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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