about mechanism of drug absorption, biopharmaceutics, M pharm 2nd sem

1. MECHANISM OF DRUG ABSORPTION
Presenting to,
Dr. YOGANANDA R
Professor and HOD
Department of Pharmaceutics
SJMCP, Chitradurga
Presenting by ,
ANUKUMAR E
2nd Sem, M Pharm
Department of Pharmaceutics
SJMCP, Chitradurga

2. MECHANISM OF DRUG ABSORPTION
Contents
• Introduction of drug absorption.
• Mechanism of Drug absorption
a) Transcellular
1. Passive transport process
a) Passive diffusion
b) Pore transport
c) Ion-pair transport
d) Facilitated diffusions
2. Active transport process
a) Primary active transport.
b) Secondary active transport.
b) Paracellular
c) Vesicular
1. Pinocytosis
2. Phagocytosis
• Reference

3. Introduction of drug absorption.
• 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.

4. Mechanism Of Drug Absorption
The three broad categories of drug transport mechanisms
involved in the absorption are:
1. Transcellular / intracellular transport
2. Paracellular/ intercellular transport
3. Vesicular transport

5. Transcellular / intracellular transport
• It is defined as the passage of drugs across the GI
epithelium.
• The three steps involved in transcellular transport of
drug are:
1. Permeation of GI epithelial cell membrane
2. Moment across the intracellular space (cytosol).
3. Permeation of the lateral or basolateral
membrane.

6. • The various transcellular transport processes
involved in the drug absorption are.
1. passive transport process.
2. active transport process.
1. Passive transport process:
can be further classified into following types.
a) passive diffusion
b) pore transport
c) Ion-pair transport
d) Facilitated or mediated diffusion

7. 2. Active transport process.
It is are of 2 types, as shown below
a) Primary active transport
b) Secondary active transport
– symport
– Antiport.

8. 2. Paracellular/ intercellular transport
• It is defined as the transport of drugs through the
junctions between the GI epithelial cells.
• The two paracellular transport mechanism involved in
the drug transport as shown below.
1. Permeation through tight junctions of epithelial
cells
2. Persortion

9. 3. Vesicular transport or Endocytosis.
• These are also energy dependent processes but involves
transport of substances within vesicles into a cell. Since
the mechanism involves transport across the cell
membrane, it can be classified into two categories.
a) Pinocytosis
b) Phagocytosis.

10. Compares the transcellular, paracellular and
vesicular transport mechanism

11. Passive diffusion
• Also called as non ionic diffusion,
• it is the major process for the absorption of more
than 90% of the drugs.
• It is defined as the difference in the drug
concentration on either side of the membrane.
• The driving force for this process is the
concentration or electrochemical gradient.

13. Fick’s 1st Law Of Diffusion
dQ/ dt = DAKm/w (C git-C)
h
dQ/ dt- rate of drug diffusion ( amount/ time).
D – diffusion coefficient of the drug through the
membrane.
A- surface area of the absorbing membrane for drug
diffusion.
Km/w- partition coefficient of the drug b/w the lipoidal
membrane and aqs GIT.
(C git-C)- difference in concentration of the drug in the
GI fluid and the plasma
h – thickness of the membrane

14. • Certain characteristic of passive diffusion can be
generalized.
a) Down hill transport
b) Greater the surface area & lesser the thickness of
the membrane, faster the diffusion.
c) Equilibrium is attained when the concentration on
either side of the membrane become equal.
d) Greater the membrane/ water partition coefficient of
drug, faster the absorption.
• Passive diffusion process is energy independent but
depends more or less on the square root of the
molecular size of the drugs.
• The mol. Wt. of the most drugs lie between 100 to
400 Daltons which can be effectively absorbed
passively.

15. Relative Permeability Of Different Molecules
To Lipid Bilayer.

16. 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 in the cell membrane.
• Important in the absorption of low mol. wt., low
mol. size & generally water-soluble drugs
e.g. urea, water &sugars.

17. Pore transport.
• The driving force for the passage of the drugs is
the hydrostatic or the osmoticpressure

18. Pore transport.
• The rate of absorption via pore transport depends on
the number & size of the pores, & given as follows:
dc = N. R2
. A . ∆C
dt (η) (h)
where,
dc = rate of the absorption.
dt
N = number of pores
R = radius of pores
∆C = concentration gradient
η = viscosity of fluid in the pores

19. Ion pair transport.
• It is another mechanism is able to explain the
absorption of such drugs which ionize at all pH
condition.
• 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.

20. Ion pair transport.
• Such neutral complexes have both the required
lipophilicity as well as aqueous solubility for
passive diffusion.
E.g. propranol

21. Ion pair transport.

22. Carrier- mediated transport.
• 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 solutemolecule
• The carrier then returns to its original site to
accept a fresh moleculeof solute.
• There are two types of carrier mediated transport
system:
a) facilitated diffusion
b) active transport

23. Carrier- mediated transport
• .

24. Carrier- mediated transport

25. a) Facilitated Diffusion
• 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.
• 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

26. a) Facilitated Diffusion

27. b) Active Transport
• 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.
• It is classified as primary and secondary active transport

28. Active Transport

29. • 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.

30. Comparison of active and passive transport
mechanism

31. Endocytosis.
• 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.

32. Endocytosis.
• Endocytosis includes two types of processes
1. Phagocytosis
2. Pinocytosis
Phagocytosis
• This process involves the absorptive uptake of solid
particulates, macromolecules.
• It is also called as cell eating.
Pinocytosis
• This process is important in the absorption of
oil soluble vitamins & in the uptake of nutrients.

33. Endocytosis.

34. Comparison

35. Reference
• D.M.Brahmankar & Sunil B. Jaiswal,
Biopharmaceutics & pharmacokinetics 2nd ed.,
vallabh prakashan pg no.5-23
• www.google.com

36. Thank U