Absorption of drugs

ABSORPTION

7/4/2012 Dept. of Pharmaceutics 1

CONTENTS
 Introduction of absorption.
 Structure of the Cell Membrane.
 Gastro intestinal absorption of drugs.
 Mechanism of Drug absorption.
 References.


Introduction of Absorption
 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.


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

Time


CELL MEMBRANE
 Also called the plasma membrane, plasmalemma or
phospholipid bilayer.
 The plasma membrane is a flexible yet sturdy barrier that
surrounds & contains the cytoplasm of a cell.

 Cell membrane mainly consists of:
1> Lipid bilayer-
-phospholipid
-Cholesterol
-Glycolipids.
2>Proitens-
-Integral membrane proteins
-Lipid anchored proteins
-Peripheral Proteins

LIPID BILAYER


LIPID BILAYER
 The basic structural framework of the plasma
membrane is the lipid bilayer.
 Consists primarily of a thin layer of amphipathic
phospholipids which spontaneously arrange so that
the hydrophobic “tail” regions are shielded from the
surrounding polar fluid, causing the more hydrophilic
“head” regions to associate with the cytosolic &
extracellular faces of the resulting bilayer.
 This forms a continuous, spherical lipid bilayer app.
7nm thick.

 It consists of two back to back layers made up of
three types: Phospholipid, Cholesterol, Glycolipids.

1) Phospholipids :
Principal type of lipid in
membrane about 75 %.
Contains polar and non polar
region.
Polar region is hydrophilic and
non polar region is hydrophobic.
Non polar head contain two fatty
acid chain.
One chain is straight fatty acid
chain.( Saturated )
Another tail have cis double bond
and have kink in tail.
( Unsaturated )

CHOLESTEROL
 Amount in membrane is 20 %.
 Insert in membrane with same orientation as
phospholipids molecules.
 Polar head of cholesterol is aligned with polar head of
phospholipids.
FUNCTION:
 Immobilize first few hydrocarbons groups

phospholipids molecules.
 Prevents crystallization of hydrocarbons &

phase shift in membrane


OH


GLYCOLIPIDS
 Another component of membrane lipids present about 5 %.

 Carbohydrate groups form polar “head”.

 Fatty acids “tails” are non polar.

 Present in membrane layer that faces the extracellular fluid.

 This is one reason due to which bilayer is asymmetric.

 FUNCTIONS:
Protective
Insulator
Site of receptor binding

COMPOSITION OF PROTEINS

PROTEINS

LIPID
INTEGRAL PERIPHERAL
ANCHORED
PROTEINS PROTEINS
PROTEINS


INTEGRAL PROTEINS

 Also known as “Transmembrane protein”.
 Have hydrophilic and hydrophobic domain.
 Hydrophobic domain anchore within the cell
membrane and hydrophilic domain interacts with
external molecules.
 Hydrophobic domain consists of one, multiple or
combination of α – helices and ß – sheets protein
mofits.
 Ex. – Ion Channels, Proton pump, GPCR


LIPID ANCHORED PROTEIN

 Covalently bound to single or multiple lipid
molecules.

 Hydrophobically inert into cell membrane & anchor
the protein.

 The protein itself is not in contact with membrane.

 Ex. – G Proteins.

PERIPHERAL PROTEINS
 Attached to integral membrane proteins OR
associated with peripheral regions of lipid bilayer.

 Have only temporary interaction with biological
membrane.

 Once reacted with molecule, dissociates to carry on
its work in cytoplasm.

 Ex. – Some Enzyme, Some Hormone

GASTRO INTESTINAL ABSORPTION
OF DRUGS


 Stomach :
 The surface area for absorption of drugs is relatively small in
the stomach due to the absence of macrovilli & microvilli.
 Extent of drug absorption is affected by variation in the time it
takes the stomach to empty, i.e., how long the dosage form is
able to reside in stomach.
 Drugs which are acid labile must not be in contact with the
acidic environment of the stomach.
 Stomach emptying applies more to the solid dosage forms
because the drug has to dissolve in the GI fluid before it is
available for absorption.
 Since solubility & dissolution rate of most drugs is a function
of pH, it follows that, a delivery system carrying a drug that is
predominantly absorbed from the stomach, must stay in the
stomach for an extended period of time in order to assure
maximum dissolution & therefore to extent of absorption.

 Small Intestine :

 The drugs which are predominantly absorbed through the small
intestine, the transit time of a dosage form is the major
determinant of extent of absorption.

 Various studies to determine transit time:

 Early studies using indirect methods placed the average normal
transit time through the small intestine at about 7 hours.
 These studies were based on the detection of hydrogen after an
oral dose of lactulose. (Fermentation of lactulose by colon
bacteria yields hydrogen in the breath).


 Newer studies suggest the transit time to be about 3 to
4 hours.
 Use gamma scintigraphy.

 Thus, if the transit time in small intestine for most
healthy adults is between 3 to 4 hours, a drug may
take about 4 to 8 hours to pass through the stomach &
small intestine during fasting state.
 During the fed state, the small intestine transit time
may take about 8 to 12 hours.


 Large intestine :

 The major function of large intestine is to absorb
water from ingestible food residues which are
delivered to the large intestine in a fluid state, &
eliminate them from the body as semi solid feces.

 Only a few drugs are absorbed in this region.


MECHANISM OF DRUG
ABSORPTION
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


1) PASSIVE DIFFUSION

 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.


 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

 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.


2) Pore transport
 Also known as convective transport, bulk flow or
filtration.
 Important in the absorption of low mol. Wt. (less than
100). Low molecular size (smaller than the diameter
of the pore) & generally water-soluble drugs through
narrow, aqueous filled channels or pores in the
membrane structure.
e.g. urea, water & sugars.
 The driving force for the passage of the drugs is the
hydrostatic or the osmotic pressure difference across
the membrane.

 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


3) CARRIER MEDIATED
TRANSPORT MECHANISM
 Involves a carrier (a component of the membrane)
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

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.

 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.


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.

 If drugs (especially used in cancer) have structural similarities to such
agents, they are absorbed actively.
 A good example of competitive inhibition of drug absorption via active
transport is the impaired absorption of levodopa when ingested with meals
rich in proteins.

 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.


4) IONIC OR ELECTROCHEMICAL
DIFFUSION
 This charge influences the permeation of drugs.
 Molecular forms of solutes are unaffected by the
membrane charge & permeate faster than ionic forms.
 The permeation of anions & cations is also influenced
by pH.
 Thus, at a given pH, the rate of permeation may be as
follows:
Unionized molecule > anions > cations


 The permeation of ionized drugs, particularly the
cationic drugs, depend on the potential difference or
electrical gradient as the driving force across the
membrane.
 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.

5) 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.
 Such neutral complexes have both the required
lipophilicity as well as aqueous solubility for passive
diffusion.
 This phenomenon is known as ion-pair transport.


6) 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 intracellularly.

 In endocytosis, there are three process:

A) Phagocytosis

B) Pinocytosis

C) Transcytosis


A) Phagocytosis


B) Pinocytosis

 This process is
important in the
absorption of oil
soluble vitamins & in
the uptake of
nutrients.


C) Transcytosis

 It is a phenomenon in which endocytic vesicle
is transferred from one extracellular
compartment to another.


REFERENCES
1. Biopharmaceutics & pharmacokinetics by
D.M.Brahmankar & Sunil B. Jaiswal.
P.L.Madan.
G.R.Chatwal.
4. Human anatomy & physiology by Tortora.
5. www.google.com.


Thank you


Absorption of drugs

More Related Content

What's hot (20)

Viewers also liked (20)

Similar to Absorption of drugs (20)

More from Danish Kurien (12)

Recently uploaded (20)

Absorption of drugs