Ajman University of Science & Technology

Faculty of Pharmacy & Health Sciences

..

LABORATORY MANUAL FOR

PHYSICAL PHARMACY-II
Central Committee
Department of Pharmaceutics

..
2000 - 2001

Dear Students,
The central committee of department of pharmaceutics, Faculty of
Pharmacy and Health Sciences, is pleased to introduce to you the
Laboratory Manual of Physical Pharmacy-II (700212). The manual
covers experiments deal with the principles discussed in didactic
lectures. These experiments employ fundamental principles of physical
pharmacy required to design, prepare physically and chemically stable
heterogeneous dosage forms and ensure their therapeutic safety and
efficacy. The central committee set this manual for all the branches to
ensure the uniformity of student outcome.
Best Regards
Central Committee
Department of pharmaceutics,
Faculty of Pharmacy and Health Sciences

Table of Contents
Part
No.
Part 1
Exp.(1)

Content

Page
No.

Analysis of Drugs by Visible Spectroscopy

Determination of the standard curve of potassium
permanganate at 570 and 540nm.
Determination of the standard curve of sodium
salicylate (reacted with ferric nitrate) at 540 and500 nm

Part 2

10

Drug stability ( solution kinetics )

Exp.(2)

Determination of the rate constants and half-life of the

alkaline hydrolysis of P-nitrophenyl acetate in the presence of
Tris buffer ( pH 8.5 and concentration 0.05)
Effect of temperature and determination of the activation
energy of the alkaline hydrolysis of P-nitro-phenyl acetate in
the presence of Tris buffer

15

Exp.(3)

27

Part 3

Buffer catalysis of the alkaline hydrolysis of

P-nitrophenyl acetate.

Interfacial Phenomena

Exp.(4)

Micellar Solubilization by Non-ionic Surfactants

38

Exp.(5)

Spreading Coefficient and Emulsification

41

Exp.(6)

Determination of The Adsorption Parameters of

Oxalic Acid on Charcoal

Part 4

Colloidal dispersion

Exp.(7) Purification of colloids :

preparation of hydrophobic colloids
preparation of hydrophilic colloids
Exp.(8) Properties of colloidal dispersion :
Determination of the diffusion coefficient for crystal
violet through gelatin gel.
Determination of the type of charge of a colloid
3

46

51

54

Exp.(9)

Part 5
Exp.(10)

Part 6
Exp.(11)
Exp.(12)

Determination of the iso-electric point of egg albumin

Stability of colloidal dispersions
Incompatibilities of pharmaceutical colloids
Protective action of hydrophilic colloids

59

Heterogeneous Dosage forms :

Dispensing of pharmaceutical suspensions

Preparation of the effects of various agents on the
flocculation properties of suspending materials.

65

Rheology

Measurement of viscosity of Newtonian fluid by

capillary tube and Failing Sphere.
Measurement of viscosity of Non-Newtonian fluid by
Rotational Viscometer.

74
75

Part I
Analysis of Drugs by Visible Spectroscopy

Introduction
When matter interacts with an energy source (heat, sound, electricity, light, etc.)
some of the energy can be absorbed, causing the particles to be elevated to different
energy levels. In some cases, the particles can be excited totally out of the original
chemical system holding them in place. Under certain conditions, though, the amount of
energy absorbed can be controlled, and information about the chemical system can be
obtained. This is the case in absorption spectroscopy.
If we monitor a beam of light shining through a sample containing a substance that can
absorb one of the beam's wavelengths, we can obtain a plot of the amount of light
absorbed versus the wavelength. This plot is known as an absorption spectrum, and
shows which particular wavelengths of light a chemical species can absorb.

A primary use of absorption spectroscopy lies in its applicability to quantitative

measurements. This is a function of how much light is absorbed, and how that relates to
the amount of the absorber present in the sample. The following derivation presents the
basics of this relationship.
When we shine a light beam of a certain wavelength () and initial intensity (I 0 )
through an absorbing sample contained in a spectrophotometer cell, the intensity of the
light beam transmitted through the sample (I t ) is dependent on three factors.

The first factor is whether the sample will absorb light at that wavelength

The second is the amount of sample that the light must pass through or,
the cell width (b).

The third factor is the concentration of the absorbing species in the

sample solution (C).

The fraction of light transmitted, or transmittance (T), is defined as the following:

(1)
and,
Percentage of light transmitted (% T) = T 100

(2)

where,
I 0 = initial intensity of the light beam, and
I t = transmitted intensity of the light beam
The transmittance of the sample varies logarithmically with the cell width and the
concentration of the absorbing species in the following way:
log (1/T) = -log T = (proportionally constant) b C

(3)

The proportionality constant depends on:

The chemical nature of the individual absorber.

The wavelength at which the measurements are being made.

The units of b and C.

In visible absorption spectroscopy, b is normally measured in centimeters. If C is

also measured in mol/L (molar concentration, M), the proportionality constant is defined
as the molar absorptivity (), which has units of l/M-cm. If C is measured in any other
units (e.g., g/l), the constant is simply called the absorptivity (a), whose units will depend
on C. Under normal operating conditions, "" or "a are determined experimentally by
measuring a standard of known concentration.

Factors that Determine Transmitted Light Intensity

The preceding relationship relates the amount of light transmitted through the sample to
the concentration and cell width. We frequently like to think in terms of how much light
is absorbed by the sample, so we define a new term, absorbance (A):
A = log (1/T) = -log T

(4)

Making all of the appropriate substitutions, we get:

A = b C (when C = mol/L or M)

(5)

or,
A = a b C (when C = g/l or other units)

(6)

This equation is known as Beer's Law, which shows the linear relationship between the
absorbance and the concentration of the absorbing species.
In chemical analysis, the following two methods can utilize Beer's Law:

1. Absolute Calculations
Absorptivity or molar absorptivity is calculated by measuring the absorbance of a
standard of known concentration in a cell known cell width. This calculated value is then
used to determine an unknown concentration of the same absorbing species from the
absorbance measurement at that concentration.
2.

Working Curve Analysis

The absorbance of a series of three to five standard solutions are measured and
plotted on graph paper against the concentrations of these standards. This is known as a
Beer's Law plot. The absorbance of an unknown concentration is then measured, and its
concentration is determined directly from the plot.
This method is more commonly used than the absolute calculation,
because experimental error will average out over the number of standards.

Beer's Law Plot

Experiment 1

Determination of the standard curve of potassium

permanganate at 570 and 540nm.

Procedure :
1. Prepare 6 different dilutions of Potassium Permanganate by using a 0.01%
stock solution (ss) as in Table 1.
9

2. Set up the wavelength of spectrophotometer to 540 nm. Use distilled water as

a blank.
3. Rinse one of the cuvette with distilled water and fill it with the water. Place it
in the first sample compartment. Rinse another cuvette with small portions of
the first standard solution, and fill it with the solution. Put the cuvette in the
second sample compartment. Repeat the rinse/fill for the other solutions using
additional cells and put them in sample compartments.
4. Put the sample tray in the blank position. Push [Auto Zero]. Then measure the
absorbance of each of your solutions.
5. Set up the wavelength of spectrophotometer to 570 nm. Use distilled water as
a blank. Repeat steps 3-4 and list results in Tables 2.

Table 1: Potassium Permanganate dilutions using 0.01% stock solution (ss),

their concentrations and the resulted absorbance at 540 nm.

#
1
2
3
4
5
6

mls of ss
1
2
4
6
8
10

mls of water
9
8
6
4
2
0

% of dilution
10
20
40
60
80
100

Conc. of solution Absorbance

0.001
0.002
0.004
0.006
0.008
0.01

Table 2: Potassium Permanganate dilutions using 0.01% stock solution (ss),

their concentrations and the resulted absorbance at 570 nm.

#
1
2
3
4
5
6

10

mls of ss
1
2
4
6
8
10

mls of water
9
8
6
4
2
0

% of dilution
10
20
40
60
80
100

Conc. of solution Absorbance

0.001
0.002
0.004
0.006
0.008
0.01

Analysis of Results
Plot absorbance v.s concentration to construct Beers plot. Calculate the slope of the plot
using the following Eq.
Slope = (Abs2 Abs1) / (Conc2 Conc1) = absorptivity = a
The concentration of the unknown sample can be obtained by dividing absorbance
by the slope.

Determination of the standard curve of sodium salicylate

(reacted with ferric nitrate) at 540 and 500 nm
Procedure

Prepare 6 different dilutions of sodium salicylate by using a 0.01%

stock solution (ss) as in Table 3. Take 8 ml of each working solution and add
2 ml of the ferric nitrate solution provided to produce a color.
Set up the wavelength of spectrophotometer to 540 nm. Use ferric nitrate
reagent (1% ferric nitrate in 1% nitric acid) as a blank.
Rinse one of the cuvette with ferric nitrate reagent and fill it with the reagent.
Place it in the first sample compartment. Rinse another cuvette with small
portions of the first colored standard solution, and fill it with the solution. Put
the cuvette in the second sample compartment. Repeat the rinse/fill for the
other solutions using additional cells and put them in sample compartments.
Put the sample tray in the blank position. Push [Auto Zero]. Then measure the
absorbance of each of your solutions.
Set up the wavelength of spectrophotometer to 500 nm. Use ferric nitrate
reagents as a blank. Repeat steps 3-4 and list results in Tables 4.

Table 3: Sodium salicylate dilutions using 0.01% stock solution (ss), their
concentrations and the resulted absorbance at 540 nm

#
1
2
3
4

11

mls of ss mls of water % of dilution

1
9
10
2
8
20
4
6
40
6
4
60

Conc. of ferric complex

0.0008
0.0016
0.0032
0.0045

Absorbance

5
6

8
10

2
0

80
100

0.0064
0.008

Table 4: Sodium salicylate dilutions using 0.01% stock solution (ss), their
concentrations and the resulted absorbance at 500 nm

#
1
2
3
4
5
6

mls of ss mls of water % of dilution

1
9
10
2
8
20
4
6
40
6
4
60
8
2
80
10
0
100

Conc. of ferric complex

0.0008
0.0016
0.0032
0.0045
0.0064
0.008

Absorbance

Analysis of Results
Plot absorbance v.s concentration to construct Beers plot at the two wavelengths.
Calculate the slope of the plots using the following Eq.
Slope = (Abs2 Abs1) / (Conc2 Conc1) = absorptivity = a
The concentration of the unknown sample can be obtained by dividing absorbance by the
slope.

Determining concentrations of unknown:

1. Take the 2 ml remaining from each test tube of the previous experiment for sodium
salicylates and add them as follows to get at the end 3 test tubes:
1+2 ; 3+4 ; 5+6
2. Add 1 ml of Ferric Nitrate to the 3 tubes
3. Set up the Spectrophotometer at 540nm wavelength and proceed as before.
4. Measure absorbance of the samples and use the standard curve or its slope to calculate
concentrations.
12

Unknown
1+2
3+4
5+6

Theoretical
Concentration in 10-3
1.5
5
9

Absorbance

First method
Concentration of the first mixture = Abs1 / slope
Concentration of the second mixture = Abs2 / slope
Concentration of the third mixture = Abs3 / slope
Second method:
Is graphical as shown on the plot itself; it consists on relaying the absorbance to the
plot itself and then finding the corresponding concentration.

13

Part 2
Drug Stability ( Solution Kinetics )

Experiment 2
This experiment provides an introduction to the simplest type of solution kinetics
usually encountered. We will study in this experiment a specific reaction that is the Ester
Hydrolysis.
R-COOR + H2O

RCOOH + ROH

.The ester used is: p-nitrophenylacetate

O

14

NO2

O C CH3

In this experiment we will determine the rate constant of the alkaline hydrolysis of pnitrophenylacetate in the presence of Tris Buffer (pH = 8.5 and at 0.5 M).
The kinetic parameters you will determine are :
1. The observed Rate constant of the hydrolysis and the half life of the reaction at
different temperatures (27, 37 and 47o C ).
2. The heat of activation for the overall reaction.
3. Buffer catalysis of the alkaline hydrolysis of p. nitrophenylacete.
Theoretical considerations
Let E represent the ester . Then in the absence of buffer the rate (velocity) of the
hydrolysis reaction over the entire pH range can be written:
v = KH [E] [H+] + KW [E] + KOH [E][OH-] ---------------------- ( 1 )
Where
v
: reaction rate
+
KH : second order rate for acid catalyzed hydrolysis.
KOH- : second order rate for base catalyzed hydrolysis.
KW : first order constant for the uncatalyzed hydrolysis.
At very low pH only the term containing KH+ will be important , while at very
high pH only the term containing KOH - will be important. At an intermediate pH it may
be necessary to write all three terms, because at least one of them will always be
relatively small.
In the presence of buffer catalysis, the rate of the hydrolysis reaction over the entire
pH can be written:
v= KH [E] [H+] + KW [E] + KOH [E][OH-] + KB [B] [E]------- ( 2 )
Where KB = second order rate constant for buffer catalysis and [B] = buffer
concentration. Considering the high pH range only KOH and KB are important . Then the
reaction rate becomes:
v = KOH [E][OH-] + KB [B] [E]------------------------------------- ( 3 )

15

A. Measuring of the observed rate constant :

For high pH and in the presence of buffer catalysis, the rate of the reaction can be
Eq. ( 3 ) However, if the pH and the buffer concentration are held essentially constant
throughout the reaction , Eq. ( 3 ) becomes:
v=

{ KOH [OH-] + KB [B] } [E] =

Kobs [E]----------------( 4 )

Where Kobs = KOH [OH-] + KB [B] ------------------------------( 5 )

Eq. ( 4 ) represents a first order reaction .( This would be called a pseudo or apparent
first order reaction ) . The dependence of E on time can be written:
Log [E/Eo] =

[Kobs/2.303]* t ----------------------( 6 )

Where [Eo ]is the ester concentration at time zero and [ E ] is its concentration at time t .
Now suppose that during the hydrolysis of this ester the solution Absorbance undergoes a
change . If Beers law is followed by all absorbing species , it can be shown that :
[ E ]/ [Eo ]

= [A At ]/ [A At ]----------------------------( 7 )

where A O is the Absorbance at

t = 0 , At

at

t = t , and A at t =

Thus, Eq. (6) Becomes :

Log [A At ]/ [A At ] = -Kobs t ---------------------( 8 )

Or
Log [100*[A At ]/ [A ]] = Log 100 -Kobs t
Therefore, a plot of [(A oo At )] (Absorbance) or [100*[A At ]/ [A ]] (as %) one
of the vertical axis of a semi-log paper vs time should give a straight line . The slope of
this line is equal to [Kobs / 2.303], which, therefore, permits the evaluation of
Kobs.

16

B. Determination of the Halflife of the reaction :

A quantity often used in the discussing first-order reaction is the half-life, t ,
which is the time required for the concentration to decrease to one-half its initial value .
The half-life of a first-order reaction is related to the rate constant by Eq. (9):

t = [ 0.693 / Kobs ] ------------------------------------------------------- ( 9 )

The dimension of a first-order rate constant is time-1; and the usual units are sec-1.

C. Determination of the Heat of Activation :

The temperature of the environment always influences the observed rate constant of
any reaction. This influence can be quantitatively followed by the use of Arrhenius
Expression,
#
K = A e (-H /RT)
Where
K
R
A
H#

= The rate constant

= The gas constant
= Pre-exponential coefficient
= The heat of activation

= The temperature of the environment in Kelvin (oK)

Equation (10) predicts that the higher the temperature the greater the rate constant
and therefore the faster the rate of reaction. On the other hand at constant temperature (To
K) the pre exponential coefficient, the greater the activation energy, the slower the
reaction, and more rate is influenced by the given temperature. Equation (10) can be
regulated to read:
Log k Log A (H# /2.303RT)
Therefore a plot of log K (on the vertical axis ) vs . 1 / To K should give a straight
line . The slope of this line is equal to -H# / 2.303 R .

17

Determination of the kinetic parameters ( Kobs, t , H# ) of the

alkaline hydrolysis of p-nitrophenylacetate in the presence of Tris
buffer ( pH = 8.5 and 0.5 M):

Experimentation:

In this experiment students will be divided into six groups. Each group will
determine the rate constant and the half-life (of the alkaline hydrolysis of pnitrophenyl acetate in Tris buffer of pH 8.5 and 0.05 M ) at one temperature. Therefore,
o
o
two groups will study the ester hydrolysis at 27 C , others at 37 C and the last two
o
groups at 47 C.
18

Materials:
Each group of students will be provided with the following :
o
1. Water bath adjusted to a specific temperature (either; 27, 37 or 47 C.
2. A 100 ml volumetric flask preheated to the temperature of your water bath containing
98 ml of Tris buffer solution of pH 8.5 and 0.05M of total Tris buffer.
3. A Stopwatch.
4. A bucket of ice.
5. Ten test tubes.
6. A 5-ml pipette.
7. P-nitrophenylacetate stock solution (in acetonitrile) containing 0.5 mg/ml
8. Spectrophotometer 22RS, and two cuvettes.
Procedure:
1. Each group should divide the duties between themselves with the help of the TA in
charge
2. Set the wavelength of spectrophotometer 22RS to 398.5nm and check its
operation using a blank solution (Tris buffer at pH 8.33 and contains0.05M total
Tris buffer).
3. Pipette 2.0 ml of ester stock solution into the flask, shake well and note the time
(i.e.:, At = 0 when t = 0).
4. Withdraw 5 ml from the flask as function of time and tabulate your data in columns
with headings as in table (5).
5. Immediately after withdrawing the sample, measure the Absorbance at max =
398.5 (against buffer) otherwise, place the sample in ice to stop the reaction until
you are ready to measure the Absorbance.

6 6. Since the laboratory period is less than the time required for the
complete hydrolysis of P-nitrophenyl acetate, you are provided with
absorbance at time infinity (i.e. A = 1.015 )
Table 5
Temperature:__________
Time ( min )

0
15
19

At
0

(A At )
1.015 ?

%= (A At ) X 100

30
45
60
75
90
105
120
135
150

20

1.015?

Percentage Remaining

100

10

1
0

50

100
Time (min)

21

150

200

Table 6
Temperature:__________
Time ( min )

At
0

15
30
45
60
75
90
105
120
135
150

22

1.015?

(A At )
1.015 ?

%= (A At ) X 100

Percentage Remaining

100

10

1
0

50

100
Time (min)

23

150

200

Table 7
Temperature:__________
Time ( min )

At
0

15
30
45
60
75
90
105
120
135
150

24

1.015?

(A At )
1.015 ?

%= (A At ) X 100

Percentage Remaining

100

10

1
0

50

100
Time (min)

25

150

200

Data analysis :
1. The data generated by the six groups will be posted on the blackboard.
2. Every student should take the six sets of data and analyze it as follows :
a.

Plot % (A At ) v.s. time for the three temperatures or plot ( A At )

calculate the slope and then Kobs = slope x 2.303

b.

Calculate ( half-life t ) for the ester hydrolysis at three temperatures

(t

0.693 / Kobs )

c. Plot log (Kobs ) v.s. (1 / ToK ) and calculate the heat of activation for the
reaction from the slop.

26

Experiment 3
Solution Kinetics
Tris buffer catalysis of the alkaline hydrolysis of p-nitrophenyl
acetate at pH 8.5 :
Last weeks we determined the kinetic parameters for the alkaline hydrolysis of pnitrophenylacetae. in this experiment we plan to study
o
Tris Buffer catalysis of this reaction at 27 C.
Theoretical considerations:
o
Let us consider the ester hydrolysis at pH 8.5 and at 27 C .
Under this condition, pH and the temperature are constant and KH and KW are negligible
then the rate of ester hydrolysis can be written as:
v = { KOH [OH ]- + KB [B ] } [E]
Where
Kobs =

KOH - [OH ] + KB [B ]

(Terms are defined in experiment (2)).

Therefore a plot of (Kobs) vs. Buffer concentration [B] will yield straight line with slope
= KB and intercept = KOH [OH-].

Experimentation:
We will divide you in six groups .Each group will conduct a experiment (Kinetics
o
of the alkaline hydrolysis of p-nitrophenylacetate in Tris buffer ) at 27 C and at
different buffer concentrations.

27

Materials:
Each group of students will be provided with the following :
o
1. Water bath adjusted ( by a thermostat ) to 27 C .
2. A 100 ml volumetric flask containing 98 ml of Tris buffer solution of pH 8.5 and
either 0.125 M of 0.025 M total Tris .
3. Stop-watch .
4. A bucket of ice .
5. Ten test tubes.
6. 5 ml pipette .
7. p-nitrophenylacetae stock solution ( in acetonitrite ) containing 0.5 mg/ml
8. spectrum 20 , and two cuvettes.
Procedure :
1. Pipette 2 ml of p-nitrophenylacetae stock solution into the 100 ml volumetric flask
containing 98 ml of Tris buffer solution with proper concentration (0.0125 or 0.025)
o
are preheated to27 C .
2. Withdraw 5 ml from the flask every 15 minutes and measure the absorbance at 398.5
nm (against buffer ).
3. Tabulate your data in Table 8-10 .

Table 8
28

Buffer Conc. ________

Time ( min )

At

(A oo At )

1.015 -

15
30
45
60
75
90
105
120
135
150

29

1.015

log (A oo At )

Percentage Remaining

100

10

1
0

50

100
Time (min)

30

150

200

Table 9
Buffer Conc. ________
Time ( min )

At

(A oo At )

1.015 -

15
30
45
60
75
90
105
120
135
150

31

1.015

log (A oo At )

Percentage Remaining

100

10

1
0

50

100
Time (min)

32

150

200

Table 10
Buffer Conc. ________
Time ( min )

At

(A oo At )

1.015 -

15
30
45
60
75
90
105
120
135
150

33

1.015

log (A oo At )

Percentage Remaining

100

10

1
0

50

100
Time (min)

34

150

200

Data analysis :
1.The data generated by the six groups will be posted on the blackboard .
2.Every student should take the six sets of data and analyze it as follows :
a. plot log (A oo At ) vs time for all the data generated
b. calculate (Kobs and t ) at each buffer concentration
c. plot Kobs vs Tris conc. (0.0125,0.025 and 0.05 from exp. No.2 ) and calculate KB
(Tris catalytic constant)and KOH

Note : ( Kw [H+] [OH-] - 10 14 )

35

36

Part 3
Interfacial Phenomena

37

Experiment 4
Micellar Solubilization
Introduction :
The solubilizing power of water surfactant solutions is of great importance in the
preparation of dosage forms containing sparingly soluble drug . The factors affecting
micellar solubilization are many and their interrelationship complex. In general, the
degree of solubilization is a function of the physiochemical properties of the surfactant
and solubilizate .
In this experiment, the effect of surfactant structure on the solubility of
undissociated salicylic acid will be investigated. The surfactants used will be nonionic
Tween 60 (polyoxyethelene (20) sorption monostearate) , Tween 40 ( polyoxyethelene
(20) sorbitan monopalmitate ). Solubility determinations will also be conducted in Tween
60 solutions buffered at higher pHs to determine the effect of solute ionization on
solubilization. At the conclusion of this experiment you should be aware of the effect of
surfactant structure and solubilizate Ionization State on solubilization.
Experimental :
A. you will find on the side bench saturated solutions of salicylic acid in the various
surfactant solutions . They are labeled with the name and concentration ( %W/V ) of the
particular surfactant . Besides surfactant, each solution contain 0.1N HCL to insure that
the salicylic acid remains undissociated in solution. Each solution, after dilution, will be
assayed by the usual method using Trindars reagent .Use distilled water as a blank.
Tween 20
(% w/v )
0
0.5
1.0
1.5
3.0
5.0

38

Absorbance Concentration
(mg/ml)

Dilution

Solubility
(mg/ml)

Tween 40
(% w/v )
0.5
1.0
1.5
3.0
5.0

Absorbance Concentration
(mg/ml)

Dilution

Solubility
(mg/ml)

Tween 60
(% w/v )
0.5
1.0
1.5
3.0
5.0

Absorbance Concentration
(mg/ml)

Dilution

Solubility
(mg/ml)

B. After completing part A , analyze the salicylic acid saturated solutions of Tween 60
buffered at pH 3.0 and pH 3.8 .

pH 3.0
Tween 60
(% w/v )
0
0.5
1.0
1.5
3.0
5.0

39

Absorbance Concentration
(mg/ml)

Dilution

Solubility
(mg/ml)

pH 3.8
Tween 60
(% w/v )
0
0.5
1.0
1.5
3.0
5.0

Absorbance Concentration
(mg/ml)

Dilution

Solubility
(mg/ml)

Data Analysis :
1. Plot salicylic solubility vs. surfactant concentration for each surfactant.
2. Plot the ratio of total solubility to aqueous solubility vs. surfactant concentration for
each pH.
Conclusion:

40

Experiment 5

Introduction

Spreading Coefficient and Emulsification

Becher has define an emulsion as a heterogeneous system , consisting of at least

one immiscible liquid in the form of droplets , whose diameter , in general exceeds 0.1 u .
Such systems possess a minimal stability which may be accentuated by such additives as
surface active agents , finely divided solids , etc.
The process of emulsification involves the adsorption of an emulsifying ( surface
active agent ) agent at the interface between the oil and water phase , resulting in a
lowering of the interfacial tension existing between the two phase .
Depending on the nature and concentration of the emulsifier and the phase volume ratio
the resultant emulsion may be of the Oil-in-Water or Water-in-Oil type.
1.
2.
3.
4.

On completing this experiment , each student should :

Realize the relationship between spreading coefficient and emulsion formation .
Be able to test for the difference between O/W and W/O emulsion .
Be able to prepare emulsions using the hand homogenizer .
Realize the potential for incompatibilities when using surface active agents in the
preparation of emulsions .

Procedure :
A. Spreading coefficient and Emulsification
1. Fill two large beakers with tap water , after thoroughly cleaning with soap and water ,
and rinsing thoroughly . Lightly sprinkle some lycopodium powder into the surface of the
water in both beakers . After waiting for the powder to stop spreading
,place a drop of mineral oil onto the surface in the center of one of the beakers and a drop
of oleic acid in the same manner in the second beaker .
a. describe what occurs in the case of :
Mineral oil
Oleic acid

41

b. The initial spreading coefficients of mineral oil and oleic acid are
13.4 and
24.6, respectively . Do these values agree with your
observations ?

c. why was the surface of the water covered initially with the
lycopodium powder ?

2. Add 40 ml of water and 10 ml of mineral oil to a 50 ml stoppered cylinder . Repeat this

with oleic acid in place of the mineral oil. Shake both cylinders vigorously for two
minutes and set the cylinders down on the lab bench . Compare the times required for
each of the systems to separate completely into two phases .
a. Separation times :
Mineral oil emulsion
Oleic acid emulsion
b. How does the separation time compare with the relative spreading
coefficients ?

3. Shake the two emulsions again and pass them through a hand homogenizer , Save
the products until next week .
a. How do the emulsions appear at the end of the first lab ?
b. How do the emulsions appear at the end of a week ?

c. Dose the homogenizer aid in the end of a week ?

42

B. Emulsification with surface active agents

1. Add 10 g of mineral oil to 1.5 g of span 80 , 3.5 g of Tween 80 and 35 ml . of water to
a 50 ml cylinder and shake vigorously . How does this compare with the mineral oil
emulsion prepared earlier ?

2. Repeat the formula above , but complete the process by passing this batch through the
homogenizer . How does this compare with the homogenizer mineral oil emulsion
prepared without surface active agents , i.e. , the emulsion in A-3 ?

4. Add 25 g of mineral oil to 205 g of Arlacel 83 .Add 17.5 g of water very slowly
with vigorous agitation . Pass the emulsion through a homogenizer .

a. What is the meaning of the word Tween ?

b. What is the meaning of the word Span ?

c. What is Arlacel ?

43

C. Determination of Emulsion Type

1.
Dilution Method . Place a drop of the emulsions
( homogenized ) prepared in parts B-2 and B-3 of this experiment onto a water surface .
If it tends to this out over the water , or if it mixes readily with the water , the emulsion is
of the O/W type . If on the other hand the oil phase is the external phase of the emulsion
then the emulsion does not tend to mix or spread .
2.
Dye-Method . Add 2 to 4 drops of a 1 % F.D. 7 C. Red No. 1
solution
( water soluble dye ) to a portion of the emulsion . If water is the continuous ( external )
phase the color will spread throughout the emulsion . If , on the other hand , the on a
speckled appearance .
a. Emulsion B-2 is a ( W/O ) (O/W ) emulsion.
b. Emulsion B-3 is a (W/O ) (O/W) emulsion .
D. Compatibility of Surface Active Agents
Prepare 100 ml . of 1 % aqueous solutions of the following surface active agents . Store
in 4 oz. Prescription bottles .
a. Sodium lauryl sulfate
b. Benzalkonium chloride ( already prepared )
c. Tween 80
1. Add 5 ml . of a 1% CaCL2 of each of the above solutions . Use test tubes . Which
surfactants could not be used to prepare emulsions containing CaCL2 ? Explain.

2.Place 5 ml of the sodium lauryl sulfate solution and 5 ml of the Tween 80 solution in
separate test tube . To each tube , add 1 ml of the benzalkonium chloride solution . Which
surfactant could be used to prepare an emulsion containing
E. Phase Volume Ratio
Place 25 ml of a 10 % solution of Arlacel 83 dissolve in mineral oil in a 250 ml beaker .
Add water in 5 ml increments with repaid manual stirring until 25 ml . of water has been
added .Use a glass test tube for stirring the emulsion . Note the gradual changes in the
apparent viscosity . Why does the viscosity change with the addition of water ?
44

Continue to add water in small increments , with vigorous agitation after each addition ,
until a total of 200 ml . of water has been added .Homogenize and determine if the
emulsion is O/W or W/O
F. Emulsion Stability
Take one of the O/W emulsions and divide into 4x10 ml portions and subject to the
following conditions :
1.
2.
3.
4.

Heat in boiling water

Put in an ice bath.
Add 5 ml of ethanol.
Add 5 ml of 1.0 M NaCl

Record your observations .

45

Experiment 6
Determination of The Adsorption Parameters of Oxalic Acid
on Charcoal
This experiment will demonstrate the adsorption phenomena and teach us to
determine to determine the adsorption parameters.
Introduction:
In general, colloidal dispersions have the property of adsorbing solutes at their
surfaces. Thermodynamically, such adsorption process occurs to reduce the surface free
energy of the dispersion and therefore increases its stability. The degree of adsorption of a
solute (adsorbate) on the adsorbent, depends on 5 factors:
1.
2.
3.
4.
5.

The chemical nature of the adsorbent and the adsorbate.

The specific surface area of the adsorbent.
The temperature of the adsorbate
The concentration of the adsorbate
The pressure of the adsorbate

At a constant temperature, the relation between the amount adsorbed and the
concentration in a limited concentration range may be represented by one of three
adsorption isotherms.
These 3 adsorptions theories were found by:
Freundlich: Y = X / m =K. Ce 1/n

1
1
1
1
1
1
1

Langmuir: Y = X / m = {(Ym.b.Ce) / (1 +bCe)}

Bruner, Emmett, Teller => BET:
Y = {(Ym.b.x) / [(1-x) X [1+(b-1)x]]}
Where:
x
: weight of adsorbate in grams, adsorbed by m grams of the adsorbent..
K & n : Freundlichs Empirical constants
Ce
: Equilibrium Constant
Ym
: Weight of the adsorbate in grams, adsorbed by one gram of the adsorbent to
form a mono layer.
B
: Equilibrium constant of the adsorption process
46

K1

Adsorbate + Vacant Sites

Occupied Sites

K2

The adsorption parameters of Freundlich

K & n in Freundlich equation from the linearized equation.
Log Y = Log K + 1 / n X Log Ce
Therefore, a plot of Log Y (on the vertical axis) vs Log Ce should give us a straight line.
The slope of this line is equal to 1 / n, and the intercept is equal to Log K, so we can
evaluate K & n.
The adsorption parameters of Langmuir equations.
Ym & b in Langmuir equation.
We have seen that Langmuir equation is:
Y = X / m = {(Ym.b.Ce) / (1 +bCe)}
To linearize this equation; we took the reciprocal and multiply it by Ce to get:
Ce / Y = Ce / Ym + 1 / (Ym.b)
Therefore, a plot of Ce / Y (on the vertical axis) vs Ce should give us a straight line.
The slope of this line is equal to 1 / Ym, and the intercept is equal to
1 / (Ym.b), so we can evaluate Ym & b.
Procedure:
1.

In each of the 6 Erlenmeyer flasks provided, introduce 5 g of the adsorbent

(Charcoal).
2. To each of them add 5o ml of a known dilution of a standard solution of
Oxalic Acid provided (e.g. 1N, 0.8N, 0.4N, 0.1N) according to the following
table:

Flask 1 ml of 1N
47

Distilled Water Normality

1
2
3
4
5
6

3.
4.
5.
6.

48

Oxalic Acid
50
40
30
20
10
5

Of Oxalic Acid
1N
0.8N
0.6N
0.4N
0.2N
0.1N

0
10
20
30
40
45

Shake occasionally for 15 min and set aside for half an hour to achieve
equilibrium
Filter and reject the first portion of the filtrate after washing the receiver
with it.
Triturate 25ml of the aliquot filtrate in each case with 0.5N Sodium
Hydroxide using Phenolphthalein as an indicator (2 drops).
Calculate the amount adsorbed in each case and list your result in the
following table.
Oxalic
Acid
Conc.

Ml
ml
from of H20
1N
to 50ml
Oxalic

Initial
Conc.
(Ci)

1N
0.8N
0.6N
0.4N
0.2N
0.1N

50
40
30
20
10
5

2.25
1.8
1.35
0.9
0.45
0.225

0
10
20
30
40
45

End
Point

After calculations the table will be as follows:

Equilibrium conc.
(Ce)

Amount Adsorbed
X = Ci Ce

Log Ce

Y=X/m

Log Y

Ce / Y

X 50 {volume / (E.P X 0.0225)}

Data Analysis:
Make the following plots.
Plot 1: Y vs Ce
Plot 2: Ce/Y vs Ce
Plot 3: Log Y vs Log Ce

The first plot (Plot 1) shows that the adsorption phenomena deals with the
occupancy at the surface and as the vacancy increases, the rate of occupancy
increases, and at the end, when no more vacancy is available, the rate of occupancy
will be equal to 0.

The second plot (Plot 2) reflects the linearized form of Langmuir equation. It
will help us finding the Langmuir adsorption parameters: Ym and b.

The third plot (Plot 3) in fact, reflects the linearized form of Freundlich
adsorption isotherm equation. It is useful to find the Freundlich adsorption
parameters: K and n.

49

Part 4
Colloidal dispersion

50

Experiment 7
Preparation and Purification
There are two main methods of preparing a colloid:
1.
Dispersion i.e. splitting coarse aggregations of a substance into
colloidal units. This may be achieved by use of:
a.
Mechanical milling or grinding e.g. colloid mills.
b.
Irradiation with ultrasonic waves.
c.
Electrical dispersion methods Electrolytic disintegration )
Peptization e.g. with solvents or electrolytes).
2.

A.

Condensation Method i.e. aggregating very small atoms, ions, and

small molecules into colloidal particles. This may be achieved by:
a.
Chemical reactions.
b.
Decreasing the solubility by lowering the temperature or
changing the solvent.

Preparation of Colloids

Materials
Arsenius oxide, ferric chloride, silver nitrate, sodium chloride, sulphur,
alcohol, gelatin, hydrogen sulphide, acacia, sodium carbonate, tannic acid.
1.

Preparation of hydrophilic Colloidals :

a. Preparation of Acacia Mucilage:

Prepare 25 ml of a 5% dispersion of acacia in water.
b. Preparation of Gelatin Dispersions:
Prepare 25 ml of dispersions of each of 1.0% w/v and 2.5%
w/v gelatin in water
2.

Preparation of hydrophobic Colloidals :

a. Preparation of Ferric hydroxide sol.:

Into 75 ml. of boiling distilled water and poured 1.2 ml of
32% Ferric chloride solution. The hydrolysis _of the Ferric
51

chloride occurs instantly and a deep red _ sol. of Ferric

hydroxide forms.
b. Preparation of Silver chloride sol. :
Mix 10 ml of each of 5% silver nitrate and 10% sodium
chloride solution. The precipitate of silver chloride formed is
filtered. The residue on the filter paper may be peptized by
washing with distilled water to produce the required colloidal sol.
c. Preparation of Sulphur sol. :
This may be prepared by pouring a saturated solution of
sulphur in alcohol or acetone into water just below the boiling
point. The alcohol or acetone vaporizes leaving the water insoluble
sulphur colloidal dispersion when alcoholic solution of resins and
balsams are poured into water.
Preparation of Colloidal Silver sol.:
To 500 ml distilled water add 20 ml of 0.1N AgNO3 and 10
ml of 1% tannic acid solution. Heat this solution to 70-80oC and
slowly add 10 ml of 1% Na2CO3 solution with stirring a "teacolored" colloidal silver solution results which has the appearance
of the sol.

B. Purification of Ferric Hydroxide Sol. By Dialysis Using Cellophane

Bag :
Purification is concerned essentially with the removal of excess
electrolytes which usually get absorbed onto colloidal particles during their
preparation. Purification may be achieved by various methods:
a.
Dialysis.
b.
Electrodialysis.
c.
Ultrafilteration.

52

The most important of which is the dialysis. Electrolytes passes through

semi permeable membrane but not the colloidal particles. Therefore placing
ferric hydroxide sol. in a cellophane bag immersed in distilled water will
purify Ferric hydroxide sol. from any adsorbed chloride ions.
Procedure:
1. Form a cellophane bag on the stem of a glass funnel.
Fill the bag to 1/2 of its volume with Ferric hydroxide sol.and immerse in
250 ml beaker full of distilled water.
Test for chloride ions in the water of the beaker at a series of time
intervals.
4. Change the water in the beaker at regular time intervals and find out the
time necessary for the complete removal of electrolyte from the sol.
2.

3.

Experiment 8
Properties of colloidal dispersion
A.

Determination of the diffusion coefficient for crystal violet through

gelatin gel.

The diffusion coefficient (D) of a neutral particle can be determined using

equation 1, if the solution of this substance with a concentration C, is placed
on a gel and the distance, X, of the diffused particle in the gel is determined as
a function of time (t). The diffusion measurement (X) can be done by the aid
of a standard gel with a concentration C.
53

Ct = Co * Exp (-X2 /4Dt)

Ln Ct = Ln Co - (-X2 /4Dt)
D is defined as the amount of solute which would diffuse across unit
area under concentration gradient of unity, in unit time, if the rate was
constant during that time.
In this experiments, the diffusion coefficient of crystal violet in
gelatin solution containing 0.9% sodium chloride will be determined.
It is assumed that the dye diffuses through the water held by the
gel. Gelatin sol. was chosen because the crystal violet does not interact
or get hold by gelatin
Procedure:
1. Prepare 250 ml of 5% gelatin in saline solution (0.9% NaCl )
2. Distribute the gelatin into seven test tubes.
3. Use one tube of gelatin to prepare standard gel. with a concentration
of 1 in 500,000 w/w crystal violet in water this will be used as the
standard for the color diffusion measurements.
4. Prepare three solutions of crystal violet in distilled water containing 1
in 200 w/w, 1 in 400 w/w, and 1 in 600 w/w crystal violet in water.
5. Place about 5 ml of each solution on the top of two gels, cover to
prevent evaporation and place in test tube rack at room temperature.
6. Measure accurately the distance between the solution/gel interface
and the diffused crystal violet that is equivalent to concentration of 1 in
500,000 (the standard gel prepared in step 3). The mean of the readings
should be taken-this value is x mm.
7.
Record x values in Table 6 as a function of time.

1. Calculate the average of D for each dye concentration as shown in the

Table I .
Table I
Time
(hrs)
54

X2

X2
D=---------------------*
[4t(logCo - logC)2.303

(1/200)
W/W

(1/400)
W/W

(1/600)
W/W

(1/200)
W/W

(1/400)
W/W

(1/600)
W/W

0.5
1.0
1.5
2.0
2.5
WEEK

*Co= 1/200 w/w 1/40 w/w 1/60 w/w crystal violet .

C = 1/5000 w/w crystal violet .

B.

Determination of the type of the charge of a colloid

If one end of a filter paper strip is dipped into a colored hydrosol, the
ascent of the color will depend on the charge of the colloid. If the colloid has a
positive charge a distinct preparation between the dispersed phase and the
dispersing medium occurs in the ascending portion of the sol. such a
separation does not occur if a negatively charged colored sol. is used. This
phenomenon is probably due to the fact that the wetted filter paper acquiring a
negative charge. The negatively charged cellulose fibers will allow negatively
charged colloids to rise but it will attract and hold positively charged colloids
preventing the ascent of a positive hydrosol.
Procedure:
1. Prepare 1% aqueous solution of Amaranth and a 1% aqueous solution of
methylene blue.
2. Place 70 ml of each solution in 100 ml beaker.
3. Into each solution place the end of a strip of filter paper holded specially by
a stand, and observe at different time intervals.
4. Report your observation and conclusion to your instructor.
55

C.

Determination of the Isoelectric point of Egg Albumin

Proteins (e.g. Albumin) behave as amphoteric colloid and ionize

both as acids and bases. There is a definite hydrogen ion concentration at
which there is no resultant charge on the protein molecule and its
electrophoteric mobility is very small. This particular pH value is known as
the isoelectric point, and the solubility of protein at this point passes through a
minima.
In this particular experiment the extent of turbidity or precipitation
of a colloid at certain pH values is determined. This turbidity increased to a
maximum at the isoelectric point.

Material :
Albumin, ethyl alcohol, Mc livaine's buffer solutions (A 0.2 Molar
disodium phosphate and A 0.1 Molar citric acid. 0.1 M sodium hydroxide)
Procedure:
a. Preparation of Egg Albumin Solution:
1.
3.
4.
5.
6.

Approximately 0.5 gram of egg albumin is placed in 100 ml beaker

and wetted drop wise with distilled water.
As each drop is added it is ground into the powder until paste is
formed.
This paste should be carefully thinned down to about 50-70 ml.
The solution is clarified by the addition of 5 ml 0.1 M sodium
hydroxide.
The solution is subsequently diluted to 100 ml. and at this stage
any solid matter must be filtered off.

b. Effect of pH on Egg Albumin:

56

1. A series of eight test tubes containing buffer solution in the pH

range of 3-8 are prepared by mixing Mclivain standard solutions A
& B as in the Table II .
2. One milliliter of protein solution is added to each of these tubes and
mixed rapidly.
3. The series of test tubes should be left to stand for a few minutes, and
the relative turbidities matched at each pH value.
4. The pH which shows the most intense turbidity is the isoelectric
point of Egg Albumin.

Table II

Test
tube
No.

pH

1
2
3
4
5
6
7
8

3
4
4.5
5
5.5
6
7
8

ML of A ML of B

2.05
3.85
5.15
5.57
5.8
6.32
8.24
9.73

1 ml
protein

Observation

7.95
6.15
4.85
4.43
4.20
3.68
1.76
0.27

A= Disod. Phosphate 0.2 Molar (35.60 g/L) Na2HPO4.2H2O.

B= Citric acid 0.1 Molar (21.01 g/L) citric . 12H2O.
57

Experiment 9
Stability of Colloidal Dispersions
Lyophobic colloids have been affinity or the dispersing medium and are
not solvated. They are stabilized by a charge acquired by preferential
absorption of ions. Lyophilic colloids on the other hand, are highly solvated as
well as charged. The charge is usually a result of ionization. Their stability,
however, stems mainly from salvation effects.
Lyophobic colloids will precipitate if their electrical charge is
neutralized often remain dispersed as they solvated.
Materials:
Ferric hydroxide sol. silver sol., 2% acacia mucilage, 1% gelatin sol.
at pH 2. Different electrolyte concentrations as shown in Table 90% ethanol.
Procedure:
1. Triturate 5 ml of each of the above mentioned solutions in a test tube with
each of the electrolyte solutions in turn. Report the approximate
concentration in mol/L necessary for the precipitation of the colloid. Time
may be allowed for precipitation to take place.
2. The various solutions may be mixed with an equal volume of ethanol.
3. Evaporate 5 ml of each of the above solutions on a water bath to dryness.
Examine the residue and try to redisperse it by the gradual
addition of 5 ml of water.
58

4. Tabulate your observations.

5. Interpret the results in the light of the Schulze-Hardy rule, as well as
salvation effects.

Table III

Electrolyte

Ferric
Hydroxide

Silver Sol.

2% Acacia (-)

Solution

Ml .added M/1

Ml .added
m.M/1

Ml .added
m.M/1

1.0 M NaCl
0.01M BaCl2
0.001M ALCL3
0.01M Na2SO4
0.001M K3
[(Fe*)(CN)+6]
1.0M MgCL2
1.0M BaCL2
1.0M CaCL2
1.0M KCNS*
1.0M KBr
1.0M K.citrate
1.0M K2 SO4
Saturated
Na2SO4
Alcohol 90%
Evaporation of
solution
and
redispersion of
the residue.

59

1%Gelatin
pH2 (+)
Ml .added
m.M/1

* Only hydrophilic colloids .

Some Incompatibilities of Pharmaceutical Colloids

Sensitization in colloidal systems may result from any of the factors
which cause a decrease in stability of the colloid. Thus electrolytes of opposite
charge may precipitate lyophobic colloids. Dehydration by alcohol or too high
salt concentrations may lead to instabilities in hydrophilic sols. Even
protective colloids in concentrations below that which may protect can cause
precipitation in colloidal systems.
Materials :

Dil. HCl, Gelatin (Pharmagel A & Pharmagel B), Arsenius sulphide sol.
Ferric
hydroxide sol., Silver sol.
Procedure:

1. To 5 ml of a 2% mucilage of acacia add 5 ml of dil. HCl and report your

observation.
2. To 5 ml of a 2% mucilage of acacia dd 1 ml of Ferric chloride T.S.
Record your observation.
3. To 3 ml of a 2% mucilage of acacia add 5 ml of each of 1% Pharmagel A
solution (lime treated gelatin, I.E.P. 4.7 - 5) and 1% Pharmagel B solution,
acid treated gelatin, I.E.P. 7-9). Record your observation.
4. Mix 5 ml of each silver sol., and Ferric hydroxide sol. Record your
60

Interpret all your result in the light of:

a. Type of colloidal dispersion.
b. Electrolyte type, concentration & degree of dissociation.
c. Charge on the colloid & pH of the medium.
d. Salvation & desolation effects

Protective Action Of Lypophilic Colloids

Lyophobic colloids are readily precipitated by electrolytes. The
concentration of electrolyte required to cause such precipitation depends upon
the nature and concentration of the colloid, the method of precipitation and the
nature and valence of the electrolyte ions. Lyophobic colloids can be protected
from precipitation by the addition of lyophilic colloids e.g. gelatin and starch,
so that within certain limits precipitation will not occur.
In this experiment a constant volume of sodium chloride solution is
added to prepare (aresenius or silver sulphide) sols. containing progressively
larger amounts of the protective agents, e.g. starch. The minimum
concentration of added starch required to achieve complete protection is
recorded.
Materials:
Silver sol., 10% sodium chloride solution, 1.0% starch solution, 0.5%
acacia mucilage, 0.1% gelatin sol., Test tubes, burettes.
Procedure:
1. Three sets of eight clean test tubes each containing 5 ml of the silver sol.
are placed in a suitable rack.
2. The starch, acacia or gelatin sol. are placed in the test tubes in the
quantities shown in the Table below and mixed.
3. To each tube 1 ml of sodium chloride is then added.
4. The solutions should then be allowed to settle, if necessary for 4 or 5
days, in order that the precipitation effect may be observed.
5. Record your observations in the following tables.
Tube No. 8 in each set contains the blank, i.e. the protective colloid is
added but no sodium chloride is added. This solution should become slightly
61

turbid and visually identical with the solution in test tube No. 7 (i.e. tube with
the maximum quantity of protective colloid.

RESULTS
Using starch as a protective colloids
Test tube
No.

Sol. (ml)

Starch sol.
(ml)

1
2
3
4
5
6
7
8

5
5
5
5
5
5
5
5

0
1
2
3
4
5
6
6

Sodium
chloride
sol.(ml)
1

Observation after a
minimum period of 24
hours.

1
1
1
1
1
1

Using Acacia mucilage as a protective colloids

Test tube
No.

Sol. (ml)

Acacia
mucilage (ml)

1
2
3
4
5
6
7
8

5
5
5
5
5
5
5
5

0
1
2
3
4
5
6
6

Sodium
chloride
sol.(ml)
1

Observation after a
minimum period of 24
hours.

1
1
1
1
1
1

Using Gelatin sol. as a protective colloids

Test tube
No.
62

Sol. (ml)

Gelatin sol.
(ml)

Sodium
chloride

Observation after a
minimum period of 24

1
2
3
4
5
6
7
8

63

5
5
5
5
5
5
5
5

0
1
2
3
4
5
6
6

sol.(ml)
1
1
1
1
1
1
1

hours.

Part 5
Heterogeneous Dosage forms

64

Experiment 10
Dispensing of Pharmaceutical Suspension
In this laboratory period , students will be trained to dispense two suspension.
A. Magnesium Trisilicate Mixture B.P (1980 )
Rx
Magnesium trisilicate
Light magnesium Carbonate
Sodium Bicarbonate
Concentrated peppermint emulsion
Double strength chloroform water
Purified water sufficient to produce

50
50
50
25
500
1000 ml

Sig .: send 50 ml . 10 ml to be taken when necessary .

Calculations and Experimental Procedure :

Calculate the amounts required for 50 ml of the mixture . The suspending agent to
be used id either the powder of gum acacia (10%) or gum tragacanth (2%) , the
needed amount of these powders necessary to make the suspension is calculated
according to the total volume of the mixture .
In the mortar , mix thoroughly the fine powders of magnesium trisilicate , light
magnesium carbonate with the calculated amount of the gum used .
Dissolve the sodium bicarbonate in the two thirds of free amount of vehicle.
Pour gradually , with triturating about half of the amount of vehicle to prepare at
first a smooth cream and then a fine suspension devoid of any lumps . If necessary ,
strain through a piece of muslin.
Mix the two solutions , wash , the mortar with successive small amounts of
peppermint water left and mix the washings with the mixture prepared .

65

B. Phenacetin Suspension
Rx
Phenacetin
Glycerin
Methyl cellulose
Aromatic elixir
m.f.t. , Mist . mette dim
sig . Fl to be taken every 4 hours for pain .

Calculations and Procedure :

1. Calculate the metric equivalents and prepare half the amount .
2. Phenacetin is a sparingly soluble powder so it is prepared as suspension using a
dispersion stabilizer.
3. Methyl cellulose is used as dispersion stabilizer and is very often used in the form of
mucilage in the prescription compounding . So it can be handled by :
a. mixing the methyl cellulose thoroughly with 1/3 of the required amount of
water as hot water ( 80 to 90 o )
b. After complete dispersion cool and immerse in a beaker contains crushed ice.
c. Add the remainder of water as cold water drop by drop with continuous stirring
till a clear gel is obtained .
4. Phenacetin powder is weighed and triturated thoroughly in mortar into fine powder .
5. Add Methyl cellulose mucilage gradually with trituration .
6. Add aromatic elixir and complete the volume .

66

 Determination of the effect of various agents on the Flocculation

properties of suspended materials :
Introduction :
A pharmaceutical suspension may be defined as a coarse dispersion containing
finely divided insoluble material suspended in a liquid medium or available in dry form
to be distributed in the liquid when desired . We are only concerned with the former in
the present exercise.
For a suspension to be acceptable it must be composed of small uniformly sized
particles which do not settle rapidly. Those particles that do not settle should not pack
into a hard cake but should be redispersed completely and uniformly with the minimum
of agitation. In addition, the suspension should not be so viscous that it does not pour
freely from a bottle.
Deflocculated particles in suspension settle slowly but the sediment, which is
ultimately, formed packs closely in the bottom of the vessel. The result is a cake, which is
difficult to redisperse. Consequently, it is more desirable to prepare a flocculated
dispersion. The floccules produced are large in comparison with the individual particles
and hence settle rapidly. However, the floccules form a loose, open scaffold-like
structure, which is easily dispersed with the minimum of agitation. The theory behind this
approach has been covered in lecture. The main purpose of this experiment is to
determine the effect of various agents on the flocculation properties of suspended
materials.
Procedure:
This experiment will require two- lab periods. During the first session , you will
prepare the various systems described below and make initial measurements and
observations . In two weeks , you will accomplish the second phase of the work by
making final measurements and compiling the results . The following are provided
Solution A (Surfactant)
Aerosol 0.7 1.67 g.
Distilled water to 1 L .
Solution B (cationic flocculating agent)
ALCL3, 6H2O
0.95 g.
Distilled water to 100 ml.
Solution C (anionic flocculating agent)
KH2PO4
2.0 g.
Distilled water to 100 ml.
Solution D (suspending agent)
67

Carboxymethylcellulose
Distilled water to 100 ml.

0.02 g.

Solution E (suspending agent )

Carboxymethylcellulose
0.06 g.
Distilled water to 100 ml.
Sulfamethazine (Negative zeta potential)
Bismuth subnitrate (Positive zeta potential )
A. Place 1.6 g. of Bismuth subnitrate in to each of eleven large test tubes.
Add 0 to 20 ml of solution C , in 2 ml increments .
Add solution C and distilled water to the tubes according to the schedule below. Shake to
disperse , Label and allow to stand . Record sedimentation volumes , F = Hu /Ho , after 1
hour and after 2 weeks . Plot F versus molar concentration of KH2PO4 , using data form
2nd week .
TABLE - I
Test tube
1
2
3
4
5
6
7
8
9
10
11

ml. sol.
C.
0.0
2.0
4.0
6.0
8.0
10.0
12.0
14.0
16.0
18.0
20.0

ml. water

M, KH2PO4

F ( 1 hr. )

F (2 weeks)

20.0
18.0
16.0
14.0
12.0
10.0
8.0
6.0
4.0
2.0
0.0

B. Prepare the eight systems below . Soon after preparing each system , enter description
in Table II , noting general appearance and obvious troublesome or unsightly
conditions . Use Table III for conservations and measurements made after two
weeks of standing . Be sure that you determine the ease of redispersion after
measuring the sedimentation volumes.
System 1 :
To 8 ml of distilled water in a
68

test tube , add 0.4 g of sulfamethazine and stir.

System 2 : Prepare the following :

Solution A
18.0 ml
Sulfamethazine
0.8 g
Distilled water to
20.0 ml
Place Sulfamethazine in a test tube , add solution A and invert several times . Add
water to 20 ml. Then shake well.
System 3 : Prepare the following :
Solution A
18.0 ml
Sulfamethazine
0.8 g
Solution B
2.0 ml
Place Sulfamethazine in a test tube , add solution A and invert several times . Add
Solution B then shake well. Report your observations.
System 4 : Prepare the following :
Solution A
14.0 ml
Sulfamethazine
0.8 g
Solution B
2.0 ml
Solution E
4.0 ml
Place Sulfamethazine in a test tube , add solution A and invert several times . Then add 2
ml of Solution B , cap and shake . Finally add 4.0 ml of Solution E and shake well .
System 5: To 1.6 g of bismuth subnitrate in a test tube add water to 20 ml . Shake, save
for 2 weeks and observe . Report your findings
System 6 : Prepare the following :
Solution C
2.0 ml
Bismuth subnitrate
1.6 g
Distilled water to
20.0 ml
Place bismuth subnitrate in a test tube , add water , shake and then add solution C . Shake
well , label and keep for 2 weeks.
System 7 : Prepare the following :
Solution D
18.0 ml
Solution C
2.0 ml
Bismuth subnitrate
1.6 g
Add solution D to Bismuth subnitrate in a test tube , shake , and add solution C . Shake
and observe product . Save for 2 weeks and then record your observations.
System 8 : Prepare the following :
Solution E
18.0 ml
Solution C
2.0 ml
Bismuth subnitrate
1.6 g
Prepare as in # 7 above .
69

TABLE II
Item
1

70

Description

Explanation

TABLE III
Observations of the second lab. Session, Schedule:
System
1

71

Caking
yes or no

Ease of
redispersion

Explanation

Data Analysis:
Write the observation about the best suspending agent.
Study the effect of KH2PO4 on the flocculation properties of
suspension.
Fill out the Table 1 in the Lab. Manual and write your comment on
it. (Solution A, B, D, and E on sulfanilamide)
Fill out the Table II and Table III 1 in the Lab. Manual and write
your comment on the results.

72

Part 6
Rheology

73

Experiment 11
Measurement of viscosity using an Ostwald Viscometer
a) Determine the flow time of the liquid of known viscosity as water ( = 1 c p )
b) Determine the flow rate (Time) of the liquid of unknown viscosity at the same
temperature.
c) Calculate the viscosity (Kinematics) of the unknown liquid using the following
formula.
1 / 2 = t1 / t2
Where 1 and t1 are the viscosity and time of flow of the unknown fluid and
2 and t2 are the viscosity of water (1 c p) and time of flow respectively.

Procedure:
1. Clean and dry the viscometer.
2. Fill by means of arm (hg) so that the level in this arm stand is within 0.2mm of the
mark (g) when the tube is clamped vertically.
3. By means of a rubber tube suck the liquid to about 1 cm above mark (b).
4. Note the time of flow back through the tube between the marks (b) and (c).
5. Take three reading and find the average.
6. Calculate the kinematics viscosity of the liquid of unknown viscosity using the above
equation.

74

Experiment 12
Temperature dependency of viscosity
The viscosity of a liquid is inversely proportional to the temperature of this liquid.
This relationship is quantitatively expressed by the modified Arrhenius equations.
Log = log A Ev/2.303 R .1/T
Firstly, Study the viscosity change of 1% gelatin solution by temperature. Secondly,
determination of the equations constants A and Ev form the constructed graph.
Procedure:
Determine the dynamic viscosity of the gelatin solution 2% using Ostwald viscometer at
25, 35 , 45 .
Tabulate your results, log, T (K) and 1/T and plot log against 1/T. Calculate the
values of A and Ev form the intercept of the y- axis and slope of the straight line,
respectively.
Conclusion:
Knowing the Constants A and Ev for a particular system enables
Prediction of viscosity values at any desired temperature without
repeating the experimental work.

75