Nasal drug delivery
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NASAL DRUG DELIVERY SYSTEM
description
Transcript of Nasal drug delivery
NASAL DRUG DELIVERY SYSTEM
Inhalation/pulmonary drug delivery system includes
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Metered dose inhalers
Dry powder inhalers
Inhalation nasal sprays
Inhalation solutions & suspensions (for
nebulizers)
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Historically, nasal drug delivery
system has received interest since
ancient times
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Therapy through intranasal administration has been an accepted form of treatment in the Ayurvedic system of Indian medicine.
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Merits
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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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Merits...
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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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Limitations
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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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NASAL ROUTE- medical aspects
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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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Cross-sectional view
Nasal site of drug spray & absorption
Pathways for nasal absorption
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Cross-sectional view
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a – nasal vestibule d – middle turbinate
b – palate e – superior turbinate (olfactory mucosa)
c – inferior turbinate f – nasopharynx
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Site of drug
spray &
absorption
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Pathways for nasal absorption
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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
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Transneuronal absorption
13Olfactory nerve – 1st cranial sensory nerve
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Nasal enzymes
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• 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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Nasal enzymes – contd.,
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Progesterone and testosterone were metabolized by several steroid hydroxylases in the nasal mucosa of rats.
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Nasal pH
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• 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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Therapeutic class of drugs for nasal route
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Therapeutic class of drugs
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1. 2 adrenergic agonists
2. Corticosteroids3. Antiviral
4. Antibiotics
6. More recently, vaccines
5. Antifungal
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Drugs commonly administered through pulmonary route include
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1. Terbutaline Sulphate - 2 adrenergic agonist
2. Salbutamol - 2 adrenergic agonist
4. Ipratropium Bromide - anticholinergic
5. Sodium Chromoglycate – mast cell
stabilizer
3. Budesonide - corticosteroid
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Formulation
Developme
nt
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Formulation Development
Dosage formDosage form
Formulation considerationsFormulation considerations
Factors affecting drug absorptionFactors affecting drug absorption
Physiological
Pharmaceutical21 3/23/2011
Dosage forms
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Liquid dropLiquid spray/nebulizers AerosolSuspension spray/nebulizers
GelSustained release
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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
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Physiological effects
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- 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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Physiological effects....
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- 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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Pharmaceutical effects
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- Physico-chemical properties of a drug
candidate
- Spray pump devices
- Methods to enhance drug absorption
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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
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Methods to enhance nasal absorption of drugs
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Structural modification
Salt or ester formation
Formulation design
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SPRAY PUMP DEVICES
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Unidose
Bidose
Multidose
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Applications
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Delivery of non-peptide pharmaceuticals
Delivery of peptide-based pharmaceuticals
Delivery of diagnostic drugs
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Delivery of non-peptide pharmaceuticals
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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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Delivery of peptide-based pharmaceuticals
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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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Delivery of diagnostic drugs
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Diagnostic agents such as
Phenolsulfonphthalein – kidney function
Secretin – pancreatic disorders
Pentagastrin – secretory function of
gastric acid
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CONCLUSION
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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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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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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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Recent activities indicate a bright prospect for site-specific delivery of biotechnological products such as Insulin & other hormones
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THANK YOUTHANK YOU
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