This document discusses the mechanisms of drug absorption in the gastrointestinal (GI) tract. There are three main categories of mechanisms: 1) transcellular/intracellular transport, which involves permeation across cell membranes; 2) paracellular/intercellular transport through spaces between cells; and 3) vesicular or corpuscular transport via endocytosis. Transcellular transport includes both passive processes like diffusion and active processes requiring energy. Paracellular transport occurs through tight junctions or temporary openings between cells. Vesicular transport involves engulfing materials in membrane vesicles.
Biopharmaceutics: Mechanisms of Drug AbsorptionSURYAKANTVERMA2
Biopharmaceutics is defined as the study of factors influencing the rate and amount of drug that reaches the systemic circulation and the use of this information to optimise the therapeutic efficacy of the drug products.
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Introduction
Mechanisms of protein drug binding
Kinetics of protein drug binding
Classes of protein drug binding.
1. Binding of drug to blood components.
(a) Plasma proteins
(b) Blood cells
2. Binding of drug to extravascular tissue protein
Determination of Protein-drug Binding
Factors affecting protein drug binding
Significance of protein/tissue binding of drug
The phenomenon of complex formation of drug with protein is called as Protein drug binding. The proteins are particularly responsible for such an interaction. A drug can interact with several tissue components.
Drug Absorption ,m.pharm, semester 2, 1st yearManshiRana2
Drug absorption is the process of movement of unchanged drug from the site of administration to systemic circulation.
Absorption is the process of movement of unchanged drug from the site of administration to the site of measurement i.e. Plasma.
Introduction
Mechanisms of protein drug binding
Kinetics of protein drug binding
Classes of protein drug binding.
1. Binding of drug to blood components.
(a) Plasma proteins
(b) Blood cells
2. Binding of drug to extravascular tissue protein
Determination of Protein-drug Binding
Factors affecting protein drug binding
Significance of protein/tissue binding of drug
The phenomenon of complex formation of drug with protein is called as Protein drug binding. The proteins are particularly responsible for such an interaction. A drug can interact with several tissue components.
Drug Absorption ,m.pharm, semester 2, 1st yearManshiRana2
Drug absorption is the process of movement of unchanged drug from the site of administration to systemic circulation.
Absorption is the process of movement of unchanged drug from the site of administration to the site of measurement i.e. Plasma.
Drug absorption from git , Drug absorption from git , DIGESTION AND ABSORPTION , Transcellular / intracellular , transport , .Passive Transport Processes , Passive diffusion , Pore transport , Ion- pair transport , Facilitated or mediated diffusion
, Active transport processes , Primary , Secondary , Symport (Co-transport) , Antiport (Counter transport) , Paracellular / Intercellular Transport , Permeation through tight junctions of epithelial cells , Persorption , Vesicular or Corpuscular Transport (Endocytosis) , Pinocytosis , Phagocytosis , FACTORS INFLUENCING ABSORPTION OF DRUGS , DRUG DISSOLUTION , Factors affecting dissolution rate , DISSOLUTION APPARATUS , IVIVC (In vitro- in vivo correlation) , ROLE OF DOSAGE FORM , Transport model , pH Microclimate , Intracellular pH environment , Tight junction complex
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MECHANISMS OF DRUG ABSORPTION
1. 1
MECHANISMS OF
DRUG
ABSORPTION
Dr. Shubhrajit Mantry
D.Pharm, B.Pharm, M.Pharm, Ph.D
Associate Professor
Department of Pharmaceutics
Sharadchandra Pawar College of Pharmacy,
Pune, Maharashtra, India
2. MECHANISMS OF DRUG ABSORPTION
2
The three broad categories are
1.Transcellular/intracellular transport
2.Paracellular/Intercellular Transport
3.Vesicular or Corpuscular Transport (Endocytosis)
3. 3
1. Transcellular/intracellular transport :
It is defined as the passage of drugs across the GI epithelium. 3 steps
involved
–Permeation of GI epithelial cell membrane
–Movement across the intracellular space (cytosol).
–Permeation of the lateral or basolateral membrane.
The various transcellular transport processes involved in drug absorption are –
• Primary active transport
• Secondary active
transport
(Symport & Antiport)
• Passive diffusion
• Pore Transport
• Ion-Pair Transport
• Facilitated Diffusion
B. Active Transport processA. Passive Transport Processes
4. 4
A. Passive Transport Processes – These transport processes do not
require energy other than that of molecular motion (Brownian motion)
to pass through the lipid bilayer. Passive transport processes can be
further classified into following types –
–Passive diffusion.
–Pore transport.
–Ion-pair transport.
–Facilitated- or mediated-diffusion.
5. Passive Diffusion
Also called non-ionic diffusion, it is the major process for absorption of more than
90% of the drugs. 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.
( )C-C
h
DAK
dt
dQ
GIT
m/w
=
5
Adolf Eugen Fick
7. Ion-Pair Transport
7
Absorption of drugs like quaternary ammonium compounds (+) and sulphonic acids (-),
which ionise (convert into molecules) under all pH conditions is known as ion-pair transport.
Such neutral complexes have both the required lipophilicity as well as aqueous solubility for
passive diffusion. Such a phenomenon is called as ion-pair transport.
Propranolol, a basic drug that forms an ion pair with oleic acid, is absorbed by this
mechanism.
Ion-pair transport of a cationic drug
8. Facilitated Diffusion
• It is a carrier-mediated transport system that operates down the
concentration gradient (downhill transport) but at a much a faster rate
than can be accounted by simple passive diffusion.
• The driving force is concentration gradient (hence a passive process).
Since no energy expenditure is involved, the process is not inhibited
by metabolic poisons that interfere with energy production.
Facilitated diffusion of vitamin B12
8
9. 9
Figure: Comparison of rate of absorption vs. drug concentration plots for
passive and carrier-mediated transport process.
10. 10
B. Active Transport Processes
This transport process requires energy from ATP (Adenosine
triphosphate) to move drug molecules from extracellular to
intracellular.
These are of two types –
A. Primary active transport.
B. Secondary active transport – this process is further
subdivided into two types:
I. Symport (co-transport).
II. Antiport (counter-transport).
Adenosine triphosphate (ATP) is a complex organic chemical that
provides energy to drive many processes in living cells, e.g. muscle contraction,
nerve impulse propagation, and chemical synthesis.
11. 11
Primary active transport – In this process, there is direct ATP
requirement. Moreover, the process transfers only one ion or molecule
and in only one direction, and hence called as uniporter e.g. absorption
of glucose.
12. 12
Secondary active transport – In these processes, there is no direct requirement of
ATP i.e. it takes advantage of previously existing concentration gradient. The
energy required in transporting an ion aids transport of another ion or molecule
(co-transport or coupled transport) either in the same direction or in the opposite
direction. Accordingly this process is further subdivided into:
a. symport (co-transport) – involves movement of both molecules in the
same direction e.g. Na+
-glucose symporter
b. Antiport (counter-transport) – involves movement of molecules in the
opposite direction e.g. H+
ions using the Na+
gradient in the kidneys.
15. 15
B. PARACELLULAR / INTERCELLULAR TRANSPORT
It is defined as the transport of drugs through the junctions between
the GI epithelial cells. The two paracellular transport mechanisms
involved in drug absorption are:
Permeation through tight junctions of epithelial cells
This process basically occurs through openings which are little bigger
than the aqueous pores. Compounds such as insulin and cardiac
glycosides are taken up this mechanism.
Persorption
It is permeation of drug through temporary openings formed by
shedding (entering) of two neighbouring epithelial cells into the lumen.
16. 16
C. Vesicular or Corpuscular Transport (Endocytosis)
It is a minor transport mechanism which involves engulfing extracellular
materials within a segment of the cell membrane to form a vesicle. Hence
this is also called as vesicular transport or endocytosis.
Vesicular transport of drugs can be classed into two categories :
Phagocytosis (cell eating): adsorptive uptake of solid particulates, and
Pinocytosis (cell drinking): uptake of fluid solute.