nasal drug delivery
DESCRIPTION
TRANSCRIPT
![Page 1: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/1.jpg)
NASAL DRUG DELIVERY SYSTEM
![Page 2: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/2.jpg)
Inhalation/pulmonary drug delivery system includes
2
Metered dose inhalers
Dry powder inhalers
Inhalation nasal sprays
Inhalation solutions & suspensions (for
nebulizers)
3/23/2011
![Page 3: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/3.jpg)
Historically, nasal drug delivery
system has received interest since
ancient times
3
Therapy through intranasal administration has been an accepted form of treatment in the Ayurvedic system of Indian medicine.
3/23/2011
![Page 4: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/4.jpg)
Merits
4
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.
3/23/2011
![Page 5: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/5.jpg)
Merits...
5
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.
3/23/2011
![Page 6: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/6.jpg)
Limitations
6
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
3/23/2011
![Page 7: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/7.jpg)
NASAL ROUTE- medical aspects
7 3/23/2011
![Page 8: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/8.jpg)
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
3/23/2011
![Page 9: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/9.jpg)
9
Cross-sectional view
Nasal site of drug spray & absorption
Pathways for nasal absorption
3/23/2011
![Page 10: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/10.jpg)
Cross-sectional view
10
a – nasal vestibule d – middle turbinate
b – palate e – superior turbinate (olfactory mucosa)
c – inferior turbinate f – nasopharynx
3/23/2011
![Page 11: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/11.jpg)
Site of drug
spray &
absorption
11 3/23/2011
![Page 12: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/12.jpg)
Pathways for nasal absorption
12
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
3/23/2011
![Page 13: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/13.jpg)
Transneuronal absorption
13Olfactory nerve – 1st cranial sensory nerve
3/23/2011
![Page 14: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/14.jpg)
Nasal enzymes
14
• 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
3/23/2011
![Page 15: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/15.jpg)
Nasal enzymes – contd.,
15
Progesterone and testosterone were metabolized by several steroid hydroxylases in the nasal mucosa of rats.
3/23/2011
![Page 16: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/16.jpg)
Nasal pH
16
• 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
3/23/2011
![Page 17: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/17.jpg)
Therapeutic class of drugs for nasal route
17 3/23/2011
![Page 18: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/18.jpg)
Therapeutic class of drugs
18
1. 2 adrenergic agonists
2. Corticosteroids3. Antiviral
4. Antibiotics
6. More recently, vaccines
5. Antifungal
3/23/2011
![Page 19: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/19.jpg)
Drugs commonly administered through pulmonary route include
19
1. Terbutaline Sulphate - 2 adrenergic agonist
2. Salbutamol - 2 adrenergic agonist
4. Ipratropium Bromide - anticholinergic
5. Sodium Chromoglycate – mast cell
stabilizer
3. Budesonide - corticosteroid
3/23/2011
![Page 20: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/20.jpg)
Formulation
Developme
nt
20 3/23/2011
![Page 21: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/21.jpg)
Formulation Development
Dosage formDosage form
Formulation considerationsFormulation considerations
Factors affecting drug absorptionFactors affecting drug absorption
Physiological
Pharmaceutical21 3/23/2011
![Page 22: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/22.jpg)
Dosage forms
22
Liquid dropLiquid spray/nebulizers AerosolSuspension spray/nebulizers
GelSustained release
3/23/2011
![Page 23: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/23.jpg)
Factors
affecting drug
absorption
Drug concentration
Vehicle of drug delivery
Mucosal contact time
pH of the absorption site
Size of the drug molecule
Relative lipid solubility
Degree of drug’s ionization
23 3/23/2011
![Page 24: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/24.jpg)
Physiological effects
24
- Drug metabolism in the respiratory tract & reduction of systemic effect
- Protein binding
- Mucociliary transport causing increased or decreased drug residence time
3/23/2011
![Page 25: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/25.jpg)
Physiological effects....
25
- Local toxic effects of the drug
E.g., edema, cell injury, or altered tissue
defenses
- Local or systemic effects of propellants, preservatives, or carriers
3/23/2011
![Page 26: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/26.jpg)
Pharmaceutical effects
26
- Physico-chemical properties of a drug
candidate
- Spray pump devices
- Methods to enhance drug absorption
3/23/2011
![Page 27: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/27.jpg)
1. Effect of particle size
2. Effect of molecular size
3. Effect of solution pH
5. Effect of drug concentration
4. Effect of drug lipophilicity
27 3/23/2011
![Page 28: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/28.jpg)
Methods to enhance nasal absorption of drugs
28
Structural modification
Salt or ester formation
Formulation design
3/23/2011
![Page 29: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/29.jpg)
SPRAY PUMP DEVICES
29
Unidose
Bidose
Multidose
3/23/2011
![Page 30: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/30.jpg)
Applications
30
Delivery of non-peptide pharmaceuticals
Delivery of peptide-based pharmaceuticals
Delivery of diagnostic drugs
3/23/2011
![Page 31: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/31.jpg)
Delivery of non-peptide pharmaceuticals
31
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%
3/23/2011
![Page 32: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/32.jpg)
Delivery of peptide-based pharmaceuticals
32
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
3/23/2011
![Page 33: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/33.jpg)
Delivery of diagnostic drugs
33
Diagnostic agents such as
Phenolsulfonphthalein – kidney function
Secretin – pancreatic disorders
Pentagastrin – secretory function of
gastric acid
3/23/2011
![Page 34: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/34.jpg)
CONCLUSION
34
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
3/23/2011
![Page 35: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/35.jpg)
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
3/23/2011
![Page 36: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/36.jpg)
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
3/23/2011
![Page 37: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/37.jpg)
37
Recent activities indicate a bright prospect for site-specific delivery of biotechnological products such as Insulin & other hormones
3/23/2011
![Page 38: Nasal drug delivery](https://reader033.vdocument.in/reader033/viewer/2022061219/54b90c114a795995028b4597/html5/thumbnails/38.jpg)
THANK YOUTHANK YOU
38 3/23/2011