KOMAR UNIVERSITY

OF SCIENCE AND TECHNOLOGY

Monica Diyya,
Department of Pharmacy,
College of Medicine.
 Course Name: Physical Pharmacy-I

UNIT IV: Buffers and Buffered Isotonic solutions

UNIT IV
Lesson No: 04A-Buffers-Buffer equation-Buffer Capacity-
Biological and pharmaceutical buffers

2
 Contents

➢Buffer: Definition
➢Buffer equation for weak acids
➢Buffer equation for weak bases
➢Factors affecting pH of buffer solutions
➢Buffer capacity
➢Biological, pharmaceutical buffers

KUST/Pharmacy/Monicadiyya 3
 Buffer solutions
Buffer solutions are solutions of compounds or
mixtures of compounds which resist changes in
their pH upon addition of small quantities of an
acid or alkali.

Most buffer solutions usually consist of a mixture

of a weak acid and one of its salts (or) weak base
and one of its salts.

KUST/Pharmacy/Monicadiyya 4
 Buffer solutions

5
KUST/Pharmacy/Monicadiyya
 Buffer Action
The ability of certain solutions to resist change in
their pH upon addition of an acid or a base is
known as Buffer Action.

Eg: Consider solution of NaCl in water. Its pH

value is 7.
• Addition of even 1mL of 1N HCl solution to 1 litre
of NaCl solution, lowers its pH value from 7 to
about 3.
• Addition of even 1mL of 1N NaOH solution to
1litre of NaCl solution raises its pH to about 11.
• NaCl is therefore not a buffer.
6
KUST/Pharmacy/Monicadiyya
 BUFFER EQUATION
or
HENDERSON HASSELBALCH EQUATION
• The pH of a buffer solution and the change in the pH
upon addition of an acid or a base can be calculated
based on the use of the buffer equation.

• This expression is developed by considering the effect of

a salt on the ionization of a weak acid or a weak base
when the salt and the acid or base have an ion in
common.

• The buffer equation is a useful expression used in

preparation of buffered pharmaceutical solutions.
• It is satisfactory for calculations within the pH range of 4
to 10.
7
Buffer equation or Henderson-Hasselbalch
equation for weak acid and its salt.

[𝑠𝑎𝑙𝑡]
pH = pKa + log
[𝑎𝑐𝑖𝑑]

Buffer equation or Henderson-Hasselbalch

equation for weak base and its salt.

[𝒃𝒂𝒔𝒆]
pH = pKw –pKb + log
[𝒔𝒂𝒍𝒕]

8
Practical Problem No.1:
Calculate the pH of the buffer solution consisting of
0.1M each of acetic acid and sodium acetate (pKa of
acetic acid = 4.76)
Solution:
concentration of acetic acid [acid] = 0.1M
concentration of sodium acetate[salt] = 0.1M
pKa of acetic acid = 4.76
According to Henderson-Hasselbalch equation,
[𝑠𝑎𝑙𝑡]
pH = pKa + log
[𝑎𝑐𝑖𝑑]
0.1
pH = 4.76 + log
0.1

pH = 4.76
9
Practical problem No.2:
Estimate the pH of a solution containing 0.10 mole of
ephedrine and0 0.01 mole of ephedrine hydrochloride per
→
litre of solutions. [pKb of ephedrine is 4.64] ←
Solution:
Concentration of ephedrine [Base] = 0.10 mole
Concentration of ephedrine hydrochloride [Salt] = 0.01
mole
pKb of Ephedrine = 4.64
Ionic product of water pKw = 14
For a weak base and its salt,
[𝑏𝑎𝑠𝑒]
pH = pKw –pKb + log
, [𝑠𝑎𝑙𝑡] → .

[0.1]
pH = 14 - 4.64 + log
[0.01]
pH = 14 – 4.64 +1
pH = 10.36
10
 FACTORS AFFECTING PH OF BUFFER SOLUTIONS

The pH of the buffer solution may be affected by

fluctuation in the temperature, by its dilution with a
solvent or by the addition of a neutral salt.
1. Temperature Effects:
pKa value of a buffer is dependent on temperature.
Eg: Buffers containing a base and its salt show greater
changes with temperature.
➢An increase in temperature lowers pH of a buffer
solution containing boric acid and sodium borate
and raises the pH of a buffer solution containing
acetic acid and sodium acetate.

KUST/Pharmacy/Monicadiyya 11
2. Dilution Effects:
Dilution of an aqueous buffer solution with water in
moderate quantities shows only a small effect on the
pH of the buffer solution.
➢Dilution of an acidic buffer shows an increase in pH
while dilution of a basic buffer shows a decrease.
Dilution value: Dilution value is defined as the change
in pH brought by the dilution of a buffer solution with
an equal volume of water.
➢The dilution values for most pharmaceutical buffer
systems are usually less than 0.1 pH unit.

3. Salt Effects:
Salt added to acidic buffers lowers its pH while that
added to a basic buffer increases its pH (because of
changes in the activity coefficients of the ions)
12
 BUFFER CAPACITY (β)
The buffer capacity of a solution is a measure of its
magnitude of resistance to change in pH on addition
of an acid or a base.
“Buffer capacity is the quantity of strong acid or base
that must be added to change the pH of one litre of
buffer solution by one pH unit.”
• It is also referred to as buffer index, buffer efficiency,
buffer coefficient or buffer value.

• The buffer capacity, ‘β’ has been defined as the ratio

of the increment of strong base or acid to the small
change in pH brought about by this addition.
Thus,
Δ𝐵
β=
[Δ𝑝𝐻]
 𝜟𝑩
β=
[𝜟𝒑𝑯]

𝜟𝑩: number of moles of strong acid or base per liter of

buffer.
𝜟𝒑𝑯: change in pH.
Note: When one of the buffer components is depleted
completely, the solution lose its buffering capacity and
can no longer resist the change in pH.
• According to the equation, a solution has a buffer
capacity of 1 when 1 litre of it requires 1 gram
equivalent of a strong base or strong acid to change
the pH by 1 unit.
• The smaller the pH change in a solution after the
addition of a specified amount of acid or base, the
greater is the buffer capacity of a solution.
 Buffer capacity (exact equation):

𝑲𝒂[𝑯𝟑𝑶+]
𝜷 = 𝟐. 𝟑𝑪
(𝑲𝒂 + 𝑯𝟑𝑶+ 𝟐

C is the total buffer concentration (the sum of the molar

concentrations of the acid and the salt).

This equation allows the calculation of buffer capacity at any pH

(even when no acid or base has been added to the buffer).

The equation shows that an increase in the concentration of the

buffer components ( 𝑪 ) results in a greater buffer capacity (𝜷).
A buffer solution containing a weak acid and its salts has a
maximum buffer capacity (βmax) when the pH = pKa for the
weak acid or in equivalent terms when [𝑯𝟑𝑶]+ equals Ka .
We have,
𝑲𝒂[𝑯𝟑𝑶+]
𝜷 = 𝟐. 𝟑03𝑪
(𝑲𝒂 +[𝑯𝟑𝑶+] )2
Substitute [𝑯𝟑𝑶]+ for 𝑲𝒂 in the above equation, we get

𝜷max = 𝟐. 𝟑03𝑪 [𝑯𝟑𝑶+]2

(2[𝑯𝟑𝑶+] )2

2.303 For most buffer systems, a total buffer

𝜷max = C concentration of between 0.5 and 0.05
4 mol per litre gives an adequate buffer
capacity over a pH range of about 2
𝜷max= 0.576 C units.
Practical problem No.3

x
A buffer solution contained 0.1M each of acetic acid
and sodium acetate and its pH was 4.76. To this, 0.01
moles of sodium hydroxide was added and the pH of
resultant solution was 4.85. Calculate the buffer
capacity, β.
f
Solution:
Change in the pH ( ΔpH) = 4.85-4.76
= 0.09

9
Quantity of sodium hydroxide added (Δ B) = 0.01
moles

ΔB
Buffer capacity, β =
ΔpH
0.01
β= = 0.11.
0.09
 Practical problem No.04
At a hydrogen ion concentration of 1.75 × 10–5, what is the
capacity of a buffer containing 0.10 mole each of acetic
acid and sodium acetate per liter of solution? (Ka = 1.75 ×
10–5 )
when 2 Given numbers #one
& Kaw
C = [Acid] + [Salt] = 0.1+ 0.1 = 0.20 mole/liter
-

𝑲𝒂[𝑯𝟑 𝑶+]
equal
Erectly
𝜷 = 𝟐. 𝟑𝑪
(𝑲𝒂 + 𝑯𝟑𝑶+ 𝟐
2

a
𝜷 = 𝟐. 𝟑 × 0.2 × (1.75 × 10 )(1.75 × 10 ) = 0.115 𝑚𝑜𝑙/𝐿
–5 –5

[(1.75 × 10–5) + (1.75 × 10–5)]2

Or, directly we can use, as pH=pKa;

𝜷 = 0.576 C
 Practical Problem No.05

What is the maximum buffer capacity of an acetate

buffer with a total concentration of 0.040
mole/liter?

𝜷𝒎𝒂𝒙 = 𝟎. 𝟓𝟕𝟔 𝑪
𝜷𝒎𝒂𝒙 = 0.576 × 0.04 = 0.02304
 BIOLOGICAL BUFFERS

Some body fluids have natural buffer capacity

➢The pH of the blood is maintained at about 7.4

by primary buffer components in the plasma
and secondary buffer components in the
erythrocytes.
The plasma contains carbonic acid-carbonate
and the acid/alkali sodium salts of phosphoric
acid buffer system.

H2CO3 ↔ HCO3 + H+
The Erythrocytes contain two buffer systems:
oxyhaemoglobin-haemoglobin and acid/alkali
(potassium) salts of phosphoric acid.

H2PO4 ↔ HPO42- + H+
HbH+ + O2 ↔ + O2Hb + H+
• Hb: hemoglobin, O2Hb: oxyhemoglobin

• Value of buffer capacity of blood ranges from 0.025

to 0.039 gram equivalents per litre per pH unit (as
per literature).
• When pH of the blood decreases/increases beyond
this range, detrimental effects will be seen.
➢ The pH of Lacrimal fluid/tears is about 7.4 with a
range of 7.0 to 8.0.
Tears have been found to have a great degree of
buffer capacity and dilution of upto 1:15 with neutral
distilled water is possible before an appreciable
change in pH is noticed.

➢The average pH of urine is about 6.0 with a range

of 4.5 to 7.8
When the pH of urine is altered beyond this range,
remedial action is taken by the kidneys in the form
of retention or excretion of hydrogen ions in order to
maintain the pH within the range.
 PHARMACEUTICAL BUFFERS

Buffer solutions are widely used to

adjust pH of aqueous pharmaceutical
solutions to ensure:
1. Tissue irritation prevention
2. Optimum therapeutic effect
3. Maximum drug stability
4. Maximum drug solubility
5. pH of the product within the optimal
physiological pH range.
 1. Buffers in Tablet Formulations

• Buffers have been used in tablets and capsules

to control the pH in the microenvironment
surrounding the drug particles.

• Buffers have been employed in formulations

containing acidic drugs to reduce gastric
irritation.

• Buffering agents that have been in solid oral

dosage forms include antacids such as sodium
bicarbonate, magnesium carbonate and sodium
citrate.
 2. Buffers in Ophthalmic Preparations
• Buffers are generally used in ophthalmic
preparations to maintain the pH within the
physiological pH range of the lacrimal fluid.

• The lacrimal fluid has a good buffering capacity and

solutions with pH values between 3.5 and 10.5 can
usually be tolerated with little discomfort.

• Most of the ophthalmic drugs are weakly acidic or

basic.

• At low pH, these drugs dissociate and go into

solution and remain stable. At such lower pH the
therapeutic effect is lower since only the
undissociated form of the drug is able to penetrate
the lipoidal membrane.
• Buffers are therefore added to adjust the pH to a
value that is best with regard to the solubility and
stability of the drug and which is well tolerated by
the eye.
• When the solution is instilled into the eye, the pH
slowly rises to that of tear solution and the weak
acid/base (drug) gets converted into the
undissociated form which provides the maximum
therapeutic effect.
• The buffering agents most commonly used in
ophthalmic preparations include borate,
phosphate and carbonate buffers.
• These preparations are also made isotonic to
prevent discomfort and injury to the surface of
the eye.
 3. Buffers in Parenteral Preparations
• The consideration of pH in case of parenteral
products is highly important since a highly alkaline
pH (above 9) can cause tissue necrosis while an
acidic pH (below 3) can result in extreme pain at the
site of injection.

• The ideal pH of a parenteral product is 7.4, the pH of

blood.

• The buffer capacity of small-volume parenterals is

however kept low so that the pH can be adjusted by
the blood-buffer system.

• The most commonly used buffers in parenteral

products are acetate, phosphate, citrate and
glutamate buffers.
 4. Buffers in Creams and Ointments

• Topical products usually have a tendency to

undergo change in the pH during storage which
may adversely affect the stability of the drug.

• Buffers are therefore included in such

preparations to maintain the stability of the
product.

• The most commonly used buffers in creams and

ointments include citric acid and its salts or
phosphoric acid and its salts.