Introduction to various mechanisms of absorption of drugs

1. Department of Pharmaceutics
R. C. Patel Institute of Pharmaceutical
Education & Research, Shirpur .

2. CONTENTS
 Introduction of absorption.
 Structure of the Cell Membrane.
 Mechanism of Drug absorption.
 Conclusion
 References
2

3. Introduction of Absorption1,3,4,5
 Definition :
The process of movement of unchanged
drug from the site of administration to systemic
circulation.
There always exist a correlation between the plasma
concentration of a drug & the therapeutic response &
thus, absorption can also be defined as the process of
movement of unchanged drug from the site of
administration to the site of measurement.
i.e., plasma.
3

4. Minimum effective conc.
Therapeutic success of a
rapidly & completely
absorbed drug.
Therapeutic failure of a
slowly absorbed drug.
Subtherapeutic level
Time
Plasma
Drug
Conc.
Not only the
magnitude of drug
that comes into the
systemic circulation
but also the rate at
which it is absorbed
is important this is
clear from the figure.
4

5. 5
Cell membrane structure2,6

6. MECHANISM OF DRUG
ABSORPTION1,2,3,4,5
1) Passive diffusion
2) Pore transport
3) Carrier- mediated transport
a) Facilitated diffusion
b) Active transport
4) Ionic or Electrochemical diffusion
5) Ion-pair transport
6) Endocytosis
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7. 7
1) Passive Diffusion1,2,3,4,5,6
 Also known as non-ionic
diffusion.
 It is defined as the
difference in the drug
concentration on either
side of the membrane.
 Absorption of 90% of
drugs.
 The driving force for this
process is the
concentration or
electrochemical gradient.

8. 8
 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 & the rate of diffusion is directly
proportional to the concentration
gradient across the membrane.
dQ = D A Km/w (CGIT – C)
dt h

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10. 10

11. 11
1. Downhill transport.
2. Greater the surface area & lesser the thickness of the
membrane, faster the diffusion.
3. Equilibrium is attained when the concentration on either side
of the membrane become equal.
4. Greater the membrane/ water partition coefficient of drug,
faster the absorption.
5. The unionized species are 3-4 times more faster transported
6. It is energy dependent and nonsaturable
 Certain characteristic of passive diffusion can
be generalized.

12. 2) Pore transport1,2,5
 It is convective transport, bulk
flow or filtration.
 Important in the absorption of
low mol. wt., low mol. size &
generally water-soluble drugs
e.g. urea, water & sugars.
 The driving force for the passage
of the drugs is the hydrostatic or
the osmotic pressure
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13. 13

14. 3) Carrier Mediated System1,2,3,4,5
 Involves a carrier which binds reversibly with the
solute molecules to be transported to yield the
carrier solute complex which transverses across the
membrane to the other side where it dissociates to
yield the solute molecule
 The carrier then returns to its original site to accept
a fresh molecule of solute.
 There are two types of carrier mediated transport
system:
a) facilitated diffusion
b) active transport
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15. 15

16. 16

17. 17

18. 18
a) Facilitated Diffusion1,2,3,4,6
 This mechanism involves
the driving force is
concentration gradient.
 In this system, no
expenditure of energy is
involved (down-hill
transport), therefore the
process is not inhibited
by metabolic poisons
that interfere with energy
production.

19. 19
 Limited importance in the absorption of drugs.
e.g. Such a transport system include entry of
glucose into RBCs & intestinal absorption of
vitamins B1 & B2.
 A classical example of passive facilitated diffusion
is the gastro-intestinal absorption of vitamin B12.
 An intrinsic factor (IF), a glycoprotein produced by
the gastric parietal cells, forms a complex with
vitamin B12 which is then transported across the
intestinal membrane by a carrier system.

20. 20
b) Active transport1,2,3,4,5,6
 More important process
than facilitated diffusion.
 The driving force is against
the concentration gradient
or uphill transport.
 Since the process is uphill,
energy is required in the
work done by the barrier.
 As the process requires
expenditure of energy, it can
be inhibited by metabolic
poisons that interfere with
energy production.

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 The rate of absorption by active transport can be
determined by applying the equation used for
Michalies-menten kinetics:
dc = [C].(dc/dt)max
dt Km + [C]
Where,
(dc/dt)max = maximal rate of drug
absorption at high drug concentration.
[C] = concentration of drug available
for absorption
Km = affinity constant of drug for the
barrier.

25. 4) Ionic or electrochemical diffusion1,4
 The charge on
membrane
influences the
permeation of
drugs.
25
Gastrointestinal
lumen
Unionized form
Membrane
Rapid absorbed
Blood
Moderate absorbed-
Anion
+
Cation with high K.E
-
+Slowly absorbed

26. 26
 Once inside the membrane, the cations are
attached to negatively charged intracellular
membrane, thus giving rise to an electrical
gradient.
 If the same drug is moving from a higher to lower
concentration, i.e., moving down the electrical
gradient , the phenomenon is known as
electrochemical diffusion.
 Molecular forms of solutes are unaffected by the
membrane charge & permeate faster than cationic forms.
 Thus, at a given pH, the rate of permeation may be as
follows:
 Unionized molecule > anions > cations

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28. 28
5) Ion pair transport1,4,5
 It is another
mechanism is
able to explain
the absorption
of such drugs
which ionize at
all pH
condition.
Gastrointestinal
lumen
Cationic
drug
Endogenus
anion
Neutral ion pair
complex
Membrane Blood
Free
drug
Dissociation
of complex
Passive
Diffusion

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 Transport of charged molecules due to the
formation of a neutral complex with another
charged molecule carrying an opposite charge.
 Drugs have low o/w partition coefficient values, yet
these penetrate the membrane by forming
reversible neutral complexes with endogenous
ions.
e.g. mucin of GIT.
 Such neutral complexes have both the required
lipophilicity as well as aqueous solubility for
passive diffusion.
 E.g. propranol

30. 6) Endocytosis1,2,4,5
 It involves engulfing extracellular materials within a segment of the cell
membrane to form a saccule or a vesicle (hence also called as
corpuscular or vesicular transport) which is then pinched off
intracellular.
 Sometimes ,an endocytotic vesicle is transferred from one compartment
to another. Such phenomenon is called transcytosis.
 Endocytosis includes two types of processes
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1. Phagocytosis
2. pinocytosis

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A) Phagocytosis1,2,4,7
 This process involves
the absorptive uptake of
solid particulates,
macromolecules.
It is also called as cell
eating.

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34. 34
B) Pinocytosis1,2,4
 This process is
important in the
absorption of oil
soluble vitamins &
in the uptake of
nutrients.

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36. Conclusion
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 Drugs which are hydrophobic, MW in range 100-
400 absorbed passively.
 Hydrophilic & MW less than 100 absorbed by
pore transport.
 Drugs ionizes at all pH conditions absorbed after
complexing with oppositely charged ions through ion
pair transport.
 Structure specific drugs with affinity for carriers
transported from specific sites most absorbed by
carrier mediated transport
 Macromolecular nutrients & drugs as solid
particles or oily droplets absorbed by Endocytosis.

37. REFERENCES
1. D.M.Brahmankar & Sunil B. Jaiswal, Biopharmaceutics &
pharmacokinetics 2nd ed., vallabh prakashan pg no.5-23
2. Gerard J. Tortora Bryan H. Derrickson, Principles of Anatomy &
Physiology, 12th edition, vol.1st John Wiley & Sons,Inc. ,pg no.63, 77
3. Milo Gibaldi ,Biopharmaceutics & clinical pharmacokinetics 4th
edition, pg no.24-27
4. J.S. Kulkarni, A.P Pawar, V.P. Shedbalkar Biopharmaceutics &
pharmacokinetics, 1st ed., CBS publishers pg no.1-12
5. H. P. Tipnis & Amrita Bajaj, Principles & Applications of
Biopharmaceutics & Pharmacokinetics 1st ed., Career publication pg
no.19-23
6. http://www.pharmacology2000.com
7. http://www.inpharm.com
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Thank you