Drug Absorption from Gastrointestinal Tract M.Pharm syllabus based.

1. DRUG ABSORTION FROM THE
GASTROINTESTINAL TRACT
By, Feba Elsa Mathew
2nd semester M.Pharm
Submitted to, Mrs. Juna Brigit Chacko
Asst. professor
Dept. of Pharmaceutics

2. CONTENTS
DRUG ABSORTION FROM THE GASTROINTESTINAL TRACT:
GASTROINTESTINAL TRACT
MECHANISM OF DRUG ABSORTION
FACTORS AFFECTING DRUG ABSORTION

3. Definition of some terms
 Biopharmaceutics:
It is defined as the study of factors influencing the rate and amount of drugs reaches
the systemic circulation and the use of this information in optimise the therapeutic
efficacy of drug products.
 Bioavailability: is defined as the rate and extent of drug absorption
 Pharmacokinetics: is defined as the study of time course of drug ADME and their
relationship with its therapeutics and toxic effects of the drug. Pharmacokinetics is the
kinetics of ADME OR KADME

4. Drugadministrationandtherapycannowbeconvenientlydividedinto
fourorprocess
The pharmaceutical phase: It concern with
a) Physicochemical properties of the drug and
b) Design and manufacture of an effective drug product for administration by suitable
route.
The pharmacokinetic phase: It concern with the ADME of the drug as elicited by the plasma
drug concentration-time profile and its relationship with the dose, dosage forms and dosing
frequency and route of administration.
The Pharmacodynamic phase: It is concerned with the biochemical and physiological effects
of drug and its mechanism of action.
The Therapeutic Phase: It concern with the translation of pharmacological effect into clinical
benefit

5. Absorption of Drugs
Absorption is the process of movement of drug from its site of administration to the
systemic circulation.
DRUG ABSORTION: is defined as the process of movement of unwanted drug from the site of
administration to systemic circulation.

6. Gastrointestinal tract
Basic structure
The gastrointestinal tract is a muscular tube lined by a special layer of cells, called
epithelium.
Although each section of the tract has specialized functions, the entire tract has a
similar basic structure with regional variations.

7. The wall is divided into four layers as follows:
1. Mucosa
The innermost layer of the digestive tract has specialized epithelial cells supported by an
underlying connective tissue layer called the lamina propria. The lamina propria contains blood
vessels, nerves, lymphoid tissue and glands that support the mucosa. Depending on its
function, the epithelium may be simple (a single layer) or stratified (multiple layers).
2. Submucosa
The submucosa surrounds the muscularis mucosa and consists of fat, fibrous connective tissue
and larger vessels and nerves. At its outer margin there is a specialized nerve plexus called the
submucosal plexus or Meissner plexus. This supplies the mucosa and submucosa.

8. 3. Muscularis externa
This smooth muscle layer has inner circular and outer longitudinal layers of muscle
fibers separated by the myenteric plexus or Auerbach plexus. Neural innervations
control the contraction of these muscles and hence the mechanical breakdown and
peristalsis of the food within the lumen.
4. Serosa/mesentery
The outer layer of the GIT is formed by fat and another layer of epithelial cells called
mesothelium.

9. Cell membrane structure and physiology
For a drug to be absorbed and distributed into organs and tissues and eliminated from the
body, it must pass through one or more biological membranes/barriers at various locations.
Such a movement of drug across the membrane is called as drug transport.

10. The cellular membrane consist of a double layer of amphiphilic phospholipid molecules
arranged in such a fashion that their hydrocarbon chains are oriented inwards to form the
hydrophobic or lipophilic phase and their polar heads oriented to form the hydrophobic or
lipophilic phase and their polar heads oriented to form the outer and inner hydrophilic
boundaries of the cellular membrane that face the surrounding aqueous environment.
The bio membrane acts like semipermeable barrier permitting rapid and limited passage of
some compounds while restricting that of others

11. Mechanisms of drug absorption
The three board categories of drug transport mechanisms involved in absorption are:-
A. Transcellular/ intracellular transport
B. Paracellular/ intercellular transport
C. Vesicular transport

12. Transcellular/intracellular transport
It is defined as the passage of drugs across the GI epithelium. It is the most common
pathway for drug transport .
3 steps involved in transcellular trans[ort of drugs are –
i. Permeation of GI epithelial cell membrane
ii. Movement across the intracellular space
iii. Permeation of the lateral or basolateral membrane
Two types of transcellular transport are:
1. Passive transport processes
2. Active transport processes

13. Passive Transport Processes: These transport processes do not require energy other than
that of molecular motion(Brownian motion) to pass through the lipid bilayer. They are
classified into:
a) Passive diffusion
b) Pore transport
c) Ion-pair transport
d) Facilitated- or mediated-diffusion
Active Transport Processes: These transport processes require energy from ATP to move drug
molecule from extracellular to intracellular milieu. They are of two types:
a. Primary active transport
b. Secondary active transport – they are
i. Symport (Co-transport)
ii. Antiport (counter-transport)

14. Paracellular/ Intercellular Transport
It is defined as the transport of drugs through the junction between the GI epithelial
cells. This pathway is of minor importance in drug absorption.
The two mechanisms involved in drug absorption are-
1. Permeation through tight junctions of epithelial cell
2. Persorption

15. Vesicular or Corpuscular Transport
(Endocytosis)
Like active transport, these are also energy dependent processes but involve
transport pf substances within vesicles into a cell. Since the mechanism involves
transport across the cell membrane.
They re classified into two categories
1. Pinocytosis
2. Phagocytosis

16. Summary of important transport processes
and drugs absorbed through them
ABSORPTION
MECHANISM
DRUGS ABSORBED
Passive
Diffusion
Most drug having high lipophilicity and MW
in the 100-400
Pore Transport Water- soluble drugs of MW less than 100
Ion-pair
Transport
Drugs that ionise at all pH conditions
absorbed after complexing with oppositely
changed ions
Carrier-
mediated
Transport
Structure-specific drugs with affinity for
carriers transported from specific sites
Endocytosis Macromolecular nutrients and drugs as solid
particles or oily droplets

17. Factors affecting Drug Absorption
The chain of events that occur following administration of a solid dosage form such as
a tablet or a capsule until its absorption into systemic circulation.
The process consist of four steps:
1. Disintegration of the drug product.
2. Deaggregation and subsequent release of the drug.
3. Dissolution of the drug in the fluids at the absorption site.
4. Absorption i.e. movement of dissolved drug through the GI membrane into the
systemic circulation and away from the absorption

19. In a series of kinetic or rate processes, the rate at which the drug reaches the systemic
circulation is determined by the slowest of the various steps involved in the sequence.
Such step is called as the rate determining or rate-limiting step(RDS).
The rate and extent of drug absorption from its dosage form can be influenced by a
number of factors in all these steps. The various factors that influence drug
absorption called as biopharmaceutic factors in dosage for design.

20. Biopharmaceutic factors of dosage form
design
PHARMACEUTICAL FACTORS: include factors relating to the physiochemical
properties of the drug and dosage form characteristics and pharmaceutical ingredients.
Physicochemical properties of drug substances
1. Drug solubility and dissolution rate
2. Particle size and effective surface area
3. Polymorphism and amorphism
4. Pseudo polymorphism (hydrates/solvates)
5. Salt form of the drug
6. Lipophilicity of the drug
7. pKa of the drug and gastrointestinal pH
8. Drug stability
9. stereochemical nature of the drug

21. Dosage form characteristics and a Pharmaceutical Ingredients (Pharmaco-technical
factors):
1. Disintegration time(tablets/capsules)
2. Dissolution time
3. Manufacturing variables
4. Pharmaceutical Ingredients (excipients/ adjuvants)
5. Nature and type of dosage form
6. Product age and storage conditions

22. PATIENT-RELATED FACTORS: include factors relating to the anatomical,
physiological and pathological characteristics of the patient.
1. Age
2. Gastric emptying time
3. Intestinal transit time
4. Gastrointestinal pH
5. Disease state
6. Blood flow through the GIT
7. Gastrointestinal contents
a) Other drugs
b) Food
c) Fluids
d) Other normal GI contents

23. 8. Contact time with gastrointestinal mucosa
9. Presystemic metabolism by
1.Luminal enzymes
2.Gut wall enzymes
3.Bacterial enzymes
4.Hepatic enzymes

25. Reference
https://healthengine.com.au/info/gastrointestinal-
system
Biopharmaceutics and pharmacokinetics –A treatise
D M Brahmankar, Sunil B. Jaiswal
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