1st pf

1. Solubility
IMRAN TARIQ
(Assistant Professor)

2. Definition
• Solubility is the property of a solid, liquid, or gaseous
chemical substance called solute to dissolve in a
solid, liquid, or gaseous solvent to form a
homogeneous solution of the solute in the solvent.
• The solubility of a substance fundamentally depends
on the used solvent as well as on temperature and
pressure. The extent of the solubility of a substance
in a specific solvent is measured as the saturation
concentration, where adding more solute does not
increase the concentration of the solution.

3. • Solubility in a qualitative term may be defined as the
spontaneous interaction may be defined as the spontaneous
interaction of two or more substances to from a homogeneous
molecular dispersion.
• In quantitative term, solubility may be defined in following ways:
• “Grams of solute that will dissolve in 100 grams of solvent to
make saturated solution at a stated temperature”.
• Or
• “Grams of solute that will dissolve in 100 mls of solvent to
make saturated solution at a stated temperature”.

4. According to B.P. (British Pharmacopoeia);
•“No. of parts of solvent required to dissolve one part of solute at a
stated temperature”.
According to U.S.P. (United State Pharmacopoeia);
•“The number of millilitres of solvent in which one gram of solute
will dissolve”.
•→ Here, the term ‘one part’ represents 1gm or 1ml.

5. Factors affecting
Solubility

6. Solubility of solids in
liquids

7. Temperature
• Most solids dissolve with absorption of heat and the
solubility of such solids increases as the temperature
increases, e.g., solubility of NaCl, NaNO3, KNO3 in
water increases with temperature.
• For solids which dissolve with the evolution of heat,
increase in temperature causes a decrease in
solubility, e.g., solubility of Ca(OH)2 in water.
• Effect of temperature on the solubility of soilds can be
represented by the use of ‘solubility curve’.

8. SOLUBILITY CURVES:
•Solubility curves are the curves drawn between the
solubility and temperature. It shows the effect of
temperature on the solubility of substances. The
solubility curves of substances like calcium acetate and
calcium chromate shows decrease in solubility, while
those of sodium nitrate, lead nitrate shows a
considerable increase of solubility with increase in
temperature.

10. • Many drugs behave as weak acid or weak base, so
their solubility is affected by the pH of the aqueous
solvents. The ionized form of acidic or basic drug is
considered as soluble whereas unionized from as
insoluble. A weakly basic drug is more soluble in
acidic medium and an acidic drug is more soluble in
basic medium because these can ionize properly,
and are insoluble in their relevant medium due to
poor ionization (due to common H+
or common OH-
).

11. • A weakly acidic drug such as Acetyl salicylic acid
(Aspirin) will be more soluble in alkaline medium, since
it may ionize properly or secondly it may be converted
to more soluble salt such as sodium salicylate.
Conversely, acetyl salicylic acid may be precipitated if
some strong acid is added to aqueous solution of
Acetyl salicylic acid (due to common H+
ions →
common ion effect)
• Similarly basic drug such as sulphonamide (Antibiotic)
will be more soluble in acidic medium. Basic drug will
be precipitated from aqueous solution, if the pH of
solution is raised by the addition of strong base (due to
common OH-
ions common ion effect).→

12. Particle size
• The particle size of the solids also
affects its solubility in a given solvent.
Generally, a decrease in the particle
size causes an increase in the solubility.
This is because a decrease in particle
size results in increase in surface area
and surface free energy which
increases solubility.

13. Molecular structure
modifications
• Slight modification in the molecular structure of solids
may lead to marked changes in their solubility in the
given solvent. For example, if a weak acid
( CH3COOH weak electrolyte, poor soluble) is→
converted into its salt (CH3COONa), its ionic
dissociation in water increases markedly leading to
an increase in the interaction between the solute and
the solvent which ultimately leads to an increase in
the solubility.

14. • Solubility can also be decreased by modifications such as
esterification.
ESTERIFICATION
• Chloramphenicol (antibiotic) ----------------------- Chloramphenicol palmitate→
• Soluble Poor Soluble
• Such a decrease in solubility is sometimes beneficial in
pharmaceutical practice since this decrease in solubility helps in
taste masking of certain drugs such as chloramphenicol (very
bitter) to chloramphenicol palmitate (tasteless).

15. Common ion effect
• “The process in which solubility of a
weak electrolyte is reduced by the
addition of a strong electrolyte which
has common ion to that of weak
electrolyte”.
• Ionization of sodium chloride in water
can be represented by equilibrium
constant expression as:

16. NaCl (SOLID) Na+↔ (aq ) + Cl -
(aq)
Kc = [Na+] [Cl-
] / [NaCl]
HCl ionizes in water as:
HCl H+↔ (aq) + Cl-
(aq)
•On passing HCl gas through aqueous solution of
NaCl , concentration of Cl-
ions is increased,
therefore some of the NaCl is precipitated out to
maintain the constant value of the equilibrium
constant. This is called as common ion effect
which reduces solubility.

17. Effect of complex
formation
• The apparent solubility of some solutes in a liquid
may be increased or decreased by the addition of a
substance that forms a complex which is either more
or less soluble.
• Solubility of iodine in water is increased by the
addition of potassium iodide which forms a soluble
complex (KI3).
• I2 + KI --------------------------------- KI→ 3
Insoluble Soluble

18. • On the other hand, solubility of
tetracycline is reduced when it forms
complex with calcium.
• Tetracycline ( antibiotic) + Ca diet ----------- Ca-tetracycline (a comlex)→
Soluble Poor soluble

19. Effect of surfactants
(solubilising agent):
• Solubility of poor soluble drugs may be
enhanced by a technique known as micellar
solubilisation, which involves the use of
surfactants for increasing the solubility.
• When a surfactant having a hydro-philic (water
loving) and a lipo-philic (or hydrophobic
water hating) portion is added to a liquid, it→
re-arranges itself to from a spherical
aggregate known as micelle

20. • In aqueous medium, the surfactant
molecule orientate in such a manner
that their hydrophilic portion faces the
water and the lipophilic portion (hydro-
phobic) resides in the micellar interior.
An insoluble compound added to the
surfactant liquid, enters the micelle
interior and gets solubilised.

22. • Similarly, In non- aqueous medium (e.g.
oil), the surfactant molecule orientate in
such a manner that their hydrophobic
portion faces the non-aqueous liquid
and the hydrophilic portion resides in
the micellar interior. An insoluble
compound ( such as water) added to
the surfactant liquid, enters the micelle
interior and gets solubilised.

24. Effect of non-electrolytes
on the solubility of
electrolytes:
• The solubility of electrolytes in water primarily depends on the
dissociation of the dissolved molecules into ions. The ease with
which the electrolyte dissociates depends on the dielectric
effect (ability of solvent to produce charge separation between
positive and negative ions of an electrolyte and keep them ionized)
of the solvent, which depends on the polar nature of the solvent.
• Addition of a water soluble non-electrolyte such as alcohol to an
aqueous solution of a sparingly soluble salt decreases the
solubility of sparingly soluble electrolyte i.e. salt. This effect is due
to lowering of the dielectric effect (charge separation ability) of the
solvent by the non-electrolyte, and this in turn reduces dissociation
of the salt.

25. the
solubility of non-
electrolytes
• Solubility of non-electrolytes depends primarily on the
formation of weak inter-molecular bonds (Vander
waal‘s forces, hydrogen bonding) between their
molecules and those of water.
• Addition of an electrolyte having more affinity towards
water reduces the solubility of non-electrolytes by
competing for the aqueous solvent and breaking the
intermolecular bonds between non-electrolyte and
water. This process is also known as salting out.

26. Solubility of liquids in
liquids

27. Liquid – liquid system may be divided into
the following categories according to the
solution of liquids in one another.
•Completely miscible
•Practically immiscible or insoluble
•Partially miscible
The term ‘miscible’ refers to the solubility
of the components in liquid – liquid
systems.

28. Complete miscibility
• In this system, liquids are completely miscible
(soluble) when they are mixed in any
proportions. For example, polar and polar
solvents such as water – alcohol, alcohol –
glycerine, water – glycerine etc. are said to
be completely miscible since they mix in all
proportions. Similarly, non-polar and non –
polar solvents are also completely miscible
such as CCl4 and Benzene.

29. Practically immiscible
(insoluble):
• These liquids do not mix in any
proportion. If they are shaken
vigorously, they mix but soon form the
layers on standing. These liquids are
entirely different from each other
chemically as well as polarity wise. For
example, castor oil (organic & non-
polar) is completely immiscible with
water ( inorganic & polar).

30. Partially miscible:
• These liquids are miscible to each other but to a
limited extent i.e. partially. These liquids mix but form
two layers. Each layer is a solution of one liquid into
the other. Some liquid ‘A’ is dissolved into ‘B’ and
some liquid ‘B’ is dissolved into liquid ‘A’. Both of
these layers (i.e. solutions) are known as conjugate
solutions. If such a mixture is heated, the two layers
disappear and form one layer. The temperature at
which two partially miscible liquids become
completely miscible is called “critical solution
temperature or upper consulate
temperature”.

31. • For example, when water and phenol
are mixed in equal quantities, they form
two layers at 25CO
. The upper layer
contains solution of 95% water + 5%
phenol, and lower layer contains
solution of 70% phenol + 30 % water.
But at 68.4 CO
(critical solution
temperature), two layers disappear to
form one phenol-water solution

32. Other examples of partially miscible liquids include;
Aniline – water, nicotine – water, triethylamine – water
etc.

33. Solubility of gases in
liquids

34. Effect of pressure:
• The pressure of the gas above the solution is
important in gaseous solutions since this significantly
affects the solubility of the dissolved gas. Greater the
pressure of the gas above the solution, greater will be
the solubility of the gas in the solution and vice versa.
• The effect of the pressure of the gas is given by the
Henry ‘s law which states that ‘ in a dilute solution,
the mass of a gas which dissolves in a given volume
of a liquid at a constant temperature is directly
proportional to the partial pressure of the gas.

35. • According to Henry’s law:
C = Pδ
Where,
• C is the concentration of the dissolved gas in grams per
litre of the solvent
• P is the partial pressure in mm of Hg of the undissolved
gas above the solution and can be obtained by
subtracting the vapour pressure of the solvent from the
total pressure of the solution.
• δ is the proportionality constant and is referred as
solubility coefficient.
• the solubility of gases generally increase with increase in
pressure and on the release of pressure, the solubility
decreases and the gas escape.

36. Effect of temperature:
• Temperature also has a marked influence on
the solubility of a gas in a liquid. As the
temperature increases, the solubility of most
of the gases decreases owing to the greater
tendency of the gas to expand in comparison
to the solvent. It is therefore essential that
caution must be exercised when opening the
container containing the gaseous solution
under elevated temperature.

37. Salting out:
• “Process in which solubility of a non - electrolyte is
reduced by the addition of an electrolyte having more
affinity to the solvent than that of non-electrolyte”.
• Gases (non-electrolyte) are often liberated from the
solution when an electrolyte such as sodium chloride
is added. It can be demonstrated by adding a small
amount of sodium chloride to a carbonated solution
(cold drinks). The liberation of the gas is due to the
attraction of salt ions to the water molecules which
reduces the availability of solvent molecules for the
gas molecules due its greater affinity for water than
that of gas molecules.

38. Effect of chemical
reaction:
• Chemical reaction if any between a gas and a solvent
greatly increases the solubility of the gas in the
solvent. For example, when ammonia and sulphur
dioxide dissolve into water, following reaction takes
place;
•
• NH3 (g)+ H2O(L) NH↔ 4OH(aq.) NH↔ 4+(aq) + OH-
(aq.)
•
• SO2(g)+ H2O(L) H↔ 2SO3 (aq.) H+↔ (aq) + HSO3
-
(aq)