ROUTES OF ADMINISTRATION

Irene Brinkmann
PHARMACY PRACTICE & POLICY
Learning Objectives
Describe/Identify the factors that influence the choice of the route of
administration
Define the different routes of administration
Describe the importance/role of each route of administration
Describe the advantages and disadvantages of each route
Introduction
• Means through which a drug enters the body
• Location (where is the drug administered?)

• Dependent on
• Convenience (ease of administration)
• Condition being treated (Where? (Local vs. Systemic) Severity?)
• Population (age? Patient’s state?)
• Drug-related factors (pharmacokinetics - ADME? Stability? Compatibility?)

•The route via which a drug is administered needs to ensure that optimal
quantities of the drug reach the desired site of action
What happens to a drug once
administered?
Routes of administration
1. Enteral administration
2. Parenteral administration
3. Inhalation
4. Topical application
5. Vaginal administration
6. Transdermal
Enteral Administration
•Refers to the administration of drugs via the GUT
•There are various types of enteral administration
• Oral
• Sublingual/buccal
• Rectal
• Other (Nasogastric tube)
Oral Administration
•Most commonly used
• It can be for both local or systemic effects
• Drugs may be in liquid or solid form
• Drugs that are administered orally are more likely to have a reduced bioavailability
• This may be due to the first-pass effect which refers to the metabolism (GUT & Liver) of the
drug and subsequent reduction in drug concentration before reaching the systemic
circulation
• Other factors such as solubility and dissolution of the drug, co-administration with chelating
agents, gastric pH, etc. may also affect the bioavailability of the drug
First-pass effect
 Oral Administration cont’d
Advantages:
• Can be self-administered
• Widespread acceptance by the patients due to convenience
• Safest route when used properly
Disadvantages:
• Onset of action is slow
• Variable absorption rates
• Gastric emptying is influenced by various factors like food or other drugs
• Degradation of some drugs before reaching the site of absorption into the bloodstream (first-pass
effect)
• Some compounds are not able to effectively traverse the intestinal epithelial membrane cells
• Irritation of the mucous lining of the gastrointestinal tract
• Drug solubility may be altered by the presence of other substances e.g. calcium
• Not suitable for certain patient populations
Sublingual/Buccal Administration
• Administration of the drug under the tongue (sublingual) or in the buccal cavity
(cheeks)
• The tongue & buccal cavity are highly vascular which ensures adequate absorption
of the drug
• Drugs administered sublingually have a quick onset but short duration of action
• Drugs administered buccally have a quick onset and long duration of action
• It has the benefit of by-passing the first-pass effect
• The drug may be formulated as a dispersible tablet or spray
Advantages:
• Rapid absorption is due to the abundant mucosal network of systemic veins and
lymphatics, thereby leading to a rapid onset of action.
• If there is any immediate untoward event, the tablet can be removed.
• Avoids first-pass hepatic metabolism.
• This route is useful in patients having swallowing difficulties.
• Convenience
Sublingual/Buccal Administration cont’d
Disadvantages:
•Prone to inappropriate use
•Excessive salivation may cause quick dissolution which can lead to an irregular
absorption
•Patients may find it difficult to accept an unpalatable tablet.
Rectal Administration
•Administration of drugs via the rectum
•Formulations may be solids, semi-solids or liquids
•Produces a local and/or systemic effect
•There is limited fluid but the muscular movements spread the drug over a large and
promote absorption
•Partially avoids the first-pass effect
• The rectum has 3 veins; Middle and inferior rectal veins drain into the systemic circulation
but the upper rectal vein drains into the portal system (hepatic portal vein)
• Bioavailability is reduced
Rectal Administration cont’d
Advantages
A relatively large amount of the drug can be administered.
Those drugs destroyed by the acidic medium in the stomach and those metabolized
by pancreatic enzymes can be administered effectively.
Safe and convenient for infants and the elderly or even unconscious patients
It can be used in emergency situations, such as in infants having seizures when the
intravenous route is unavailable.
The absorption rate is uninfluenced by the ingestion of food or the gastric emptying
rate
Less degradation of drugs compared to that in the upper gastrointestinal tract.
Disadvantages:
Some hydrophilic drugs like antibiotics and peptide drugs are unsuitable for rectal
administration as they are not readily absorbed.
Some drugs can cause rectal irritation and proctitis, leading to ulceration and
bleeding.
May have irregular and unpredictable absorption
Poor patient acceptability
Parenteral Administration
•Refers to the administration of drugs by routes other than the digestive tract
• Refers to the various injection routes

•Often used when

• Drugs cannot be administered orally (patient-related factors e.g. NPO or drug-
related factors)
• Patient’s condition (hypertensive emergencies, sepsis, shock, unconscious, etc.)

•For systemic use (some for localized effect)

•The main parenteral routes include:
• Intravenous administration: administration of a drug directly into the systemic
circulation via a vein
• Subcutaneous administration: administration of a drug into the subcutaneous
layer of the skin
• Intramuscular administration: administration of a drug into the muscle layers
Intravenous Administration
•Most common parenteral route
•The drug is administered directly into the systemic circulation via a vein
•More control over blood drug concentrations
Advantages
There is direct administration into the systemic circulation
Fast onset of action
100% bioavailability

Disadvantages
Causes pain
Chance of infection
May cause thrombophlebitis when administered in the lower extremities
Water-in-oil emulsions or suspensions may not be used
Intramuscular Administration
•Intramuscular Injection: administration of the drug into a relaxed muscle
• Formulations may be small-volume aqueous solutions for rapid onset or oily for
prolonged action

Advantages
Avoids first-pass effect
Useful for depot preparations for sustained dosing over a more extended period
(improves adherence in patients)

Disadvantages
 The injection site may be painful
Complications may arise if administration is done inappropriately; abscesses,
peripheral nerve injury, or puncture of a blood vessel leading to inadvertent
intravascular administration
Subcutaneous Administration
•Subcutaneous Injection: administration of the drug into the subcutaneous
layer
•Used when
• The bioavailability is too low when given orally (LMWH)
• Other routes may produce adverse effects
• Prolonged action is desired (e.g. insulin)

Advantages
Better bioavailability
Easy to administer and requires minimal skills (patient can self-administer)
Can provide a prolonged effect

Disadvantages
Rate of absorption is difficult to control
Local complications – irritation and pain (rotation required)
Other Routes of
Administration
1. Trans nasal: Drug is absorbed by passive diffusion across the well-
vascularized respiratory epithelium directly into the systemic circulation
2. Inhalation: Drug is absorbed into the pulmonary circulation to enter
directly into the systemic circulation
3. Vaginal: administration into the vagina
4. Transdermal: Drug is delivered through the skin
5. Topical
Vaginal Administration
•Most commonly used for local conditions
• Has high absorption & better bioavailability than oral route

•Drugs formulated for this route may be

• Pessaries
• Tablets
• Capsules
• Solutions
• Sprays, foams, ointments
• Devices

Advantages
Useful in the delivery of low and continuous dosing of medication to help achieve
stable drug levels
A variety of formulations can be given vaginally

Disadvantages
 Inconvenient
Inhalation
• Administration of volatile substances via the nose or mouth or by use of inhaler
devices
• Inhalation of volatile substances or by use of inhaler devices via the nose of the
mouth
• This route is predominately used for local administration to treat respiratory
conditions (e.g. asthma) but it can also be used for systemic effects
• Particle size needs to be between 1 and 10 µm
Advantages
 Avoids first-pass hepatic metabolism
 Only smaller doses are enough to achieve equivalent therapeutic effects as the oral route
 Rapid absorption from lungs

Disadvantages
 Inappropriate use can lead to poor outcomes (inhaler techniques)
 Clearance of particles by the mucus lining the airways.
 Only 10–40% of the drug from a conventional inhalation device is deposited in the lungs.
Transdermal Administration
•A form of topical administration – the desired effect is systemic.
• The Transdermal Delivery System releases the drug to the skin at a controlled
rate
Advantages
Elimination of variables that affect GIT absorption
Improves patient compliance and the use of drugs with short half-lives
Blood levels do not fall immediately to zero after removal (drugs associated with
withdrawal)
Appropriate for drugs with a low Therapeutic Index

Disadvantages
 Not suitable for all drugs
 Blood levels do not fall immediately to zero after removal
Trans nasal Administration
•Traditionally used for producing local effects – however; systemic use is possible
• Drugs are in the form of drops, sprays, creams or gels
Advantages
Good absorption (vascular supply)
Avoids first-pass effect (higher bioavailability)
Avoids the effects of gastric stasis and vomiting.
Ease of administration

Disadvantages
Nasal cavity diseases and conditions may result in impaired absorption
The dose is limited due to the small area available for absorption
This route does not apply to all drugs
References
1. A.J. Winfield, J.A. Rees, I. Smith (2009). Pharmaceutical Practice 4 th edition
2. Timothy F. Herman, Cynthia Santos: First-Pass Effect (Nov 3, 2023)
https://www.ncbi.nlm.nih.gov/books/NBK551679/
3. J. Kim, O.D. Jesus (2023). Medication Routes of Administration.
https://www.ncbi.nlm.nih.gov/books/NBK568677/