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RESPIRATORY DRUG DELIVERY SYSTEM

BYSUNILBOREDDY

Novel Drug Delivery System

Nasal Drug Delivery System

Medical aspects

Formulation Development

Applications

Conclusion

CONTENTS

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Novel drug delivery is one of

the fastest growing

healthcare sectors, with

sales of drugs incorporating

novel drug delivery systems

increasing @ an annual rate

of 15%

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By 2010, the US drug

delivery market alone will

be worth $30 billion

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Why Novel Drug

Delivery system?

To optimize drug’s therapeutic

effect, convenience and dose

To enhance a product’s life-cycle

To improve `patient compliance

To target drug delivery

To control overall healthcare costs

To facilitate biological drug delivery

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Drug Delivery Systems

Oral Inject-able Mucosal

Trans-derma

lOcular

Vaginal/Anal

Needle

Needle-less

Nasal

Buccal

Pulmo-nary

Active

Passive

Topical

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Global drug delivery market by administration

mode

Oral 53%

Inhalation 32%

Transdermal 8%

Injectable/Implant

3%

Ocular 2%

Nasal 2%

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NASAL

DRUG DELIVERY SYSTEM

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Inhalation/pulmonary drug delivery system

includes

Metered dose inhalers

Dry powder inhalers

Inhalation nasal sprays

Inhalation solutions & suspensions (for

nebulizers)

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Nasal Drug Delivery System

&

Opportunity

Annual market growth

Merits

Limitations

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Annual growth of locally acting

products

Annual growth of systemically acting

products

11%

30%

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Lower dose & hence lower side effects

Merits...

For CNS drugs, better site for rapid onset of

action

Eg. Inhalation anesthesia, Morphine etc.

Useful for both local & systemic drug delivery

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Limitations

Pathologic conditions such as cold or allergies

may alter significantly the nasal

bioavailability

Once administered, rapid removal of the

therapeutic agent from the site of absorption

is difficult

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NASAL ROUTE

- medical aspects

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The respiratory tract, which includes the

nasal mucosa hypopharynx 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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DRUG DELIVERY TO RESPIRATORY SYSTEM

Cross-sectional view

Pathways for nasal absorption

Nasal site of drug spray & 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

Site of drug

spray &

absorption

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Pathways for nasal

absorption

Absorption into the cerebrospinal fluid

Absorption through the supporting cells & the

surrounding capillary bed

- venous drainage

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Transneuronal

absorption

Olfactory nerve – 1st cranial sensory nerve

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Venous

drainage

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•Cyto chrome P 450 dependent Lactate dehydrogenase, Oxidoreductase, Hydrolases, lactic dehydogenase, malic enzymes, lysosomal proteinases, steroid hydroxylase.

Nasal enzymes

Nasal pH•Nasal secretion of adult : 5.5-6.5

•Infants and children: 5-6.7

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Therapeutic class of drugs for nasal route

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Therapeutic class of drugs

1. 2 adrenergic agonists

2. Corticosteroids

3. Antiviral

4. Antibiotics

6. More recently, vaccines

5. Antifungal

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Drugs commonly administered through

pulmonary route include

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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FormulationDevelopme

nt

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Formulation

Development

Dosage formDosage form

Formulation considerationsFormulation

considerations

Physiological

Pharmaceutical

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Dosage

forms

Liquid drop

Liquid spray/nebulizers

Suspension

spray/nebulizersGel

Sustained release

Aerosol

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Physiological effects

- Drug metabolism in the respiratory tract &

reduction of systemic effect

- Local toxic effects of the drug

Eg., edema, cell injury, or altered tissue

defenses

Local or systemic effects of propellants,

preservatives, or carriers

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Pharmaceutical

- 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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1. Effect of particle size (aerodynamic size distribution)

- Large particles (> 7 microns) will be lost in the

gastrointestinal tract

- Intermediate particles (3 to 7 microns) reach the

actual site of action

- Small particles (< 3 microns) will be lost in

exhaled

breathe

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2. Effect of molecular size

- Higher the molecular size, lower the nasal

absorption

Absorption enhancers:

Polyacrylic acid

Sodium Glycocholate

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.

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4. Effect of drug lipophilicity-

- Lipid soluble drugs are absorbed more rapidly

than water soluble drugs

5. Effect of drug concentration

- Absorption depends on the initial concentration

of

the drug

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Methods to enhance nasal absorption of

drugs

Structural modification

Formulation design

Salt or ester formation

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SPRAY PUMP DEVICES

- Unidose

- Multidose

- Bidose

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Bidose

Unido

se38

Multidose

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Applicatio

nsDelivery of non-peptide

pharmaceuticals

Delivery of diagnostic drugs

Delivery of peptide-based

pharmaceuticals

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1. 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%41

2. Delivery of peptide-based

pharmaceuticals

Eg. Insulin, Calcitonin, Pituitary hormones etc.

Nasal route is proving to be the best route for

such biotechnological products

3. Delivery of diagnostic drugs

Diagnostic agents such as

Phenolsulfonphthalein – kidney function

Secretin – pancreatic disorders

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CONCLUSIO

N

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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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