PHARMACOLOGY

Factors affecting the absorption of drugs ::

1.particle size ::

Smaller the particle size greater is the absorption A tablet containing larger aggregates cannot be disintegrated easily and therefore their absorption is slow 

        Smaller particle size is necessary for drugs like aspirin corticosteroids chloramphenicol griseofulvin tolbutamide spironolactone etc so that dosage can be reduced without loosing efficacy Sometimes larger size is required as in case of bephenium hydroxynaphthoate (anthelmintic) to reduce its absorption and thus making the treatment more effective and less toxic 

Most drugs are weak acids or bases present in solution as both non-ionized and ionized forms 

2.Solubility and ionisation ::

Non ionized drugs are more lipid soluble and therefore absorbed more readily than the ionized drugs which are less lipid soluble 

            Weak acids are ionized to a lesser extent at acidic pH The pH of stomach is acidic and so acidic drugs are usually absorbed from the stomach e.g. salicylates 

Weak bases are ionized to a lesser extent at alkaline pH The pH of the intestine is alkaline therefore basic drugs like pethidine ephedrine etc are usually absorbed from the intestine 

    Ionization also depends on isonisation constants (pKa and pKb) of the drug as given by Hendersen Hasselbach equation ::

pKa - pH = log _[Non-ionized____________(for acidic drugs) 

                            [Ionized]

pH - pKb=log  -[Non-ionized]

                           ---------------------(for basic drugs)

                                [Ionized]

pH partition ::

As mentioned above ionization affects absorption and distribution of drugs pH partition means a phenomenon wherein the weak acids tend to accumulate in compartments of relatively high pH whereas weak bases accumulate in compartments of relatively low pH In fact pH partition theory states that the absorption of a weak electrolyte is a function of the extent to which drug exists in its unionized state in the aqueous solution at the site of absorption The passive diffusion of unionized drug takes place untill equilibrium is reached 

Ion trapping ::

After partitioning of unionized form (from stomach/intestine to blood ) drug reaches blood circulation which has alkaline pH (7.4) and hence the drug will exist in the ionized form because of this effect (conversion of unionized form to ionized form of a drug ) once the drug is absorbed into blood circulation it cannot pass back into the stomach/intestine This effect is referred as ion trapping