Buffer

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pH
 pH = - log [ H+] or pH = - log [ H3O+ ]

Example I
What is the pH of solution with [ H+] = 32 X 10-5 M/L ?

pH = - log [ H+]
pH = - log 32 X 10-5
pH = 3.495

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Example II
The hydronium ion concentration of 0.1 M solution was found to
the 1.32 X 10-3 M, What is the pH of the solution?

pH = - log [ H3O+ ]
pH = - log [ 1.32 X 10-3 ]
pH = 2.88
Example III
If the pH of a solution is 4.72, what is the hydrogen ion
concentration?

pH = - log [ H+ ]
- log [ H+ ] = 4.72
log [ H+ ] = - 4.72 take anti-log for both side
[ H+ ] = 1.91 X 10-5 3
 pH = 0 H+ = 1 M/l = 1 X 100 = 1
 pH = 1 H+ = 1 X 10-1 = 0.1 M/L
 pH = 2 H+ = 1 X 10-2 = 0.01 M/L
 pH = 3 H+ = 1 X 10-3 = 0.001 M/L

 Note : the change in one pH unit means 10 fold change in [H+].

 pH + pOH = 14

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Introduction
 When a minute trace of hydrochloric acid is added to pure
water, a significant increase in hydrogen-ion concentration
occur immediately.
 In a similar manner, when a minute trace of sodium
hydroxide is added to pure water, it cause correspondingly
large increase in the hydroxyl-ion concentration.
 These change take place because water alone cannot
neutralize even trace of acid or base, i.e. it has no ability to
resist change in hydrogen-ion concentration or pH.
 Therefore, it is said to be unbuffered.
 E.g. CO2 + H2O H2CO3 decrease pH from 7 to 5.8
These change of pH are of great concern in pharmaceutical
preparation also NaCl solution ability to resist change of pH.
To ensure stability and solubility, we used to control pH by using
a buffer 5
 Buffer :
Compound or a mixture of compound which by presence in
solution to resist change in pH up of addition of small
quantities of acid, base or a solvent.

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Adjustment of pH by the buffer

 pH important for stability & solubility, therefore should be

adjusted pH by buffer .

 Also pH play important role in :

.Parenteral dosage form-1
.Eye drops-2
3-Nasal drops.

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Adjustment of pH by the buffer
 Degree of acidity and alkalinity depends on the relative
concentration of H+ ion and OH- ion.
if H+ > OH- = acidic
H+ = OH- = neutral
H+ < OH- = alkaline

 Acidity and alkali may be strong or weak:

1- weak acid, pH 3.5- 7 2- strong acid, pH 0-3.5
3- weak base, pH 7-10 4- strong base, pH 10.5-14

0 3.5 7 10.5 14
Strong base Weak base Weak acid Strong acid

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 The product of H+ ion and OH- ion in the any aqueous liquid is
constant i.e. Kw = [ H+] [ OH- ]

 Increase of one tend to decrease of another.

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:Some notes about buffer

1-Buffers solution should be prepared using freshly boiled and

cooled water.

2- Buffers solution should be stored in containers of Alkali-free

glass.

3-Buffers solution should be discarded no later than three

months from the date of manufacture.

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:Selection of buffer system depends on

1. pH rang.

2. Buffer capacity desired.

3. The purpose for which it is required.

4. Compatibility with active ingredients.

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Method of preparation of buffer

1. Buffer equation.

2. Buffer table.

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 Buffer solution consist of mixture of weak acid and its
conjugate base or weak base and its conjugate acid.

 Weak acid + its salt

e.g. acetic acid + sodium acetate
CH3COOH CH3COONa

 Weak base + its salt

e.g. Ammonia + Ammonium chloride
NH3 + NH4Cl

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Henderson-Hasselbalch Equation
buffer equation for weak acid and its salt

Dissociation Constant of weak acid is given by the equation :

Where :
A- = Salt
HA = Acid

we isolate the H+ and put it on the left-hand side of the equation:

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take the negative log of each of the three terms in the last
equation, they become:
- log [H+]  this is the pH
- log Ka  this is the pKa
- log ([HA] / [A-])  to get rid of the negative sign + log ([A-] /
[HA])

Inserting these last three items (the pH, the pKa and the
rearranged log term), we arrive at the Henderson-Hasselbalch
Equation:

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common way the Henderson-Hasselbalch Equation is presented
in a textbook explanation:

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 Remember that, in a buffer, the two substances differ by only a
proton. The substance with the proton is the acid and the substance
without the proton is the salt.

 However, remember that the salt of a weak acid is a base (and the
salt of a weak base is an acid).

 Consequently, another common way to write the Henderson-

Hasselbalch Equation is to substitute "base" for "salt form"
(sometimes you will see "conjugate base" or "base form"). This is
probably the most useful way to decribe the interactions between the
acidic form (the HA) and the basic form (the A-).

 Here it is:

 Remember this: the base is the one WITHOUT the proton and the
acid is the one WITH the proton.
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Buffer equation of weak base & its salt
Dissociation Constant of weak acid is given by the equation :

( B + ) ( OH- )
Kb = --------------------
( BOH)

Where : B + = Salt
BOH = Base

[Base]
pH = pKw – pKb + log ----------
[ Salt]
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An alternate form of the Henderson-
Hasselbalch Equation
 The last discussion used pH and pKa. There is a alternate
form of the Henderson-Hasselbalch Equation using pOH and
pKb.

[Salt]
pOH = pKb + log -----------
[Base]

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Mechanism of action of buffer

1 – Acid / Its salt e.g. CH3COOH/CH3COONa.

CH3COOH + OH-  CH3COO- + H2O

This means acid will react with base (OH- ( to neutralize it.

CH3COO-/Na+ + H3O+  CH3COOH + H2O

This means salt of weak acid will react with acid ( H3O ) to
neutralize it.

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Mechanism of action of buffer… cont

2 – Base / Its salt e.g. NH3/NH4Cl.

NH3 + H3O+  NH4+ + H2O

This means base will react with acid to neutralize it.

NH4+ + OH-  NH3 + H2O

This means salt of weak base will react with base (OH- ) to
neutralize it.

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pH + pOH = 14

For acid & its salt :

[Salt]
pH = pKa + log ----------
[Acid]

For base & its salt :

[Salt]
pOH = pKb + log ----------- or
[Base]

[Base]
pH = pKw – pKb + log ----------
[ Salt] 22
 Example I
What is the molar ratio of salt/acid required to prepare an acetate buffer
pH = 5 ?
Ka = 1.8 X 10-5

pKa = - log Ka
pKa = - log 1.8 X 10-5 = 4.75
pH = pKa + log salt/acid
5 = 4.75 + log salt/acid
log salt/acid = 5 – 4.75 = 0.25 take anti-log for both side
salt/acid = 1.78
So, Ratio of salt/acid = 1.78/1
Mole fraction of acid = 1 / ( 1.78 + 1) =0.3597 X 100 = 35.97 %
Mole fraction of salt = 1.78 / ( 1.78 + 1) =0.6403 X 100 = 64.03 %

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mole fraction multiply by 100 to get of mole %
Example II
Prepare 200 ml of acetate buffer pH = 6 with molar conc. = 0.4 M &
Ka = 1.8 X 10-5 ?

pKa = - log Ka
pKa = - log 1.8 X 10-5 = 4.75
pH = pKa + log salt/acid
6 = 4.75 + log salt/acid
log salt/acid = 6 – 4.75 = 1.25 take anti-log for both side
salt/acid = 17.78/1

Molecular weight of acetic acid ( CH3COOH ) = 60

Molecular weight of sodium acetate ( CH3COONa ) = 82

Weight of acid = mole fraction X Conc. X M.wt X V (L)

= 1/18.78 X 0.4 X 60 X0.2
= 0.26 g
Weight of salt = mole fraction X Conc. X M.wt X V (L)
= 17.78/18.78 X 0.4 X 82 X0.2 24

= 6.21 g
 Example III
If we add 0.1 M sodium acetate to 0.09 M acetic acid .What is the
pH if you know Ka = 1.8 X 10-5 ?

pKa = - log Ka
pKa = - log 1.8 X 10-5 = 4.75
pH = pKa + log salt/acid
pH = 4.75 + log 0.1/0.09
pH = 4.796

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Example IV

What is the pH of of a solution containing 0.1 mole of

ephedrine base and 0.01 mole of ephedrine HCl / liter
of solution ?
pKb of ephedrine = 4.64
pH = pKw - pKb + log base/salt
pH = 14 - 4.64 + log 0.1/0.01
pH = 9.36 + log 10 = 10.36
Or
pOH = pKb + log salt/base
pOH = 4.64 + log 0.01/0.1
pOH = 4.64 + log 0.1 = 3.64
pH + pOH = 14
pH = 14 – pOH
pH = 14 – 3.64 = 10.36 26
Change in pH with addition of an acid or base

Calculate the change in pH of a buffer solution with the addition

of a given amount of acid or base in the following example :

Example
Calculate the change in pH after adding 0.04 mol of sodium
hydroxide to a liter of a buffer solution containing 0.2 M conc.
of sodium acetate and acetic acid. The pKa value of acetic
acid is 4.76 at 25 OC.
The pH of the buffer solution is calculated by using the buffer
equation
pH = pKa + log salt/acid
pH = 4.76 + log 0.2/0.2
pH = 4.76
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Change in pH with addition of an acid or base

salt + base
pH = pKa + log ------------------------
acid - base

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 salt + base
pH = pKa + log -----------------------
acid - base

0.2 + 0.04
pH = 4.76 + log -------------------
0.2 - 0.04

pH = 4.76 + 0.1761 = 4.9361 = 4.94

Because the pH before addition sodium hydroxide was 4.74, the
change in pH = 4.94 – 4.76 = 0.18 unit.

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Buffer Capacity
 The ability of buffer solution to resist change in pH upon
addition of acid or base.

Ka . [H+]
Buffer Capacity “ B “ = 2.303 X C X -----------------
( Ka + [H+] )2

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 Example I
At hydrogen ion conc. of 1.75 X 10-5 (4.76), what is the capacity of a
buffer containing 0.1 mole each of acetic acid and sodium acetate /
liter of solution ?
Ka = 1.75 x 10-5

Total C = [acid] + [ salt] = 0.1 + 0.1 = 0.2 mol/L

Ka . [H+]
Buffer Capacity “ B “ = 2.303 X C X -----------------
( Ka + [H+] )2

(1.75 X 10-5 ) . (1.75 X 10-5 )

Buffer Capacity “ B “ = 2.303 X 0.2 X ----------------------------------------
[(1.75 X 10-5 ) + (1.75 X 10-5 )]2

B = 0.115
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