Gastrointestinal absorption of drugs

VARIOUS DRUGS ABSORBTION MECHANISM

1. GASTROINTESTINAL ABSORPTION OF DRUGS Presented By- ROHIT R.K.S.D college of pharmacy, Kaithal ( Hry ) M.Pharma 1 st year (Pharmaceutics)

2. 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

3. 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 Stomach Small Intestine Large Intestine Colon

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5. 5 Stomach : Relatively small surface area due to the absence of 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. o pH of stomach: fast – 2 to 6 & non fast – 1.5 to 2

6. 6 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. Fasting transit time in adult : 4-8 hrs from stomach & small intestine. During the fed state, the small intestine transit time may take about 8 to 12 hours. Surface area : 10 – 14 ft 2 pH : 6 - 7

7. 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

8. 8 MECHANISM OF DRUG ABSORPTION Passive diffusion Pore transport Carrier- mediated transport Facilitated diffusion Active transport Ionic or Electrochemical diffusion Ion-pair transport Endocytosis

9. 9 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’.

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11. 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” = dt dQ D A K o/w (C git – C plm ) V h

12. 12 Pore transport: o It is also called as Convective transport, Bulk flow or filtration. o The driving force for this process is the ‘ hydrostatic pressure or the osmotic differences across the membrane’. o The process is important in the absorption of low molecular weight, low molecular size drugs. o Example: Urea, Water, Sugar

13. The rate of absorption via pore transport depends on the number & size of the pores, & given as follows: = dc N. R 2 . A . ∆C dt (η) (h) 13 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

14. 14 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

15. 15 Facilitated diffusion : o In this mechanism driving force is concentration gradient. o 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.

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17. 17 o E.g. Such a transport system include entry of glucose into RBCs & intestinal absorption of vitamins B 1 & B 2 . o A classical example of passive facilitated diffusion is the gastro- intestinal absorption of vitamin B 12 . o An intrinsic factor (IF) , a glycoprotein produced by the gastric parietal cells , forms a complex with vitamin B 12 which is then transported across the intestinal membrane by a carrier system .

18. 18 Active transport: o It is process where the materials are transported across membranes against a concentration gradient. o The drug is transported from a region of lower to one of higher concentration i.e.. against the concentration gradient or ‘uphill transport’. o Examples : Sodium, potassium, iron, glucose and vitamins like niacin, pyridoxine and ascorbic acid.

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20. 20 Ionic / electrochemical diffusion: o The charge on the membrane influences the permeation of drugs. o Molecular forms of solutes are unaffected by the membrane charge and permeate faster than ionic form. o Unionized molecule > Anions > Cations o The permeation of ionized drugs, particularly the cationic drugs, depend on the potential difference or electrical gradient as the driving force across the membrane.

21. 21 o The permeation of ionized drugs, particularly the cationic drugs, depend on the potential difference or electrical gradient as the driving force across the membrane. o Once inside the membrane, the cations are attached to negatively charged intracellular membrane, thus giving rise to an electrical gradient. o 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.

22. 22 Ion pair transport: o Some agents penetrate the membrane by forming reversible neutral complexes with endogenous ions of the GIT like mucin. o Such neutral complexes have both the required lipophilicity as well as aqueous solubility for passive diffusion. Such phenomena is called ion-pair transport. o Quaternary ammonium compounds and sulfonic acid which ionized under all pH conditions.

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24. 24 Endocytosis : o Also called Corpuscular or Vesicular transport o 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. o Includes two type of process: Phagocytosis and Pinocytosis o Fats, starch, vitamins like A, D, E, K

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27. 27 Thank You