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Nasal Drug Delivery System
Nasal Drug Delivery System
NASAL
CONTENTS
Novel Drug Delivery System
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Novel drug delivery is one of the fastest growing healthcare sectors, with sales of drugs incorporating novel drug
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Novel drug delivery companies have existed since the late 1960s, when Alza and Elan pioneered the oral methods of
The introduction of hypodermic devices but especially metered dose inhalers & nasal sprays, promoted the concept and absolute need for specific drug delivery
Today there are between 300 & 350 companies worldwide with an interest in drug delivery, operating in a fierce environment where the number of drug launches
More novel technologies such as pulmonary delivery of insulin or needle-less human growth hormone
Oral
Injectable
Mucosal
Topical
Transdermal
Ocular
Vaginal/ Anal
Needle Needleless
Active Passive
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&
Opportunity
Annual market growth
Development time vis-a-vis new chemical entity Development cost vis-a-vis new chemical entity Merits Limitations
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30%
11%
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10 14 years
2 5 years
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$300-600 mio
$50 mio
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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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Merits...
Lower dose & hence lower side effects Useful for both local & systemic drug delivery
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Limitations
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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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Transneuronal absorption
Venous drainage
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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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Nasal pH
Nasal secretion of adult : 5.5-6.5
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2. Corticosteroids
3. Antiviral 4. Antibiotics 5. Antifungal 6. More recently, vaccines
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Drugs commonly administered through pulmonary route include 1. Terbutaline Sulphate - 2 adrenergic agonist 2. Salbutamol - 2 adrenergic agonist
3. Budesonide - corticosteroid
4. Ipratropium Bromide - anticholinergic 5. Sodium Chromoglycate mast cell stabilizer
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Formulation Development
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Formulation Development Dosage form Factors affecting drug absorption Formulation considerations
Physiological Pharmaceutical
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Dosage forms
Liquid drop Liquid spray/nebulizers Aerosol Suspension spray/nebulizers Gel Sustained release
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Drug concentration
Vehicle of drug delivery Mucosal contact time Degree of drugs ionization pH of the absorption site Size of the drug molecule Relative lipid solubility
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Physiological effects
Drug metabolism in the respiratory tract &
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Physiological effects....
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Pharmaceutical
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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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- A good systemic bioavailability can be achieved for molecules with a molecular weight of up to 1000 Daltons when no absorption enhancer is used
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Sodium Deoxycholate
Polysorbate 80 etc.
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3. Effect of solution pH
- Nasal absorption is pH dependent
- Absorption is higher at a pH lower than the dissociation constant (pKa) of the molecule - Absorption is lower as the pH increases beyond the dissociation constant
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the drug
- The absorption follows first-order kinetics
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Structural modification
Salt or ester formation Formulation design
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- Unidose
- Bidose - Multidose
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Bidose Unidose
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Multidose
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Applications
Delivery of non-peptide pharmaceuticals
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- estradiol
- propranolol
- nitroglycerin
- sodium chromoglyate can be rapidly absorbed through the nasal mucosa with a systemic bioavailability of approximately 100%
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biotechnological products
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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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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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