Komar University: of Science and Technology

KOMAR UNIVERSITY
OF SCIENCE AND TECHNOLOGY

Monica Diyya,
Department of Pharmacy,
College of Medicine.
Course Name: Physical Pharmacy-I
UNIT II: Solubility and Related Phenomena
UNIT II
Lesson No: 02C Solubility of Liquids in Liquids
2
UNIT II
Lesson 02C
Contents
➢Factors effecting solubility (Solubility of liquids in liquids)

➢Phase equilibrium: One component system
➢Partition coefficient: Concept
KUST/Pharmacy/MonicaDiyya 3
Solubility of Liquids in Liquids
Examples of pharmaceutical solutions containing a liquid
dissolved in another liquid include hydroalcoholic solutions,
aromatic waters such as Chloroform water, Peppermint water,
spirits and elixirs.
Ideal and Real Solutions
Ideal Solutions Nonideal Solutions
Raoult’s Law: a. Negative deviation
0 b. Positive deviation
Pi = Pi  X i
4
Raoult’s Law states,
At a definite temperature, the partial pressure (PA) of a component

(A) in a liquid mixture is equal to vapour pressure in the pure state
(POA) multiplied by the mole fraction of the component(XA) in the
solution. It is expressed as:
PA = PAO XA
Ideal solutions are those which obey Raoult’s law over the whole
range of composition at all temperatures.
However, in practice, there are deviations from Raoult’s Law. Such
solutions showing deviations are called real (or non-ideal) solutions.
Raoult’s Law Deviation:
i. Positive deviation
ii. Negative deviation
KUST/Pharmacy/Monica Diyya 5
• If the deviation is negative, it leads to increased solubility
because of hydrogen bonding between the polar components.
• If the deviation is positive, it leads to decreased solubility

because of association of the molecules of one of the
components to form dimers or polymers of high order.
Positive deviation is due to difference in the cohesive forces or

internal pressures of the molecules of each constituent.
6
Raoult’s Law
i. Positive deviation ii. Negative deviation
A A A B
A A A B
Cannot mingle Associated with

with each other hydrogen bonding
due to difference between polar
in the cohesive components
forces or internal
pressures of the Increased
molecules of each solubility
constituent
Eg: Chloroform
Decreased & acetone
solubility
Eg: Polymers
KUST/Pharmacy/Monica Diyya
7
Solubility of Liquids in liquids
• Frequently two or more liquids are mixed together in the

preparation of pharmaceutical products (e.g. aromatic waters,
spirits, elixirs, lotions, sprays, and medicated oils).
• Liquid–liquid systems can be divided into two categories
according to the solubility of the substances in one another:
1. Complete miscibility
2. Partial miscibility.
Complete Miscibility
• Polar and semipolar solvents, such as water and alcohol,

alcohol and acetone, are said to be completely miscible
because they mix in all proportions.
• Nonpolar solvents such as benzene and CCl4 are also
completely miscible.
• These liquids are miscible because the broken attractive
forces in both pure liquids are re-established in the mixture.
Partial Miscibility
• Partial miscible liquids are the liquids that form two

miscible liquid layers, each of which is a saturated solution
of one liquid in the other.
• The two liquid phases are called conjugate liquid phases.
• The mutual solubility of partially miscible liquids is
influenced by temperature.
• Partially miscible liquids are influenced by temperature. The
two conjugate phases changed to a homogenous single
phase at the critical solution temperature (or consolute
temperature).
Behavior of Dettol in water
Phenol-Water System
For certain systems such as a solution of phenol and water,

the mutual solubilities of the two conjugate liquid phases
increase with temperature and at a temperature called
critical solution temperature (or consolute temperature) they
are miscible and at this temperature a homogeneous or a
single phase results for any composition.
Phenol and water show an upper critical solution

temperature (or Upper consolute temperature) of 66.80C and
are miscible at this critical temperature in all proportions.
Partially miscible liquids are influenced by temperature. The
two conjugate phases changed to a homogenous single
phase at the upper critical solution temperature (or upper
consolute temperature).
Phenol-Water System:
Triethylamine-Water System
Some liquid pairs (e.g. triethylamine and water) exhibit a

lower consolute temperature of 18.50C, below which the two
members are soluble in all proportions and above which two
separate layers form.
14
Nicotine -Water System
Few mixtures (e.g. nicotine
and water) show both an
upper and a lower
consolute temp. with an
intermediate temp. region
in which the two liquids
are only partially miscible.
Upper critical solution
temperature is found to be
2080C and lower critical
solution temperature is
found to be 60.80C
15
A final type exhibits no critical solution temperature (e.g. ethyl
ether and water shows partial miscibility over the entire
temperature range at which the mixture exists.
TERNARY SYSTEMS
“Addition of third component to a pair of partially miscible
liquids produce a ternary system.”
If the added component is soluble in only one of the two
components or if its solubility in the two liquids is markedly
different, the mutual solubility of the liquid pair is decreased.
If the third substance is soluble in both liquids to roughly the
same extent, the mutual solubility of the liquid pair is
increased.
16
PHASE EQUILIBRIUM:
One component System
In thermodynamics, the triple point of a substance is
the temperature and pressure at which the
three phases (gas, liquid, and solid) of that substance coexist
in thermodynamic equilibrium.
➢It is that temperature and pressure at which

the sublimation curve, melting curve and
the vaporisation curve meet.
18
Triple point of Water
B
A A
O
C
At triple point, all three phases are in equilibrium at the temperature of 0.00980C
19
In the pressure-temperature diagram (P-T diagram)
Curve OA: It is known as Vapor pressure curve (along the vapor
pressure curve, vapor and liquid coexist in equilibrium)
Its upper limit is at the critical temperature 3740C for water, and
its lower end terminates at 0.00980C, called the triple point.
Curve OC: It is known as sublimation curve (vapor and solid exist in
equilibrium)
Curve OB: It is known as melting point curve (liquid and solid exist
in equilibrium)
The result of changes in pressure (at fixed temperature) or
changes in temperature (at fixed pressure) becomes evident by
referring to the phase diagram.
20
THE PARTITION COEFFICIENT (K) -CONCEPT
The partition law :

A solute will distribute itself between two immiscible
solvents so that the ratio of its conc. in each solvent is
equal to the ratio of its solubility in each one
Ko/w = Co/ Cw
Co = molar conc. in organic layer
Cw = molar conc. in aqueous layer
Ko/w = partition coefficient or distribution
constant (equilibrium constant)
• If a liquid or solid substance is added to a mixture of two
immiscible liquids, it will become distributed between the
two layers in a definite concentration ratio.
• If the substance is added in an amount insufficient to

saturate the solutions, it will still become distributed
between the two layers in a definite concentration ratio.
• The movement of a solute from one phase to another is
called partitioning.
22
Determination of K
• The most commonly used method for the determination of the
partitioning coefficient of a drug is the Shake-Flask method.
• A drug whose K is to be determined is traditionally added to a
separating funnel containing two immiscible phases.
Value of K Drug Property

K > 1 or Log P > 0 Implies that the drug
has affinity for lipid
membranes.
K<1 or LogP < 0 The drug has affinity
for water or
hydrophilic layer
23
Distribution and Partitioning of compound - Pharmaceutical Significance
Partitioning and distribution phenomena are involved in several areas

of pharmaceutical interest which include:
• Preservation of oil-water systems (emulsions).

• The absorption and distribution of drugs throughout the body.
• Extraction of active drug principles from crude drugs.
24

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KOMAR UNIVERSITY

OF SCIENCE AND TECHNOLOGY

➢Factors effecting solubility (Solubility of liquids in liquids)

At a definite temperature, the partial pressure (PA) of a component

• If the deviation is positive, it leads to decreased solubility

Positive deviation is due to difference in the cohesive forces or

i. Positive deviation ii. Negative deviation

Cannot mingle Associated with

• Frequently two or more liquids are mixed together in the

• Polar and semipolar solvents, such as water and alcohol,

• Partial miscible liquids are the liquids that form two

For certain systems such as a solution of phenol and water,

Phenol and water show an upper critical solution

Some liquid pairs (e.g. triethylamine and water) exhibit a

➢It is that temperature and pressure at which

The partition law :

• If the substance is added in an amount insufficient to

Value of K Drug Property

Partitioning and distribution phenomena are involved in several areas

• Preservation of oil-water systems (emulsions).

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