Pharmaceutical Solutions and Solubility:

- Factors affecting solubility and rate of solution

- Solutions of liquids in liquids
- The distribution of solutes btw immiscible liquids and applications of the distribution
law in pharmacy
- Colligative ppties of solutions
- Phase equilibra; the phase rule, systs of one and two components and applications in
pharmacy eg eutectic mixture and sublimation (freeze) drying.

Solution
A solution may be defined as a mixture of two or more components that form a single phase
which is homogeneous down to the molecular level. The component that determines the
phase of the solution is termed the solvent and usually constitutes the largest proportion of
the system. The other components are termed solutes, and these are dispersed as molecules
or ions throughout the solvent, i.e. they are said to be dissolved in the solvent.

Rate of Solution (Dissolution)

The transfer of molecules or ions from a solid state into solution is known as dissolution. The
extent to which the dissolution proceeds under a given set of experimental conditions is
referred to as the solubility of the solute in the solvent.

Solubility
The solubility of a substance is the amount of it that passes into solution when equilibrium is
established between the solution and excess (undissolved) substance. The solution that is
obtained under these given temperature and pressure conditions is said to be saturated.
The extent of solubility of different substances varies from almost imperceptible amounts to
relatively large quantities. For any given solute, the solubility has a constant value at
constant temperature and pressure. The solubility of a substance in a solvent can be
described with terms such as “Very soluble, Freely soluble, Soluble, Sparingly soluble,
Slightly soluble, Very slightly soluble or Practically insoluble or insoluble.
A super saturated solution is produced when a solute is dissolved in a solvent at a particular
elevated temperature and the excess solid solute is removed and the resulting solution is
cooled to a lower temp. This is usually unstable and the excess dissolved solute can be
recovered by vigorous shaking, scratching the side of the vessel or introducing into the
solution a small crystal of the solute, which will act as a nuclei, precipitating the solute out of
solution.

Mechanism of solution formation

For a solution to form there must be an affinity between the solvent and the solute
molecules. This affinity must be greater than that of the solvent for its own molecules as well
as that the solute for its own self. It is commonly said that like dissolves like. By implication;
polar solvents will dissolve polar solutes while non-polar solvents will dissolve non-polar
substance.

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Factors Affecting Solubility
1. Temperature
Temperature can have four possible ways of affecting a solution depending on the nature of
both solute and solvent.
1. Endothermic process with a positive heat of solution. Here, heat is taken up when
solid dissolves in liquid. Therefore, increase in temperature will increase the
solubility of the solid. e.g. KNO3 (potassium nitrate).
2. Exothermic process with a negative heat of solution. In this case, the dissolution
involves the liberation of heat and an increase in temperature will result in a decrease
in solubility e.g. calcium acetate (CH3COO)2 Ca.2H2O.
3. A combination process where dissolution is either endothermic or exothermic up to a
transition temperature and then reverses e.g. Na2SO4.10H2O (endo-exo).
4. This involves little absorption of heat in which case significant changes in
temperature may not necessarily influence the solubility significantly e.g. NaCl.
Solubility curves are often used to indicate the effect of temperature on the solubility
of a given substance.

Transition
point KNO3

Na2SO4
(andydrous) NaCl
Na2SO4 10H2O
(decahydrate) ca-acetate

305.55K Temp Temp

Figure 1: Effect of temperature on solubility of different solutes in a solvent

2. Particle size
Solubility increases as particle size decrease and this is due to the changes in interfacial
energy that accompany the dissolution of particles of varying sizes. Fine particles are
associated with large surface area and high interfacial or surface energy. This makes them
highly unstable and reactive facilitating their solubility.
This effect may be significant in the storage of Pharmaceutical suspensions, since the smaller
particles in such a suspension will be more soluble than the larger ones. As the small
particles disappear, the overall solubility of the suspended drug will decrease and growth of
the particles will occur. The occurrence of crystal growth by this mechanism is of particular
importance in the storage of suspensions intended of injections e.g. procaine penicillin
(fortified) after mixing with water for injection.
Solubility of solids differs in different solvent systems (polar to non-polar). Water is the most
common solvent encountered in pharmaceutical practice especially for preparations
intended for internal use. Ethanol and water in different proportions are also used. Water
can also be combined with simple organic solvents such as chloroform, ether, acetone,
glycols and all these influence the solubility properties to varying degree.

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3. pH
Many drugs behave as weak acids or bases and their solubility’s are therefore affected by the
pH of an aqueous solvent. E.g. a weakly acidic drug such as acetylsalicylic acid (ASA) will be
more soluble in alkaline solution since it will be converted to the more soluble salt. This drug
however is better absorbed in the acidic environment of the stomach since it will be non-
ionic or unionized in an acid environment). The drug will be precipitated from aqueous
solution if the pH is lowered by the addition of a strong acid and vice-versa for a weakly basic
drug.
4. Additional Factors
(a) Common ion effect: The solubility of a sparingly soluble electrolyte is decreased by the
addition of a second electrolyte that possesses a similar ion to the first.
(b) Effect of indifferent electrolytes: The solubility of a sparingly soluble electrolyte may be
increased by the addition of a second electrolyte that does not possess ions common to the
first i.e. an indifferent electrolyte.

(c) Effect of non-electrolytes on the solubility of electrolyte: The solubility of electrolytes

depends on the dissociation of dissolved molecules into ions. The ease of this dissociation is
affected by the dielectric property of the solvent, which is a measure of the polar nature of the
solvent. Liquids with a high dielectric constant (e.g. water and formic acid) are able to reduce
the attractive forces that operate between oppositely charged ions produced by dissociation of
an electrolyte. If a water-soluble non-electrolyte such as alcohol is added to an aqueous
solution of a sparingly soluble electrolyte, the solubility of the latter is decreased because the
alcohol lowers the dielectric constant of the solvent and ionic dissociation of the electrolyte
becomes more difficult.

(d) Effect of Electrolytes on the solubility of Non-electrolytes: Non-electrolytes do not

dissociate into ions in aqueous solution and in dilute solutions, the dissolved species therefore
consists of single molecules. Their solubility in water depends on the formation of weak
intermolecular bonds (Hydrogen bonds) between their molecules and those of water. The
presence of a very soluble electrolyte e.g. (NH 4)SO4 ammonium sulphate the ions which have
a marked affinity for water will reduce the solubility of the non-electrolyte by competing for
the aqueous solvent and breaking the intermolecular bonds between the non-electrolyte and
water. The effect is important in the precipitation of proteins.

(e) Effect of complex formation: The apparent solubility of a solute in a particular liquid may
be increased by the addition of a third substance which forms an intermolecular complex with
the solute. The solubility of complex will determine the apparent change in the solubility of
the original solute.
[1] Para-aminobenzoic acid + various dicarboxylic acids = increased the solubility of PABA.
[2] 4-hydroxybenzoic acids, salicylic acids, chloramphenicol and phenol + various amides.
[3] Hgl2 (mercuric iodide) is made aqueous soluble by dissolving in aqueous solution of Kl
(potassium Iodide) because of the formation of water soluble complex (K2 (Hgl4))

(f) Effect of surface active agent: These compounds are capable of forming large aggregates
at certain concentrations in aqueous solution. Organic compounds with low water solubility
are taken into the interior of these aggregates and the apparent water solubility of the organic
compounds are increased. The phenomenon is termed solubilisation.

(g) Molecular structure: Changes in molecular structure and state can alter the solubility of
substances e.g. phenol and benzene, salts and bases of alkaloidal drugs such as quinine.

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DISSOLUTION RATE (RATE OF SOLUTION)
This is the rate at which a dissolving solute particle diffuses through the stagnant layer to the
bulk solution. The driving force behind the movement of the solute molecule through the
stagnant layer is the difference in concentration that exists between the concentration of the
solute (C1) in the stagnant layer at the surface of the solid and its concentration (C 2) on the
farthest side of the stagnant layer. The greater this differences in concentration (C 1-C2), the
faster the rate of solution.
According to Noyes-Whitney equation, the rate of solution is also directly proportional to the
area of the solid, (A in cm 2) exposed to the solvent and inversely proportional to the length of
the path through which the dissolved solute molecule must diffuse. It is given by:
D. A.C1 - C2
Rate of solution =
L
Where D = proportionality constant called diffusion coefficient in cm2/sec.
C1 is also equal to the saturation solubility of the solute and
C2 (under sink condition) is negligible

Therefore simplifying the equation:

D. A.C1
Dissolution rate =
L

Bulk solution
Stagnant layer Solid particle
C2 L

C1

Figure 2: A solid particle in a

dissolution medium

From the equation above, the rate at

which materials dissolves is affected by:
(1) Size of the particle: For a given mass of solute, decrease in size leads to an increase
in surface area and hence increase dissolution rate.
(2) Stirring: This decreases the thickness of the stagnant layer, which is inversely
proportional to the rate of solution.
(3) Nature of solute: The more soluble the solute, the faster the dissolution rate
(4) Viscosity of solvent: With a viscous liquid solvent, the rate of solution decreases.
Diffusion coefficient is inversely proportional to the viscosity of solvents.

SOLUTION OF LIQUID IN LIQUID

Water and alcohol mix in all proportions, whereas water and mercury do not mix at all.
Between these extremes of complete miscibility and complete immiscibility, all degrees of
partial miscibility or solubility may exist. When ether is added to water, the solution

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solubility is limited. A point is reached when the ether will result in the formation of two
liquid layers, one the upper layer consisting of ether containing about 3% of water, the other
the lower layer consisting of water containing about 10% of ether.

IDEAL SOLUTION AND RAOULT’S LAW

The vapour pressure of a solution is a particularly important property since it serves as a
quantitative expression of its escaping tendency.
Raoult’s Law states that in an ideal solution, the partial vapour pressure of each volatile
constituent is equal to the vapour pressure of the pure constituent multiplied by its mole
fraction in the solution. Thus for two constituents A & B:
PA = PAO. XA
PB = PBO. XB
Where PA and PB are partial vapour pressures of the constituents over the solution when the
mole fraction concentrations are X A and XB respectively, while PAO PBO are the vapour
pressures of the pure components.
For example: Given that the vapour pressure of ethylene chloride in the pure state is 236
mmHg at 50 °C, then in a solution consisting of a mole fraction of 0.4 ethylene chloride and
0.6 benzene, the partial VP of ethylene chloride is 40% of 236 = 94.4 mmHg. Thus, in an
ideal solution, when liquids A and B are mixed, the VP of A is reduced by dilution with B in a
manner depending on the mole fractions of A and B present in the final solution.

Real solutions
Ideality in solutions presupposes complete uniformity of attraction forces. But the attractive
forces between A and B may be greater than those between A and A or B and B. This may
occur even though the liquids are miscible in all proportions. These are real or non-ideal
mixtures. They do not adhere to Raoult’s Law throughout the entire range of composition.
Two types of deviation from Raoult’s Law are recognized: Negative (attraction between
molecules of different species exceed the attractions between like molecules) and Positive
deviation (the presence of a different specie molecule reduces the attraction between like
molecules).

THE DISTRIBUTION OF SOLUTE BETWEEN IMMISCIBLE LIQUID

The Distribution Law

If a solute is in the same molecular condition in two different solvents, the ratio in which the
solute distributes itself between the two solvents is called the distribution coefficient or
partition coefficient which is constant at constant temperature.
In the presence of several solutes, the distribution of each solute takes place independently of
the others
Partition coefficient: When a substance is distributed between immiscible solvents, A
and B,

Partition (Distribution) coefficient = = = =

Since saturated solutions of the same solute in the two immiscible solvents are in
equilibrium, the distribution coefficient is equal to the ratio of the solubility of the solute in
solvent A to its solubility in solvent B. In most cases however, K is not strictly constant for all

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ranges of concentrations in the two solvents the value of K derived from solubilities is
therefore only approximate.

Applications of distribution law

(1) Extraction: The extraction of a solute from solution by shaking with an immiscible
solvent is frequently used in the preparation and assay of materials containing
alkaloids (active form of crude extract).
If an aqueous solution of an alkaloidal salt e.g quinine sulphate is made alkaline and
shaken with chloroform, the alkaloidal base distributes itself in favour of the
chloroform phase. Successive extractions will deplete the aqueous phase of alkaloid.
If the separated chloroform layers are combined and extracted with an acidic
solution, the alkaloid (as salt) passes into aqueous phase and is relatively free from
extraneous material such as plant pigments and tannis which do not possess the
same solubility characteristics.
For example, consider a substance s, soluble 10 g in 100 ml of water and 80 g in 100
ml of chloroform, therefore K = 8. Extraction is more efficiently done with repeated
quantities (aliquots) of the extracting solvents rather than using one quantity. i.e., it
is more efficient to use 25 ml of chloroform four times than to use 100 ml of
chloroform at once.
(2) This phenomenon is also used in chromatography (partition chromatography). When the rate
and extent of movement of a component of the crude is proportional to its relative affinity
between the mobile phase and the stationary phase

(3) Drug passing through biologic membrane: Partition Coefficient is important in

processes involving the absorption, transport and distribution of drugs throughout the body
since the drugs have to partition between the aqueous body fluids and the lipoidal cell
membrane surface.

(4) Preservation of emulsions and cream: They comprise two immiscible phases, which
have been stabilized; the aqueous phase can allow the growth of microorganism hence the
need for a higher concentration of preservation here. Unfortunately, this preservation can
partition in favour of the oily phase thereby decreasing the effective amount in the aqueous
phase.

(5) Release of Drugs from certain Dosage forms: The effect of partition between
water immiscible bases (as in suppositories and ointments) and body fluids is made
use of in the formulation of products intended to provide a prolonged release of
drugs.

COLLIGATIVE PROPERTIES
These are physical properties which depend mainly on the number of particles in a solution.
The colligative properties are: Osmotic pressure, vapour pressure lowering, freezing pH
depression and boiling point elevation.
The CPs arise from the attractive forces that are exerted by the solute on the solvent e.g.
solute attractive forces reduce the tendency of the solvent to escape from the liquid as vapour
hence the reduction of the V.P of the pure solvent.

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Vapour Pressure Lowering
The vapour pressure of a solution may be determined directly by means of a manometer.
When a non-volatile solute is dissolved in a liquid solvent, the vapour pressure of the solvent
is lowered. This is due to the reduction in the surface available for evaporation of solvent by
the molecules, which have little or no vapour pressure of their own. For ideal solution of
non-electrolytes the vapour pressure of the solution follows Raoult’s Law

Boiling – point Elevation

The boiling point of a liquid is the temperature at which the vapour pressure is equal to the
atmospheric pressure.We know that on the addition of a non -volatile solute to a pure
solvent,the vapour pressure of the solution decreases.Therefore, to make vapour pressure
equal to atmospheric pressure we have to increase the temperature of the solution.The
differences in the boiling point of the solution and the boiling point of the pure solvent is
termed as elevation in boiling point.

Freezing – Point Depression

The freezing point of a solvent is defined as the temp at which solid and liquid forms of the
solvent co-exist in equilibrium at a fixed external pressure (760 mmHg or 1 atmos). At this
temperature, the solid and liquid forms must have the same V.P or else the one with a higher
V.P will convert to the one with a lower V.P. Since the V.P of a solution is lower than that of
its pure solvent, it is obvious that solid solvent and solution can only exist at a lower temp
than would solid solvent and pure solvent at equilibrium.
The freezing point of a dilute solution of a non-electrolyte solution (and the b.pt elevation)
can be used to determine the molecule wt of the solute. However, the freezing pt depression
is more advantageous than the boiling pt elevation by virtue of its larger magnitude.

Osmotic Pressure (O.P)

This is proportional to the concentration of the solute or the attractive force (between the
solute and solvent) on the solution. For non-electrolytes, O.P of two solutions of the same
molar concentration is identical while for electrolytes, the O.P will depend on the amount or
number of ions produced in solution.
PV = nRT is used to calculate the O.P of a dilute solution of a non-electrolyte
While PV = inRT is used to calculate the O.P of a dilute solution of an electrolyte
Where i = the value approaches the number of ions produced by the ionization of a stronger
electrolyte. The O.P is the most important of the colligative properties in pharmacy and
medicine.

Importance or Applications of C.Ps.

In the preparation of isotonic I.V infusions and lachrymal fluids (eye, ear and nose drops).
In experimental physiology in preparation of solutions (Krebs, normal saline etc) to prevent
changes or injuries to tissues arising from osmosis.
In determination of mol wt of solute in non-electrolytes or the extent of ionization in
electrolytes.

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 PHASE EQUILIBRIUM

The phase rule

It was formulated by J. Willard Gibbs, it helps (is used) to relate the effect of the least
number of independent variables (e.g. temp pressure and concentration) upon the various
phases (solid, liquid and gaseous) that can co-exist in an equilibrium system containing a
given number of components.
The phase rule is expressed as follows: F = C – P + 2
Where F = number of degrees of freedom in the system
C = the number of components
P = the number of phases present

A phase (P) is a physically distinct, homogenous part of a system separated by definite

boundaries from other parts of the system e.g. 2 or 3 phase system (ice, liquid water and
water vapour),If two liquids are immiscible(e.g oil and water)they will constitute two
separate phases.Two miscible liquids(e.g water and alcohol) constitute one phase only.
The number of components ©: This is the smallest number of constituents by which the
composition of each phase in the system at equilibrium can be expressed in the form of a
chemical formula or equation. For example, the number of components in the equilibrium
mixture of ice, water and vapour (a 3 phase system) is one.
Ca CO3 = CaO + CO2 (a 3 phase system) has 2 components. i.e. CaO = CaO – CO 2 i.e.
representing each phase with any two of the chemical species.
The number of Degrees of Freedom (F): This is the least number of intensive
variations (temp, pressure, concentration (composition), refractive index, density, viscosity
e.t.c) that must be fixed in other to describe the system completely.

SYSTEM CONTAINING ONE COMPONENT

Water existing in three phases (solid, liquid and gas) is often used to describe this system.
The phase diagram is shown below.

VP (mmHg)
B C
Liquid

M. pt
Solid B. pt

4.58 D

Vapour
Sublimation
A

273 647 Temp (k)

Phase diagram for water at moderate temperature and

pressure
Boiling point: The curve DC = V.P vapour pressure curve or Boiling point curve. Its upper
limit is at critical temp (344 0C or 647K) for water and vapour. Its lower end at 0.0098 0C
called triple point. Along the vapour pressure curve, vapour and liquid co-exist in

Page 8 of 14
equilibrium. The temp and pressure cannot be varied independently otherwise a change
from a two-phase system to a single – phase system will occur.
Melting Point: The curve DB is the melting point curve at which liquid and solid are in
equilibrium. The negative slope of DB shows that the freezing point of water decreases with
increasing external pressure.
Sublimation: The curve AD is the sublimation curve, and here vapour and solid exist
together in equilibrium. Sublimation or freeze-drying is a separation technique where water
is removed by means of sublimation (heating at pressure below the triple point). This is
useful for compounds that are heat sensitive. The point D, is the triple point of water at
which water exist as solid, liquid and gas in equilibrium.
At any temperature below the triple point, an increase in the pressure of the system turns the
vapour first to ice and then with further increase to liquid. The temperature at which a solid
melts depends on the pressure. If the pressure is that of the liquid and solid in equilibrium
with the vapour, the temperature is known as the triple point, whereas, if the pressure is 1
atmosphere, the temperature is the normal freezing point.
At the triple point: F = 1 = 3 + 2 = 0

SYSTEMS CONTAINING TWO COMPONENTS

Liquid – liquid systems (Solutions of liquid in liquid)
a) Completely miscible liquids: 2 liquids and 2 phases (liquid and gas) F = 2.
b) Partially miscible liquids
c) Immiscible liquids: F = 2 – 3 + 2 (2 liquid phases + 1 vapour phase).

Liquid – Gas systems

Henry’ Law: At constant temperature the solubility of a gas in a liquid and pressure of the
gas above the liquid, X = Kp Where X = mole fraction of dissolved gas. K = Henry’s Law
constant. Henry’s Law is most applicable at high temp and low pressures. It is applied in the
preparation of effervescent solution containing CO 2 and in preparing CO2 free water for
injection.

Solid – Solid Systems

When two solids are melted together and the resultant liquid cooled then the components
may be deposited independently or as a single homogeneous phase (solid solutions) thus
both components form the lattice structure of the solid solution e.g. Alloys of Gold/Silver,
Cu/sulphur etc. They can also be classified as completely, partially and immiscible systems.

Solid – vapour systems

The conversion of anhydrous salt to a hydrated form, the transition of one hydrated form to a
higher hydrate and the phenomenon of deliquescence, hygroscopicity, efflorescence and
exsiccation are examples of the equilibria systems containing solid and water vapour.

Solid – liquid Systems

Systems that are completely miscible as liquids and incompletely miscible s solids: 3 classes
exist:
a. System that show formation of a eutectic mixture
b. Systems that show compounds with congruent melting point
c. Systems that show compounds with incongruent melting point
Page 9 of 14
 Condensed Systems
Any system in which the V.P or gaseous phase is not accounted for, is a condensed system.
The greatest value of F’ = 2 as equilibrium is represented by temp/composition diagram at
constant pressure. The reduced phase rule is used since V.P effect is very small.
Therefore F’ = C – P + 1 Where F’ = no. of degree of freedom + pressure.

LIQUID – LUQUID SYSTEM OF TWO COMPONENTS (PHENOL –

WATER)
The two – component system existing in one phase has 3 degrees of freedom (i.e., temp,
pressure and composition) hence condensed diagram of phenol and water can be used to
describe this systems.

80 80
c
60 b y d 60 Tie line
x
40 2 liquid phases 40
20 20
a e Single phase
0 20 40 60 80 0 Phenol
100%
0% Phenol
100% Water 80 60 40 20 0% Water

Phase diagram of Phenol and Water

The curve abcde shows the limits of temperature and concentration within which two liquid
phases exist in equilibrium. The regions outside this curve contain systems having only one
liquid phase. At point x system contain 100% water at 50 0C, the addition of known
increments of phenol to a fixed weight of water, the whole being maintained at 50 0C, will
result in the formation of a single liquid phase until the point b is reached at which a minute
amount of a second phase appears. The concentration of phenol and water at which this
occurs is 11% by weight of phenol in water. Analysis of the second phase, which separates out
on the bottom, shows it to contain 63% by weight of phenol in water. Hence, above this 63%
value a single phase of phenol rich water is seen.
The line bd drawn across the region containing two phases is termed a tie line; it is always
parallel to the base line in two component systems. An important feature of phase diagrams
is that all systems prepared on a tie line at equilibrium, will separate into phases of constant
composition. These phases are termed conjugate phases.
Working on a tie line also enables us to calculate the composition of each phase in addition
to the weight of the phase. For example, any system represented by a point on the line bd, at
500C separates to give a pair of conjugate phases whose composition is b and d. The relative
amounts of the two layers or phases may vary e.g., A system containing 24% by wt of phenol
and 76% by wt of water (pt Y) at equilibrium at 50°C will give 2 liquid phases. The upper
layer contains 11% phenol in water (pt b) and the lower containing 63% phenol in water (pt
d).

The weight of the two phases can be calculated as:

Weight of phase A = Length dy 63 – 24 39 = 3
Weight of phase B Length yb 24 – 11 13 1

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This system contains: 75 g of phase A & 25 g of phase B.
Wt of phenol in phase A = 11/100 x 75/1 = 8.25 g
Wt of phenol in phase B = 63/100 x 25/1 = 15.75 g

Eutectic mixtures
A eutectic mixture is defined as a mixture of two or more components, which usually do not
interact to form a new chemical compound but which at certain ratios, inhibit the
crystallization process of one another resulting in a system having a lower melting point than
either of the components. Eutectic mixtures, can be formed between Active Pharmaceutical
Ingredients (APIs), between APIs and excipient or between excipient; thereby providing a
vast scope for its applications in pharmaceutical industry. At eutectic point, the number of
degree of freedom is zero
Eutectic mixture formation is usually, governed by the following factors:
(a)the components must be miscible in liquid state and mostly immiscible in solid state
(b) Intimate contact between eutectic forming materials is necessary for contact induced
melting point depression
(c)the components should have chemical groups that can interact to form physical bonds
such has intermolecular hydrogen bonding etc.,
(d) the molecules which are in accordance to modified VantHoff’s equation can form
eutectic mixtures.

Where A and B are the compounds/

components
α and β are their states i.e. solid or
liquids for A & B, respectively.
L is the solution of A in B or B in A
formed
At eutectic point; L, αA and βB are in
equilibrium

A typical diagrammatic illustration of a eutectic mixture

Application of eutectic mixtures in the Pharmaceutical

Industry
1. During pre-formulation stage, compatibility studies between APIs (active
pharmaceutical ingredients) and excipient play a crucial role in excipient selection.
Testing for eutectic mixture formation can help in anticipation of probable physical
incompatibility between drug and excipient molecules.
2. Eutectic mixtures are commonly used in drug designing and delivery processes for
various routes of administration. E.g. Ibuprofen, Thymol eutectic mixtures tested for
Page 11 of 14
 transdermal delivery of Ibuprofen improved skin penetration. It showed 5.9 times the
flux from a saturated aqueous solution with thymol pretreated skin and 12.7 times the
flux from a saturated aqueous solution across non-pretreated skin
3. During manufacturing of pharmaceutical dosage form, it is extremely necessary to
anticipate the formation of eutectics and avoid manufacturing problems if any. For
example, during tablet compaction the heat produced in the punch and die cavities
may lead to fusion or melting of tablet powder compacts leading to manufacturing
defects. Thus knowledge of eutectic points of powder components may help avoid
these problems.
4. During pharmaceutical analysis, understanding of eutectic mixtures can help in the
identification of compounds having similar melting points. Compounds having
similar melting points, as a rule will have different eutectic point with other
component. This knowledge could be used to identify compounds like Ergotamine,
Allobarbital etc. The listed drugs can be distinguished by their tendency to form
eutectic mixtures with Benzanilide.

Page 12 of 14
Some sample questions
1. The solution formed at the point of solubility is called (a) aqueous solution (b) saturated
solution (c) supersaturated solution (d) dilute solution
2. Ideally, as the concentration of a solution approaches the solubility concentration the
dissolution rate (a) increases (b) decreases (c) does not change (d) is affected by the salt
3. Assuming the saturation solubility of veramicine at 300C is 10g/ml, a solution of
veramicine containing 100g/10ml at the same temperature is (a) supersaturated solution
(b) a syrup (c) a simple solution (d) saturated solution
4. Based on the state of matter, how many kinds of solutions can we have? (a) 3 (b) 6 (c) 9
(d) 12
5. A pharmaceutical solution is an example of (a) a colloidal dispersion (b) a coarse
dispersion (c) a molecular dispersion (d) a semi liquid dispersion
6. All of the following are examples of colligative properties except (a) elevation of boiling
point (b) freezing point depression (c) vapour pressure lowering (d) specific gravity
7. in condensed systems (a) the solid phase is ignored (b) the liquid phase is ignored (c) the
gaseous phase is ignored (d) the degree of freedom is ignored
8. solubility gives us information on how far while dissolution rate tell us _____ a solution
is formed (a) how well (b) how good (c) how fast (d) how far
9. the total sums of mole fractions of a solution is (a) unity (b) multiples (c) a fraction (d) a
ratio
10. the degree of freedom of a eutectic mixture at its eutectic point is (a) 0 (b) 1 (c) 2 (d) 3
11. The solution formed at the point of solubility is called (a) aqueous solution (b) saturated
solution (c) supersaturated solution (d) dilute solution
12.Ideally, as the concentration of a solution approaches the solubility concentration the
dissolution rate (a) increases (b) decreases (c) does not change (d) is affected by the salt
13.Assuming the saturation solubility of veramicine at 300C is 10g/ml, a solution of
veramicine containing 100g/10ml at the same temperature is (a) supersaturated solution
(b) a syrup (c) a simple solution (d) saturated solution
14.Based on the state of matter, how many kinds of solutions can we have? (a) 3 (b) 6 (c) 9
(d) 12
15.A pharmaceutical solution is an example of (a) a colloidal dispersion (b) a coarse
dispersion (c) a molecular dispersion (d) a semi liquid dispersion
16.All of the following are examples of colligative properties except (a) elevation of boiling
point (b) freezing point depression (c) vapour pressure lowering (d) specific gravity
17.in condensed systems (a) the solid phase is ignored (b) the liquid phase is ignored (c) the
gaseous phase is ignored (d) the degree of freedom is ignored
18. solubility gives us information on how far while dissolution rate tell us _____ a
solution is formed (a) how well (b) how good (c) how fast (d) how far
19.the total sums of mole fractions of a solution is (a) unity (b) multiples (c) a fraction (d) a
ratio
20. the degree of freedom of a eutectic mixture at its eutectic point is (a) 0 (b) 1 (c) 2 (d) 3

 The distribution law is very important in Pharmacy and Medicine. Justify this claim.
 Discuss the effects of temperature on the rate of solubility.
 Discuss the applications of colligative properties in Pharmacy
 What are the applications of eutectic mixtures in the pharmaceutical industry?
 Define the following: Solution, Solubility, dissolution rate. What are the factors that
affect dissolution rate?
 Discuss the phase equilibria of a single component system like water. Show any two
possible applications of this phenomenon in pharmacy
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 Give four examples of two component systems that are of practical applications in the
Industry
 Discuss the phenol/water phase equilibria at moderate temperature with relevant
illustrations

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