Pka

Pka

1. Presented by, R.Venkatesan . M.Pharm 1 st semester Dept. pharmaceutical analysis Karnataka college of pharmacy Bangalore 25-Feb-2023 Presented to, Dr.C.Sreedhar , Professor and HOD Dept. pharmaceutical analysis Karnataka college of pharmacy Bangalore ADVANCED PHARMACEUTICAL ANALYSIS PKa

2. Introduction 01 Henderson-Hasselbalch equation 02 Determination 03 Application 04 CONTENT KARNATAKA COLLEGE OF PHARMACY 2

3. Substance dissociate into ions is known as dissociation constant (Ka). It also called acid dissociation constant, acidity constant and acid ionization constant it denoted as Ka. Ionization – atom or molecule acquires a negative or positive charge by gaining or lossing electron. Dissociation constant KARNATAKA COLLEGE OF PHARMACY 3

4. Method for detection of dissociation constant is known as ( Pka ). Pka can be defined as the negative logarithm of base 10 dissociation constant (Ka). Let consider the dissociation of compound ‘HA’ HA A - + H + KARNATAKA COLLEGE OF PHARMACY 4

5. Henderson-Hasselbalch equation When a weakly acidic or basic drug partially ionizes in GI fluid, generally the unionized molecules are absorbed quickly. Handerson hasselbach equation provides to estimate the ionized and unionized form of drug. KARNATAKA COLLEGE OF PHARMACY 5

6. Depends on PH Compound should be unionized before crossing the biological barrier because as ionized molecule can’t completely cross the barrier. Ionized - Hydrophilic it decreases absorption Unionized – Lipophilic increses absorption The rate of absorption of a drug which depends of the both ionized and unionized form. And this two form is depends on the Pka and PH. Characteristics dissociation constant KARNATAKA COLLEGE OF PHARMACY 6

7. DETERMINATION OF PKa Conductivity method Solubility method Potentiometric method Spectrophotometric method KARNATAKA COLLEGE OF PHARMACY 7

8. Conductivity (or specific conductance) of an electrolyte solution is a measure of its ability to conduct electricity. Weak electrolytes are partially dissociate in solution. Hence for such electrolytes the dissociation constant (Ka) is given by Ostwald’s dilution law as follows. 1. Conductivity method   C = the molar concentration, α = degree of dissociation KARNATAKA COLLEGE OF PHARMACY 8

9. 2. Solubility method A derivation of the Henderson hasselbalch equation allows us to determine the pka from solubility data. log S = (log S O – pKa ) + pH Plot the graph pH vs log S KARNATAKA COLLEGE OF PHARMACY 9

10. 3. Potentiometric method In potentiometric titration, a sample is titrated with acid or base using pH electrode to monitor the course of titration. The pKa value is calculated from the change in shape of the titration curve compared with that of blank titration without sample is present. Relationship between pH and pKa pH = pKa + log 10 [A - ]/[H] KARNATAKA COLLEGE OF PHARMACY 10

11. 4. Spectrophotometric method Uv visible spectroscopy is mainly used for the quantitative estimation of drug. Here, uv visible spectroscopy used for determination of pKa . Like we use acidic and basic medium as a solvent for ionization. After we measure absorbance. KARNATAKA COLLEGE OF PHARMACY 11

12. EX: pKa Determination of Paracetamol 100mg of Paracetamol dilute 100ml with distilled water(1mg/1ml) Pipette out 10 ml from above solution make upto 100ml with distilled water. Pipette out 1ml make up 10ml using NaOH Pipette out 1ml make up 10ml using Hcl Pipette out 1ml make up 10ml using Phosphate buffer Finally Check the absorbance at 237nm by using respective blank solution KARNATAKA COLLEGE OF PHARMACY 12

13. Application Dissociation constant is incorporated in Henderson hasselbalch equation to calculate the extent of ionization ( or dissociation ), i.e percent unionized and ionized form of drug. The absorption of drugs in gastrointestinal tracl can be predicted using dissociation constant of drug and pH at different sites of GIT. The concentration of solution can be calculated KARNATAKA COLLEGE OF PHARMACY 13

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