This document is a presentation on determining the dissociation constant (pKa) of pharmaceutical compounds. It begins with introducing pKa as the negative logarithm of the acid dissociation constant (Ka) and how the Henderson-Hasselbalch equation relates pKa to the ionized and un-ionized forms of an acid or base. It then describes four common methods to determine pKa: conductivity, solubility, potentiometric, and spectrophotometric titration. As an example, it outlines using UV-visible spectroscopy to determine the pKa of paracetamol by measuring its absorbance in solutions with varying pH. In closing, it notes some applications of pKa values in predicting drug absorption and calculating solution

1. Presented by,
R.Venkatesan.
M.Pharm 1st 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
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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
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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+
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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.
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6. • Depends on PH
• Compound should be unionized before crossing the biological
barrier because as ionized molecule can’t completely cross the
barrier.
1. Ionized - Hydrophilic it decreases absorption
2. 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
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7. DETERMINATION
OF PKa
1.Conductivity method
2.Solubility method
3.Potentiometric method
4.Spectrophotometric method
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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
𝑘𝑎 =
𝑐α2
1 − α
C = the molar concentration,
α = degree of dissociation
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9. 2. Solubility method
• A derivation of the Henderson hasselbalch equation
allows us to determine the pka from solubility data.
log S = (log SO – pKa) + pH
• Plot the graph pH vs log S
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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 + log10 [A
-
]/[H]
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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.
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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
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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
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14. THANK
YOU