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PHARMACEUTICS AND DRUG DELIVERY SYSTEMS The pH Partition Theory and Dissociation Constant pKa: - Drugs are absorbed from the biological membranes by passive diffusion depending on the fraction of the un-ienized form of the drug at the pH of the fluids close to that of the biological membrane, ~ The degree of ionization of the drug depends on both the pKa and the pH of the drug solution. - The GIT acts as a lipophilic barrier, and thus ionized drugs are mere hydrophilic than un-ienized ones and have minimal membrane transport. ~ The solution pH affects the overall partition coefficient of an ionizable substance. ~ The pka of a molecule is the pH at which a S0:S0 mixture of acid and conjugated base coexists in equilibrium. - For an acidic drug the acid form predominates at a pH lower than the pKa, and the conjugated base form dominates at a pH higher than the pka ~ Fer a basic drug, the base form (un-ienized) dominates at pH values higher than the pKa, and the conjugated acidic form (ionized) dominates at pH values below the pKa. ~ The extent of ionization of a drug molecule is given by the following Henderson-Hasselbalch equations, which describe a relationship between ionized and un-ionized species of a weak acid or base: Weakly acidic drugs: pH = pk. + leg([A-/IHA)) Weakly basic drug: pH = pKa + leg([B]J/[BH*+]) [HA] - conc of un-icnized acid [A-] - conc of ionized base [B] - conc of un-ienized base [BH+] - conc of ienized base Although pH partition theery is useful, it often does net held true. Fer example, most weak acids are well absorbed from the small intestine, which is contrary to the prediction of the pH partition hypothesis. Similarly, NH4+ compounds are ionized at all pH levels but are readily absorbed from the alt. Charged drugs, such as NH4+ compounds and tetracyclines, may interact with opposite-charged organic ions, resulting in a neutral species that is absorbable. Some drugs are absorbed by means of active transport.