Methods of Drug Delivery

An Overview
 Drug Delivery Methods
• Choice of the route of administration depends on the disease,
the effect desired, and the product available
• Drugs may be administered directly to the organ affected by
disease or given systemically

http://www.nae.edu/File.aspx?id=13306 Various routes of drug delivery.

 Drug Delivery Methods

Jain, Kewal K. Drug Delivery Systems. Totowa, NJ: Humana, 2008.

 Oral Drug Delivery
• Advantages:
– Ease of administration
– Widespread acceptance
 Oral Drug Delivery
• Limitations:
– Variable absorption rates
• Sustained release and controlled release systems
– High acid content and digestive enzymes
– Polar compounds cannot effectively traverse the cells of the epithelial membrane
– Many drugs become insoluble at low pH levels
– Drugs may be inactivated in the liver
– Some drugs irritate the gastrointestinal tract
– May not be suitable to target specific organs

Wang, Binghe; Siahaan, Teruna; Soltero, Richard (2005). Drug Delivery - Principles and Applications.. John Wiley & Sons. Page 17.
 Parenteral Drug Delivery
• Injection of substances by:
– Subcutaneous (SC, Sub-Q)
– Intramuscular (IM)
– Intravenous (IV)
• Most commonly used invasive method of drug
delivery

http://pharmrx.yolasite.com/blogs/page/3
 Parenteral Drug Delivery
• Advantages:
– Rapid onset of action
– Predictable and almost complete bioavailability
– Avoidance of the GI tract
– Reliable delivery to very ill and comatose patients
– Predictable and controllable route of delivery for
peptides and macromolecules

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 Parenteral Drug Delivery
• Limitations:
– Pain
– Patient compliance problems

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 Subcutaneous Drug Delivery
• Introduction of the drug to a layer of subcutaneous
fatty tissue by the use of a hypodermic needle
• Influencing factors:
– Size of molecules
– Viscosity
– Anatomical characteristics at
injection site
• Vascularity
• Amount of fatty tissue
• etc..

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 Subcutaneous Drug Delivery
• Advantages:
– Large portions of the body are available for
injection

Example: subcutaneous insulin infusion

http://www.ourdiabetes.com/insulin-pumps.htm
 Subcutaneous Drug Delivery
• Limitations:
– Lower rate of absorption and slower onset of action than
IM or IV
– Rate of absorption is difficult to control
– Local complications:
• Irritation
• Pain at site of injection
• etc…
– Injection sites have to
be changed frequently

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 Intramuscular Drug Delivery
• Given into skeletal muscles
• Onset of action is faster than Sub-Q but slower than IV
• Release rate influencing factors:
– Compactness of the depot
– Concentration and particle size of drug
– Nature of solvent
– Physical form of drug
– Drug flow characteristics
– Injection volume

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ex/nd7090g.htm
 Intramuscular Drug Delivery
• Limitations:
– Pain at injection site
– Amount to inject is
limited
– Peptides can degrade
at the site of injection
– Complications:
• Nerve injury
• Hematoma
• Abscess
– May introduce the drug directly into the blood circulation
if vessel is punctured
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 Intravenous Drug Delivery

• Injection in the aqueous form into a

superficial vein or continuous infusion
via a needle or a catheter placed in a
superficial or deep vein
• Rapid onset following the injection
• Selected in emergencies

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 Intravenous Drug Delivery
• Advantages:
– None of the drug is lost
– Smaller doses are required
– Rate of infusion can be controlled
– Can give timed administration of intermittent doses via an
intravenous catheter
– Particles in the IV solution are distributed depending on the
particle size:
• > 7 µm: lungs
• < 0.1 µm: bone marrow
• 0.1 - 0.7 µm: liver and spleen

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 Intravenous Drug Delivery
– Limitations:
• Immune reactions
• Drug solution in the extravascular space may lead to
irritation and tissue necrosis
• Infections
• Air embolism

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 Transdermal Drug Delivery

Mitragotri, S. 2005. Immunization without needles. Nature Reviews. Immunology 5(12): 905–916.

 Transdermal Drug Delivery
• Drug delivery influencing factors:
– Diffusion gradient driven
– Delivery system must be kept in continuous
contact with the skin for a considerable time
– Successful substances are characterized by:
• Low molecular weight (≤500 Da)
• Lipophilicity
• Effectiveness at low dosage

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 Transdermal Drug Delivery
• Advantages:
– No reminders to take medicine
– Bypassing the GI tract avoids
irritation
– Avoid partial first-pass
metabolism
– Steady absorption of drug

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 Transdermal Drug Delivery
• Limitations:
– Skin’s function is to keep things out of the body
– Major barrier is the stratum corneum (top layer of
the epidermis)
• Hygroscopic
• Impermeable to water
• Tough, flexible membrane
• Intercellular space is rich in lipids

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 Transmucosal Drug Delivery
• Mucous membranes cover all of the internal passages
of the body
– Buccal
– Nasal
– Rectal
• Movement of drugs across the mucous membranes
occurs by diffusion
– Often uses hydrogels
• Permeability can be enhanced by the use of
surfactants

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 Transmucosal Drug Delivery
• Advantages:
– Avoidance of an injection
– Lower cost than injectables
– Increase of therapeutic efficiency
– Rapid absorption
– Bypassing first pass metabolism by the liver

http://www.hcplive.com/print.php?url=http://www.hcplive.com/articles/Newly-Approved-Opioid-Aids-in-Cancer-Pain
Buccal Drug Delivery
• Advantages:
– Quick absorption and rapid onset
– Tablet can be removed in case of an undesirable
effect
– Avoids the first pass liver metabolism
– Tablet can remain for a prolonged period
– Can be used for patients with swallowing
difficulties

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 Buccal Drug Delivery
• Limitations:
– Tablet cannot be chewed or swallowed
– Saliva impacts dissolution and absorption
– Bad-tasting tablet will have low patient
acceptability

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 Nasal Drug Delivery
• Drug delivery influencing factors:
– The rate of nasal secretion
– Ciliary movement
– Vascularity of the nose
– Metabolism of drugs in the nasal cavity
– Diseases affecting the nasal mucous membrane

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 Nasal Drug Delivery
• Advantages:
– High permeability
– Highly vascularized
– Rapid absorption
– Avoidance of first pass effect
– Ease/familiarity of administration by the patients
– Higher bioavilability of the drugs
– Most feasible route for the delivery of peptides

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 Nasal Drug Delivery
• Limitations:
• Diseases may result in impaired absorption
• Small area available for absorption
• Limited time for absorption
• The nasal route of delivery is not applicable to all drugs
– Polar drugs
– Some macromolecules

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 Colorectal Drug Delivery
• Drug delivery influencing factors:
– Blood flow to and from the absorptive epithelium
– Dietary components
– Lipid-soluble molecules
– The rate of gastric emptying
– Motility patterns of the colon
– Targeted area
• Upper colon
• Lower colon
• Rectum
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 Colorectal Drug Delivery
• Advantages
– Ingested materials remain in the colon for a much longer time
– Large amounts can be administered
– Avoids stomach acid and/or pancreatic enzymes
– Avoid first pass metabolism
– Lower degradation of the drugs
– This route is safe and convenient particularly for the infants and the
elderly
– Useful in the treatment of emergencies, when IV is not available
– Rate of absorbance not influenced the
rate of gastric emptying

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 Colorectal Drug Delivery
• Limitations:
– Some hydrophilic drugs are not easily absorbed
– Drugs may cause rectal irritation

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 Pulmonary Drug Delivery
• Advantages:
– Large surface area available for absorption
– Close proximity to blood flow
– Avoidance of first pass liver metabolism
– Smaller does are required

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 Pulmonary Drug Delivery
• Disadvantages:
– Large molecules may get trapped
– Mucous lining the pulmonary airways clears the
deposited particles
– Only 10-40% of the drug is usually deposited in
the lungs

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 Cardiovascular Drug Delivery
• Vascular system supplies blood the body
• Can have systemic effects or be targeted to an organ
• Methods for delivery
– Into the myocardium:
• Direct intramyocardial injection
• Drug eluting implanted devices
– Drug delivery via coronary venous system
– Injection into coronary arteries via cardiac
catheter
– Intrapericardial drug delivery

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 Drug Delivery to the Central Nervous System
(CNS)
• Challenges:
– Blood-brain barrier
• Limits the access of drugs to the brain substance
• Treatment of CNS disease mostly by systemically
administered drugs
• Most research directed toward
controlled release
• Little attention has been paid to
delivery of drugs to the brain
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 Intraosseous Infusion
• Originally used in children
• Uses a bone marrow aspiration needle in the tibia or the
sternum
• Not a common route for drug delivery
• Alternative route for the administration during resuscitation
of critically ill and injured patients
• Advantages:
– Absorbed almost immediately into the
systemic circulation
– Marrow cavity functions as a rigid vein that
does not collapse

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