The document summarizes key concepts about solubility phenomena presented in a seminar. It defines important terms like solution, solvent, solute, and discusses factors affecting solubility such as polarity of solvents and solutes. It also describes concepts like ideal and real solutions, Raoult's law, and deviations from it. Different types of solutions are explained including gas-liquid, liquid-liquid, and solid-liquid solutions. The document also discusses solubility expression, fractional distillation, and properties of partially miscible liquids.

1. SEMINAR ON
SOLUBILTY PHENOMENA
PRESENTED BY:
DHIRAJ SHRESTHA
DEPT OF PHARMACEUTICS
N.E.T. Pharmacy College
FACILITATED BY:
mr. SARFARAZ MD.
DEPT OF PHARMACEUTICS
N.E.T. Pharmacy College

2. SOLUTION
 Solution is a homogenous mixture in which
once substance is said to be dissolved in
other.
 Solutions are also known as true solution or
molecular dispersions.
 In solution, the substance that is present in
large proportion is termed as solvent,and
that in small proportion is solute.
 Based on proportion of a soulte present in
solvent, sloution may be classified as dilute
and concentrated.

3. A solution can be classified acording to the states in which solute and
solvent occur. Nine types of solution is possible.
But in pharmacy only 3 types are significant
1. Gas in liquid
2. Liquids in liquids
3. Solids in liquids

4. CONCENTRATION EXPRESSION
The concentration of a solution can be expressed either in terms of quantity
of solute in a definite volume of solution or as the quantity of a solute in
definite mass of solvent or solution.

5.  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.
 In simple terms, solubility is ability of a substance
(solute) to dissolve in a solvent.
 Quantitavily , solubility is the amount of solute that
dissolves in a unit volume of a solvent to form a
saturated solution under specified conditions of tempr
and pressure.
 Solubility is expressed in concentration terms usually as
moles of solute per 100 gm of solvent.

6. SOLVENT-SOLUTE INTERACTIONS
 Water is a good solvent for salts, sugars, and similar
compounds, whereas mineral oil and benzene are often
solvents for substances that are only slightly soluble in
water.
 This empirical findings suggests that , “like dissolves
like.”
 POLAR solvents dissolves ionic solutes and other
POLAR substances.
 NONPOLAR substances are generally soluble in other
NONPOLAR solvents.

7. Polar Solvents
Eg. Water, Glycols, methyl and ethyl alcohols etc.
Polar solvents such as water acts as solvents due to
following raesons.
1. Bcoz of their high dielectric constant (water-80) , they
reduce the force of attraction b/w +vely charged ions in
crystals such as NaCl.
Choloroform has d.c. 5 and benzene 2 hence ionic
compnds are practically insoluble in them.
2. They break covalent bonds of potentially strong
electrolytes by acid-base rxn bcoz these solvents are
amphoteric.
eg. HCl + H2O H2O+ + Cl-

8.  Weak organic acids are not appreciably ionized by water;
their partial solubility is attributed to H-bonding. Phenols
and carboxylic acids are readily soluble in solution of
strong bases.
RCOOH + H2O Negligible
RCOOH + NaOH RCOO
- Na +
3. Polar solvents are capable of solvating molecules and
ions through dipole interaction forces, particularly H-
bond formation, which leads to solubility of compnd.
The solute most be polar in nature bcoz it often most
compete for the bonds of already associated structure.

9. Nonpolar solvents
Eg.Hexane, benzene, ethyl ether, pet. ether, carbon tetrachloride
(d.c. 5), mineral and fixed veg. oils(d.c. 0)
 These solvents are unable to reduce the attraction b/w the
ions bcoz of their low dielectric constants.
 Also they can’t break covalent bonds and ionize weak
electrolytes bcoz they are aprotic and cannot form H-bridges
with non electrolytes.
 Hence ionic and polar solutes are not soluble or only slightly
soluble in non-polar solvents.
 Nonpolar solvents, however, can disolve nonpolar solutes
with similar internal pressure through induced dipole
interction. The solute are kept in solution by weak van der
Waals-London type of forces.

10. Semipolar solvents
Eg. Aldehyde , ketones, ether, ester (d.c. 20) etc.
 These can induce a certain degree of polarity in
nonpolar solvent molecules ,so that, for example,
benzene which is readily polarizable, becomes soluble in
alcohol.
 Semipolar compoonds can act as intermediate
solvents to bring out miscibility of polar and nonpolar
liquids.
Eg. Acetone increases the solubilty of ether in water.

11. SOLUBILITY OF LIQUIDS IN LIQUIDS
 Hydroalcholic solutions, aromatic waters, spirits and
elixirs are some example of liq. in liq. solutions.
 Liquid-liquid mixtures are of three types.
 Miscible liquids: Miscible in all proportions.
eg. Ethyl alcohol and water.
 Partially miscible liquids: Miscible only at a certain
proportions
eg. Phenol and water
 Immiscible liquids: Completely immiscible regardless of
relative amount of each component.
eg. Carbontetrachloride and water.
Binary solution : A solution composed of only two
substances .The components are referred as solvent
and solute.

12. IDEAL SOLUTION
 An ideal solution is one in which there is no change in
the properties of components, other than dilution , when
they are mixed to form the solution.
 No heat is evolved or absorbed during the mixing
process, and the final volume of the solution represents
an aditive property of individual constituents (no
shrinkage or expansion).
 Ideal solution are formed by mixing substance with
similar properties.
eg. 100ml methanol + 100ml ethanol gives final solution
with vol 200ml, and no heat is absorbed or evolved.
Thus solution is nearly ideal.
 Intermolecular forces between unlike molecules should
be equal to those between similar molecules: the
conditions of an ideal solution.

13. RAOULT’S LAW
 It states that, in an ideal solution, the vapour pressure of
each volatile constituent is equal to the vapour pressure of
pure constituent multiplied by its mole fraction in the
solution.
 For a mixture of two miscible liquids (A and B), the total vapor
pressure is the sum of the individual vapor pressures:
Ptotal = PA + PB
where
PA = P˚A XA
liquid And PB = P˚B XB
liquid
where
P˚A is the vapor pressure of pure liquid A
P˚B is the vapor pressure of pure liquid B
XA
liquid is the mole fraction of A and
XB
liquid is the mole fraction of B
where
XA
liquid = moles A/moles A + B and
XB
liquid = moles B/moles A +B

14. REAL SOLUTION
 Many pairs of liquids are present in which there is no
uniformity of attractive forces i.e. the adhesive and cohesive
forces of attraction are not uniform between the two liquids,
so that they show deviation from the Raoult's law which is
applied only to ideal solutions.
 Such mixture are real or non-ideal , i.e. they don’t adhere to
Raoult’s law in entire range of composition.
 Two types of deviation from Raoult’s law
1. Positive deviation: When the cohesive forces between like
molecules are greater than the adhesive forces, the
dissimilarities of polarity or internal pressure will lead both
components to escape solution more easily. Therefore, the
vapor pressure will be greater than expected from the
Raoult's law, showing positive deviation.
Eg.(1) benzene and methyl alcohol, (2) carbon
disulfide and acetone, and (3) chloroform and ethanol.

16.  Negative deviation: If the vapor pressure of a
mixture is lower than expected from Raoult's law,
there is said to be a negative deviation.
 Because the adhesive forces between different
components are stronger than the
average cohesive forces between like components.
In consequence each component is retained in the
liquid phase by attractive forces which are stronger
than in the pure liquid so that its partial vapor
pressure is lower.
 For example, the system of chloroform
and acetone has a negative deviation from
Raoult's law, indicating an attractive interaction
between the two components ( hydrogen bond.)

17. DISTILLATION OF BINARY MISTURES
 The relationship b/w vapour pressure(and hence b.pt.)
and composition of binary liq. phase is underlying
principle in distillation.
 The higher the vap. Pressure of a liq , the more volatile it
is , the lower is its b.pt.
 Since the vapour of a binary mixture is always richer in
the more volatile constituent, distilation can be used to
separate the more volatile constituent from less volatile
constituent.
 Consider a mix.of high boiling liq A and low boiling boiling
liq B.
Distillation is the process of heating a liq.until it boils , then
condensating and collecting the resulatant hot vapours.

18.  Mixture having compositn a is
distilled at b.pt b, then
compositn of vapour formed
will be v1 .
 v1 will be in eqbm with liq
having compositn c , which is
the compositn of distilate
when condensed.
 If the difference b/w vapour
pressure of components is
large distilation will result in
complete seprn of
components.
 Component with high vapour
pressure i.e. low b.pt will
separate first.

19. FRACTIONAL DISTILLATION
 It is a process in which vaporistion of liq mixture gives a
mixture of constituent from which the desired one is
seperated in pure form.
 Also k/a rectifiaction.
 Principle : When a liq mixture is distilled, partial
condenstion of the vapour is allowed to occur in the
fractionating column.
 In column ascending vapor from still is alowd to come in
contct with condensng vapor returning to still.
 This results in the enrichment of vapor with more volatile
component.
 By condensing the vapour and reheating the liq
repeatdly, eqbm b/w liq and vapour is set up at each
stage, which ultimately results in the seperation of more
volatile component.

20.  If you boil a liquid mixture C1,
you will get a vapour with
composition C2, which you can
condense to give a liquid of that
same composition (the pale blue
lines).
 If you reboil liquid C2, it will give
a vapour with composition C3.
Again you can condense that to
give a liquid of the same new
composition (the red lines).
 Reboiling the liquid C3 will give
a vapour still richer in the more
volatile component B (the green
lines). You can see that if you
were to do this once or twice
more, you would be able to
collect a liquid which was
virtually pure B.
Phase diagram showing
Fractional distillation

21.  Zeotropic
mixture(solution): A
complete seperation of two
miscible liq is possible by
fractional distillation.
eg. Methanol and water.
o Azeotropic
mixture(solution): A
complete seperation of two
miscible liq is not possible
by fractional distillation.
o Also k/a constant boiling
mixtures.
eg. Ethyl alcohol and water
Fig: Fractional distillation
appartus

22. DISTILLATION OF AZEOTROPIC MIXTURES
 When a non ideal solution is distilled it produces either
pure A or pure B plus azeotropic mixture.
 If the vapor pressure curve shows –ve deviation from
Raoult’s law, the azeotrope has highest b,pt of all
mixture possible. It is therefore less volatile and
remains in flask,whereas either pure A or pure B is
distilled off. They are known as maxm b.pt azeotropic
solution.
 If the vapor pressure curve shows +ve deviation from
Raoult’s law, the azeotrope has lowest b,pt and is
distilled off. Either pure A or pure B remains in flask.
They are known as minimum b.pt azeotropic solution.

23. Mixture % composition of
azeotrope
Boiling point (pressure = 1
atm)
1
.
Nitric acid-Water 68% Nitric acid 125.5°C
2
.
Acetic acid-Pyridine 65% Pyridine 139.0° C
3
.
Chloroform-Aceton 80% Chloroform 65.0° C
4
.
Hydrogen chloride-Water 79.8% Water 108.6° C
Mixture % Composition of
azeotrope
Boiling point
(pressure = 1 atm)
1.
2.
3.
4.
Water-Ethanol
Pyridine-Water
Ethanol-Benzene
Acetic acid-Toluene
95.97 Ethanol
57.00 Pyridine
32.40 Ethanol
28.00 Acetic-acid
78.13oC
92.6oC
67.8oC
105.4oC
Table:Maximum boiling point azeotropic mixtures
Table:Minimum boiling point azeotropic mixtures

24. Azeotropic mixture can be seperated by azeotropic distillation in
which azeotropic mixture is broken by addition of a third
substance, which forms a new azeotrope with one of
components.
Eg. Benzene is added in azeotropic mixture of ethyl alcohol and
water
Maximum b. pt azeotropic
mixtures
Minimum b. pt.
azeotropic mixtures

25. PARTIALLY MISCIBLE LIQUIDS
(CONJUGATE MIXTURES)
 It is defined as a two liquid system in which their mutual
solubility in one another is limited
Eg. When equal volume of phenol and water is shaken
together at cnstnt tempr for certain period of time and set
aside, at eqbm, upper layer is phenol saturated with water
and lower layer is water saturated with phenol.
 When tepmr is increased mutual solubilty of one liquid in
another increases. The tempr at which two conjugate
solution are mutually soluble is k/a miscibility tempr.
 When solubility of one liq. in another (in x-axis) is ploted
against miscibility tempr(y-axis), a specific pattern is
obtained for a particular conjugate liq. system. These
solubilty tempr profiles are known as miscibility curves or
phase diagram.

26. CRITICAL SOLUTION TEMPERATURE (CST)
 The lower critical solution temperature (LCST)
or lower consolute temperature is the critical
temperature below which the components of a mixture
are miscible for all compositions.The
word lower indicates that the LCST is a lower bound to a
temperature interval of partial miscibility, or miscibility for
certain compositions only.
 The upper critical solution temperature (UCST)
or upper consolute temperature is the critical
temperature above which the components of a mixture
are miscible in all proportions. The word upper indicates
that the UCST is an upper bound to a temperature
range of partial miscibility, or miscibility for certain
compositions only.

27. PHENOL-WATER SYSTEM
 The parabolic curve represents the
miscibilty of phenol and water.
 Left hand side-represnt conjugate
solution,which represent % (w/w)of
phenol in water. Incrsd tempr increase
solubilty of phenol in water.
 Right-represent % (w/w)of water in
phenol.Incrsd Tempr incrses solubilty of
water in phenol.
 Two crves meet at maxima in tempr-
compositn curve. The point corespond
to tempr of 66.80C and phenol
compositn of 33% w/w. This tempr is
known UCST.
 At any tempr above CST phenol and
water are miscible in all proportion.

28.  Outside the curve, phenol and water are miscible.
 Under curve, normally liquid exist as two layers.
Complete miscibilty is posible depending on
compositn of mixture.
 The tie line(bc) is represented by line drawn parallel
to the base line from points in the curve at any tempr
in phase diagram of partially miscible liq. All system
present on tie line , at eqbm, will separate into phase
of cnstnt compositn.
 Therefore, at desired tempr, a tie line can be drawn
and relative amount of each component in two layers
are calculated.
wt of phase A/ wt of phase B == length dc/length bd

29. LCST-18.50 C
Compositn-50% w/w
Triethylamine-Water System
UCST-208 C, compositn-32%
LCST-61 C, compositn22% nicotine in water
Nicotine-Water System

30. Application of CST
 Deciding the proportion of two liq. to be taken
during formulation of solution, when a single phase
product is desirable.
 CST is a characteristic of a system and can be
hence used for testing the purity of a substance.
 It can also be used to determine the % composition
of added component in the conjugate solution.

31. SOLUBILITY OF SOLID IN LIQUIDS
 A saturated solution contains the maximum
amount of a solute that will dissolve in a given
solvent at a specific temperature.
 An unsaturated solution contains less solute than
the solvent has the capacity to dissolve at a specific
temperature.
 A supersaturated solution contains more solute
than is present in a saturated solution at a specific
temperature.

33. DETERMINATION OF SOLUBILTY
 Following steps
1. Preparation of saturated solution at constant tempr.
2. Seperation of undisolved drug(solute) from saturated solution.
3. Determination of concn of drug in solution by analytical method.
To obtain a saturated solution at the required tempr ,an excess amount
of powdered solid is agitated continuously with solvent until eqbm is
achieved at cnstnt tempr. For volatile substances, solvent and solute
are sealed in a glass ampoule and rotated on a wheel that is
immersed in water bath.
A sample of the saturated solution is seperated from the undissolved by
filtration at the same initial tempr.
Analysis of the filterd solution by any suitable chemical or gravimetric
analysis. Spectrophotometric and HPLC methods provide accurate
estimation.

34. SOLUBILTY OF GASES IN LIQUIDS
 Eg. Liq. Ammonia and Hydrochloric acid
 The solubilty of a gas in liquid is expressed as concn of
the dissolved gas, when it is in eqbm with the pure gas
above the solution.
 Factors affecting solubility of gases in liquids
 Pressure
 Temperature
 Presence of electrolytes and non-electrolytes
 Chemical interaction with the solvent

35.  Effect of pressure : Given by Henry’s law, which states that
the concn of dissolved gas is proportional to the partial
pressure of the gas above the solution at cnstnt tempr.
Mathematically,
c= p where
c= concn of dissolved gas, mol/lt
p=partial pressure of gas above solution, kPa
=solubility coeff., mol/l.kPa
 Presence of gas above solution is important considerstion in
gaseous solution. If this pressure increases more gas goes in
solution at eqbm.
 The solubilty of gases increases with increase in pressure
and on the release of pressure, the solubilty decreases and
gas escapes.
 Effect of tempr: As tempr increases solubility decreases.
This is due to a) tendrncy of gas to expand b)increse in
pressure at elevated tempr.

36.  Effect of electrolytes and non-electroltes:
Solubility of gas in liq. is reduced by addition of
electrolytes(eg.NaCl) and non-electrolytes
(eg.Sugar). This is k/a salting out. This is due to
more affinity b/w solvent and electrolyte and non-
electrolyte than b/w solvent and gas.
 Effect of chemical rxn: Chemical rxn if any b/w
gas and solvnt greatly increase solubility.
Eg. HCl reacts with water by H-bonding when it
dissolves in water. The solubilty of HCl in water is
10,000 times more than oxygen in water

37. FACTORS AFFECTING SOLUBILITY OF SOLIDS
IN LIQUIDS
 Effect of tempr:  Depends in heat
of solution.
 If endothermic
solubility↑ with ↑
in tempr.
 If exothermic
solubility ↓with ↑
in tempr.
 If heat of solution
is zero solubility
doesn’t change
with tempr.

38.  Particle size :
 Solvent :
 pH effect:
 Complexation:
 Surfactants :