Drug Absorption

1. Submitted By : Submitted To :
Sadeq Ameen Mrs.C.RubinaReichal

2. Contents :
a) Definition
b) Structure of Cell membrane
c) Mechanism of Drug Absorption
d) Phases of Drug transfer from GI absorption
site into SC
e) Route of Drug transfer from Absorption site
into Systemic Circulation
f) Factors affecting Absorption

3. Definition :
Drug absorption is defined as the process of
movement of unchanged drug from the site of
administration to systemic circulation

4. Structure of Cell Membrane
:

5. Mechansim of Drug Absorption
 Transcellular/intracellular transport
 Paracellular/intercellular transport
 Vesicular transport

6. Transcellular/intercellular
transport
it is defined as the passage of drugs across the GI
epithelium . It is the most common pathway for drug
transport ,
Steps of transport of drugs
1. Permeation of GI epithelial cell membrane
2. Movement across the intracellular space (cytosol)
3. Permeation of the lateral or basolateral membrane
Process of Transcellular transport
A) Passive Transport Process
B) Active Transport Process

7. Cont….
A) Passive Transport Processes:
This process does not require energy other than that of molecular
motion to pass through the lipid bilayer
PTP can be further classified into following types:
a) Passive Diffusion b) Pore Transport
c) Ion-pair transport d) Facilitated diffusion
B) Active Transport Processes :
These process require energy from ATP to move drug molecules from
extracellular to intracellular milieu , They are of two types
1) Primary active
2) Secondary active transport ( subdivided into
i)Symport (co-transport)
ii) Antiport(counter-transport)

8. Paracellular/Intercellular
Transport
It is defined as the transport of drugs through the junctions between the
GI epithelial cells , this pathway is of minor importance in drug
absorption
It is involved in :
1. Permeation through tight junctions of epithelial cells
2. Persorption
PT differs from Pore transport in that the former involves transfer of
drug across epithelium and through the cellular junctions whereas
in the case of latter , the molecules are transferred from outside of
the epithelial cell into the cell through pores present in the cell
membrane

9. Vesicular or Corpuscular
Transport (Endocytosis)
Like active transport , these are also energy dependent processes but
involve transport of substance within vesicles into a cell .
Vesicular transport of drugs can be classed into two categories-
1.Pinocytosis
2.Phagocytosis

10. Passive Diffusion :
Also called non-ionic diffusion , it is the major process for absorption
of more than 90% of the drugs .
The driving force for this process is the concentration or
electrochemical gradient
It is defined as the difference in the drug concentration on either side
of the membrane
Passive diffusion is best expressed by Fick’s first law of diffusion
which states that the drug molecules diffuse from a region of
higher concentration to one of lower concentration until
equilibrium is attained and that the rate of diffusion is directly
proportional to the concentration gradient across the membrane
It can be mathematically expressed by the following equation :

11. Pore transport:
It is also called as convective transport, bulk flow or
filtration .
This mechanism is responsible for transport of molecules
into the cell through the protein channels present
channels present in the cell membrane .

12. Ion-Pair Transport :
Yet another mechanism that explains the absorption of
drugs like quaternary ammonium compounds and
sulphonic acids , which ionise under all pH condition, is
ion-pair transport .
Despite their low o/w partition coefficient values, such
agents penetrate the membrane by forming reversible
neutral complexes with endogenous ions of the GIT like
Mucin .

13. Facilitated Diffusion :
It is a carrier-mediated transport system that operates down
the concentration gradient (downhill transport) but at
much faster rate than can be accounted by simple
passive diffusion .
The driving force is concentration gradient since no energy
expenditure involved

14. Phases of drug transfer from GI
Absorption site into Systemic circulation :
Absorption of drugs through the GI epithelium can be
divided into three phases :
1. Pre-uptake phase : the two important pre-uptake
processes are :
a) Dissolution of drug in the GI and/or
b) Metabolism of drug in the GI lumen
2. Uptake phase : which includes
a) Delivery of the drug to the absorption site in the GIT
b) Metabolism of drug by enzyme in the GI epithelium
c) Passage of drug through the GI epithelium

15. Cont…,
3) Post-uptake phase :
Three important post uptake processes are :
a) Metabolism of the drug by the liver (first-pass hepatic
metabolism)
b) Enterohepatic circulation of drug – during the first pass
through the liver
c) Transfer of drug into the systemic circulation

16. Route of Drug transfer from Absorption
site into Systemic Circulation
A drug is transferred from the absorption site into systemic
circulation by one of the two routes :
1. Splanchnic circulation : it is the network of blood
vessels that supply the GIT. It is the major route for
absorption of drug into the systemic circulation
2. Lymphatic circulation : it is the path of minor
importance in drug absorption into systemic circulation
for two reasons---
i) The lymph vessels are less accessible than the
capillaries .
ii) The lymph slow is exceptionally slow .

17. Factors affecting Drug Absorption
(A) Pharmaceutical Factors : Include factors relating to
the physiochemical properties of the drug, and dosage
form characteristics and pharmaceutical ingredients
I. Physiochemical properties of drug substance
II. Dosage form characteristics and pharmaceutical
ingredients
(B) Patient-Related Factors

18. Physiochemical properties of Drug
Substance
 Drug solubility and dissolution rate
 Particle size and effective surface area
 Polymorphism and amorphism
 Pseudopolymorphism (hydrates/solvates)
 Salt form of the drug
 Lipophilicity of the drug
 pKa of the drug and gastrointestinal pH
 Drug stability
 Stereochemical nature of the Drug

19. Dosage form characteristics and
Pharmaceutical Ingredients
i) Disintegration time
ii) Dissolution time
iii) Manufacturing variables
iv) Pharmaceutical ingredients
v) Nature and type of dosage form
vi) Product age and storage conditions

20. Patient Related Factors :
 Age
 Gastric emptying time
 Intestinal transit time
 Gastrointestinal pH
 Disease states
 Blood flow through the GIT
 Gastrointestinal contents (other drugs ,Food , Fluids)
 Content time with Gastrointestinal mucosa
 Presystemic Metabolism

21. Reference :
 Biopharmaceutical and Pharmacokinetics –
A Treatise
D.M. BRAHMANKAR
SUNIL B. JAISWAL
o Network