PowerPoint Presentation: DRUG ABSORPTION MECHANISMS PRESENTED BY : Sharanya.S 09DG1R0043. T.K.R.C.O.P Introduction of Absorption: Introduction of Absorption Definition : “ The process of movement of unchanged drug from the site of administration to systemic circulation .” There always present a correlation between 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. 2. .: . . PowerPoint Presentation: Mechanism of drug absorption 1.Passive diffusion 2. Carrier- mediated transport: a) .Active diffusion b). Facilitated diffusion 3. Pore Transport 4. Ionic or Electrochemical diffusion 5. Ion-pair transport 6. Endocytosis 4 PowerPoint Presentation: Passive Diffusion The driving force for this process is the electro chemical gradient or concentration. Concentration gradient is defined as the difference in the drug concentration on either side of the membrane. It is also known as non-ionic diffusion. 5 PowerPoint Presentation: High conc Low conc PowerPoint Presentation: Passive Diffusion Characters common. Occurs along concentration gradient. Not saturable Requires no energy No carrier is needed Depends on lipid solubility. Depends on pka of drug - pH of medium . 7 .: . Expressed by Fick’s 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 = D A K o/w (C git – C plm 8 dt h PowerPoint Presentation: Active Absorption Relatively unusual. Occurs against concentration gradient. Requires carrier and energy. Specific Saturable. Iron absorption. Uptake of levodopa by brain. 9 PowerPoint Presentation: Active transport Passive transport Against concentration gradient (From low to high) Along concentration gradient (From high to low) Needs carriers No carriers Selective, saturable Not selective Not saturable Energy is required No energy PowerPoint Presentation: Facilitated Diffusion Occurs along concentration gradient. Requires carriers Selective. Saturable. No energy is required . 12 PowerPoint Presentation: Carrier-mediated facilitated diffusion Active transport Along concentration gradient (From high to low) Against concentration gradient (From low to high) Needs carriers Needs carriers Selective, saturable Selective, saturable No energy is required Energy is required Pore Transport : Pore Transport 1. Also known as convective transport, bulk flow or filtration. 2. 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. 3. The driving force for the passage of the drugs is the hydrostatic or the osmotic pressure difference across the membrane. .: . 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 ) 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 16 Ionic or Electrochemical diffusion: Ionic or Electrochemical diffusion 1.This charge influences the permeation of drugs. 2. Molecular forms of solutes are unaffected by the membrane charge & permeate faster than ionic forms. 3. The permeation of anions & cations is also influenced by pH. 4. Thus , at a given pH, the rate of permeation may be as follows: Unionized molecule > anions > cations .: . 5. The permeation of ionized drugs, particularly the cationic drugs, depend on the potential difference or electrical gradient as the driving force across the membrane. 6. Once inside the membrane, the cations are attached to negatively charged intracellular membrane, thus giving rise to an electrical gradient . 7. 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: I on pair transport 1. It is another mechanism to explain the absorption of such drugs which ionize at all pH condition 2. Transport of charged molecules due to the formation of a neutral complex with another charged molecule carrying an opposite charge. 3. 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. Endocytosis: E ndocytosis 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. 20 .: . In endocytosis, there are two process A) Phagocytosis (cell eating) B) Pinocytosis (cell drinking) Phagocytosis :- uptake of solid particles 21 Pinocytosis: Pinocytosis This process is important in the absorption of oil soluble vitamins & in the uptake of nutrients. PowerPoint Presentation: 1. DM.Brahmankar, Biopharmaceutics and Pharmacokinetics . page.no-10-29. 2. V.Venkateshwarlu, Biopharmaceutics and Pharmacokinetics. page .no-19-26. Kulakarni, Biopharmaceutics and pharmacokinetics . Page no-4-13. Dr.Javedali, AText Book Of Biopharmaceutics & Pharmacokinetics. page no-8-15. www.wikipedia.com . www.authorstream.com. .: .