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1. NASAL DRUG DELIVERY SYSTEM

2. Inhalation/pulmonary drug delivery
system includes
Metered dose inhalers
Dry powder inhalers
Inhalation solutions & suspensions (for nebulizers)
Inhalation nasal sprays
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3. Historically, nasal drug delivery system
has received interest since ancient times
Therapy through intranasal administration has
been an accepted form of treatment in the
Ayurvedic system of Indian medicine.
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4. Merits
Avoidance of hepatic first-pass metabolism.
Rate of absorption comparable to IV
medication.
Rapid onset of pharmacological action.
User-friendly, painless, non-invasive, needle-
free administration mode.
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5. Merits...
 Lower dose & hence lower side effects
 Useful for both local & systemic drug delivery
 For CNS drugs, better site for rapid onset of
action
E.g.. Inhalation anesthesia, Morphine etc.
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6. 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
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7. NASAL ROUTE
- medical aspects
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8.  The respiratory tract, which includes the
 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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9. Cross-sectional view
Nasal site of drug spray & absorption
Pathways for nasal absorption
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10. Cross-sectional view
a – nasal vestibule d – middle turbinate
b – palate e – superior turbinate (olfactory mucosa)
c – inferior turbinate f – nasopharynx
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11. Site of drug
spray &
absorption
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12. Pathways for nasal
absorption
 Absorption through the olfactory neurons
- transneuronal absorption. Olfactory epithelium is
considered as a portal for substances to enter CNS
 Absorption through the supporting cells & the surrounding
capillary bed
- venous drainage
 Absorption into the cerebrospinal fluid
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13. Transneuronal absorption
Olfactory nerve – 1st cranial sensory nerve
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14. Nasal enzymes
• Cytochrome P 450 dependent onooxygenases, Lactate
dehydrogenase, Oxidoreductase, Hydrolases, Esterase, lactic
dehydogenase, malic enzymes, lysosomal proteinases, steroid
hydroxylases., etc.
• Cytochrome P450 dependent mono oxygenases has been
reported to catalyse the metabolism of xenobiotics, nasal
decongestants, nocotine, cocaine, phenacetin, nitrosamine
progesterone etc.
• Insulin zinc free was hydrolysed slowly by leusine
aminopeptidase,
• PG of E series was inactivated 15 hydroxyprostaglandin
dehydrogenase
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15. Nasal enzymes – contd.,
Progesterone and testosterone were
metabolized by several steroid
hydroxylases in the nasal mucosa of rats.
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16. Nasal pH
• 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
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17. Therapeutic class of drugs
for nasal route
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18. Therapeutic class of drugs
1. β2 adrenergic agonists
2. Corticosteroids
3. Antiviral
4. Antibiotics
5. Antifungal
6. More recently, vaccines
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19. Drugs commonly administered
through pulmonary route include
1. Terbutaline Sulphate - β2 adrenergic agonist
2. Salbutamol - β2 adrenergic agonist
3. Budesonide - corticosteroid
4. Ipratropium Bromide - anticholinergic
5. Sodium Chromoglycate – mast cell stabilizer
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20. Formulation
Development
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21. Formulation Development
Dosage form
Dosage form
Factors affecting drug absorption
Factors affecting drug absorption
Formulation considerations
Formulation considerations
Physiological
Pharmaceutical
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22. Dosage forms
Liquid drop
Liquid spray/nebulizers
Aerosol
Suspension spray/nebulizers
Gel
Sustained release
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23. Drug concentration
Factors affecting
Vehicle of drug delivery
drug absorption
Mucosal contact time
Degree of drug’s ionization
pH of the absorption site
Size of the drug molecule
Relative lipid solubility
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24. Physiological effects
- Drug metabolism in the respiratory tract &
reduction of systemic effect
- Protein binding
- Mucociliary transport causing increased or
decreased drug residence time
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25. Physiological effects....
- Local toxic effects of the drug
E.g., edema, cell injury, or altered tissue
defenses
- Local or systemic effects of propellants,
preservatives, or carriers
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26. Pharmaceutical effects
- Physico-chemical properties of a drug
candidate
- Spray pump devices
- Methods to enhance drug absorption
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27. 1. Effect of particle size
2. Effect of molecular size
3. Effect of solution pH
4. Effect of drug lipophilicity
5. Effect of drug concentration
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28. Methods to enhance nasal
absorption of drugs
 Structural modification
 Salt or ester formation
 Formulation design
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29. SPRAY PUMP DEVICES
Unidose
Bidose
Multidose
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30. Applications
Delivery of non-peptide
pharmaceuticals
Delivery of peptide-based
pharmaceuticals
Delivery of diagnostic drugs
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31. 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%
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32. 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
E.g. Insulin, Calcitonin, Pituitary hormones etc.
 Nasal route is proving to be the best route for
such biotechnological products
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33. Delivery of diagnostic drugs
Diagnostic agents such as
• Phenolsulfonphthalein – kidney function
• Secretin – pancreatic disorders
• Pentagastrin – secretory function of
gastric acid
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34. CONCLUSION
 Nasal route is a part of drug delivery
strategy that is emerging to be a
fastest growing drug delivery system
with an annual growth of
 11% for locally acting drugs
 &
 30% for systemically acting drugs
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35.  Nasal drug delivery offers such
benefits as
 Rapid onset of action with lower
dose & minimal side effects
 Has an advantage of site-specific
delivery with improved
therapeutic effects
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36. Attractive for delicate molecules
allowing systemic administration
without significant degradation
Nasal drug delivery system offers
flexibility for multiple formulations
ranging from nasal drop to
suspension spray
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37. Recent activities indicate a bright
prospect for site-specific delivery of
biotechnological products such as
Insulin & other hormones
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38. THANK YOU
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