Routes of Drug Administration

The route of drug administration refers to the path by which a drug is brought into contact with the body to exert its therapeutic effect. The selection of the appropriate route plays a pivotal role in determining the onset, intensity, duration, and efficacy of the drug action. Various factors—including the drug’s physicochemical properties, therapeutic objective, required speed of onset, target tissue, patient compliance, and risk of adverse effects—must be considered when choosing the most suitable administration route.

This document provides a detailed and professional explanation of all major routes of administration, their classifications, mechanisms, examples, advantages, disadvantages, and clinical implications. All data reflect global pharmacological standards and regulatory principles applied in clinical pharmacology and pharmaceutical sciences.

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1. Classification of Routes of Drug Administration

Routes of administration are broadly categorized into:

A. Enteral (via the gastrointestinal tract)

• Oral (PO)

• Sublingual (SL)

• Buccal

• Rectal

B. Parenteral (bypasses the GI tract)

• Intravenous (IV)

• Intramuscular (IM)

• Subcutaneous (SC)

• Intradermal (ID)

• Intrathecal

• Intra-arterial

• Intra-articular

• Intrapleural

C. Topical/Local

• Cutaneous (dermal)

• Ophthalmic

• Otic

• Nasal

• Vaginal

• Rectal (also systemic)

D. Pulmonary

• Inhalation (aerosols, gases, vapors)

E. Transdermal

• Patch-based systemic delivery via intact skin

F. Others

• Intranasal (systemic)

• Intraperitoneal (in research)

• Intravitreal (ophthalmology)

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2. Enteral Routes

A. Oral (Per Os, PO)

Mechanism: Drug swallowed, absorbed through gastric or intestinal mucosa into portal circulation.

Examples: Paracetamol, ibuprofen, metformin

Advantages:

• Convenient and non-invasive

• Economical

• Good for chronic therapy

Disadvantages:

• Subject to first-pass metabolism in the liver

• Variable bioavailability due to pH, food, motility

• Not suitable for unconscious patients

B. Sublingual (SL)

Mechanism: Drug placed under the tongue, absorbed through the sublingual mucosa directly into systemic circulation.

Examples: Nitroglycerin, buprenorphine

Advantages:

• Rapid absorption

• Avoids first-pass metabolism

Disadvantages:

• Limited to small, lipid-soluble drugs

• Taste may be unpleasant

C. Buccal

Mechanism: Drug placed between cheek and gum for mucosal absorption.

Examples: Fentanyl buccal tablets

Advantages:

• Sustained release possible

• Avoids hepatic metabolism

Disadvantages:

• May be affected by saliva

• Patient discomfort

D. Rectal

Mechanism: Drug inserted into rectum; absorbed by rectal venous plexus (partially avoids first-pass metabolism).

Examples: Diazepam (in seizures), paracetamol suppositories

Advantages:

• Useful in vomiting/unconscious patients

• Partial bypass of hepatic metabolism

Disadvantages:

• Variable absorption

• Patient discomfort, social resistance

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3. Parenteral Routes

A. Intravenous (IV)

Mechanism: Drug injected directly into the bloodstream.

Examples: Antibiotics (e.g., ceftriaxone), chemotherapy (e.g., paclitaxel)

Advantages:

• Immediate onset

• 100% bioavailability

• Precise control of dose

Disadvantages:

• Requires sterile technique

• Risk of thrombosis, infection

• Costly and invasive

B. Intramuscular (IM)

Mechanism: Drug injected into a skeletal muscle.

Examples: Vaccines, haloperidol

Advantages:

• Sustained release possible

• Faster than oral route

Disadvantages:

• Pain at site

• Absorption depends on blood flow

• Not suitable for anticoagulated patients

C. Subcutaneous (SC)

Mechanism: Drug injected into the subcutaneous tissue.

Examples: Insulin, heparin

Advantages:

• Can be self-administered

• Slower, sustained absorption

Disadvantages:

• Limited to non-irritant drugs

• Slower onset than IM

D. Intradermal (ID)

Mechanism: Drug injected just beneath the epidermis.

Examples: Tuberculin test (PPD), allergy testing

Advantages:

• Minimal dose required

• Diagnostic utility

Disadvantages:

• Technical expertise needed

• Limited drug volume

E. Intrathecal

Mechanism: Drug injected into the cerebrospinal fluid (CSF) within the subarachnoid space.

Examples: Spinal anesthesia, intrathecal chemotherapy (e.g., methotrexate)

Advantages:

• Direct CNS access

• Avoids blood-brain barrier

Disadvantages:

• High infection risk

• Invasive and technically demanding

F. Intra-arterial

Used in: Diagnostic angiography, chemotherapy targeting tumors

G. Intra-articular

Used in: Local corticosteroid injection into joints (e.g., rheumatoid arthritis)

H. Intrapleural/Intrapertioneal

Used for: Local chemotherapeutic administration or research studies

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4. Topical and Local Routes

A. Cutaneous (Dermal)

Mechanism: Applied to skin for local effect.

Examples: Antifungal creams (clotrimazole), corticosteroids (hydrocortisone)

Advantages:

• Non-invasive

• Minimal systemic effects

Disadvantages:

• Skin barrier may limit penetration

• Potential for irritation

B. Ophthalmic (Eye drops/ointments)

Examples: Timolol (glaucoma), ciprofloxacin eye drops

Challenges:

• Requires sterility

• Limited corneal absorption

C. Otic (Ear)

Examples: Antibiotic ear drops for otitis externa

Note: Must be non-ototoxic if tympanic membrane is perforated

D. Nasal (Local or systemic)

Examples:

• Local: Oxymetazoline (decongestant)

• Systemic: Desmopressin, naloxone

Advantages:

• Rapid absorption via nasal mucosa

• Avoids first-pass metabolism

E. Vaginal

Examples: Antifungal pessaries, estrogen creams

Applications:

• Local infection treatment

• Hormone replacement

F. Rectal (Local use)

Examples: Bisacodyl (laxative), mesalazine (proctitis)

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5. Pulmonary Route

A. Inhalation (Gaseous or aerosolized drugs)

Mechanism: Delivered via alveoli into pulmonary circulation.

Examples:

• Salbutamol (asthma)

• Anesthetics (sevoflurane)

• Nitrous oxide

Advantages:

• Rapid systemic absorption

• Targeted delivery for respiratory diseases

• Bypasses first-pass metabolism

Disadvantages:

• Requires inhalation technique mastery

• Device dependence (inhalers, nebulizers)

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6. Transdermal Route

Mechanism: Drug absorbed through the skin for systemic effect.

Examples: Fentanyl patches, nicotine patches, hormone replacement therapy

Advantages:

• Steady plasma levels (controlled release)

• Improves compliance

• Avoids GI tract and hepatic metabolism

Disadvantages:

• Skin irritation

• Limited to lipophilic drugs with low molecular weight

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7. Other Specialized Routes

A. Intranasal

Systemic absorption through nasal mucosa. Used for hormones (e.g., oxytocin), naloxone, migraine therapy.

B. Intravitreal

Injection into the vitreous humor of the eye for conditions like macular degeneration.

C. Intravesical

For bladder cancer treatment (e.g., BCG therapy).

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8. Comparative Summary of Major Routes

Route	Speed	Bioavailability	Invasiveness	First-Pass Metabolism
Oral	Slow	Variable	No	Yes
Sublingual	Rapid	High	No	No
IV	Immediate	100%	Yes	No
IM	Moderate	High	Yes	No
SC	Slow	Moderate	Yes	No
Inhalation	Rapid	High	No	No
Rectal	Moderate	Variable	No	Partial
Transdermal	Slow	Variable	No	No
Topical	Variable	Local effect	No	No

9. Factors Affecting Route Selection

• Physicochemical properties of the drug: solubility, stability, pKa, molecular weight

• Target organ/system

• Onset and duration required

• Patient condition: unconscious, vomiting, dysphagia

• Risk of adverse effects

• Drug abuse potential

• Therapeutic context: acute vs. chronic, hospital vs. home use