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Gastrointestinal absorption Physicochemical Considerations

Gastrointestinal absorption Physicochemical Considerations. The absorption and hence the bioavailability of drugs is influenced by many of its physicochemical properties: pKa Lipid solubility Dissolution rate Chemical stability Complexation.

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Gastrointestinal absorption Physicochemical Considerations

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  1. Gastrointestinal absorptionPhysicochemical Considerations

  2. The absorption and hence the bioavailability of drugs is influenced by many of its physicochemical properties: pKa Lipid solubility Dissolution rate Chemical stability Complexation

  3. Absorption of drugs from solutionpH partition theory of drug absorption • Basic framework for the understanding of drug absorption • The theory is based on the assumption that: 1. GIT is a simple lipid barrier to the transport of drugs and molecules. 2. Consequently, the un-ionized form of an acidic or basic drug if sufficiently lipid soluble, is absorbed but the ionized form not.

  4. Drug pKa and gastrointestinal pH Handerson-Hasselbalch equation. • For an acid pH- pKa = log ([A-]/[HA]) • For a base pKa-pH = log ([BH+]/[B])

  5. According to the pH partition hypothesis, if the pH on the different sides of the membrane is different, then • The drug (weak acid, weak base) will ionize to different degrees on respective sides of the membrane • The total drug concentration (ionized plus unionized) on either part of the membrane will be unequal. • The compartment in which the drug is more highly ionized will contain the greater drug concentration

  6. Notes: • Equilibrium is never attained • pH range of GIT is 1-8: • very weak acids (pKa>8) acids with pKa 2.5-7.5 strong acids pKa<1 weak bases bases pKa 5-11 strong bases Lipid solubility

  7. Deviations from the pH partition hypothesis • Absorption of the ionized form of a drug • Mucosal unstirred layer • Microclimate pH • Ion pairs • Concentration in tissue by active uptake mechanisms

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