includes:
➢A relatively large surface area for drug absorption.
➢Rapid drug onset.
➢No first-pass metabolism.
➢Non-invasiveness.
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16. Systemic absorption of the drug through the mucus
layer
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17. Mechanism of drug absorption
❖Paracellular mechanism-
➢Process in which drug transported between cell and transcytosis by
vesicle carrier.
➢It is a slow process, in which passive diffusion take place.
❖Transcellular mechanism-
➢Process in which drug diffuse through a membrane.
➢It is an active transport process.
❖Via trigeminal Nerves-
➢Compounds that may be absorbed by the trigeminal nerve are transported
to the ganglion, where they enter the brain.
➢The transportation of molecules from the nasal cavity to the parenchyma
of the brain occurs along both the olfactory or trigeminal nerves.
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19. Dosage Forms
Liquid Drops
Liquid Spray
Nasal Powder
Suspension Spray
Gel
Sustained Release
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20. Nasal Drops
• Nasal drops are one of the most convenient & simple
systems for nasal delivery. These are instilled into the
nose by dropper.
• Aqueous oily solutions, since the later inhibit the
movement of cilia in the nasal mucosa. If kept for
longer periods, may reach the lungs & cause lipoid
pneumonia.
• Nasal drops should be isotonic having neutral pH &
viscosity similar to nasal secretions by using
methylcellulose.
E.g.:- ephedrine nasal drops B.P.C, Otrivin nasal drops.
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21. Nasal Spray
• These are aqueous or alcoholic preparations.
Applied to the mucous membrane of nose by
atomizer.
• Only fine droplets are required so they may reach
the lungs. By using metered pumps & actuators a
nasal spray can deliver an exact dose from 25 to
200µm.
e.g.:- adrenaline & atropine spray B.P.C
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22. Nasal Powder
➢Dry powders are less frequently used in
nasal drug delivery.
➢Major advantage of this dosage form are
the lack of preservatives and the improved
stability of the formulation.
➢Compared to solutions, the administration
of powder could result in prolonged contact
with the nasal mucosa.
E .g:- sinu air nasal powder
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23. Nasal Gels
1. Nasal gels are high-viscosity thickened solutions
or suspensions.
2.Without special application techniques, it only
occupies a narrow distribution area in the nasal
cavity, where it is placed directly.
3.Reduction of taste impact due to reduced
swallowing.
4. Reduction of irritation by using emollient.
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24. Nasal Vaccines
• Nasal mucosa is the first site of contact with
inhaled antigens and therefore , it is used for
respiratory infections.
• Nasal vaccination is a promising alternative to
the parenteral route , because it is able to
enhance the systemic levels of specific
immunoglobulin G & immunoglobulin A.
E.g : Nasal vaccines against influenza A & B Virus
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25. Compressed air nebulizer
➢ A nebulizer is a device used to
administer medication in the form
of a mist inhaled into the lungs.
➢ The compressed air is filling into
the device, so it is called
compressed air nebulizers.
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27. Liposomes:-
• These are phospholipid vesicles
composed by bilayer enclosing one or
more aqueous compartments, in these
compartment drugs can be entrapped
or adsorbed.
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28. Microsphere:-
➢Microsphere has an important role in
nasal drug delivery.
➢Enhancing absorption, sustained
release.
➢It protects the drug from enzymatic
degradation.
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29. Pressurized MDI:-
➢A metered-dose inhaler (MDI) is a
device that delivers a specific amount
of medication to the lungs, in the
form of a short burst of aerosolized
medicine that is inhaled by the
patient.
➢Propellants in MDIs typically make up
more than 99 % of the delivered
dose.
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30. Dry powder inhaler
➢ Dry powder inhalers are devices
through which a dry powder
formulation is delivered for local or
systemic effect via the pulmonary
route.
➢ Dry powder inhalers are bolus drug
delivery.
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31. Metered-dose pump spray
• Most of the pharmaceutical
nasal preparations on the
market containing solutions,
emulsions or suspensions are
delivered by metered-dose
pump spray.
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32. Formulation Consideration:
Viscosity Modifiers
Solubilizers
Surfactants
Absorption Enhancers
Preservatives
Anti-oxidant
Bio-adhesive Polymers
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33. 1. VISCOSITY MODIFIERS
• These agents increase the viscosity of solution prolonging the
therapeutic activity of preparation.
• Highly viscous formulations interfere with the normal functions like
ciliary beating or muco-ciliary clearance and thus alter the
permeability of drug.
e.g.: hydroxy propyl cellulose, Carbopol, Cellulose agents, Dextran,
Chitosan, etc.
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34. 2.SOLUBILIZERS
• Aqueous solubility of drug is always a limitation for nasal drug
delivery.
• e.g.: glycol, alcohol, labrasol, transcutol(diethylene glycol monoethyl
ether), small quantities of alcohol, surfactant.
• In such cases surfactants or cyclodextrins (HP- β -cyclodextrin) are
used , these serve as a biocompatible solubilizer & stabilizer in
combination with lipophilic absorption enhancers.
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35. 3. SURFACTANTS
Modify the permeability of nasal mucosa & facilitate the nasal
absorption of drugs.
E.g. SLS, Poly acrylic acid, sod. glycolate
4. PRESERVATIVES
These are used to prevent the growth of microorganisms.
e.g.: parabens, benzalkonium chloride, phenyl ethyl alcohol, EDTA etc.
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36. 5. BIOADHESIVE POLYMERS
• Increases the residence time of drug in nasal cavity and a higher local
drug concentration in the mucus lining on the nasal mucosal surface
• E.g.: Methylcellulose, Carboxy methylcellulose Hydroxyl propyl
cellulose
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37. 6. ANTIOXIDANTS
• These are used to prevent drug oxidation.
• E.g.: sodium meta bisulphite , sodium bisulfite, butylated hydroxy
toluene& tocopherol etc.
7. ABSORBTION ENHANCERS
(a) Surfactants: Sodium glycolate, Sodium deoxycolate
(b) Chitosan
(c) Cyclodextrins Hydroxypropyl-ß-cyclodextrin, Dimethyl-ß-
cyclodextrin
(d) Complexing agents: EDTA
(e) Fatty acid salts: Oleic acid ,Caprylic acid, Lauric acid
(f) Phospholipids: L-α- lyso-phosphatidyl choline
(g) Fusidates: Sodium taurodi-hydro-fusidate
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38. EVALUATION OF NASAL FORMULATION
➢ To improving the efficiency and effectiveness of active principles,
formulations and devices, another important objective of pharmaceutical
research is improving the link between in-vitro test data and in vivo
performance.
➢In vitro nasal permeation study:-
o In vitro diffusion study
o In-vivo nasal absorption study
➢Ex vivo nasal perfusion model
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39. In Vivo Nasal Absorption studies
• Animal models for nasal absorption studies The animal models
employed for nasal absorption studies can be two types, viz., whole
animal or in vivo model and an isolated organ perfusion or ex vivo
model,
• 1.RAT MODEL
• 2.RABBIT MODEL
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40. In vitro nasal permeation studies
(diffusion):
• The nasal diffusion cell is fabricated in glass.
• The lid has 3 opening, each for sampling,
thermometer, and a donor tube chamber.
• The nasal mucosa of sheep was separated &
stoned in distilled water containing few drops at
gentamycin injection. Mucosal surface is
attached to donor chamber tube.
• The donor chamber tube is placed such a way
that it just touches the diffusion medium in
recipient chamber. At predetermined intervals,
samples (0.5 ml) from recipient chamber are
with draw and transferred to amber colored
ampoules. The samples are estimated for drug
content by suitable analytical technique .
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41. In Vivo Nasal Absorption studies:
1. Rabbit model
• Rabbit is anaesthetized by intramuscular injection of a
combination of ketamine and xylazine.
• The rabbit's head is held in an upright position and the
drug solution is administered by nasal spray each nostril.
• The blood samples are collected by an indwelling
catheter in the marginal ear vein.
During the experiment the body temperature of the rabbit
is maintained at 37°C with the help of a heating pad.
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42. 2. Rat model
• The rat is anaesthesized. An incision is made in the
neck and the trachea is cannulated with a
polyethylene tube. Another tube is inserted through
the oesophagus towards the posterior region of the
nasal cavity.
• The drug solution is delivered to the nasal cavity
through the nostril or through the cannulation
tubing.
The blood samples are collected from the femoral
vein.
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43. RECENT ADVANCEMENT IN NASAL DRUG DELIVERY
➢Firstly, during exhalation the soft palate closes automatically, separating
the nasal and oral cavities.
➢Secondly, during the closure of the soft palate, there is a communication
pathway between the two nostrils.
➢The device is inserted into one nostril by a sealing nozzle and the patient
blows into the mouthpiece.
➢The combination of closed soft palate and sealed nozzle creates an air-flow
that enters one nostril, turns 180° through the communication pathway
and exits through the other nostril (bidirectional flow).
➢By adding an exit resistor to give additional control of the input pressure, it
is possible to optimize distribution to the sinuses and the middle ear.
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46. Applications
1.Delivery of non-peptide pharmaceuticals
Ex. Progesterone, estradiol, propranolol
2.Delivery of peptide based pharmaceuticals
Eg. Insulin, Calcitonin, Pituitary hormones etc.
3.Delivery of Diagnostic Drugs
Phenolsulfonphthalein – kidney function.
Secretin –pancreatic disorders
Pentagastrin – secretory function of gastric acid
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47. 4. Delivery of drugs to Brain:
For treatment of Parkinson’s disease, Alzheimer disease.
For delivery of MSH, ACTH, Insulin to brain.
5. Delivery of vaccines
The nasal mucosa is the first site contacts with inhaled pathogens. The
nasal passages are rich in lymphoid tissue. Creation of both mucosal
and systemic immune responses. Low cost, patient friendly, non-
injectable ,safe.
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48. References:
❑Alnasser Sulaiman, “ A review on nasal drug delivery system and its contribution in therapeutic
management.” Asian journal of pharmaceutical and clinical research,2019,2-3.
❑https://www.google.com/search?q=nasal+delivery+monkey+model&tbm=isch&ved=2ahUKEwiq2
JHu1P32AhUS_TgGHQxMC7AQ2-
cCegQIABAC&oq=nasal+delivery+monkey+model&cp=ChJtb2JpbGUtZ3dzLXdpei1pbWcQAzoHCC
MQ7wMQJzoECB4QClCMBVjPF2CiHWgAcAB4AIABzQGIAdkOkgEFMC45LjGYAQAQHAAQE&sclient
=mobile-gws-wiz-img&ei=RplMYqodkvrj4Q-MmK2ACw&bih=758&biw=412&client=ms-android-
samsung-gj-rev1&prmd=niv
❑https://www.researchgate.net/publication/490102_Nasal_drug_delivery_system_-_an_overview
❑https://www.researchgate.net/publication/41038_Intranasal_Drug_Delivery_How_Why_and_Wh
at_for
❑Sharma K Pramod, Garg Garima and Mohd Salim,“ Review on nasal drug delivery system with
recent advancement.” International Journal of Pharmacy and Pharmaceutical Sciences.2011,1-3.
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49. Thank you😃
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