Lecture 4
Solubility and Distribution
Phenomena
A solution
is a system in which molecules of a solute
are dissolved in a solvent.
Solubility
is defined as the maximum solute concentration in a certain
solvent at a certain temperature.
4g 5g 6g 7g 8g 9g
How Does a Solution Form?
The intermolecular forces between solute and solvent particles
must be strong enough to compete with those between solute
particles and those between solvent particles.
Based on states of matter, a total of nine possible types mixtures
can be formed as shown in Table
Solutions can be classified based on the amount of solute
present in the solvent are as follows
A. Unsaturated Solution: It is the one in which
the amount of solute present is less than that
required for saturation.
B. Saturated Solution: At this stage the
undissolved solute is in equilibrium with
dissolved solute.
C. Super Saturated Solution: It is the one that
contains higher amounts of dissolved solute
than the solvent would take up under normal
temperature and pressure condition.
Saturated sugar solution
Imagine there is a saturated sugar solution
There are undissolved sugar crystals at the bottom
of the solution.
This can be shown by the equation,
Since the amount of sugar at the bottom does not change once
equilibrium is attained, the process stops. it seems that sugar does
not go into solution or come out of solution anymore. However,
this is not true.
The amounts of undissolved sugar crystals and sugar in solution
do not change because the rate at which sugar molecules go into
solution is the same rate as sugar molecules coming out of solution
(forming crystals).
Substance solubility can be expressed in number of parts of
solvent required for dissolving one part of solute.
Solubility curve
Solubility curve
Solute-Solvent Interactions “Like dissolves Like”
Polar substances tend to dissolve in polar solvents, while
nonpolar substances tend to dissolve in nonpolar solvents
Types of solvents:
Polar solvents
Nonpolar solvents
Semipolar solvents
Polar Solvents
Polar solvents dissolve ionic solutes and polar substances.
The solubility of a drug in polar solvent depends on:
1. The polarity of the solute and the solvent.
2. The ability of the solute to form hydrogen bonds.
(oxygen- and nitrogen-containing compounds that can form hydrogen
bonds with water)
3. The ratio of polar to nonpolar groups of the molecule
(When additional polar groups are present in the molecule water
solubility increases greatly).
As the length of a nonpolar chain of an aliphatic alcohol
increases, the solubility in water decreases
Branching of the carbon chain reduces the nonpolar effect and
leads to increased water solubility
Non-polar Solvents
Non-polar solvents have the capacity of dissolving non polar
compounds with similar attractive forces through dipole interactions
(van der waals London forces) (e.g. CCl4 can dissolve oils and
fats).
Ionic and polar solutes are not soluble in nonpolar solvents (e.g.
hydrocarbons) because:
Nonpolar solvents are unable to reduce the attraction between the
ions of strong and weak electrolytes because of the solvents' low
dielectric constants.
Nonpolar solvents cannot form hydrogen bridges with
nonelectrolytes.
Semi-polar Solvents
Semi-polar solvents act as intermediate solvents that generate
miscibility between polar and non-polar liquids
(e.g. Acetone increases the solubility of ether in water).
They are used as solvents for increasing solubility of non-polar
substances in polar substances or polar substances in non-polar
substances
e.g., Propylene glycol improve solubility of water in peppermint oil.
Solubility of Gas in Liquid
The solubility of gases in liquids depends on:
1. The mass of gas molecules
2. Pressure
3. Temperature
4. Presence of salt
5. Chemical reactions with solvent
1) The Mass of Gas Molecules
The solubility of gas molecules typically increases with increasing
mass of the gas molecules.
2) Pressure
Effect of pressure on solubility of gas in liquids is expressed by
Henry’s law.
Henry’s law
very dilute solution at constant temperature the concentration of
dissolved gas is proportional to partial pressure of gas above the
solution at equilibrium. Pressure Effects
CαP C=kP
Where
C is the concentration of dissolved gas in grams/litre of solvent,
P is partial pressure is milliliters,
K is Henry’s law constant or solubility coefficient.
Gases increase in solubility with an increase in pressure.
Increasing the pressure results in more collisions of the gas
molecules with the surface of the solvent (more solvation); and
hence greater solubility.
3) Temperature
Gases decrease in solubility with an increase in temperature.
Increasing temperature (causes an increase in kinetic energy of gas
molecules which leads to breakdown of intermolecular bonds and
gas escaping from solution).
E.g. Carbon dioxide gases escape faster from a carbonated drink as the
temperature increases.
For the same reason gas perfumes, body sprays etc. are exercised with
caution in warm and hot climates. These containers should not be
disposed in fire as the gas expands rapidly and results in bursting of
container.
4) Presence of Salts
Introduction of electrolyte to solution that has dissolved gas
results in liberation of gases from the solution.
This phenomenon is called "Salting Out".
This is due to the higher affinity of electrolyte to water
molecules, which reduces the density of aqueous environment
adjacent to the gas molecules.
5) Effect of Chemical Reaction
Henry's law is strictly applicable to gas which
does not react with the solvent.
The reaction between the gas and solvent alters
the solubility..
Obeyness of Henry’s low
Carbon dioxide (CO2) is more soluble in water than (O2, and
N2)?
The reason of poor solubility of O2 or N2, Ar or H2 in water is
that they just occupy the intermolecular spaces and stays there
by interaction with its surrounding molecules by weak van der
Waals forces.
CO2 when dissolves in water it interacts with surrounding H2O
molecules by forming strong H-bond with H atoms of water
molecules.
Obeyness of Henry’s low
Gases type and obeyness of Henry‘s law
Slightly soluble soluble gases
gases e.g. O2, N2, H2 e.g. CO2, Cl2 show
obey Henry‘s law considerable
deviation from Henry's law.
Very soluble gases
e.g. Ammonia (NH3).
donnot obey Henry‘s law
Solubility of liquid in Liquid
Raoult’s low For binary solutions
(a solution formed with no energy change, when the intermolecular
attractive forces between the molecules of the solvent are the same as
those between the molecules in the separate components).
Ideal Solutions
obey Raoult's law
Ex.
1. benzene + toluene
2. n- hexane + n- heptane
E = 10 E = 10 3. ethyl bromide + ethyl iodide
Total E = 10 – 10 = zero
Real Solutions
The majority of solutions don’t exhibit ideal behavior because,
forces of interaction are unequal.
These are the binary solutions which show either positive or
negative deviation from Raoult's law
Deviation from Raoult’s law
i. Positive deviation the attraction forces between solute and
solvent molecules are weaker than those exerted between
solute molecules themselves or the solvent molecules
themselves, deviation increases the miscibility decreases,
Benzene + water : immiscible (very large positive deviation)
E = 10 E=2
Total E = 10 – 2 = 8
ii. Negative deviation the solute and solvent molecules have
strong mutual affinity that results in the formation of a complex or
compound, deviation decreases the complexation increases,
chloroform + acetone
Pyridine + acetic acid
water + nitric acid
E = 10 E = 15
Total E = 10 – 15 = -5
Complete Miscibility
Represents complete solubility of two or more solvents in all
proportions.
Polar and semi-polar 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
complete solubility
Partial Miscibility
systems which are soluble in each other in definite proportions.
Eg: Ether and water, Nicotine and water; phenol and water
Partially miscible liquids are influenced by temperature
1) phenol and water
When water and phenol are mixed, two
liquid layers are formed each containing
some of the other liquid in the dissolved
state called conjugated phase
The two conjugate phases changed to a
homogenous single phase at the critical
solution temperature
2) Trimethylamine and water
exhibit a lower consolute temperature, below which the two
members are soluble in all proportions and above which two
separate layers form
3) nicotine and water
how both an upper and a lower consolute temp. with an
intermediate temp. region in which the two liquids are only
partially miscible
Immiscibility
Represents systems that do not mix up with each other in any
proportion.
Eg : Water and liquid petrolatum.
Factors Affecting Solubility of Liquids in Liquids
1. Temperature
Effect of temperature is more on the partially miscible liquids.
In case of phenol and water, miscibility of two conjugate systems
increases with temperature
In case Trimethylamine and water miscibility increased when
temperature is lowered.
nicotine and water exhibit both upper and lower consolute
temperature,
ethyl ether and water exhibit neither upper or lower consolute
temperature
2. Presence of Foreign Substances
1. If added substance is soluble in only one of the components of
binary system, then the mutual solubility of liquid pair decreases.
E.g.: If naphthalene is added to mixture of phenol and water, upper
consolute temperature is raised.
2. If added substance is soluble in both the components of binary
system then mutual solubility of liquid pair increase.
E.g.: Addition of sodium oleate to phenol-water system upper
consolute temperature is lowered.
3. Three Component System
Phase equilibria that exist in three component system is usually
complex. They are useful in several areas of pharmaceutical
processing such as crystallization, salt form selection, etc. A
triangular diagram showing solubility of peppermint oil in
various proportions of water and polyethylene glycol
4. Dielectric Constant
As dielectric constant shows considerable effect on the polarity, it
is an important factor to be considered in solubility of liquids in
liquids.
5. Molecular Connectivity
Solubility depends on the structural features and functional
groups of a particular component.
