FAR 381

Routes of administration

Werner Cordier
PhD, PGCHE
Department of Pharmacology

Tel: (012) 319-2521 werner.cordier@up.ac.za

 Routes of administration
Route important for absorption to site of action
Ocular Aural
Nasal
Inhalation Oral
Sub-lingual
Buccal
Topical Inhalation
Transdermal
Injectables
Subcutaneous
Rectal Intramuscular
Vaginal Intravenous
Intradermal
 Oral administration
(definition)

Most often used for majority of drugs, where formulation is

swallowed from oral cavity

• GIT absorption
– Drug needs to dissolve in GIT
• Liquids often easier absorbed due to soluble nature
– Subjected to harsh environmental factors (e.g. acid,
enzymes, first-pass effect)
• Degrades or converts compounds
– Must pass through biological membranes to be
absorbed
– Small intestines are the primary site of absorption due
to absorptive surface (villi and microvilli)
 Oral administration
(factors affecting GIT absorption)

• Gastrointestinal motility
– Affects how long drug stays in GIT lumen
– Absorption typically better the sooner a drug reaches
the small intestines

• Splanchnic blood flow

– Rich blood flow from GIT lumen increases absorption

• Food and drug interactions

– Alters drug absorption through interactions
 Oral administration
(factors affecting GIT absorption)

• Particle size, formulation and physicochemical factors

– Absorption profile dependent on drug characteristics
(e.g. solubility, charge, size, chemistry)
– Formulation may offer time delay or protection

Drug released
once outer layer
degraded
Outer
resistant
layer

Inner core
containing drug
 Oral administration
(advantages and disadvantages)

• Advantages
– Convenient and cheap
– Typically higher compliance rates
– Comfortable preparation for most individuals
– Various formulations available

• Disadvantages
– Needs to survive stomach acidity, digestive enzymes
and bacterial enzymes (i.e. first-pass effect)
– Subject to food interactions
– Cannot be given to unconscious, non-compliant or
vomiting patients
 Sublingual administration
(definition)

Absorption directly from the oral cavity by placement under

tongue
• Advantages over oral administration
– Rapidly absorbed due to rich blood supply, thus quick
onset of action
– Useful for drugs unstable at gastric pH or GIT enzyme
systems
– Bypasses first-pass effect

• Disadvantages over oral administration

– May cause oral irritation
– Saliva-soluble drugs only
 Sublingual administration
(forms)

• Soluble tablets
– Tablets dissolve with little residue in oral cavity

• Drops or spray
– Concentrated solution dripped or sprayed under tongue

• Lozenge
– Metred and patient-controlled
rate of dissolution
 Administration to epithelium
(definition)

Administration of solubilised drugs to different epithelial

surfaces of the body

• Cutaneous: epithelium of the skin

• Nasal: mucosa overlying nasal-associated lymphoid

tissue

• Eye: epithelium of the conjunctival sac

• Lungs: inhalation to alveoli

 Administration to epithelium
(cutaneous administration)

Administered to skin for localised effect or trans-dermal

absorption to systemic circulation

Cutaneous
Topical Transdermal
administration

• The skin barrier

– Hydrophobic (water-insoluble) barrier
– Drugs must have moderate lipophilicity (fat-soluble) to
cross cells either transcellularly or intercellularly
– Highly hydrophilic drugs have low permeation, and
thus remain on the surface
• Can use permeability enhancers (e.g. DMSO)
 Administration to epithelium
(topical cutaneous administration)

Preparation applied to skin and works locally

• Advantages
– Ease of use
– Little systemic absorption occurs due to intact skin
and dermis, thus low risk of systemic side effects

• Disadvantages
– Accurate dose cannot be specified
– Skin irritation or discomfort of use
– Lipophilic preparations may enter circulation (e.g.
corticosteroids) and cause systemic side effects
 Administration to epithelium
(transdermal cutaneous administration)

Preparation on patch/implant allows for transfer of drug into

systemic circulation

• Advantages
– Controlled state of drug delivery
– Bypasses first-pass effect

• Disadvantages
– Too slow for emergencies
– Skin irritation or discomfort of use
– Affected by condition of skin and circulation
 Administration to epithelium
(nasal administration)

Preparation applied to nasal mucosa for localised effects in

the nose or sinuses

• Advantages
– Quick relief of nasal symptoms
– Less systemic effects

• Disadvantages if used chronically

– Rebound congestion

• Forms
– Nasal sprays or drops
 Administration to epithelium
(ocular administration)

Preparation applied to conjunctiva for localised effects

within the eye

• Advantages
– Produces less systemic effects

• Disadvantages
– May be unpleasant to the eye
– Cloudy vision

• Forms
– Eye drops or lotion
 Administration to epithelium
(pulmonary inhalation administration)

Gaseous drug inhaled into lungs for localised effect

• Advantages
– Rapid adjustment to plasma concentration
– Localised to lungs
– Less systemic side effects

• Disadvantages
– Unpleasant taste or oral irritation

• Forms
– Metered-dose inhalers or nebulizers
 Rectal administration
(definition)

Preparation inserted into rectum for localised or systemic

effect

• Advantages over oral administration

– Faster onset and higher bioavailability
– Bypasses two-thirds of first pass effect
– Can be used when patient nauseous/vomiting
– Alternative to oral administration in home setting

• Disadvantages
– Unreliable absorptive profile
– Uncomfortable
 Rectal administration
(forms)

• Suppository
– Drug delivery system into the rectum

• Enema
– Liquid-drug delivery system into the rectum and/or colon

• Rectal catheter
– Placed into rectum for continuous use
 Injectable routes
Preparation injected into various areas for rapid distribution
of drug to site required

Intramuscular
90° angle Subcutaneous
45° angle
Intravenous
35° angle

Epidermis
Dermis Vein
Subcutaneous tissue
Muscle
 Injectable routes
(intravenous)

Preparation injected directly into systemic circulation

• Advantages
– Fastest, best control and most certain route
– Bypasses first-pass effect

• Disadvantages
– Invasive and uncomfortable procedure
– Scarring of veins
– Drug must be hydrophilic
 Injectable routes
(intravenous)

• Specific indications
– Rapid action required or emergency procedure
– Drug causes tissue irritation
– Drug has poor absorption profile
 Injectable routes
(subcutaneous)

Preparation injected directly under the skin

• Advantages
– Bypasses first-pass effect
– Can be given by patient
– Complete absorption

• Disadvantages
– Pain and tissue damage
– Slow absorption route
 Injectable routes
(intramuscular)

Preparation injected into the muscle

• Advantages
– Bypasses first-pass effect
– Depot formulations can be used for non-compliant or
out-patients

• Disadvantages
– Pain and tissue damage
– Given by trained personnel
– Injection site affects absorption and may be erratic
 Injectable routes
(subcutaneous and intramuscular)

• Absorption limited by
– Diffusion through tissue
– Removal by local blood flow

• Methods for increasing absorption

– Hyaluronidase breaks down intracellular matrix

• Methods for delaying absorption

– Poorly soluble or solid forms injected
– Vasoconstrictors at site of injection
 Quiz time
1. Ryu is taking penicillin G (an acid-sensitive antibiotic).
Should this be given orally?

A. Yes
B. No

2. Can Ken take his insulin (a proteinaceous drug) orally?

A. Yes
B. No
 Quiz time
3. Zangief experiences non-convulsive status epilepticus
(an emergency). Which route is most appropriate?

A. Subcutaneous
B. Oral
C. Intravenous
D. Transdermal
E. Sublingual

4. Cammy decides to soak her skin in vitamin C to help

combat aging. Will vitamin C be absorbed by the skin?

A. Yes
B. No
 Try it by yourself
1. Suggest and justify the most appropriate route of
administration in the following scenarios:
a. Sagat requires emergency treatment due to
anaphylactic shock. (1)
b. Dhalsim requires an analgesic for severe pain
accompanied by nausea and vomiting. (1)

2. Explain the implications of the skin barrier in drug delivery

via topical or transdermal routes. (2)