VARIOUS MECHANISM OF ABSORPTION OF DRUG Department of Pharmaceutics R. C. Patel Institute of Pharmaceutical Education & Research, Shirpur .
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VARIOUS MECHANISM OF ABSORPTION OF DRUG
Department of PharmaceuticsR. C. Patel Institute of Pharmaceutical Education & Research, Shirpur .
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CONTENTSIntroduction of absorption.Structure of the Cell Membrane.Mechanism of Drug absorption.ConclusionReferences
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Introduction of Absorption1,3,4,5Definition :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.3
Minimum effective conc.Therapeutic success of a rapidly & completely absorbed drug.
Therapeutic failure of a slowly absorbed drug.
Subtherapeutic levelTimePlasmaDrug Conc.Not only the magnitude of drug that comes into the systemic circulation but also the rate at which it is absorbed is important this is clear from the figure. 4
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Cell membrane structure2,6
MECHANISM OF DRUG ABSORPTION1,2,3,4,5Passive diffusionPore transportCarrier- mediated transport a) Facilitated diffusion b) Active transportIonic or Electrochemical diffusionIon-pair transportEndocytosis
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7Passive Diffusion1,2,3,4,5,6Also 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.
8Passive diffusion is best expressed by Ficks 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
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11Downhill transport.Greater the surface area & lesser the thickness of the membrane, faster the diffusion.Equilibrium is attained when the concentration on either side of the membrane become equal.Greater the membrane/ water partition coefficient of drug, faster the absorption.The unionized species are 3-4 times more faster transported It is energy dependent and nonsaturable
Certain characteristic of passive diffusion can be generalized.
Pore transport1,2,5It is convective transport, bulk flow or filtration.Important in the absorption of low mol. wt., low mol. size & generally water-soluble drugs e.g. urea, water & sugars.The driving force for the passage of the drugs is the hydrostatic or the osmotic pressure 12
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Carrier Mediated System1,2,3,4,5Involves a carrier 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 moleculeThe 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 transport14
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18 a) Facilitated Diffusion1,2,3,4,6This 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.
19Limited 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.
20b) Active transport1,2,3,4,5,6More 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.
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24The 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.
Ionic or electrochemical diffusion1,4The charge on membrane influences the permeation of drugs.25
Gastrointestinal lumen
Unionized formMembraneRapid absorbedBloodModerate absorbed-Anion +Cation with high K.E
-+Slowly absorbed
26Once 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. Molecular forms of solutes are unaffected by the membrane charge & permeate faster than cationic forms. Thus, at a given pH, the rate of permeation may be as follows: Unionized molecule > anions > cations
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28Ion pair transport1,4,5It is another mechanism is able to explain the absorption of such drugs which ionize at all pH condition.
Gastrointestinal lumenCationic drugEndogenus anionNeutral ion pair complex Membrane BloodFree drugDissociation of complexPassive Diffusion
29Transport 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.E.g. propranol
Endocytosis1,2,4,5It 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 intracellular.Sometimes ,an endocytotic vesicle is transferred from one compartment to another. Such phenomenon is called transcytosis.Endocytosis includes two types of processes
30Phagocytosispinocytosis
31 A) Phagocytosis1,2,4,7
This process involves the absorptive uptake of solid particulates, macromolecules.It is also called as cell eating.
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34B) Pinocytosis1,2,4This process is important in the absorption of oil soluble vitamins & in the uptake of nutrients.
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Conclusion36 Drugs which are hydrophobic, MW in range 100-400 absorbed passively. Hydrophilic & MW less than 100 absorbed by pore transport. Drugs ionizes at all pH conditions absorbed after complexing with oppositely charged ions through ion pair transport. Structure specific drugs with affinity for carriers transported from specific sites most absorbed by carrier mediated transport Macromolecular nutrients & drugs as solid particles or oily droplets absorbed by Endocytosis.
REFERENCESD.M.Brahmankar & Sunil B. Jaiswal, Biopharmaceutics & pharmacokinetics 2nd ed., vallabh prakashan pg no.5-23Gerard J. Tortora Bryan H. Derrickson, Principles of Anatomy & Physiology, 12th edition, vol.1st John Wiley & Sons,Inc. ,pg no.63, 77Milo Gibaldi ,Biopharmaceutics & clinical pharmacokinetics 4th edition, pg no.24-27 J.S. Kulkarni, A.P Pawar, V.P. Shedbalkar Biopharmaceutics & pharmacokinetics, 1st ed., CBS publishers pg no.1-12H. P. Tipnis & Amrita Bajaj, Principles & Applications of Biopharmaceutics & Pharmacokinetics 1st ed., Career publication pg no.19-23http://www.pharmacology2000.comhttp://www.inpharm.com
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38Thank you
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