Physical Pharmacy (0510219)

Unit 3 / Solutions
 Ideal solution
Based on
thermodynamics
Real solution

True solution
Classification
of Aqueous Based on particle Colloidal
solution size dispersion
systems Coarse
dispersion

Non electrolyte
Based on type of Strong
solute electrolyte
electrolyte
Weak
electrolyte
2
Materials may be mixed together to form;
• a true solution
• a colloidal solutions
• a coarse dispersion .
True solution
• A true solution is a mixture of two or more
components that form a homogeneous
molecular dispersion (a one-phase system).

• In a true solution, the suspended particles:

completely dissolve .

• are not large enough to scatter light are small

enough to be evenly dispersed resulting in a
homogeneous appearance.
 Dispersion systems
• A dispersion consists of at least two phases
with one or more dispersed (internal) phases
contained in a single continuous (external)
phase.

1. coarse dispersions.
2. colloidal dispersion.
• The diameter of particles in coarse dispersions is
greater than ~500 nm (0.5 µm). Two common
pharmaceutical coarse dispersions are emulsions (liquid–
liquid dispersions) and suspensions (solid–liquid
dispersions).

• A colloidal dispersion represents a system having a

particle size intermediate between that of a true solution
and a coarse dispersion, roughly 1 to 500 nm. A colloidal
dispersion may be considered as a two-phase
(heterogeneous) system under some circumstances.

6
• colloidal dispersion:
• particle size intermediate between that of a true
solution and a coarse dispersion, roughly 1 to
500 nm.
• considered as a two-phase (heterogeneous)
system under some circumstances.
• it may also be considered as a one-phase
system (homogeneous) under other
circumstances..
• Heterogeneous colloidal dispersions:
• liposomes or microspheres in an aqueous
delivery vehicle consist of distinct particles
constituting a separate phase.

• Homogeneous colloidal dispersions:

• acacia or sodium carboxymethylcellulose in
water
• drug-polymer conjugates
• coarse dispersions:
• The diameter of particles is greater than ~500
nm (0.5 µm).

• Two common pharmaceutical coarse

dispersions are:
1. emulsions (liquid–liquid dispersions)
2. suspensions (solid–liquid dispersions).
 Types of Solutions:
♠ A solution may be classified according to the states in
which the solute and solvent occur. gas, liquid and
crystalline , nine types of homogeneous mixtures of
solute and solvent are possible.

♠ The solutes (whether gases, liquids or solids) are

divided into two main classes; non electrolytes and
electrolytes.
 Non electrolytes
Electrolytes
Types of Solutions
• Nonelectrolytes:
• are substances that do not ionize when dissolved in
water do not conduct an electric current through the
solution.

• Examples of nonelectrolytes are sucrose, glycerin,

naphthalene, and urea.

• The colligative properties of solutions of

nonelectrolytes are fairly regular (show no deviation) .
A 0.1-molar solution of a nonelectrolyte produces
approximately the same colligative effect as any other
nonelectrolytic solution of equal concentration.
• Electrolytes:
• are substances that form ions in solution, conduct
electric current,

• show apparent “anomalous” colligative properties;

that is, they produce a considerably greater freezing
point depression and boiling point elevation than do
nonelectrolytes of the same concentration.

• Examples of electrolytes are hydrochloric acid,

sodium sulfate, ephedrine, and phenobarbital.
• Electrolytes may be subdivided into:

1. strong electrolytes:
• completely ionized in water.
• Hydrochloric acid and sodium sulfate

2. weak electrolytes
• partly ionized in water.
• ephedrine and phenobarbital
 Non-electrolytes Electrolytes

Form solutions that don’t conduct Form solutions that conduct

electricity electricity

Dissolve to form molecules in Dissolve to form ions in solution

solution

Have some effect on freezing & Have a greater effect on freezing &
boiling points of their solutions boiling points of their solutions
Examples: Sugar, alcohols Examples: Acids, Bases, and Salts

15
Solution Concentration Expressions
 Normality

Eq wt = Mw / valiancy ( No. of equivalence )

Valence ( No. of equivalence ) Examples :

Na Cl Valence 1
Ca Cl2 Valence 2
FeSo4 Valence 2
KNo3 Valence 1
Ca3 (PO4) 2 Valence 6
 Normality

• Eq wt = Mw / valiancy = 151/ 2 = 75.5 g/eq

N = 41.5 (g) / 1(L) * 75.5 (g/eq) = 0.55 N

valiancy
 Ideal and Real Solutions
• ideal solution:
• no change in the properties of the components,
other than dilution, when they are mixed to form
the solution.

• No heat is evolved or absorbed during the

mixing process,

• the final volume of the solution represents an

additive property of the individual constituents.
no shrinkage or expansion occurs when the
substances are mixed.
• The constitutive properties, for example, the
vapor pressure, refractive index, surface tension,
and viscosity of the solution, are the weighted
averages of the properties of the pure individual
constituents.

• Mixing substances with similar properties forms

ideal solutions.
• when 100 mL of methanol is mixed with 100 mL
of ethanol, the final volume of the solution is 200
mL, and no heat is evolved or absorbed. The
solution is nearly ideal.

• When 100 mL of sulfuric acid is combined with

100 mL of water, the volume of the solution is
about 180 mL at room temperature, and the
mixing is attended by a considerable evolution of
heat; the solution is said to be nonideal, or real.
 Ideal Solutions and Raoult's Law

• in an ideal solution, the partial vapor pressure of

each volatile constituent is equal to the vapor
pressure of the pure constituent multiplied by its
mole fraction in the solution. Thus, for two
constituents A and B,
• Example:
• What is the partial vapor pressure of benzene
and of ethylene chloride in a solution at
a mole fraction of benzene of 0.6? The vapor
pressure of pure benzene at 50°C is 268 mmHg,
and the corresponding pA° for ethylene chloride
is 236 mmHg. (ideal solution)

Hg

Hg
• The total pressure is the sum of the partial
pressures of all the constituents

Hg
 Aerosols and Raoult's Law

• An aerosol contains the drug concentrated in a

solvent or carrier liquid and a propellant mixture of
the proper vapor characteristics.
• Propellants:
• Chlorofluorocarbons (CFCs):
• volatile hydrocarbons: used as propellants in
metered dose inhalers for treating asthma,
1. hydrofluoroalkane 134a (1,1,1,2,tetrafluoroethane)
2. hydrofluoroalkane 227 (1,1,1,2,3,3,3-
heptafluoropropane)
3. or combinations of the two.
• Example:
• The vapor pressure of pure CFC 11 (molecular
weight 137.4) at 21°C is p11° = 13.4 lb/in2 (psi)
and that of CFC 12 (molecular weight 120.9)
is p12° = 84.9 psi.
• What is the partial pressure of CFCs 11 and 12
in the 50:50 mixture, and what is the total vapor
pressure of this mixture?
• A 50:50 mixture by gram weight of the two
propellants consists of:
• 50g ÷ 137.4 g/mole = 0.364 mole of CFC 11
• 50g ÷ 120.9 g/mole = 0.414 mole of CFC 12.
• The total vapor pressure of the mixture is
 Real Solutions

• Ideality in solutions presupposes complete

uniformity of attractive forces.

• Many examples of solution pairs are known,

however, in which the “cohesive” attraction of A
for A exceeds the “adhesive” attraction existing
between A and B. Similarly, the attractive forces
between A and B may be greater than those
between A and A or B and B.

• Such mixtures are real or nonideal;

• Ideal solutions do not adhere to Raoult's law
throughout the entire range of composition.

• Two types of deviation from Raoult's law

1. negative deviation.
2. positive deviation.
• negative deviation:
• When the “adhesive” attractions between
molecules of different species exceed the
“cohesive” attractions between like molecules,

• the vapor pressure of the solution is less than

that expected from Raoult's ideal solution law,

• chloroform and acetone.

• positive deviation:
• When the interaction between A and B
molecules is less than that between molecules
of the pure constituents,

• The partial vapor pressure of the constituents is

greater than that expected from Raoult's law,

• benzene and ethyl alcohol, chloroform and ethyl

alcohol.
• In real solutions, the behavior of the component
present in high concentration (the solvent) can
be described by Raoult's law as:

• It cannot hold for the component in low

concentration (the solute).
 Henry's Law

• The molecules of solute, being in relatively small

number are completely surrounded by
molecules of solvent and so reside in a uniform
environment.

• Therefore, the partial pressure or escaping

tendency of the solute at low concentration is in
some way proportional to its mole fraction, but,
as the proportionality constant is not equal to the
vapor pressure of the pure substance.
• The vapor pressure–composition relationship of
the solute cannot be expressed by Raoult's law
but instead by an equation known as Henry's
law:

• where k for solute is less than p°solute.

• Henry's law applies to the solute and Raoult's

law applies to the solvent in dilute solutions of
real liquid pairs.
• Give 5 examples for each of followings :
• Ideal Solution
• Positive deviated solution
• Negative deviated Solution
 Physical Properties of Substances

• classified as:
1. colligative,
2. additive,
3. constitutive.

• In thermodynamics, classified as:

1. extensive properties
2. intensive properties
• Extensive properties:
• Physical properties of a system depend on the
quantity of the matter in the system
• (e.g., mass and volume),

• Intensive properties:
• is a bulk property, meaning that it is a Physical
properties of a system that does not depend on the
system size or the amount of material in the system
• (e.g., temperature, pressure, density, surface
tension, and viscosity of a pure liquid).
 Additive properties
• depend on the total contribution of the atoms in the
molecule or on the sum of the properties of the
constituents in a solution.

• An example of an additive property of a compound is

the molecular weight, that is, the sum of the masses
of the constituent atoms.

• The masses of the components of a solution are also

additive, the total mass of the solution being the sum
of the masses of the individual components.
 Constitutive properties
• depend on the arrangement and to a lesser
extent on the number and kind of atoms within a
molecule.

• Many physical properties may be partly additive

and partly constitutive.

• The refraction of light, electric properties,

surface and interfacial characteristics, and the
solubility of drugs are at least in part constitutive
and in part additive properties.
 Colligative properties
Colligative properties depend only on the
number of dissolved particles
(molecules or ions, small or large) in
solution and not on their identity.

I. Osmotic pressure
II. Vapor pressure lowering

III. Boiling point elevation

IV. Freezing point depression

Explanation
compare the properties of:
1.0 M aq. sugar solution to a 0.5 M aq. solution of NaCl.
Despite the conc. of NaCl = ½ the conc. of sucrose both
solutions have precisely the same number of dissolved
particles, why?
because each NaCl unit creates two particles upon
dissolution a Na+ and a Cl-.
Both solutions have the same colegative propertiesn as
freezing point, boiling point, vapor pressure, and
osmotic pressure because those colligative properties of
a solution only depend on the number of dissolved
particles.
Other non-colligative properties including e.g. viscosity,
surface tension, and solubility are different.
Diffusion in liquids:
Substance tend to move or diffuse from regions of
higher concentration to region of lower
concentration so the differences in
concentration disappear.
 1. Osmotic Pressure

• Osmosis is the passage of the solvent into a

solution through a semipermeable membrane.
• The solvent moves into the tube and the height of the
solution will rise till the hydrostatic pressure exerted
by the column of solution equal to osmotic pressure

Osmotic pressure
• Is the external pressure that must be applied to the
solution in order to prevent it being diluted by the
entry of solvent via osmosis.
• This process tends to equalize the escaping
tendency of the solvent on both sides of the
membrane.

• The osmotic pressure is proportional to the

reduction in vapor pressure brought about by the
concentration of solute present.

• osmotic pressure is a colligative property

 van't Hoff's equation:

• π is the osmotic pressure in atm,

• V is the volume of the solution in liters,
• n is the number of moles of solute,
• R is the gas constant, equal to 0.082 liter
atm/mole deg,
• T is the absolute temperature.
• Example
• One gram of sucrose, molecular weight 342, is
dissolved in 100 mL of solution at 25°C. What is
the osmotic pressure of the solution?
 Colligative properties

• The values of the colligative properties are

approximately the same for equal
concentrations of different nonelectrolytes
in solution regardless of the species or
chemical nature of the constituents.
 Osmotic pressure of Non-electrolytes
(not ionized)

Osmotic pressure  concentration

twice concentration twice osmotic pressure

Osmotic pressure  number of molecules

Osmotic pressure of 2 solutions having the same
molal concentration are identical
Example:
Explain why?
Solution contains 34.2 g sucrose (mol wt 342)
in 1000 g water has the same osmotic pressure
as dextrose solution (mol wt 180) contains 18
g/1000 g water?

• No. of moles of sucrose = wt/mol wt

= 34.2/342 = 0.1 molal

• No. of moles of dextrose

= 18/180 = 0.1 molal

So that the 2 solutions are iso-osmotic

• When non-volatile solute is dissolved in
solvent, the vapor pressure of solvent is
lowered
• Solvent molecules on the surface which can
escape into vapor is replaced by solute
molecules have little (if any) vapor pressure.

Why is vapor pressure lowering a colligative property?

It only depends on number of dissolved solute particles.
• The Lowering of the vapor pressure is
• The boiling point of a liquid is defined as the temperature at
which the vapor pressure of that liquid equals the
atmospheric pressure(760mm Hg).

For a solution:
the vapor pressure of the
solvent is lower at any
given temperature.
Therefore, a higher
temperature is required to
boil the solution than the
pure solvent.
 3. Elevation of the Boiling Point

• The boiling point of a solution of a nonvolatile

solute is higher than that of the pure solvent
owing to the fact that the solute lowers the vapor
pressure of the solvent.

• This is the colligative property called boiling

point elevation.

• the more of the solute that is dissolved, the

greater is the effect.
Addition of solute will decrease the vapor pressure
and so will increase the boiling point
• The elevation of the boiling point is
• ΔTb =T - To .

m: molality (because molality is temperature independent).

Kb: boiling point elevation constant that depends on the
particular solvent being used. (Kb water = 0.51)
• Normal freezing or
melting point: is the
temp. at which solid &liquid
are in equilibrium under 1
atm.
• Addition of solute will
decrease the vapor pressure
and so will decrease the
freezing point

In order for a liquid to freeze it must achieve a very ordered state that
results in the formation of a crystal.
If there are impurities in the liquid, i.e. solutes, the liquid is inherently
less ordered. Therefore, a solution is more difficult to freeze than the
pure solvent so a lower temperature is required to freeze the liquid
 4. Depression of the Freezing Point

• If a solute is dissolved in the liquid at the triple

point, the escaping tendency or vapor pressure
of the liquid solvent is lowered below that of the
pure solid solvent.

• The temperature must drop to reestablish

equilibrium between the liquid and the solid.

• Because of this fact, the freezing point of a

solution is always lower than that of the pure
solvent.
• The freezing point depression of a solvent is a
function only of the number of particles in the
solution, and for this reason it is referred to as
a colligative property.

• The more concentrated the solution, the farther

apart are the solvent and the solution curves in
the diagram and the greater is the freezing point
depression.
• Example
• What is the freezing point of a solution containing
3.42 g of sucrose and 500 g of water? The molecular
weight of sucrose is 342. In this relatively dilute
solution, Kf is approximately equal to 1.86.

the freezing point of the aqueous solution is

-0.037°C.
 Colligative properties
Colligative properties depend only on the
number of dissolved particles
(molecules or ions, small or large) in
solution and not on their identity.

I. Osmotic pressure
II. Vapor pressure lowering

III. Freezing point depression

IV. Boiling point elevation

Electrolyte Solutions
Colligative Properties of Electrolytic Solutions
and Concentrated Solutions of Nonelectrolytes
• the osmotic pressure, π, of dilute solutions of
nonelectrolytes, such as sucrose and urea,
could be expressed by the equation π = RTc

• solutions of electrolytes gave osmotic pressures

approximately two, three, and more times larger
than expected from this equation, depending on
the electrolyte investigated.
 Electrolytes osmotic pressures

• i approaches the number of ions into which the molecule

dissociated as the solution.

• 2 for solutes such as NaCl and CaSO4,

• 3 for K2SO4 and CaCl2,
• 4 for FeCl3.

• The osmotic pressures Solution of 1M K2SO4 is three

time more that of 1M urea solution
• The colligative properties in dilute solutions of
electrolytes are expressed on the molal scale by
the equations:
• Example
• Calculate the freezing point depression of:
• (a) 0.154 m solution of NaCl
The i factor for a 0.154 m solution of sodium
chloride is about 1.86

• (b) 0.154 m solution of glucose.

• Example
• What is the osmotic pressure of a 2.0 m solution
of sodium chloride at 20°C?
• The i factor for a 2.0 m solution of sodium
chloride is about 1.9.
• When electrolytes are dissolved in water, the
solute exists in the form of ions in the solution,
 Activity and Activity Coefficients

In strong electrolytes solutions The large number

of oppositely charged ions in solutions of
electrolytes influence one anther through
interionic attractive forces and also associate at
high concentration into groups known as ion
pairs (e.g., Na+Cl-) and ion triplets (Na+Cl-Na+).
 Strong electrolyte moderatly concentrated Solutions

• Because of interionic attractive forces and

ion association , in moderatly concentrated
solutions of strong electrolytes , the value of
the freezing point depression and other
Collegiative properties are less than
expected for solutions of unhindered free
ions

• Consequently, a strong electrolyte may

be completely ionized, yet incompletely
dissociated into free ions.
The freezing point depression of Solution of 1m K2SO4 more that of 5m urea solution
• Thus strong electrolytes solutions have an “effective
concentration” or an activity (a).
• The activity of ions , is less than the actual concentration of the
solute, because some of the ions are effectively “taken out of
play” by the electrostatic forces of interaction.

• Where : γm is activity coefficient,

• activity (a),
• ɱ concentration.

• γm increases for dilute strong electrolytes solutions and

decreases for concentrated strong electrolytes solutions or
concentrated non electrolytes solutions
• At infinite dilution, in which the ions are so widely
separated that they do not interact with one
another, the activity a of an ion is equal to its
concentration.

100% of the drug concentration is active free ions

 Ionic Strength

• ionic strength, µ, is used to relate interionic

attractions and activity coefficients.

• The ionic strength is defined on the molar scale

as:

• The term ci is the concentration in moles/liter of

any of the ions and zi is its valence.
• Example
• What is the ionic strength of:

• (a) 0.010 M KCl,

• (b) 0.010 M BaSO4,

(c) 0.010 M Na2SO4,

• µ of a 1:1 electrolyte is the same as the molar
concentration;

• µ of a 1:2 electrolyte is three times the

concentration;

• µ for a 2:2 electrolyte is four times the

concentration.
• Example
• A buffer contains 0.3 mole of K2HPO4 and 0.1
mole of KH2PO4 per liter of solution. Calculate
the ionic strength of the solution.
• The concentrations of the ions of K2HPO4 are
[K+] = 0.3 × 2 and [HPO42-] = 0.3.
• The values for KH2PO4 are [K+] = 0.1 and
[H2PO4-] = 0.1
 The Debye-Hückel Theory

• used to calculate the activity coefficients of drugs whose

values have not been obtained experimentally and are
not available in the literature.

• The Debye-Hückel equation for a binary electrolytes

consisting of ions with valiancy z+ and z- and present in
dilute solution ( µ < 0.02)
•Example
Calculate the mean ionic activity coefficient for 0.005 M
atropine sulfate (1:2 electrolyte) in an aqueous solution
containing 0.01 M NaCl at 25°C. For water at 25°C, A is 0.51.

atropine sulfate (1:2 electrolyte) 1X2

x
69% of the atropine sulfate is active

a = 0.005x0.69 = 0.0034 M
Concentration of active free ions