Seminar on

GASTROINTESTINAL ABSORPTION OF DRUGS

Submitted to: Mrs. Sujata (Asst. Professor) Department of Pharmaceutics

By :

Shrikant Sharma
1st year, M. Pharm.

P. K. M. Educational Trusts

R. R. College of Pharmacy
Chikkabanavara, Banglore : 560 090

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

STOMACH Relatively small surface area due to the absence of macrovilli & microvilli. Extent of drug absorption is affected by variation in gastric emptying time. Drugs which are acid sensitive must not be in contact with the acidic environment of the stomach.

Stomach emptying applies more to the solid dosage forms.

pH of stomach: fast 2 to 6 & non fast 1.5 to 2

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. The average normal transit time through the small intestine is about 7 hours. Newer studies suggest the transit time to be about 3 to 4 hours. Fasting transit time in adult : 4-8 hrs form stomach & small intestine. During the fed state, the small intestine transit time may take about 8 to 12 hours. Surface area : 10 14 ft2 pH : 6 - 7

LARGE INTESTINE 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. Transit time : up to 24 hrs. Surface area: 4-5 ft

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

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

Expressed by Ficks first law of diffusion 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 dt
=

D A Ko/w (Cgit Cplm) Vh

PORE TRANSPORT
It is also called as Convective transport, Bulk flow or filtration. The driving force for this process is the hydrostatic pressure or the osmotic differences across the

membrane.
The process is important in the absorption of low

molecular weight, low molecular size drugs.

Example: Urea, Water, Sugar

 The rate of absorption via pore transport depends on the number & size of the pores, & given as follows: N. R2. A . C

dc

dt
where, dc dt N R

() (h)

= rate of the absorption. = number of pores = radius of pores

= concentration gradient
= viscosity of fluid in the pores

CARRIER-MEDIATED TRANSPORT
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.

The carrier may be an enzyme or some other

component of the membrane.

Two types
Facilitated diffusion Active transport

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.

Passive diffusion

Carrier-mediated transport

Rate of drug absorption

Conc. Of drug at absorption site

Comparison of rate of absorption versus drug concentration plots for Passive and Carriermediated transport process

ACTIVE TRANSPORT
It is process where the materials are transported across membranes against a concentration gradient. The drug is transported from a region of lower to one of higher concentration i.e.. against the concentration gradient or uphill transport. Examples : Sodium, potassium, iron, glucose and vitamins like niacin, pyridoxine and ascorbic acid.

IONIC OR ELECTROCHEMICAL DIFFUSION

The charge on the membrane influences the permeation of drugs. Molecular forms of solutes are unaffected by the membrane charge and permeate faster than ionic form.

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.

 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.

ION-PAIR TRANSPORT
Some agents penetrate the membrane by forming reversible neutral complexes with endogenous ions of the GIT like mucin. Such neutral complexes have both the required

lipophilicity as well as aqueous solubility for

passive diffusion. Such phenomena is called ion-

pair transport.
Quaternary ammonium compounds and sulfonic acid which ionized under all pH conditions.

ION-PAIR TRANSPORT OF A CATIONIC DRUG

ENDOCYTOSIS
Also called Corpuscular or Vesicular transport It involves engulfing extracellular materials within a segment of the cell membrane to form a saccule or a vesicle which is then pinched-off

intracellularly.
Includes two type of process:

Phagocytosis and Pinocytosis

Fats, starch, vitamins like A, D, E, K

PHAGOCYTIC UPTAKE OF MACROMOLECULES

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

References
D.M. Brahmankar, S.B. Jaiswal; Biopharmaceutics & Pharmacokinetics; first edition, 12th reprint; Vallabh Prakashan; 18 39. L. Shargel; Applied Biopharmaceutics & Pharmacokinetics; fifth edition; Mc Graw Hill; 415-7. Dr. L. Prabakaran, Mr. Purushothaman; Textbook of Modern Pharmacokinetics and Biopharmaceutics; Asian Printers; First Edition 2009; Page no. 85-87. www.wikipedia.com

 Thank you