pKa is the pH at which

(B) There is 50% ionized and 50% non-ionized fraction of the drugIONIZATIONpKa is the negative logarithm of acidic disassociation constant of the weak electrolyte, which is equivalent to the pH at which 50% drug is ionized and 50% is unionized.E.g. if a drug has pKa 3.5, it means at pH 3.5 it is 50% ionized and 50% unionized.pH=pKa+log Ionization is the process in which ions are formed from neutral compounds.pH is the measure of acidity.pKa of a drug is the measure of the acid strength (i.e., its tendency to dissociate) with reference to pH scale.Many drugs are weak acids or bases that are present in the solution as both ionized & non-ionised form.Drug ionization reduces a drug's ability to cross a lipid bilayer.The non-ionised molecules are lipid soluble and cross the membrane.The ionised molecules are water soluble and cannot cross the membrane.Amount of ionization depends on pKa (dissociation constant)For acids, the smaller the pKa, the more acidic the substance is (the more easily a proton is lost, thus the lower the pH).E.g. an acid with a pKa of 2 is 10 X as strong as an acid with pKa of 3The basic strength of drugs increases with the pKa, a basic drug of pKa of 9 is 10X as strong as base with pKa 8.The relationship between pH, pKa and the extent of ionization is given by Henderson-Hasselbalch equation.WEAK ELECTROLYTES AND THE INFLUENCE OF pHMany drugs are weak acids or bases that are present in solution as both the non-ionized & ionized species.Non-ionized molecules usually are more lipid soluble and can diffuse readily across the cell membrane.Ionized molecules usually are less able to penetrate the lipid membrane because of their low lipid solubility, & passage will depend on the leakiness of the membrane related to the membrane's electrical resistance.Transmembrane distribution of a weak electrolyte is influenced by its pKa and the pH gradient across the membrane.pKa is the pH at which half the drug (weak acid or base electrolyte) is in its ionized form.