Unit- V

pH, Buffers and Isotonic solutions

Buffers:
Buffers are defined as a compound or a mixture of compounds that resists the
pH upon the addition of small quantities of acid or alkali. Buffer have definite pH
value. The pH will not change after keeping it for a long period of time. The pH
value gets altered negligibly by the addition of small quantities of acid /base.

Buffer action:
The resistance to a change in pH is known as buffer action. So buffers can
be added to show buffer action.

Buffer capacity:
The amount of acid/base required to produce a unit change in pH in a
solution is called buffer capacity.

Applications of Buffers:
 Solubility enhancement:
The pH of the pharmaceutical formulations are adjusted to an optimum value
so that the drug remains solubilised though out its shelf-life and not precipitated
out.
 Increasing stability:
To prevent hydrolysis and for maximum stability, the pH of the medium
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should be adjusted suitably.
 Improving purity:
The purity of proteins can be identified from its solubility at their isoelectric
point as they are least soluble at this point. The isoelectric pH can be maintained
using suitable buffers.
 Optimising biological activity:
Enzymes have maximum activity at definite pH values. Hence buffer of
desired pH is added to the preparation.
 Comforting the body:
The pH of the formulations that are administered to different tissues of the
body should be optimum to avoid irritation (eyes), haemolysis (blood) or burning
sensation (abraded surface).
The pH of the preparation must be added with suitable amount of buffers to
match with the pH of the physiological fluid.

Buffer systems:
The buffer systems are classified as followings
a. Weak acid and its conjugate base, i.e. salt of week acid with a strong base.
Example- acetic acid and sodium acetate.
b. Weak base and its conjugate acid, i.e. salt of week base with a strong acid.
Example- ammonium hydroxide and ammonium chloride.
c. Two salts acts as acid-base pair.
Example- Potassium hydrogen phosphate and potassium dihydrogen
phosphate.
d. Amphoteric electrolyte.
Example- Solution of glycine.
e. Solution of strong acid and solution of strong base.
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 Example- Strong HCl with KCl.
Some important buffer system and their pH is given below in table-3.

Table-3: Some important buffer system and their pH.

System pH
HCl and KCl 1.2 to 2.2
HCl and potassium hydrogen phthalate 2.2 to 4.0
Sodium hydroxide and potassium hydrogen 4.2 to 5.8
phthalate
Boric acid and sodium carbonate monohydrate 5.0 to 9.0
Potassium dihydrogen phosphate and sodium 5.8 to 8.0
hydroxide
Boric acid, sodium hydroxide and potassium 8.0-10.0
chloride

Buffer action of acidic buffer:

Consider an acid buffer, i.e. acetic acid and sodium acetate. The ionization
equation are written as:

Strong electrolyte:
H2O
CH3COONa Na+ + CH3COO- completely ionized

Weak acid:
CH3COOH + <===> H3O+ + CH3COO- slightly ionized
H2O

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 Therefore, the solution contains very few H3O+ ions, but has an excess
sodium ions and acetate ions. When a small amount of acid is added, the H3O+ ions
present in the solution react with CH3COO- as
H3O+ + CH3COO- CH3COOH + H2O
Since added free H3O+ ions are not available, pH does not change. When a
small amount of base is added, the hydroxyl ions furnished by the base are
neutralised by acetic acid as:
OH- + CH3COOH CH3COO- + H2O
Since added free OH- ions are not available, pH does not change. Thus
buffer action is maintained when a small amount of acid or base is added. This
process continues until entire acetate ions or acetic acid is consumed, action is not
unlimited.
The mechanism of buffer action of acid-base pair (example is phosphate
buffer) is similar to that mentioned above. In phosphate buffer, weak acid
conjugate base are involved, i.e. ion H2PO4- serves as weak acid and H2PO42- acts
as its conjugate base.

Buffer Action of Alkaline Buffer:

Buffer action of a mixture of a weak base and its salt, for example
ammonium hydroxide and ammonium chloride, is considered. The ionization
equation is written as:
Strong electrolyte:
H2O
NH4Cl NH4+ + Cl- - completely ionised
Weak base:
H2O
NH4OH4 <======> NH4+ + OH- - slightly ionized
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 Therefore, the solution contains very few OH- ions, but has an excess of
ammonium ions and chloride ions.
When a small amount of acid is added, the H3O+ ions obtained from acid
react with NH4OH as
H3O++ NH4OH <=====> NH4+ + 2 H2O
Since added free H3O+ ions are not available, pH does not change.
When a strong base is added, the hydroxyl ions furnished by the base are
neutralised by NH4+ as:
OH- + NH4+ <=====> NH4OH
Since added free OH- ions are not available, pH does not change. Thus
buffer action is maintained when a small amount of acid or base is added. This
process continues until entire ammonium hydroxide or ammonium ions are
consumed. Hence buffer action is not unlimited.

Ampholytic Substances:
Ampholytes and amphoteric electrolytes are the substances that capable of
acting both as an acid and a base. For example, glycine, like an acid as shown
below.
NH2CH2COOH + H2O <======> NH2CH2COO- + H3O+
Glycine also behaves as a base as shown below.
NH2CH2COO- + H3O+ <=======> +NH3CH2COO-+ H2O
These doubly charged ions are known as zwitter ions or dipolar ions he
above system reacts with H3O+ ions or OH- ions and nullify the influence of the
added substances.

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Buffer equation-Henderson-Hasselbalch equation:
The buffer equation is also known as Henderson-Hasselbalch equation. Two
separate equations are obtained for each type of buffer, acidic and basic. Buffer
equation is developed based on the effect of salt on the ionization of a weak acid,
when the salt and acid have a common ion.
An acid buffer, acetic acid and sodium acetate, is considered for deriving the
buffer equation. The ionization equilibrium equation for weak acid (acetic acid)
may be shown as:
Weak acid:
CH3COOH + H2O <====> H3O+ + CH3COO- -slightly ionized
Applying the Law of Mass Action, the acid dissociation constant (Ka) is written as:
Ka = [H3O+] [CH3COO-]/ [CH3COOH] =1.75 x 10-5 (1)
When sodium acetate is added to acetic acid, equation (1) is momentarily
disturbed. Since, salt also supplies the acetate ion, the term [CH3COOH] in the
numerator increases.
In order to re- establish the constant Ka at 1.75 x 10-5, the hydronium ion
[H3O+] in the numerator instantaneously decreases. In other words, the equilibrium
is shifted in the direction shown below.
CH3COO- + H3O+ H2O + CH3COOH
In other words, common ion, [CH3COO-] repressed ionization of acetic acid.
This is an example of common ion effect.
The pH of the final solution may be obtained by rearranging equation (1).
[H3O+] = Ka [CH3COOH] / [CH3COO-] (2)
Since, the acid is weak and ionizes slightly, [CH3COOH] may remain
unaltered.
Hence, [CH3COOH] = [acid].

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 Since salt is completely ionized, the entire [CH3COO-] may be obtained
directly from the salt and be written as [salt].
Hence, [CH3COO-] = [salt].
Substituting them in equation (2) gives:
[H3O+] = Ka [acid] / [salt] (3)
Taking logarithm of equation (3) and reversing the signs give:
- log [H3O+] = - log Ka - log [acid] / [salt] (4)
But pH = -log [H3O+] and pKa = -log Ka.
By substituting these values in equation (4) gives:
pH = pKa + log [acid] / [salt] (5)
Equation (5) is known as buffer equation or Henderson-Hasselbalch
equation for acid buffer.
Similarly buffer equation for a solution containing weak base and the
corresponding salt may be derived in a similar manner.
Equation for the calculation of [OH-] may be written as:
[OH-] = Kb [base]/[salt] (6)
Henderson-Hasselbalch’s equation for basic buffers is:
pH = pKw + pKb + log[salt]/[acid] (7)

Applications:
 For a definite pH solution, it is essential to add salt and acid (or base) to
water in a desired ratio. This ratio is determined by Henderson-Hasselbalch
equation.
 Since salt and acid are added in the preparation of a buffer solution, their
concentrations are known. Using this data, the resultant pH of a solution can be
calculated using buffer equation.

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 Equations (5) and (7) permit the calculation of the percent of drug ionized
(or ionized) in the solution. This knowledge is important in predicting the drug
absorption, because only unionized molecules can penetrate cell membranes (lipid
in nature) more readily than ionized molecules.
 The pKa of various drugs can be determined from pH of solutions
 The solubility of a substance at any pH can be predicted provided intrinsic
solubility and pKa are known.
 A suitable sält forming substance can be selected based on Henderson
Hasselbalch equation.

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