Pharmaceutical technology

Buffer solution
Thi_qar univercity
College of pharmacy
Third stage

Under supervision:
DR. Ali saied

By:
Amer faisal

²⁰²⁰

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Buffer
Thi_qar univercity / college of pharmacy / Third stage
Introduction
A buffer solution (more precisely, pH buffer or hydrogen ion buffer) is an aqueous
solution consisting of a mixture of a weak acid and its conjugate base, or vice versa. Its pH
changes very little when a small amount of strong acid or base is added to it. Buffer solutions
are used as a means of keeping pH at a nearly constant value in a wide variety of chemical
applications. In nature, there are many systems that use buffering for pH regulation. For
example, the bicarbonate buffering system is used to regulate the pH of blood.

Principles of buffering
Buffer solutions achieve their resistance to pH change because of the presence of an

HA ⇌ H+ + A−
equilibrium between the weak acid HA and its conjugate base A−:

When some strong acid is added to an equilibrium mixture of the weak acid and its conjugate
base, hydrogen ions (H+) are added, and the equilibrium is shifted to the left, in accordance
with Le Châtelier's principle. Because of this, the hydrogen ion concentration increases by
less than the amount expected for the quantity of strong acid added. Similarly, if strong alkali
is added to the mixture, the hydrogen ion concentration decreases by less than the amount
expected for the quantity of alkali added. The effect is illustrated by the simulated titration of
a weak acid with pKa = 4.7. The relative concentration of undissociated acid is shown in
blue, and of its conjugate base in red. The pH changes relatively slowly in the buffer region,
pH = pKa ± 1, centered at pH = 4.7, where [HA] = [A−]. The hydrogen ion concentration
decreases by less than the amount expected because most of the added hydroxide ion is
consumed in the reaction
OH− + HA → H2O + A−
and only a little is consumed in the neutralization reaction (which is the reaction that results
in an increase in pH)

OH− + H+ → H2O.
Once the acid is more than 95% deprotonated, the pH rises rapidly because most of the
added alkali is consumed in the neutralization reaction.

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Buffer
Thi_qar univercity / college of pharmacy / Third stage
 Buffer capacity
Buffer capacity is a quantitative measure of the resistance to change of pH of a solution
containing a buffering agent with respect to a change of acid or alkali concentration. It can
be defined as follows:

where is an infinitesimal amount of added base, or

where is an infinitesimal amount of added acid. pH is defined as −log10[H+], and d(pH) is an
infinitesimal change in pH.
With either definition the buffer capacity for a weak acid HA with dissociation
constant Ka can be expressed as

where [H+] is the concentration of hydrogen ions, and is the total concentration of added
acid. Kw is the equilibrium constant for self-ionization of water, equal to 1.0×10−14. Note that
in solution H+ exists as the hydronium ion H3O+, and further aquation of the hydronium ion
has negligible effect on the dissociation equilibrium, except at very high acid concentration.

This equation shows that there are three regions of raised buffer capacity (see figure).

 In the central region of the curve (coloured green on the plot), the second term is dominant,
and

Buffer capacity rises to a local maximum at pH = pKa. The height of this peak depends
on the value of pKa. Buffer capacity is negligible when the concentration [HA] of
buffering agent is very small and increases with increasing concentration of the
buffering agent.[2] Some authors show only this region in graphs of buffer capacity.
[1]

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Buffer
Thi_qar univercity / college of pharmacy / Third stage
 Buffer capacity falls to 33% of the maximum value at pH = pKa ± 1, to 10% at pH =
pKa ± 1.5 and to 1% at pH = pKa ± 2. For this reason the most useful range is
approximately pKa ± 1. When choosing a buffer for use at a specific pH, it should have
a pKa value as close as possible to that pH.[1]
 With strongly acidic solutions, pH less than about 2 (coloured red on the plot), the first term
in the equation dominates, and buffer capacity rises exponentially with decreasing pH:

This results from the fact that the second and third terms become negligible at very
low pH. This term is independent of the presence or absence of a buffering agent.
 With strongly alkaline solutions, pH more than about 12 (coloured blue on the plot), the third
term in the equation dominates, and buffer capacity rises exponentially with increasing pH:

This results from the fact that the first and second terms become negligible at very
high pH. This term is also independent of the presence or absence of a buffering agent.

Applications
The pH of a solution containing a buffering agent can only vary within a narrow range,
regardless of what else may be present in the solution. In biological systems this is an
essential condition for enzymes to function correctly. For example, in human blood a
mixture of carbonic acid (H
2CO
3) and bicarbonate (HCO−
3) is present in the plasma fraction; this constitutes the major mechanism for maintaining the
pH of blood between 7.35 and 7.45. Outside this narrow range (7.40 ± 0.05 pH
unit), acidosis and alkalosis metabolic conditions rapidly develop, ultimately leading to death
if the correct buffering capacity is not rapidly restored.
If the pH value of a solution rises or falls too much, the effectiveness of an enzyme decreases
in a process, known as denaturation, which is usually irreversible.[5] The majority of
biological samples that are used in research are kept in a buffer solution, often phosphate
buffered saline (PBS) at pH 7.4.
In industry, buffering agents are used in fermentation processes and in setting the correct
conditions for dyes used in colouring fabrics. They are also used in chemical analysis[4] and
calibration of pH meters.
For buffers in acid regions, the pH may be adjusted to a desired value by adding a strong
acid such as hydrochloric acid to the particular buffering agent. For alkaline buffers, a strong
base such as sodium hydroxide may be added. Alternatively, a buffer mixture can be made
from a mixture of an acid and its conjugate base. For example, an acetate buffer can be made
from a mixture of acetic acid and sodium acetate. Similarly, an alkaline buffer can be made
from a mixture of the base and its conjugate acid.

Calculating buffer pH
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Buffer
Thi_qar univercity / college of pharmacy / Third stage
Monoprotic acids
First write down the equilibrium expression

HA ⇌ A− + H+
This shows that when the acid dissociates, equal amounts of hydrogen ion and anion are
produced. The equilibrium concentrations of these three components can be calculated in
an ICE table (ICE standing for "initial, change, equilibrium").

The first row, labelled I, lists the initial conditions: the concentration of acid is C0, initially
undissociated, so the concentrations of A− and H+ would be zero; y is the initial concentration
of added strong acid, such as hydrochloric acid. If strong alkali, such as sodium hydroxide, is
added, then y will have a negative sign because alkali removes hydrogen ions from the
solution. The second row, labelled C for "change", specifies the changes that occur when the
acid dissociates. The acid concentration decreases by an amount −x, and the concentrations
of A− and H+ both increase by an amount +x. This follows from the equilibrium expression.
The third row, labelled E for "equilibrium", adds together the first two rows and shows the
concentrations at equilibrium.
To find x, use the formula for the equilibrium constant in terms of concentrations:

Substitute the concentrations with the values found in the last row of the ICE table:

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Buffer
Thi_qar univercity / college of pharmacy / Third stage
Simplify to

With specific values for C0, Ka and y, this equation can be solved for x. Assuming that
pH = −log10[H+], the pH can be calculated as pH = −log10(x + y).

Polyprotic acids

Polyprotic acids are acids that can lose more than one proton. The constant for dissociation
of the first proton may be denoted as Ka1, and the constants for dissociation of successive
protons as Ka2, etc. Citric acid is an example of a polyprotic acid H 3A, as it can lose three
protons.

When the difference between successive pKa values is less than about 3, there is overlap
between the pH range of existence of the species in equilibrium. The smaller the difference,
the more the overlap. In the case of citric acid, the overlap is extensive and solutions of citric
acid are buffered over the whole range of pH 2.5 to 7.5.
Calculation of the pH with a polyprotic acid requires a speciation calculation to be
performed. In the case of citric acid, this entails the solution of the two equations of mass
balance:

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Buffer
Thi_qar univercity / college of pharmacy / Third stage
CA is the analytical concentration of the acid, CH is the analytical concentration of added
hydrogen ions, βq are the cumulative association constants:

Kw is the constant for self-ionization of water. There are two non-linear simultaneous
equations in two unknown quantities [A3−] and [H+]. Many computer programs are available
to do this calculation. The speciation diagram for citric acid was produced with the program
HySS.

References
 https://doi.org/10.1021%2Fed077p1640
 https://en.m.wikipedia.org/wiki/Special:BookSources/978-0-471-58526-8
 https://en.m.wikipedia.org/wiki/Special:BookSources/978-0-85312-330-9
 https://doi.org/10.1021%2Fed038p559
 http://www.hyperquad.co.uk/hyss.htm
 https://en.m.wikipedia.org/wiki/Special:BookSources/978-0-495-55828-6

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Buffer
Thi_qar univercity / college of pharmacy / Third stage