Administration of drug through nasal route is referred as Nasal drug delivery system. Nasal administration is a route of administration in which the drug are insufflated through the nose for either local or systematic effect. Nasal route is an alternative to invasive administrations and provides a direct access to the systemic circulation. Penetration Enhancers: Mechanism: Inhibit enzymatic activity Reduce mucus viscosity Reduce MCC Open tight junctions Solubilize the drug

1. INTRA NASAL ROUTE
DELIVERY SYSTEMS
SUBMITTED BY:
SUHEL KHAN
M.PHARMA
DEPARTMENT OF PHARMACEUTICS

2. DEFINITION
• Administration of drug through nasal route is
referred as Nasal drug delivery system.
• Nasal administration is a route of
administration in which the drug are
insufflated through the nose for either local or
systematic effect.
• Nasal route is an alternative to invasive
administrations and provides a direct access to
the systemic circulation.

3. ADVANTAGES
• A non invasive route.
• Hepatic first –pass metabolism is absent.
• Rapid drug absorption.
• Quick onset of action.
• The bioavailability of larger drug molecules can be
improved by means of absorption enhancer or
other approach.
• Better nasal bioavailability for smaller drug
molecules.
• Drugs which can not be absorbed orally may be
delivered to the systemic circulation through
nasal drug delivery system.
• Convenient route when compared with parenteral

4. DISADVANTAGES
• The absorption enhancers used to improve nasal
drug delivery system may have histological toxicity
which is not yet clearly established
• Absorption surface area is less when compared to
GIT.
• Once the drug administered can not be removed.
• Nasal irritation.
• There is a risk of local side effects and irreversible
damage of the cilia on the nasal mucosa

5. ANATOMY OF NASAL CAVITY
It is divided into two halves by
nasal septum.
a) It contain 3 regions
b) Nasal vestibule
c) Olfactory region
d) Respiratory region
Nasal cavity is covered with
mucous membrane which
contain goblet cells that secret
mucous

6. 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.

7. MECHANISM OF ABSORPTION
• Drug passes through the mucous membrane of
nasal cavity
• Majority of Drugs are absorbed by passive
diffusion.
• Some may be by active transport, such as amino
acids.
• Literature shows that upto 1000dalton drug get
easily absorbed without help of penetration
enhancers.
• Two mechanisms involved in the transportation of
the drug which are;
I. Para-cellular transport
II. Transcellular transport

8.  Para-cellular transport
Aqueous route of transport.
Slow and passive.
 Transcellular transport
Transport through lipoidal membrane
Active transport occurs via carrier
mediated transport.

9. FACTOR AFFECTING DRUG
ABSORPTION
1) Biological factor:
I. Biochemical (Enzymatic inhibition)
II. Structural feature
2) Physiological factor:
I. Muco-ciliary clearance(MCC)
II. Nasal secretion
III. pH of nasal cavity
IV. Blood flow
V. Pathology

10. FACTOR AFFECTING DRUG
ABSORPTION
3) Drug related factors:
I. Molecular weight
II. Particle size
III. pKa & partition coefficient
IV. Solubility
V. Lipophilicity
4) Formulation related factors:
I. Dosage form
II. Contact time &drug concentration
III. Osmolarity Viscosity

11. FORMULATION CONSIDERATION
• Nasal formulation are generally administered in
small volumes in the range 25-200μ L with 100μL,
the most common dose volume.
• The excipients should be carefully selected so as to
avoid damage to the muco-epithelial layers and to
sustain normal physiological ciliary movement.

12. FORMULATION OF NASAL DRUG
DELIVERY SYSTEMS
1) Drugs: commonly used in nasal drug delivery are:
I. β2-adrenergic agonist: Terbutaline sulphate
II. Corticosteroids: Budesonide
III. Anti-cholinergic: Ipratropium bromide
IV. Mast cell stabilizer: sodium cromoglycate
2) Humectants:
I. To prevent dehydration adequate intranasal moisture is required and
II. therefore humectants are added.
III. To Prevent nasal irritation.
IV. The commonly used humectants are
V. - Glycerine
VI. - Sorbitol
VII. - Mannitol

13. 3) Viscosifying agents:
• These agents increase the viscosity of the solution,
there by prolonging
• the therapeutic activity of preparation. e.g.:
hydroxypropyl cellulose.
4) Osmotic agent:
• The osmolarity of the dosage form affect the nasal
absorption of the drug.
• The higher concentration of drug not only causes
increased bioavailability but also leads to the toxicity to
the nasal epithelium.
• The commonly used osmotic agents are
I. Sodium Chloride
II. Sodium sulfite
III. Sodium acid phosphate

14. 5) Solubilizers:
• Aqueous solubility of drug always a limitation for
nasal drug delivery.
E.g. glycol, alcohol, labrasol, transcutol.
• In such cases surfactants or cyclodextrins (HP-β -
cyclodextrin) are used ,these serve as a
biocompatible solubilizer & stabilizer in
combination with lipophilic absorption enhancers.
6) Surfactants:
• Modify the permeability of nasal mucosa &
facilitate the nasal absorption of drugs.
E.g. SLS, Poly acrylic acid, sodium glycol-
cholate.

15. 7) Bio-adhesive 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, Carboxymethylcellulose,
Hydroxyl propyl cellulose
8) preservatives:
• These are used to prevent the growth of micro
organisms. e.g.: parabens, benzalkonium chloride,
phenyl ethyl alcohol, EDTA etc.
9) antioxidants:
• These are used to prevent drug oxidation. E.g.: sodium
meta bisulphite , sodium bisulfide, butylated hydroxy
toluene& tocopherol etc.

16. 10) Penetration Enhancers:
Mechanism:
I. Inhibit enzymatic activity
II. Reduce mucus viscosity
III. Reduce MCC
IV. Open tight junctions
V. Solubilize the drug
Ideal Properties:
I. It should increase in the absorption of the drug
II. It should not cause permanent damage or alteration to the
tissue
III. It should be non irritant and nontoxic.
IV. It should be effective in small quantity.
V. The enhancing effect should occur when absorption is required
.
VI. The effect should be temporary and reversible .

18. NASAL DOSAGE FORMS
Four basic formulations must be considered, i.e. solution,
suspension, emulsion and dry powder systems.
A. LIQUID NASAL FORMULATIONS
I. Instillation and rhinyle catheter
II. Compressed air nebulizers
III. Squeezed bottle
IV. Metered-dose pump sprays
B. POWDER DOSAGE FORMS
I. Insufflators
II. Dry powder inhaler
C. PRESSURIZED MDIs
D. NASAL GELS

19. A. LIQUID NASAL FORMULATIONS
Liquid preparations are the most widely used
dosage forms for nasal administration of drugs.
They are mainly based on aqueous state
formulations.
Their humidifying effect is convenient and useful.
1. Instillation and rhinyle catheter :
• Catheters are used to deliver the drops to a
specified region of nasal cavity easily.
• Place the formulation in the tube and kept tube one
end was positioned in the nose, and the solution
was delivered into the nasal cavity by blowing
through the other end by mouth.

20. • 2. Compressed air nebulizers:
• Nebulizer is a device used to administer
medication in the form of a mist inhaled into the
lungs.
• The common technical principal for all nebulizers,
is to either use oxygen, compressed air or
ultrasonic power, as means to break up medical
solutions or suspensions into small aerosol
droplets, for direct inhalation from the
mouthpiece of the device.

21. 3. Squeezed bottle
• Squeezed nasal bottles are mainly
used as delivery device for
decongestants.
• They include a smooth plastic bottle
with a simple jet outlet. While pressing
the plastic bottle the air inside the
container is pressed out of the small
nozzle, thereby atomizing a certain
volume.
4. Metered-dose pump sprays :
• Nasal sprays, or nasal mists, are used
for the nasal delivery of a drug or
drugs (antihistamines, corticosteroids,
and topical decongestants), either
locally to generally alleviate cold or
allergy symptoms.
• Metered- dose pump sprays include
the container, the pump with the valve

22. B. POWDER DOSAGE FORMS
Dry powders are less frequently used in nasal drug
delivery.
Advantages:
• The lack of preservatives,
• The improved stability of the formulation,
• A pro-longed contact with the nasal mucosa.
1. Insufflators
• Insufflators are the devices to deliver the drug
substance for inhalation;
• It can be constructed by using a straw or tube which
contains the drug substance and sometimes it contains
syringe also.

23. • The achieved particle size of these systems is
often increased compared to the particle size
of the powder particles due to insufficient
deaggregation of the particles and results in
a high coefficient of variation for initial
deposition areas.
2. Dry powder inhaler
• Dry powder inhalers (DPIs) are devices
through which a dry powder formulation of
an active drug is delivered for local or
systemic effect via the pulmonary route.
• Dry powder inhalers are bolus drug delivery
devices that contain solid drug, suspended or
dissolved in a non polar volatile propellant
(or) in dry powder inhaler that is fluidized
when the patient inhales.
• These are commonly used to treat respiratory
diseases such as asthma, bronchitis,
emphysema and COPD and have also been

24. C. PRESSURIZED MDIS
• 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.
• It is the most commonly used delivery system for treating asthma,
chronic obstructive pulmonary disease (COPD) and other respiratory
diseases.
• To use the inhaler the patient presses down on the top of the canister,
• with their thumb supporting the lower portion of the actuator. The
propellant provides the force to generate the aerosol cloud and is also
the medium in which the active component must be suspended or
dissolved.
• Actuation of the device releases a single metered dose of the
formulation which contains the medication either dissolved or
suspended in the propellant.
• Breakup of the volatile propellant into droplets, followed by rapid

26. D. NASAL GELS
• Nasal gels are high - viscosity thickened solutions or
suspensions.
• The deposition of the gel in the nasal cavity depends on
the mode of administration, because, due to its high
viscosity the formulation has poor spreading abilities.
• Without special application techniques it only occupies a
narrow distribution area in the nasal cavity, where it is
placed directly.

27. EVALUATION OF NASAL
FORMULATIONS:
• Various approaches used to determine the drug
passes through mucosa from the formulation
1. In vitro diffusion studies:
Glass fabricated nasal diffusion cell with 3
openings: Sampling thermometer & a donor tube
chamber
Nasal mucosa of sheep: Stoned in distilled water +
sample drug
Mucosal surface attached to donor chamber tube
that touched the diffusion medium in recipient
chamber
At specific interval samples withdrawn from
recipient chamber and transferred to amber

28. 2. IN VIVO NASAL ABSORPTION
STUDIES (ANIMAL MODEL):
Rate model
Anesthetized rat by
Intraperitoneal injection
of sodium pentobarbital
& incision made at neck
Tube insert through
esophagus towards
posterior of nasal cavity
Drug solution delivered
to nasal cavity trough
nostril/cannulation
tubing
Blood sample collected
from femoral vein and
analyzed for absorbed
drug.
Rabbit model
 Rabbit anaesthetized
by Ketamine +
Xylazine IM injection
 Head held upright &
drug administered by
nasal spray into each
nostril
 Rabbit’s body temp.
maintained at 37C
with heating pad
 Blood sample collected
by catheter from
marginal ear vein/
artery.

29. APPLICATIONS
1. Delivery of non-peptide pharmaceuticals:
Low molecular weight (below 1000 Daltons) small non-
peptide lipophilic drugs are well absorbed through the nasal
mucosa even though absence of permeation enhancer.
Drugs with extensive pre-systemic metabolism, such as
progesterone, estradiol, propranolol, nitro glycerine, sodium
cromoglycate can be rapidly absorbed through the nasal
mucosa with a systemic bioavailability of approximately 100%
2. Delivery of peptide-based pharmaceuticals:
Peptides & proteins have low oral bioavailability (1–2%)
because of their physico-chemical instability and susceptibility
to hepato-gastrointestinal first-pass elimination.
Examples are insulin, calcitonin, pituitary hormones etc.,
Absorption enhancers like surfactants, glycosides, cyclodextrin
and glycols increases the bioavailability.

30. 3. Delivery of drug to brain through nasal cavity:
It is beneficial in conditions like Parkinson’s disease,
Alzheimer's disease or pain because it requires specific
targeting of drugs to brain.
It will increase the fraction of drug that reaches the C.N.S.
after the nasal delivery.
The olfactory region located at the upper remote areas of
the nasal passages offer the potential for the compound to
circumvent the B.B.B. & enter in to the brain.
4. Delivery of vaccines through nasal route:
Reason for exploiting the nasal route for vaccine delivery
are,
• Nasal mucosa is the first site of contacts with the inhaled
pathogen.
• Nasal passages are rich in lymphoid tissues.
• Creation of both mucosal and systemic immune response.

31. Nasal delivery of vaccines has been reported to not
only produce systemic but also local immune
response.
Delivering the vaccine to the nasal cavity
stimulates the production of local secretory Ig-A &
Ig-G antibodies, providing an additional first line
of defense, which helps to eliminate the
pathogens.
5. Delivery of diagnostic agents
Nasal drug delivery system can be used for the
diagnosis of various diseases and disorders in the
body.
Pancreatic disorders of the diabetic patients were
diagnosed by using the ‘Secretin’.
The secretory function of gastric acid was

32. THANK YOU