To understand the essential drug absorption mechanisms To describe the factors influencing drug absorption To explain the barriers in drug absorption To describe the routes of administration with advantages and disadvantages

1. Absorption of Drugs
&
Routes of Drug Administration
DR AWAIS IRSHAD

2. Learning objectives
After completing this topic, students should be able:
• To understand the essential drug absorption mechanisms
• To describe the factors influencing drug absorption
• To explain the barriers in drug absorption
• To describe the routes of administration with advantages and disadvantages

3. Factors Influencing Drug Absorption
Factors related to drug:
• Physical state
• Lipid-solubility
• Particle size
• Disintegration time
• Dissolution time

4. • Route of drug administration
• pH and ionization (Henderson-Hasselbalch Equation)
• Food
• Presence of other drugs
• Area of the absorbing surface
Factors related to patient:
• Intercurrent illnesses

5. Barriers in drug absorption
• Barriers of Mouth: Membrane of the buccal cavity
• Barriers of Stomach:
• Dissolution rate
• Solubility
• Permeability
• pH of stomach
• Influence of hydrolytic enzymes
• Chemical Instability

6. Barriers of Intestine:
• pH of intestine
• pka value
• Solubility
• Hydrolytic enzymes

7. Barriers of Liver:
• Bile
• Drug metabolism (Generation Of Polar Molecules)

8. Barriers of Kidneys:
• Properties of the drug (hydrophobicity and pka)
• Factors (surface area, pH etc.)

9. Bloodstream Barriers:
(i) Hydrolytic action of enzymes
(ii) Plasma protein binding
(iii) Binding with the RBC

10. Blood Tissue Barrier:
• Tight junctions
Blood Brain Barrier (BBB):
• Drugs with high hydrophobicity
• Low molecular weight

11. pH of Gastrointestinal Tract

12. Schematic representation of dissolution of a drug particle in the GI fluid

13. Effect of dosage forms
on the absorption of
drugs

14. Pathways of Drug Absorption

15. ROUTES OF DRUG ADMINISTRATION
Drug- and patient-related factors influence the choice of drug administration
routes. These factors are:
1. Characteristics of the drug
2. Emergency/routine use
3. Condition of the patient (unconscious, vomiting and diarrhea)
4. Age of the patient
5. Associateddiseases

16. Remember that there are six "rights" in the administration of
drugs:
1. Right Patient
2. Right Drug
3. Right Dose
4. Right Route
5. Right Time
6. Right Documentation

17. Routes of Drug Administration
Local: Topical
Systemic:
• Enteral: Oral, Sublingual, Rectal
• Parenteral: Injection, Inhalation, Transdermal

19. Oral Route
Most common and acceptable route for drug administration. Dosage
forms are tablet, capsule, syrup, mixture, etc.
Advantages
• Safer
• Cheaper
• Painless
• Convenient for repeated and prolonged use
• Can be self-administered

20. Disadvantages
It is not suitable for/in:
• unpalatable and highly irritant drugs.
• unabsorbable drugs (e.g. aminoglycosides).
• drugs that are destroyed by digestive juices (e.g. insulin).
• drugs with extensive first-pass metabolism (e.g. lignocaine).
• unconscious patients.
• uncooperative and unreliable patients.
• patients with severe vomiting and diarrhea.
• Not suitable for emergency

21. Sublingual Route
The preparation is kept under the tongue. The drug is absorbed through the buccal
mucous membrane and enters the systemic circulation directly, e.g. nitroglycerin for
acute angina attack.
Advantages
• Quick onset of action of the drug.
• Action can be terminated by spitting out the tablet.
• Bypasses the first-pass metabolism.
• Self-administration is possible.

22. Disadvantages
It is not suitable for:
• irritant and lipid-insoluble drugs.
• drugs with bad taste.

23. Rectal Route
Drugs can be given in the form of solid or liquid.
• Suppository
• Enema

24. Parenteral Routes
Routes of administration other than enteral route are called parenteral routes.
Advantages
Onset of action of drugs is faster, hence suitable for emergency
Useful in: -
• Unconscious patient.
• Uncooperative and unreliable patient.
• Patients with vomiting and diarrhea.
Suitable for:
• Irritant drugs.
• Drugs with high first-pass metabolism.
• Drugs not absorbed orally, destroyed by digestive juices

25. Disadvantages
• Require aseptic conditions.
• Preparation should be sterile, and is expensive.
• Require invasive techniques, which are painful.
• Cannot be usually self-administered
• Can cause local tissue injury to nerves, vessels, etc.

26. Inhalation
Volatile liquids and gases are given by inhalation for systemic effects, e.g.
general anesthetics.
Advantages
• Quick onset of action.
• Dose required is very less, so systemic toxicity is minimized.
• Amount of drug administered can be regulated.
Disadvantages
Local irritation may cause increased respiratory secretion and bronchospasm.

27. Injections
Intradermal route:
The drug is injected into the layers of the skin, e.g, BCG vaccination and drug sensitivity
tests. It is painful and a small amount of the drug can be administered.
Subcutaneous (s.c.) route:
The drug is injected into the subcutaneous tissues of the thigh, abdomen, arm, e.g.,
insulin, adrenaline
Advantages
• Self-administration of drug is possible, e.g. insulin.
• Depot preparations can be inserted into the subcutaneous tissue, e.g, Norplant for contraception.
Disadvantages
• It is suitable only for non-irritant drugs.
• Drug absorption is slow, hence not. suitable for emergency

28. Intramuscular (i.m.) route:
Drugs are injected into large muscles, such as deltoid, gluteus maximus e.g
diclofenac, etc.
Advantages
• Absorption is more rapid as compared to oral route
• Mild irritants, depot injections, soluble substances and suspensions can be
given by this route.
Disadvantages
• Aseptic conditions are needed.
• Intramuscular (i.m.) injections are painful and may cause abscess.
• Self-administration is not possible.
• There may be injury to nerves

29. Intravenous (I/V) Route:
Drugs are injected directly into the blood stream through a vein. Drugs are administered as:
·
I. Bolus:
Single. relatively large dose of a drug injected rapidly or slowly into a
vein, e.g. i.v, ranitidine in bleeding peptic ulcer. . .
2. Slow intravenous injection:
For example, i.v, morphine myocardial infarction.
3. Intravenous infusion:
• Dopamine infusion in cardiogenic shock
• Mannitol infusion in cerebral oedema
• Fluids infused intravenously in dehydration

30. Advantages
• Bioavailability is 100%.
• Quick onset of action, so it is the route of choice in emergency, e.g, diazepam in status
epilepticus.
• Large volume of fluid can be administered, e.g. severe dehydration.
• Highly irritant drugs, e.g. anticancer drugs
• Hypertonic solution can be infused by intravenous route, e.g. 20% mannitol in cerebral
oedema.

31. Disadvantages
• Local irritation may cause phlebitis.
• Self-administration is usually not possible.
• Strict aseptic conditions are needed.
• Extravasation of some drugs can cause injury, necrosis and sloughing of
tissues.
• Depot preparations cannot be given by i.v route.

32. Intrathecal route:
Drug is injected into the subarachnoid space, e.g. Lignocaine (spinal
anesthesia), antibiotics (amphotericin B), etc.
Transdermal Route (Transdermal Therapeutic System)
The drug is administered in the form of a patch or ointment that delivers the drug into the circulation
for systemic effect e.g;-
• Scopolamine Patch For Motion Sickness
• Nitroglycerin Patch/Ointment For Prophylaxis Of Angina
• Estrogen Patch For Hormone Replacement Therapy
• Clonidine Patch For Hypertension
• Fentanyl Patch For Chronic Pain
• Nicotine Patch For Tobacco De-addiction, Etc.

33. Advantages
• Self-administration is possible.
• Patient compliance is better.
• Duration of action is prolonged.
• Systemic side effects are reduced.
• Provides a constant plasma concentration of the drug.
• First-pass metabolism is bypassed.
Disadvantages
• Expensive.
• Local irritation may cause dermatitis and itching
• Patch may fall off unnoticed

34. Special Drug Delivery Systems
They have been developed to prolong duration of drug action, for targeted delivery of drugs or to
improve patient compliance
• Ocusert: It is kept beneath the lower eyelid in glaucoma. It releases the drug slowly for a week
following a single application, e.g. pilocarpine.
• Progestasert: It is an intrauterine contraceptive device that releases progesterone slowly for a
period of one year.
• Liposomes: They are minute vesicles made of phospholipids into which the drug is
incorporated. They help in targeted delivery of drugs, e.g. liposomal formulation of
amphotericin B for fungal infections.

35. Special Drug Delivery Systems
• Monoclonal antibodies: They are immunoglobulins, produced by
cell culture, selected to react with a specific antigen. They are useful
for targeted delivery of drugs, e.g. delivery of anti-cancer drugs using
monoclonal antibodies.
• Drug-eluting stents: e.g. paclitaxel releasing stents used in coronary
angioplasty.
• Computerized-miniature pumps, e.g. insulin.

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