PINES CITY COLLEGES

COLLEGE OF PHARMACY
Magsaysay Avenue, Baguio City 2600
Tel. No. (074) 445-2210 Loc. 51 Fax : (074) 445-2208
www.pcc.edu.ph

MODULE III:
EQUILIBRIUM PHENOMENA
Equilibrium Phenomena
The application of the pharmaceutical principles to drug usage forms is illustrated when drug usage
forms are categorized according to their physical state, degree of heterogeneity, and chemical composition.

The usual relevant states of matter are gases, liquid, and solids. Intermolecular forces are important in
the study of pharmaceutical systems. Intermolecular forces of attraction are weakest in gases and strongest in
solids.

Conversions from one physical state to another can involve simple overcoming intermolecular forces of
attraction by adding energy (heat).

Chemical composition can have a dramatic effect on physicochemical properties and behavior. For this
reason, it is necessary to distinguish between polymers or macromolecules and more conventional micro-
molecules.

Manifestation of Intermolecular forces

a. Cohesion b. Adhesion
-attraction of like molecules -attraction of unlike molecules

Importance of the knowledge of intermolecular forces

a. Understanding the properties of gases, liquid and solids d. Stabilization of emulsion
b. Understanding interfacial phenomena e. Compaction of powders
c. Flocculation in suspension f. Compression of granules to form tablets

Nonpolar
➢ There is equal distribution of charges
➢ Molecules have perfect symmetry
➢ Dipole moments are zero
➢ Ex: Carbon Tetrachloride

Polar
➢ Have (+) & (-) charges on different sides
➢ Molecules are asymmetric
➢ Dipole moments are numerical/ non-zero
➢ Ex: H2O, H2S

Dipolar
➢ Molecules have 2 poles of (+) & (-) charges
➢ Opposite charges attract & like charges repel
➢ Ex: Battery
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Physical Pharmacy 2nd Semester PrepBy: GMBayeng, RPh.

 Repulsive and Attractive Forces
As molecules are brought close together, the opposite charges in the two molecules are closer together
than the like charges and cause attraction to one another. When the molecules are brought so close that the
outer charge clouds touch, the molecules repeal each other like rigid elastic bodies. Thus attractive forces are
necessary in order that molecules cohere and repulsive forces are necessary in order that molecules do not
interpenetrate and annihilate each other.
At equilibrium distance the repulsive and attractive forces are equal. The potential energy between the
two molecules is at minimum and the system is stable. The principle of minimum potential energy applies not
only to molecules but also to atoms and to large objects.

Attractive Intermolecular Forces

1. Van der Waals Forces
> Named after Fan ders Waals
> sum of attractive and repulsive forces between molecules

a. Dipole – Dipole (Keesom Forces)

- dipolar molecules tend to align themselves where the (-) pole points toward the (+) pole of the next
- large groups of molecules maybe associated trough weak attractions
- responsible for more substantive structure and molecular ordering found in liquids
- 1-7 kcal/mole
- Ex: HCl

b. Dipole – Induced dipole (Debye Forces, Polarization)

- a strong, permanent interaction that is capable of inducing an electric dipole in a non-polar molecule
- 1-3 kcal/mole

c. Induced dipole- Induced dipole

- “London attraction”, “London dispersion force”, “Quantum induced instantaneous polarization”
- non-polar molecules are capable of inducing polarity in one another
- relatively weak electrostatic forces are responsible for the liquefaction of nonpolar gases
- 0.5-1 kcal/mol

These Van der Waals Forces ae associated with:

a. Condensation of gases c. Formation of metal complexes and molecular addition compounds
b. Solubility of some drugs d. Certain biologic processes and drug actions

2. Ion – Ion, Ion – Dipole and Ion – Induced Dipole Forces

- Positive – negative ion interactions in the solid state involve forces of 100-200 kcal/mol. Ionic
interactions are reduced considerably in liquid systems in the presence of other electrolytes.
- Ion – Dipole or Dipole induction by an ion, can also affect molecular aggregation
- Ex” I2 + KI → I3 + K+

3. Hydrogen Bonds or Hydrogen Bridge

- Because they are small and have a large electrostatic field, hydrogen atoms can approach highly
electronegative atoms
- Depending on the electronegativity of the second atom and the molecular environment in which
hydrogen bonding occurs, hydrogen bond energy varies from approximately 1-8 kcal/mol

States of Matter
I. Gas - no shape and volume; occupy volumes that depend very sensitively on the external variables
2

- possess compressibility and thermal expansion; special attention must be given to factors
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influencing the volume of the gases.

Physical Pharmacy 2nd Semester PrepBy: GMBayeng, RPh.

 Pressure – force acting on a unit area of surface
𝐹𝑜𝑟𝑐𝑒 (𝑎𝑐𝑡𝑖𝑛𝑔 𝑝𝑒𝑟𝑝𝑒𝑛𝑑𝑖𝑐𝑢𝑙𝑎𝑟 𝑡𝑜 𝑎𝑛 𝑎𝑟𝑒𝑎)
𝑃=
𝐴𝑟𝑒𝑎 (𝑎𝑟𝑒𝑎 𝑜𝑣𝑒𝑟 𝑤ℎ𝑖𝑐ℎ 𝑡ℎ𝑒 𝑓𝑜𝑟𝑐𝑒 𝑖𝑠 𝑑𝑖𝑠𝑡𝑟𝑖𝑏𝑢𝑡𝑒𝑑)

*Normal Atmospheric pressure is approximately equal to the average pressure of the atmosphere
at sea level.

*The pressure due to a column of fluid is P = D x g x h

*Atmosphere is equivalent to the pressure exerted by the mass of a column of mercury 760mm
high at 0°C
P = density of Hg x Height of column of Hg x gravitational acceleration
1 atm = 13,595.10 Kg/m3 x 0.76m x 9.8m/sec2
2 2
= 101,325 N/m or g/cm/sec
= 760 mmHg

Standard Condition or STP = denote a temperature of 0°C (273K) and normal atmospheric pressure (760
mmHg)

Gas Laws
At sufficiently low pressure and high temperature, all gases have been found to bey three simple
laws. These laws relate the volume of a gas to the pressure and temperature.

A gas which obeys these laws is called an IDEAL GAS LAW. This law is applied only to gasses which do
not undergo change in chemical complexity when temperature or pressure is varied. The interrelation
among volume (V), pressure (P) and the absolute temperature (T) is given by this law.

Working Equation: PV = nRT

Where P = atm
V = liter
n = moles
R = 0.08205 Latm/mole K or 8.314x107 erg/mol K or 1.987 cal/mol K
T = Kelvin

1. Boyle’s Law
When temperature is kept constant, the volume of a given mass of an ideal gas varies inversely with the
pressure to which the gas is subjected

Working Equation: P1V1 = P2V2

Where k = PV

2. Charles’ Law
At constant pressure, the volume of a given mass of gas varies directly with the absolute temperature

Working Equation: V1T2 = V2T1

Where k = V/T

3. Gay Lussac’s Law

At constant volume, the pressure of a given mass of gas varies directly with the absolute temperature
then at constant volume
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Working Equation: P1T2 = P2T1

Physical Pharmacy 2nd Semester PrepBy: GMBayeng, RPh.

 Where k = P/T

4. General Gas Law

Any two of the above three gas laws can be employed to derive the general gas laws which applies to all
possible combinations of changes

Working Equation: P1V1 = P2V2

T1 T2
5. Dalton’s Law of Partial Pressure
The total mixture of gaseous mixture is equal to the sum of the partial pressure of the components. The
partial pressure of the compound of gas mixture is the pressure which that component would exert if it
alone occupied the entire volume

Working Equation: PT = P1 + P2 + P3 +…………….

Density of Gases
As the volume of gas increase, the mass per unit volume (density) decreases proportionality,
therefore the density of gas varies inversely with its volume. If follows that the density of a gas varies
inversely with the absolute temperature and directly with the pressure.
D2 = D1 x T1 x P2
T2 P1

Collecting Gases over Water

* If a gas is collected over a non-volatile liquid, such as water, a correction is made for the
amount of water vapor present with the gas.
* A gas collected over water is saturated with water vapor which occupies the total gas volume
and exerts a particular pressure
* The partial pressure of the water is saturated with water vapour is definite for each
temperature and is independent of the nature or presence of gas
* The definite value of the vapour pressure of water may be found: PT=Pg + saturated vapour
of water

Sample Problems: Solve the following problems, find out how it arrived to the answer
1. A mass of oxygen occupies 5.0 liters under a pressure of 740 mmHg. Determine the volume of the
same mass of gas at standard pressure (760 mmHg), where the temperature is remaining constant.

**Answer: 4.8684 L

2. Exactly 100cm3 of oxygen is collected over water at 23°C and 800mmHg. Compute the standard
volume of the dry oxygen. The vapour pressure of water at 23°C is 21.1mmHg.

**Answer: 94.523 cm3

3. A steel tank contains CO2 at 27 C and a pressure of 12 atm. Determine the internal gas pressure
when the tank is heated to 100 C.

**Answer: 14.92 atm

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Physical Pharmacy 2nd Semester PrepBy: GMBayeng, RPh.

 II. Liquid - occupy a definite volume, compared to gases, liquids are relatively incompressible and
intermolecular forces is higher
- under ordinary circumstances, the density of liquid is greater than gas

Factors Affecting Liquefaction Gases

1. Temperature
2. Pressure
3. Combination of Temperature and Pressure

Critical Phenomena in Liquids

- The transaction from a gas to a liquid from a liquid to solid depend not only on the temperature but
also on the pressure to which the substance is subjected
- if the temperature is elevated, a value is reached above which it impossible to liquefy a gas
irrespective of the pressure applied

- Critical Temperature

- Critical Pressure

- The further the gas is cooled below its critical temperature, the less pressure is required to liquefy it
CT of water = 374°C or 647.15 K
CP of water = 218 atm

- The CT serves as a measure of the attractive forces between molecules for the temperature above
the critical value, the molecules possess sufficient kinetic energy so that no amount of pressure can
bring them with in the range of attractive forces that causes the particles to stick together

Principles and Guides in Liquefaction of Gases at Low CT

1. The gas must be below its CT before it can be liquefied
2. the pressure must be high enough to cause liquefaction
3. A compressed gas is cooled by expansion since expanding energy is required to overcome the
intermolecular forces of attraction

Methods of Achieving Liquefaction

1. Subjecting to intense cold by using freezing mixture
2. Allow the gas to expand rapidly that no heat enters the system by adiabatic expansion using a
Bavar or Vacuum flask
3. The gas is pre-cooled before allowing to expand by joule – Thompson effect

Vapor Pressure of Liquids

Vapor - a gas known below its CT; it is the pressure caused y gas molecules hitting the container
- substance that is a liquid or a solid at RT and that passes into the gaseous state when heated
to a sufficiently high temperature

When a liquid is placed in an evacuated container at constant temperature, the molecules with
the highest energy tend to break away from the surface of the liquid and passes into gaseous
state and some of the molecules subsequently return to the liquid state or condense

When: Rate of Condensation = Rate of Vaporization : the vapor becomes saturated,

dynamic equilibrium is established
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The pressure of the saturated vapour above the liquid is known as equilibrium vapor pressure

Physical Pharmacy 2nd Semester PrepBy: GMBayeng, RPh.

 Clausius – Clapeyron Equation = express the relationship between the VP and the absolute temperature of a
liquid

𝑃2 Hv (T2 – T1)
Working Equation: log 𝑃1 = 2.303 R T1 T2

Where: P1 and P2 = Vapor pressure

T1 and T2 = Absolute temperature in “K
Hv = Molar heat of vaporization
= Heat occupied by 1 mole of liquid when it passes into vapour state
= The heat of vaporization vary somewhat with temperature
R = 1.987 cal/deg-mole

Heat of Vaporization
- amount of change needed to change 1g of a liquid to vapour state and the amount of change to
change vapour back to liquid state

`Example: Water = MW x Hv

Heat of Fusion
- the amount of change absorbed to change 1 gram of ice to liquid and the amount of change liberated
to change liquid back to ice
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Physical Pharmacy 2nd Semester PrepBy: GMBayeng, RPh.

 Example 1: Compute for the VP of water at 120°C, the VPH2O (P1) at 100°C is 1 atm and the Hv may be
taken as 9720 cal/mol

Given: P1 = 1 atm Solution: 1. Derive formula for P2

T1 = 100°C
Hv = 9720 cal/mole
R = 1.987 cal/deg-mole

Find: P2 = ?

𝑃2 Hv (T2 – T1)
Formula: log 𝑃1 = 2.303 R T1 T2

Example 2: The VP of water at 25°C is 23.8 mm & 50°C is 92.5 mm. with the aid of a log P vs 1/T plot,
determine the VP of water at 37°C.

VP mm log P Temp °C Temp K 1/T x 10-3 K

23.8 25
37
92.5 50

Boiling Point
- the point that which the VP of the liquid is equal to the external pressure
- the temperature that which the VP of the liquid is equal to the atm pressure
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- the heat absorbed when liquid vaporizes at normal boiling point is called the heat of vaporization
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Physical Pharmacy 2nd Semester PrepBy: GMBayeng, RPh.

 2. Different solubilities
3.Form x-ray diffraction or pattern
- Commonly observed in long chain organic compounds such as fatty acids and fats
- Pharmaceutical significance: different polymorph exhibits different solubilities thus in slight
polymorph, this may affect the rate of dissolution and therefore affecting the bioavailability

-3 Characteristic Classification of Polymorphs

1. Stable – readily separates out in the form of a precipitate
2. Unstable – it remains in solution awhile and then it precipitates
3. Metastable – remain in solution for a long period of time
- 4 Polymorphic forms:
1. Unstable 2. Alpha 3. Beta 4. Stable Beta
- FYI! Chloramphenicol or Cortisone Acetate
Exist in at least 5 different polymorphs. Four were found to be unstable which in the
presence of water changes into stable form. This transformation is accompanied by
considerable caking. This should be all in the form of stable polymorphs before the
suspension is to be prepared.

2. Amorphous Solids – they are regarded as supercooled liquids of very high viscosity
- show an indefinite melting point and have rather indefinite arrangements of the structural units
eg// S, C, synthetic plastic
- they differ from crystalline solids in that they tend to flow when subjected to sufficient pressure over a
period of time
- usually isotropic (properties are the same in all directions)
- it is not always possible to determine by casual observation whether a substance is crystalline or
amorphous
eg// beeswax, and paraffin – appear amorphous but they are crystalline when heated and then
allowed to cool slowly
- Petrolatum- contains both material and could be either amorphous and crystalline
- Whether it is amorphous or crystalline, it has been shown to affect the therapeutic activity of a
drug
eg// Novobiocin: at crystalline form= no activity & poorly absorbed
At amorphous form= Therapeutic activity & readily absorbed

Melting point and Heat of fusion

The relationship between melting point and freezing point
The temperature at which the liquid phase into the solid state is the freezing point. It is also the
melting point of a pure crystalline compound. The freezing point and melting point of a pure
crystalline compound is the temperature at which the pure solid and liquid are in equilibrium.

Latent heat of fusion– the heat absorbed when a gram of solid melt or it is the heat liberated when it
freezes
- For water at 0° Celsius, the latent heat of fusion is 80 cal/g or 1440 cal/mol

*The heat added during the melting process does not bring about a change in temperature until all the
solid has disappeared

*How to get melting point?

Observe the temperature at which the solid state starts to melt and the temperature until at
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which it is fully melted

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*The change of the FPt and MPt may be obtained by one of the Clausius Clapeyron Equation

Physical Pharmacy 2nd Semester PrepBy: GMBayeng, RPh.

 Working Equation: ∆T = T (V1 – VS) Where: V1 molar volume of liquid
∆P ∆Hf VS molar volume of solid
∆Hf Change in the heat of fusion
T temperature

*Molar volume is obtained by dividing MW by density

*Molar heat of fusion – amount of heat needed to change 1 mole of liquid to 1 mole of solid

Sample problem: What is the effect of an increase of 1 atm on the FPt of water at 0°C. where the ∆Hf is
1440 cal/mol. The molar volume of water is 18.018 and the molar volume of ice is 19.65L. to convert ∆Hf
from cal-mol into ergs/mole, multiply by the factor 4.186 x 107 then multiply the equivalent with 1.013 x
106 dyne/cm2/1atm.
Given:
ANSWER: -7.296 x 1020

- Some generalizations on MPt:

1. For normal saturated HC (eg// paraffin): MPt increases with increasing MW
2. MPt of alkalines with even number of C- atoms are higher than those with odd number of C-
atoms because those with odd numbers are less efficiently packed in crystals
3. Normal COOH acids: even number of C- atoms has increasing MP than odd number because
of packing of crystals

The Liquid Crystalline State

- “Liquid Crystals” are materials in these states are in many ways intermediate between the liquid and
solid states. These have intermediate states of morbidity and rotation.
- Two main types of crystals
1. Smectic (soap and grease-like)
- molecules are mobile in two directions and can rotate about one axis
2. Nematic (thread-like)
- molecules rotate only about one axis but are mobile in three dimensions
- Cholesteric crystals exist but maybe considered as a special case of nematic type

Smectic type is of pharmaceutical significance. It is this phase that usually forms in

ternary (a more complex) mixtures containing a surfactant, water and weakly amphiphilic or non-polar additive.

Molecules that are stable to form the mesophase state are organic molecules, elongated and reticular in
shape, rigid and posse’s strong dipole and easily polarizes groups.

-How are liquid crystals prepared?

1. By heating solids 2. By the action of certain solvents on solids

-Properties and significance of liquid crystals

1. They have flow properties of liquids at the same time they posses the property of being
bifringent, a property associated by crystals.
Bifringence – the light passing through a material is divided into two components with different
viscosities and hence have different refractive indices.
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Physical Pharmacy 2nd Semester PrepBy: GMBayeng, RPh.

 2. Some crystals show consistent color changes with temperature and this has resulted in their
being used to defect areas of elevated temperature under the skin that maybe due to a disease
state or process.

3. Nematic liquid crystals are sensitive to electrical fields, a property used to advantage in
developing display systems

4. The smectic mesophase has applications in the solubilization of water-insoluble material. It

also appears that liquid crystalline phase of this type are frequently present n emulsions and
maybe responsible the enhanced physical stability owning to their highly viscous nature.
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Physical Pharmacy 2nd Semester PrepBy: GMBayeng, RPh.