Physical Pharmacy

PHR 211

Course coordinator:
Magda EL-Massik, PhD
Prof. of Pharmaceutics
Prof. Magda EL-Massik 1
 Overall aim of the course

Physical pharmacy course introduces the

physico-chemical principles of drugs and

formulations and their importance in

designing efficient dosage forms.

Prof. Magda EL-Massik 2

 Course Content
Week Topic & Lecturer
1-2 Interfacial Phenomena
(Prof. Magda El Massik)

3-6 Disperse systems

(Prof. Magda El Massik)
7-8 Rheology
(Prof. Safaa EL-Gamal)
9,12 Solubility & Distribution Phenomena
(Prof. Safaa EL-Gamal)
13 Diffusion & Dissolution Phenomena
(Prof. Safaa EL-Gamal)
14 General Revision
Prof. Magda EL-Massik 3
 Assessment Strategy

Final written examination 40 %

Oral examination 10 %

Practical examination 30 %

Mid-term & Semester work 20 %

Total 100%

Prof. Magda EL-Massik 4

 Reference books
Martin’s Physical Pharmacy and Pharmaceutical
Sciences, Fifth Edition, Patrick J. Sinko (ED),
Lippincott Williams & Wilkins 2006.

Remington, the science and practice of pharmacy,

21st Edition, Lippincott Williams and Wilkins.

Ansel's Pharmaceutical Dosage Forms & Drug

Delivery Systems, Eighth Edition, L.V.Allen, Jr.
N.G. Popovich and H.C. Ansel (Eds), Lippincott
Williams & Wilkins 2005.
Prof. Magda EL-Massik 5
Lecture 1

Interfacial
Phenomena

Prof. Magda EL-Massik,

7 /10/2008
Prof. Magda EL-Massik 6
 Objectives of lectures 1&2

To study the physical, chemical and electrical

properties of molecules situated at interfaces.
To understand how problems arising during
preparation of dosage forms (eg.; emulsions,
suspensions..) & involving interfaces can be
resolved by the use of surface active agents.

Prof. Magda EL-Massik 7

 Interfaces

Substance can exist in any of 3 phases:

gas, liquid or solid.
When two phases meet, the boundary
between them is called an interface

Prof. Magda EL-Massik 8

 Types of interfaces
Phases Examples from common use Pharmaceutical
(interface) Dosage Form
Gas – Gas No interface none
Gas – liquid (g/l) Surface of your drink Aerosols

Gas - Solid (g/s) Top of your desk Tablets &Capsules

Liquid –liquid (l/l) Oil and Vinegar Salad dressing Emulsions & lotions

Liquid - solid (l/s) coffee just spilled your on your Suspensions

desk
Solid - Solid The book you left unopened on Powder particles inside
(s/s) your desk a capsule

Prof. Magda EL-Massik 9

 Liquid interfaces
1. Surface & Interfacial tension
1.1. Definition of Surface tension:
One of the most important phenomenon in nature:

It is a property of the surface of a liquid that

causes it to behave as an elastic sheet.
It allows insects to walk on water.
It allows small objects, such as needles to
float on the surface of water.
It is involved in formation of water droplets on
various surfaces or raindrops.

The term Surface tension is typically used when

the liquid surface is in contact with gas (air).
Prof. Magda EL-Massik 10
1.2. Cause of surface tension

Surface tension is caused by the attraction between the liquid's

molecules by various intermolecular forces.

In the bulk of the liquid: each molecule is pulled equally in all directions
by neighbouring liquid molecules net force of zero .

At the surface of the liquid, molecules are pulled inwards by other

molecules deeper inside the liquid and are not attracted as intensely by
the molecules in the neighbouring medium. i.e.:
-- They develop attractive cohesive forces
with other liquid molecules situated
below & adjacent to them.
-- They create adhesive forces of attraction
With the other phase involved at
the interface.

Prof. Magda EL-Massik 11

• At l/g interface, the adhesive forces are weak;

The Net Effect

Inward force toward the bulk

Such a force pulls the molecules

of the interface together &
contracts the surface.
Development

Surface tension

Prof. Magda EL-Massik 12

Surface tension is “the force per unit length that must
be applied ‘parallel’ to the surface so as to
counterbalance the net inward pull”.

Units of this force: dyne/cm (or N/m), the force in dynes

required to break a film of length 1 cm.

Visualization of surface tension as a

person lifting a rock up the side of a
cliff by pulling the rope
in a horizontal direction

Prof. Magda EL-Massik 13

• Surface tension of various liquids
Liquid Surface tension at
20°C (in dynes/cm)

Mercury 476
Water 72.8
Oleic acid 32.5
Benzene 28.9
Ethyl alcohol 22.3

Comment on these values!!!

Prof. Magda EL-Massik 14

Surface tension values of water & ethyl alcohol
are 72.8 and 22.3 dynes/cm, although both of
them are polar solvents. Comment on this
difference.

Prof. Magda EL-Massik 15

Surface tension of liquids decreases with increase in
temperature.
E.g. 2 of H2O = 75.6 dynes/cm at 0°C
= 72.8 dynes/cm at 20°C
= 63.5 dynes/cm at 75°C Why?

Prof. Magda EL-Massik 16

1.3. Interfacial tension is “the force per unit length existing
at the interface between 2 immiscible phases”.
Units = dyne/cm (or N/m)

Surface tension versus interfacial tension

Surface tension is the tension between liquid-vapor
(gas) <LV and solid-vapor <SV; they are written 2L and 2S.

Interfacial tension is the tension between 2 immiscible

liquids 2LL, 2 solids 2SS or liquid-solid 2LS.

Comment on the following data:

Mercury, surface tension = 476 dynes/cm
interfacial tension against water= 375 dynes/cm
Why????

Prof. Magda EL-Massik 17

2.The wire frame experiment
Three sided wire frame with a movable bar of length (L) is used
to demonstrate the principle of surface tension.

A liquid film will form within the frame, when it is dipped in a

soap solution.
As soon as the apparatus is removed from the soap liquid,
the movable bar moves spontaneously in the direction of film, so
as to decrease the surface area of the liquid.

Prof. Magda EL-Massik 18

Surface tension manifested in terms of surface force.
The surface tension (2) of the solution film is a function of the
force f that must be applied to break the film over the length of
the movable bar.

As a general definition: Surface tension is the magnitude of the

force, exerted parallel to the surface of a liquid, divided by the
length L of the line over which it acts.
2 = f/ L
For the specific case
illustrated in this example.
There is an upper
surface & a lower
surface , thus the force acts
along a total length of 2 L.
2 = f/ 2L
Prof. Magda EL-Massik 19
Surface tension expressed as an energy necessary to create
surfaces
Work is being done by pulling the string down.
This work is going into creating an additional surface
area.
The work required is proportional to the number
of molecules that must be brought up to the surface,
i.e. to dA (increase in area). Therefore, we can write:

The work done to move the bar by a distance (ds)

[or to increase the surface area dA]:
W = f x ds and f = 2 x 2L
W = 2 x 2L x ds

W= 2 dA

2 =2 =
W/W/
dA;A

• In other words, 2 is the energy that must be

supplied to increase the surface area by one unit.
•
Prof. Magda EL-Massik 20
3. Measurement of surface and interfacial tension
3.1 Capillary rise method
When a capillary tube is placed in a liquid,
the liquid rises up the tube a certain distance.
Why?
The force of adhesion between the liquid
molecules and the capillary wall is greater
than the cohesion between the liquid molecules.
This will cause an upward force on the liquid
at the edges and result in a meniscus which turns upward.

The surface tension acts to hold the surface intact,

so instead of just the edges moving upward,
the whole liquid surface is dragged upward.

Surface tension, but not interfacial tension,

can be determined by this methodProf. Magda EL-Massik 21
Due to surface tension (upward force), the liquid
continues to rise in the tube.
Because of the weight of the liquid, the upward
movement is balanced by the downward force of
gravity.
Upward force = downward force
S.T. x circumference = mass x acceleration due
to gravity
2 =r 2 = =r2h>g
2 = ½rh >g
Prof. Magda EL-Massik 22
3.2. Drop weight method or drop number method
A known volume of a liquid is allowed to fall as drops from a
dropper or a graduated pipette under the effect of gravity and
the No. of drops is counted.

The drop will fall when 2 forces are balanced:

- Force due to surface tension= < x L= < x 2A r
- Gravitational force = m g
< x 2A r = m g

Taking the surface tension of distilled water as standard

reference(72.8 dyne/cm at 20°C), the surface tension of
other liquids can be calculated:
<1 / <2 = m1 / m2

<1 / <2 = V1 B1 / V2 B2

Prof. Magda EL-Massik 23

4. Spreading coefficient
A liquid (e.g. oleic acid) is placed on the surface of water, will
spread and form a film if the force of adhesion between the liquid
molecules and the water molecules is greater than the cohesive
forces between the oleic acid molecules themselves.

Consider a hypothetical cylinder (Cross sectional area: 1 cm2) of

- Sublayer liquid: S
- Spreading liquid: L

• Work of adhesion: energy required

To break the attraction between
unlike molecules. W= < x CA
Wa= <L + <S – <LS Prof. Magda EL-Massik 24
• Work of cohesion: energy required
to separate the molecules of
the spreading liquid
Wc= 2 <L

• Spreading coefficient; S
S = Wa – Wc= (2L + 2S – 2LS) - 2 <L
S= 2S – (2L + 2LS)

S, --if + ve spreading occurs

-- if – ve the liquid forms globules or floating lenses and fails
to spread over the surface (e.g. mineral oil on water).
Example:
If the surface tension of water (<S ) is 72..8 dyne/cm at 20°C,
the surface tension of benzene(<L) is 28.9 and the interfacial
tension(<LS) is 35.0, what is the spreading coefficient
Prof. Magda EL-Massik 25
Relation between molecular structures and spreading
coefficients
An oil spreads over water because it contains polar groups such
as COOH or OH
When the carbon chain increases, the ratio of polar/ non polar
character decreases and the spreading coefficient on water
decreases.
Many non polar substances such as liquid petrolatum fail to
spread on water.
Benzene (non polar) but spreads on water, because the
cohesive forces between its molecules are weaker than
adhesion for water

Prof. Magda EL-Massik 26

Applications of spreading coefficient in
pharmacy
Surfactants added to topical products to
improve spreading:
For a lotion with mineral oil base to spread
freely and evenly on the skin, its polarity and
hence its spreading coefficient should be
increased by the addition of the proper SAA.

Prof. Magda EL-Massik 27