HENDERSON HASSLE BALCH

EQUATION

By Dr. Maria Khurshid

 Learning Outcomes
• In the end of this presentation, you’ll be able to
1. Define Henderson-hasselbalch equation
2. Understand components of Henderson-
hasselbalch equation
3. Explain application of this equation in drug
pharmacokinetics and understand Ion trapping
4. Answer MCQs on basis of your knowledge
 HENDERSON HASSLEBALCH
EQUATION
• DEFINITION:
The Henderson Hasselbalch
equation is an approximate equation that shows
the relationship between the pH or pOH of a
solution and the pKa or pKb  and the ratio of
concentration of the chemical species (acid or
base)
• The Henderson-Hasselbalch equation relates
the ratio of protonated to nonprotonated
weak acid or weak base to the molecule’s pKa
and the pH of the medium

Weak electrolytes whose ionization is pH

dependent
While strong eletrolytes are completely ionized
in acidic or basic pH
pKa - pH = Log protonated/nonprotonated
pH-pKa = log nonprotonated/protonated
 Components of Henderson
hasslebalch equation
pH
• is a scale used to specify the acidity or basicity of
an aqueous solution.

• Acidic solutions (solutions with higher

concentrations of H+ ions) are measured to have
lower pH values than basic or alkaline solutions
(wikipedia)
 Components Of Henderson Hasslebalch
Equation
pKa
pKa is the negative log base ten of the Ka value (acid
disassociation constant)

• Ka denotes acid disassociation constant. It measures

how completely an acid dissociates in an aqueous
solution.
• The stronger the acid, the higher is the Ka value and
the lower pKa value & vice versa.
 Protonated & deprotonated
• Protonation is the addition of a proton to a
chemical specie.
• Deprotonation is the removal of a proton from
a chemical compound.

NOTE: acids are neutral when protonated and

negatively charged (ionized) when deprotonated,
Bases are neutral when deprotonated and positively
charged (ionized) when protonated.
• “A” – weak acids
protonated AH ⇌ A- + H+
acid conjugate base
nonionized ionized
not charged charged
lipid soluble form water soluble
neutral

• protonated
“B” – weak base
+ +
BH ⇌ B + H
ionized nonionized
charged not charged
water soluble lipid soluble form
 HENDERSON HASSELBALCH
EQUATION
• Most drugs are weak electrolytes i.e their
ionization is pH dependent

• The ionization of weak acid is given by

Henderson-Hasselbalch equation
pH=pKa + log
• If the concentration of ionized drug is equal to
concentration of unionized drug [HA] , then
=1
Since log 1 is 0, under this condition
pH= pKa
Thus, pKa is numerically equal to pH at which
the drug is 50% ionized
• If pH is increased by 1 scale, then
log=1 or =10
Similarly, if pH is reduced by 1 scale, then—
=
Thus, weakly acidic drugs, which form salt with
cations,
e.g. sodium phenobarbitone, sod. Sulfadiazine, pot.
Penicillin-V, etc. ionize more at alkaline pH &
1 scale change in pH causes 10 fold change in
ionization.
 Influence of pH on two sides of biological membrane on a
steady-state distribution of a weakly acidic drug with pKa = 6
 PRACTICAL APPLICATION OF
EQUATION

• This equation applies to both acidic and basic

drugs.
• This equation can be used in
a) Ion trapping and its implication
b) Where along the GI tract, drug are best absorbed
c) Relative drug concentration in various body fluid
compartments
 Ion trapping
• When a weak electrolyte cross a membrane to
encounter a pH in which it is converted into its ionized
formed and is not able to escape easily. This
phenomena is called ion trapping.

• For example:
Aspirin (pKa 3.5 )remain unionized in acid gastric
juice (stomach) but on entering mucosal cells pH (7.1) it
ionizes and becomes indiffusible. This is ion trapping.
• Its implication:
Ion trapping alters the urine pH to inhibit
reabsorption of toxins across the renal tubules.

A. Urine alkalinization in t/m of aspirin toxicity

When NaHCO3 is given in aspirin toxicity, urine is
alkalinized and it traps the salicylate ions and increase its
excretion.

B. Urine acidification
is done in amphetamine toxicity. Ammonium
chloride is given to acidify urine. But it is not applicable
practically because it can cause mtabolic acidosis
• “A” – weak acids deprotonated
protonated AH ⇌ A- + H+
nonionized ionized
not charged charged
lipid soluble form water soluble

• “B” – weak base deprotonated

protonated ACIDIC PH
BH+ ⇌ B + H+
ionized nonionized
charged not charged
water soluble lipid soluble form
BASIC PH
 The higher the pH relative to the pKa , the greater will
be the fraction of drug in the deprotonated form.
The lower the pH relative to the pKa, the greater will
be the fraction of drug in protonated form.
 if pH & pKa value are same, 50% each of protonated
& deprotonated is present.
• The uncharged/unionized form is the more
lipid-soluble,

• More of a weak acid will be in the lipid-

soluble form at acid pH, whereas more of a
basic drug will be in the lipid-soluble form at
alkaline pH.
 MCQs
• 1. Aspirin is weak acid with pKa of 3.5. what
percentage of given dose will be in lipid
soluble at stomach pH of 2.5.
a) About 1%
b) About 10%
c) About 90%
d) About 99%
e) Cannot be determined from above data
• A drug was injected into a tissue for treatment
of certain disease. Its pKa is 7.9. 90% of drug is
in the ionized state if the tissue pH is
a) 6.9
b) 7.9
c) Cannot be determined from above data
d) 8.9
e) 9.9
• A patient has mistakenly taken excess of a
drug that is weak acid. How can its renal
excretion be enhanced the most?
a) decreasing the pH of blood
b) Decreasing the pH of urine
c) Increasing the pH of blood
d) Increasing the pH of blood & urine
e) Increasing the pH of urine
• Aspirin is weak acid with pKa of 3.5. what
percentage of given dose will be in lipid soluble
at stomach pH of 2.5. 90%
• A drug was injected into a tissue for treatment
of certain disease. Its pKa is 7.9. 90% of drug is
in the ionized state if the tissue pH is = 6.9
• A patient has mistakenly taken excess of a drug
that is weak acid. How can its renal excretion be
enhanced the most?
THANKYOU
FOR YOUR
PATIENCE