1. NASAL DRUG
DELIVERY SYSTEM
1
NIHAL.P
1ST
YEAR M.PHARM
NATIONAL COLLEGE OF PHARMACY

2. 2
IntroductIon
Intranasal Medication administration offers a truly
“Needleless” solution to drug delivery.
Therapy through intranasal administration has been
an accepted a form of treatment in the Ayurvedic
system of Indian medicine

3. 3
Merits

4. 4
Limitations
 Once administered, rapid removal of the
therapeutic agent from the site of
absorption is difficult
 Pathologic conditions such as cold or
allergies may alter significantly the
nasal bioavailability

5. 5
NASAL ROUTE
- medical aspects

6.  The respiratory tract, which includes
the
 nasal mucosa
 hypopharynx
 large airways &
 small airways
 provides a relatively large mucosal
surface area of approx. 100 m2
(in
normal adult) for drug absorption
6

7. 7
Cross-sectional view
Pathways for nasal absorption
Nasal site of drug spray & absorption

8. Cross-sectional view
8
a – nasal vestibule d – middle turbinate
b – palate e – superior turbinate (olfactory mucosa)
c – inferior turbinate f – nasopharynx

9. 9
Site of drug
spray &
absorption

10. 10
Pathways for nasal absorption
 Absorption through the olfactory neurons
transneuronal absorption. Olfactory epithelium is
considered as a portal for substances to enter CNS
 Absorption into the cerebrospinal fluid
 Absorption through the supporting cells & the
surrounding capillary bed
venous drainage

11. 11
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.
Olfactory
mucosa
Highly
vascular nasal
mucosa
Brain
CSF

12. 12
•Nasal secretion of adult : 5.5-6.5
•Infants and children: 5-6.7
•It becomes alkaline in conditions such as
acute rhinitis, acute sinusitis.
•Lysozyme in the nasal secretion helps as
antibacterial and its activity is diminished in
alkaline pH
Nasal pH

13. 13
Therapeutic class of
drugs for nasal route

14. 14
Therapeutic class of drugs
1. β2 adrenergic agonists
2. Corticosteroids
3. Antiviral
4. Antibiotics
6. More recently, vaccines
5. Antifungal

15. 15
Drugs commonly administered through pulmonary
route include
1. Terbutaline Sulphate - β2 adrenergic agonist
2. Salbutamol - β2 adrenergic agonist
4. Ipratropium Bromide - anticholinergic
5. Sodium Chromoglycate – mast cell stabilizer
3. Budesonide - corticosteroid

16. 16
Formulation Development
Dosage formDosage form
Formulation considerationsFormulation considerations
Factors affecting drug
absorption
Factors affecting drug
absorption
Physiological
Pharmaceutical

17. 17
Dosage forms
Liquid drop
Liquid spray/nebulizers
Suspension spray/nebulizers
Gel
Sustained release
Aerosol

18. 18
Factors affecting
drug absorption
Drug concentration
Mucosal contact time
pH of the absorption site
Size of the drug particle
Relative lipid solubility
Molecule weight of the drug

19. 19
Factors Affecting Bioavailability
Delivery system characteristics:
 Nasal mucosal surface area coverage:
 Larger surface area delivery = higher bioavailability.
 Particle size:
 Particle size 10-50 microns adheres best to the nasal
mucosa.
 Smaller particles pass on to the lungs, larger particles
form droplets and run-out of the nose.

20. 20
Cont..
 Atomization results in
higher bioavailability
than either spray or
drops.
 For this reason, nasal
pharmaceuticals
come with atomized
drug delivery
systems.

21. 21
Physiological effects
- Drug metabolism in the respiratory tract &
reduction of systemic effect
- Mucociliary transport causing increased
or decreased drug residence time
- Protein binding

22. 22
Physiological
effects....
- Local or systemic effects of propellants,
preservatives, or carriers
- Local toxic effects of the drug
Eg., edema, cell injury, or altered tissue
defenses

23. 23
Methods to enhance nasal absorption of
drugs
Structural modification
Formulation design
Salt or ester formation

24. 24
SPRAY PUMP DEVICES

25. 25
Bidose
Unidos
Multidose

26. Nasal Drops
26
Nasal drops are one of the most
simple and convenient systems
developed for nasal delivery.
The main disadvantage of this
system is the lack of the dose
precision and therefore nasal
drops may not be suitable for
prescription products.
It has been reported that nasal
drops deposit human serum
albumin in the nostrils more

27. Nasal sprays
27
Both solution and suspension
formulations can be
formulated into nasal
sprays.
Due to the availability of
metered dose pumps and
actuators, a nasal spray can
deliver an exact dose from
25 to 200 μm. The particles
size and morphology(for
suspensions)of the drug and
viscosity of the formulation
determine the choice of pump

28. 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.
 But now through LPL’s new Nasal Drug Delivery System,
the patient can get immediate relief. LPL becomes the
first company in India to introduce an anti-vomiting
treatment in the form of a Nasal spray pump.

29.  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.

30. 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.

31. 31
Nasal Powder
This dosage form may be developed if solution
and suspension dosage forms cannot be
developed e.g., due to lack of drug
stability.
The advantages to the nasal powder dosage
form are the absence of preservative and
superior stability of the formulation.
Local application of drug is another
advantage of this system.
Nasal powder formulation depends on the
solubility, particles size, aerodynamic
properties and nasal irritancy of the active
drug and /or excipients.

32. 32
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.

33. Nasal vaccines
33
Nasal mucosa is first site of contact with inhaled antigens
and, therefore, its use for vaccination, especially against
respiratory infections
Nasal vaccination is a 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.
Denovirusvectored influenza and parainfluenza virus
Intra nasal H1N1 vaccine Nasovac by Serum Institute

34. Current systemic therapeutics
delivered nasally
Desmopressin for diabetes mellitus
Calcitonin for osteoporosis
Sumatriptan for migraines
Nascobal for pernicious anemia

35. 35
Nasal Drug Delivery medications
Drugs of interest in Intranasal
systems:
 Intranasal naloxone (Narcan)
 Intranasal midazolam (Versed)

36. 36
Intranasal (IN) Naloxone
 Absorption of Intranasal naloxone almost as fast
as IV in both animal and human models
 “Atomization” of medications show much better
absorption via the Intranasal route

37. 37
Examples of Intranasal Drug
Delivery Systems
Intranasal sustained-release formulation
 Nasal absorption with Clofilium tosylate, enkephalin
analogs
 Short biological half-life
Tobispray
 Dry, metered-dose nasal aerosol
 Vasoconstrictor (tramazoline), steroid (dexamethasone
isonicotinate), antibiotic (neomycin sulfate)
Other examples are :
Butorphanol, calcitocin, sumatriptan, Insulin,Vaccine
and brain targeting drugs.

38. 38
 Efficacy of cocaine by oral and intranasal administration
 Nasal : detect in plasma by 15 min, peak concentration at
60 to 120 min, decrease gradually over the next 2 to 3h
 Oral : not detected until 30 min, increased rapidly for the
next 30 min
 In vivo absorption of sulbenicillin, cephacetrile, cephazoline
 Oral : poor absorption because of high water solubility
 Intranasal : ½ of im injection (% excretion in the urine )
Cont…

39. Market product
otrivin spray (xylometazoline)
miacalcin spray (calcitonin)
vibrocil gel (phenylephrine,dimethindene
maleate )
naset-p (xylometazoline HCL)-nasal drop
nasovac H1N1 vaccine
39

40. 40
Leading pump
suppliers

41. 41
Applications
Delivery of non-peptide pharmaceuticals
Delivery of diagnostic drugs
Delivery of peptide-based pharmaceuticals

42. 42
1. Delivery of non-peptide pharmaceuticals
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%

43. 43
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
biotechnological products

44. 44
3. Delivery of diagnostic drugs
Diagnostic agents such as
• Phenolsulfonphthalein – kidney function
• Secretin – pancreatic disorders
• Pentagastrin – secretory function of gastric acid

45. 45
The journey of a thousand miles begins with a
single step…