Gastrointestinal absorption of drugs

1. GASTROINTESTINAL
ABSORPTION OF DRUGS
SIDDU K M
1ST M PHARM
DEPARTMENT OF PHARMACEUTICS
AL AMEEN COLLEGE OF PHARMACY, BENGALURU

2. CONTENTS
DEFINITION
STOMACH
SMALL INTESTINE
LARGE INTESTINE
MECHANISM OF DRUG ABSORPTION
PASSIVE DIFFUSION
PORE TRANSPORT
CARRIER MEDIATED TRANSPORT
FACILITATED DIFFUSION
ACTIVE TRANSPORT
IONIC DIFFUSION
ION PAIR TTRANSPORT
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3. Definition
• Absorption is defined as the process of movement of
unchanged drug from the site of administration to the
systemic circulation.”
Major absorption sites of GIT
1. Stomach
2. Small Intestine
3. Large Intestine
4. Colon
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5. Stomach :
o Relatively small surface area due to the absence of microvilli.
o Extent of drug absorption is affected by variation in gastric emptying time.
o Drugs which are acid sensitive must not be in contact with the acidic
environment of the stomach.
o Stomach emptying applies more to the solid dosage forms.
o pH of stomach: fast – 2 to 6 & non fast – 1.5 to 2
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6. Small intestine:
o 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.
o The average normal transit time through the small intestine is about
7 hours.
o Fasting transit time in adult : 4-8 hrs from stomach & small intestine.
o During the fed state, the small intestine transit time may take about 8
to 12 hours.
o Surface area : 10 – 14 ft2 pH : 6 - 7
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7. Large intestine :
o The major function of large intestine is to absorb water from
indigestible food residues which are delivered to the large intestine in
a fluid state & eliminate them from the body as semi solid feces.
o Transit time : up to 24 hrs
o Surface area: 4-5 ft
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8. 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
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9. Passive diffusion :
o It is defined as the difference in the drug concentration on either side
of the membrane.
o Also called nonionic diffusion
o It is the major process for absorption of more than 90% of the drugs.
o The driving force for this process is the ‘concentration or
electrochemical gradient’.
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11. • Passive diffusion is expressed mathematically by Fick’s first law of
diffusion-
“The drug molecules diffuse from a region of higher concentration to a
region of lower concentration until equilibrium is attained and the rate
of diffusion is directly proportional to the concentration gradient across
the membrane”
dQ = D A Ko/w (Cgit – Cplm)
dt V h
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12. Pore transport:
oIt is also called as Convective transport, Bulk flow or filtration.
oThe driving force for this process is the ‘hydrostatic pressure or the
osmotic differences across the membrane’.
oThe process is important in the absorption of low molecular weight,
low molecular size drugs.
oExample: Urea, Water, Sugar
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13. • 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
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14. Carrier mediated transport:
o The mechanism is thought to involve a component of the membrane called as the
carrier that binds reversibly or non-covalently with the solute molecules to be
transported.
o The carrier may be an enzyme or some other component of the membrane.
o Two types
oFacilitated diffusion
oActive transport
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15. Facilitated diffusion :
oIn this mechanism driving force is concentration gradient.
oIn 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.
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17. oE.g. Such a transport system include entry of glucose into RBCs &
intestinal absorption of vitamins B1 & B2.
oA classical example of passive facilitated diffusion is the gastro-
intestinal absorption of vitamin B12.
oAn 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.
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18. Active transport:
oIt is process where the materials are transported across membranes
against a concentration gradient.
oThe drug is transported from a region of lower to one of higher
concentration i.e.. against the concentration gradient or ‘uphill
transport’.
oExamples : Sodium, potassium, iron, glucose and vitamins like niacin,
pyridoxine and ascorbic acid.
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20. Ionic / electrochemical diffusion:
oThe charge on the membrane influences the permeation of drugs.
oMolecular forms of solutes are unaffected by the membrane charge
and permeate faster than ionic form.
oUnionized molecule > Anions > Cations
oThe permeation of ionized drugs, particularly the cationic drugs,
depend on the potential difference or electrical gradient as the
driving force across the membrane.
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21. oThe permeation of ionized drugs, particularly the cationic drugs,
depend on the potential difference or electrical gradient as the
driving force across the membrane.
oOnce inside the membrane, the cations are attached to negatively
charged intracellular membrane, thus giving rise to an electrical
gradient.
oIf 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.
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22. Ion pair transport:
oSome agents penetrate the membrane by forming reversible neutral
complexes with endogenous ions of the GIT like mucin.
oSuch neutral complexes have both the required lipophilicity as well as
aqueous solubility for passive diffusion. Such phenomena is called ion-pair
transport.
oQuaternary ammonium compounds and sulfonic acid which ionized under
all pH conditions.
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24. Endocytosis :
oAlso called Corpuscular or Vesicular transport
oIt involves engulfing extracellular materials within a segment of the cell
membrane to form a saccule or a vesicle which is then pinched-off
intracellularly.
oIncludes two type of process:
Phagocytosis and Pinocytosis
oFats, starch, vitamins like A, D, E, K
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27. Thank You
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