SATURATED
SOLUBILITY
OF
BENZOIC ACID
Solubility: It is the concentration of
a solute in a saturated solution at a
certain temperature

Classification of solutions (Based on
amount of solute):
I)
Subsaturated Solutions
II)
Saturated Solutions
III)
Super-Saturated Solutions
There are three types of solutions
(Based on nature of solute and solvent)
Gas/ liquid
Liquid/ liquid
Solid/ liquid
Solubility is affected by:







Temperature
Type of Solvent
pH
Particle size
Molecular Structure
Crystal Structure
Added Substance: e.g. electrolytes.
Determination of Solubility
This comes in two steps:
1. Preparation of saturated solution
2. Analysis of saturated solution according
to the nature of the drug
Evaporation
method
Volumetric
method
Gravimetric
method
Instrumental
method
Experiment 5

Determination of Solubility of Benzoic acid and effect of
added salt
Adsorbed oxalic acid
Free oxaic acid
0
10
20
30
40
50
Calculation of % of NaCl added:

NaCl was added to a volume of 25 ml of the
filtrate.
e.g. Conc. Of NaCl= 1X100/25= 4%
1 gm
?
25 ml
100ml
Salting out Effect
Calculation:
1.
Determination of saturated
solubility of benzoic acid:
N.V = N’.V’
Normality of
benzoic acid
Volume of
sample(5ml)
Normality of
NaoH(0.1N)
mls of
titrant
N = N’.V’/ V
N = (0.1).V’/ 5
Solubility of benzoic acid
(gm/L)= N. E
Equivalent weight of
benzoic acid= 122
(grams)
Nx E
?
1000 ml
100 ml
Conc of benzoic = N . E . 100/1000
=..............gm/100ml
Table (A):
Temperature
Burette reading
Sample
Number
Initial
reading
(a)
1
2
3
Room Temp.
(-----°C)
Final
reading
(b)
Volume of 0. IN
NaOH
required for
neutralization
(b - a) mL
2. Calculation of Conc. Of Benzoic acid
in presence of NaCl:
N.V = N’.V’
N= N’.V’/V
= (0.05). V’/5


Concentration of benzoic acid (g/l)= N.E
Concentration of benzoic acid (g/100ml)=
N.E . 100/ 1000
Table (B):
Sample
Amount of
Volume of
Number
Electrolyte
Solution
Initial
Final
added (g)
Titrated
reading
reading
(ml)
1.
0
5
2.
1
5
3.
2
5
4.
3
5
5.
4
5
6.
5
5
Burette reading
Volume
of
Solubility
(%) w/v
NaOH
Used
Benz. ac. Dissolved (g/100ml)
Plot % dissolved benzoic acid
against % of added NaCl
4.5
4
3.5
3
2.5
2
1.5
1
0.5
0
0
5
10
% w/v NaCL
15
20
PRECAUTIONS:

1.
2.

Titration with the correct Titrant:
0.1 N NaOH for benzoic acid in absence of
electrolyte.
0.05 N NaOH for benzoic acid in presence of
electrolyte.
The graph (best fitting line) must intercept the
Y axis at saturated solubility of benzoic at 0%
electrolyte.
•Effect of pH on Solubility:
Weak acids better dissolve at high pH
(basic medium), e.g. phenobarbital
 Weak bases better dissolve at low pH
(acidic medium), e.g. Atropine
 For weak electrolytes:
HP
HP
H+ + P
dissolved
(molecular)
dissolved
(ionized)
Equations of weak acids and bases:

Weak acid:

S or St=total solubility of
weak acid in the medium.
S0 or Ks=water solubility
of weak acid (unionized
form).
Ka=dissociation constant
of free acid.



Weak base:

S or St=total solubility of weak
base in the medium.
S0 or Ks=water solubility of
weak base (unionized form).
Kb=dissociation constant of free
base.
Kw=dissociation constant of
water.



Expression Terms

Total solubility (S)

Water solubility (S0)
1- Molar concentration or
(Initial molar concentration)
1-Molar solubility.
2- Total solubility
2- Solubility or water solubility.
3- Initial concentration.
3- Ks
4- Solubility of dissociated +
undissociated forms.
4- Solubility of undissociated
form.
Problems:
[1] What must be the pH of an aqueous formulation be in
order to maintain in solution 10 mg per ml. of a weakly
acidic drug M. Wt = 200, Ka = 1 x l0-5 and Ks = 0.00l
M/L.
Solution:
Desired molar concentration
=
[2] Below what pH will free phenobarbital begin to separate
from a solution having an initial concentration of 1 g of
sodium phenobarbital per 100 ml at 25oC. The molar
solubility So of phenobarbital is 0.005 and the pKa = 7.41 at
25oC. The molecular weight of sodium phenobarbital is 254.
Solution:
The molar concentration of salt initially added is: