Like all other
dosage forms, tablets and capsules are subjected to those pharmacopoeial
standards which deal with “added substances” with respect to their toxicity,
interference with analytical methods, etc. However, there are a number of
procedures which apply specifically to tablets and capsules, and which are
designed, not only to ensure that a tablet or a capsule exerts its full
pharmacological actions, but also to determine the uniformity of the physical
properties of the official tablet/capsule, irrespective of the manufacturer.
Such standards
are found in the British Pharmacopoeia and United Pharmacopoeia and include,
uniformity of diameter, uniformity of weight (mass), content of active
ingredient, uniformity of content, disintegration and dissolution. In addition
there are a number of quality control procedures, which, though widely applied,
are not defined by the pharmacopoeias (non-pharmacopoeial standards) such as
thickness, hardness and friability.
The following experiments demonstrate the
application of a number of selected physical and dosage performance tests on
samples of commercially available tablets and capsules. Students are required
to refer to official pharmacopoeias for detailed description of other tests not
carried out in this practical session. For this experiment, capsule and tablet
are being used for the assessment of quality.
For experiment
1, we will observe the physical appearance of the tablets and capsules. The
physical characteristics of the samples are examined including the shape,
colour, diameter, thickness, smell or special lines (marking). For experiment 2,
uniformity of diameter, thickness and hardness are determined. This will
actually influence the delivery of the drugs in body system.
For example, a
tablet should be hard enough to withstand the rough transportation process.
However, it should not be too hard that it will not disintegrate or metabolise
within our body. Next, tablet friability is checked in experiment 3. Friability
is the tendency for a tablet to chip, crumble or break following compression.
This is usually applied to uncoated tablets and surfaces during handling and storage
processes. The result is inspected through the percentage loss of weight.
For
experiment 4, the uniformity of weight of tablets and capsules are determined. If
the deviation of weight of tablets exceeds the limit, it may be due to factors
such as flowing properties of the powder, the speed of tableting machine, the
pressure used in compression and the type of machines used in tableting. On the
other hand, the deviation in capsule weight is normally caused by the defect of
the capsule filling machine. Finally, the last experiment is about the content
of ibuprofen. The content uniformity test is used to determine the potency and
content of active ingredient in the ibuprofen powder.
EXPERIMENT 1
Procedure:
1.
A tablet and a capsule is selected from the provided samples. Their shape, colour, diameter, thickness and/or other physical characteristics were
examined.
Result:
Back Front
Shape:
Round with hexagon shape on it
Colour:
White
Diameter:
1.3 cm
Thickness:
0.3 cm
Other
physical characteristics: has a pale yellowish spot on the tablet.
Shape : Oval
Colour : Red
Other physical characteristics : Has a strong odour, made of hard gelatin capsule, company logo and capsule weight are stamped on the capsule
EXPERIMENT 2
Procedure:
1.
10 tablets were selected. Tests for uniformity of
diameter, thickness and hardness were carried out using Tablet Testing
Instrument (PHARMATEST PTB 311).
Result:
Tablet
|
Diameter
(mm)
|
Thickness
(mm)
|
Hardness (N)
|
1
|
12.82
|
5.54
|
149.83
|
2
|
12.82
|
5.50
|
136.34
|
3
|
12.82
|
5.60
|
130.99
|
4
|
12.83
|
5.59
|
119.16
|
5
|
12.82
|
5.52
|
148.17
|
6
|
12.83
|
5.56
|
142.81
|
7
|
12.83
|
5.55
|
136.34
|
8
|
12.83
|
5.64
|
125.07
|
9
|
12.80
|
5.60
|
140.96
|
10
|
12.83
|
5.58
|
136.90
|
Discussions:
For this Experiment 2, it was stated that
the deviation of individual unit from the mean diameter should not exceed ±5%
for tablets with diameter of less than
12.5 and ±3% for diameter of 12.5 mm or more.
To know if we achieved this criteria, firstly
we had to find the mean diameter of the 10 tablets.
Mean diameter =
[ (12.82 X 4) + (12.83 X 5) + 12.80 ] / 10
= 12.82 mm
Secondly, we
calculated the difference between the mean diameter with 12.5 mm
12.82-12.5 =
0.32
Thirdly, the
difference of diameter is divided by the mean and we found out the percentage
of the deviation:
[ 0.32 / 12.82 ]
X 100% =2.50%
Therefore, the
tablets did not exceed 3% deviation of individual unit from the mean diameter.
While carrying the diameter, thickness and
hardness tests, we were supposed to carry out properly by inserting the tablets
properly in the Tablet Testing Instrument machine or else the tablets would not
be tested properly, hence, error in results.
EXPERIMENT 3 : TABLET FRIABILITY
Procedure:
1.
10 tablets were selected
and weighed all at once.
2.
All the tablets were put into
the drum of the tablet abrasion and friability tester. The rate of rotation was
set to 60 rpm and the machine was started to operate for 10 minutes.
3.
After 10 minutes, the machine
was stopped and the tablets were removed and brushed free from dusts and
powder. All tablets were weighed at once and the percentage loss of the weight
was determined.
Result:
WEIGHT (g)
|
% Weight loss (g)
|
||
Before test
|
After test
|
Difference (before-after)
|
|
5.7988
|
5.5568
|
0.242
|
(0.242/5.7988) x 100
= 4.17%
|
Discussion:
The
friability test is conducted to determine the physical strength of the uncoated
tablets towards the possible abrasion and collision that may occur in
production state or everyday handling of the tablets. To mimic this possible
condition, the friabilator machine was used with the rotation rate is set to 60
rpm for 10 minutes.
Based
on the result, the percentage weight loss of our tablets is 4.17% of their weight,
which is not good. The ideal percentage weight loss should be less than 1% of
their weight.
There
are several reasons that might be the cause of this situation. Firstly, the
tablets might have expired or kept under poor condition. As the lab session
will use the tablets from the same container, the previous students might have
introduced the tablets to humidity due to inappropriate container capping.
Next, the drum might have not be cleaned thoroughly resulting in some dust or
any other sharp object left at the edge of it. When the test is conducted, the abrasion
of the tablets with these things will cause the tablets to lose more of their
weight. Lastly, the drum of the machine was installed in the wrong way such
that the rotation will caused the tablets to be expelled from the machine. This
happened while the machine is rotating at 60rpm and the expulsion might had
caused some damages to the tablets even before we started with the test.
EXPERIMENT 4
Procedure:
a) Tablets
1.20 tablets
were selected at random and weighed .The average weight was determined.
2. The tablets
were weighed individually and the weight of each tablet was determined. The
percentage of deviation of the individual tablet from the average tablet was
determined.
3. The deviation
of individual weight from the average weight should not exceed the limits given
below.
Average
weight of tablet
|
Deviation
(%)
|
Number
of tablets
|
Less
than 80 mg.
|
±
10.0
|
Minimum
18
|
±20.0
|
Maximum
2
|
|
80
mg to 250 mg
|
±7.5
|
Minimum
18
|
±15.0
|
Maximum
2
|
|
More
than 250 mg.
|
±5.0
|
Minimum
18
|
±10.0
|
Maximum
2
|
b) Capsules
1.
20 capsules are selected at random.
2.
One capsule is weighed. The capsule is
opened and the contents are removed as completely as possible. The emptied
shells are weighed. The net weight of its contents is determined, that is by
subtracting the weight of the shells from the weight of the intact capsule.
3.
The procedure is repeated with other 19
capsules.
4.
The average net weight is determined from
the sum of the individual net weights.
5.
The percentage deviation is determined from
the average net weight for each capsule. The deviation of individual net weight
should not exceed the limits given below:
Average net weight
of capsule
|
Deviation (%)
|
Number of capsules
|
Less than 300 mg.
|
± 10.0
|
Minimum 18
|
±20.0
|
Maximum 2
|
|
300 mg or more
|
±7.5
|
Minimum 18
|
±15.0
|
Maximum 2
|
|
Result:
a) Tablet:
Paracetamol (500mg)
Weight (individual tablet)/g
|
Difference of individual tablet with the average
weight of tablets/g
|
Percentage of deviation (%)
|
0.5762
|
0.0038
|
0.66
|
0.5617
|
-0.0107
|
-1.87
|
0.6120
|
0.0396
|
6.92
|
0.5707
|
-0.0017
|
-0.30
|
0.5589
|
-0.0135
|
-2.36
|
0.5572
|
-0.0152
|
-2.66
|
0.5670
|
-0.0054
|
-0.94
|
0.5717
|
-0.0007
|
-0.12
|
0.5751
|
0.0027
|
0.47
|
0.5669
|
-0.0055
|
-0.96
|
0.5693
|
-0.0031
|
-0.54
|
0.5801
|
0.0077
|
1.35
|
0.5708
|
-0.0016
|
-0.28
|
0.5709
|
-0.0015
|
-2.62
|
0.5893
|
0.0169
|
2.95
|
0.5746
|
0.0022
|
0.38
|
0.5714
|
-0.0001
|
-0.17
|
0.5632
|
-0.0092
|
-1.61
|
0.5714
|
-0.0001
|
-0.17
|
0.5692
|
-0.0032
|
-0.56
|
b) Amoxycillin capsules (250mg)
Weight of capsule (g)
|
Weight of empty shell (g)
|
Net weight of content (g)
|
Deviation from average weight (g)
|
Percentage deviation (%)
|
|
1
|
0.3506
|
0.0638
|
0.2868
|
-0.0067
|
-2.28
|
2
|
0.3426
|
0.0653
|
0.2773
|
-0.0162
|
-5.52
|
3
|
0.3658
|
0.0622
|
0.3036
|
0.0101
|
3.44
|
4
|
0.3349
|
0.0614
|
0.2735
|
-0.0200
|
-6.81
|
5
|
0.3635
|
0.0630
|
0.3005
|
0.0070
|
2.39
|
6
|
0.3636
|
0.0638
|
0.2998
|
0.0063
|
2.15
|
7
|
0.3571
|
0.0627
|
0.2994
|
0.0009
|
0.31
|
8
|
0.3593
|
0.0635
|
0.2958
|
0.0023
|
0.78
|
9
|
0.3502
|
0.0644
|
0.2858
|
-0.0077
|
-2.62
|
10
|
0.3590
|
0.0633
|
0.2957
|
0.0022
|
0.75
|
11
|
0.3711
|
0.0618
|
0.3093
|
0.0158
|
5.38
|
12
|
0.3728
|
0.0617
|
0.3111
|
0.0176
|
6.00
|
13
|
0.3626
|
0.0638
|
0.2988
|
0.0053
|
1.81
|
14
|
0.3381
|
0.0631
|
0.2750
|
-0.0185
|
-6.30
|
15
|
0.3432
|
0.0641
|
0.2791
|
-0.0144
|
-4.91
|
16
|
0.3624
|
0.0623
|
0.3001
|
0.0066
|
2.25
|
17
|
0.3586
|
0.0643
|
0.2943
|
0.0008
|
0.27
|
18
|
0.3641
|
0.0636
|
0.3005
|
0.0070
|
2.29
|
19
|
0.3683
|
0.0630
|
0.3053
|
0.0103
|
3.51
|
20
|
0.3452
|
0.0620
|
0.2832
|
-0.0103
|
-3.51
|
Calculation:
Discussion:
The
aim of measuring the uniformity weight of tablets is to ensure that weight of
tablets in batch are in the acceptable limits and are marketable. The tablet
which we are investigating is paracetamol (500mg).The average weight of the
tablets is 0.5724 g .Thus, according to the tablet, the limits at the third column
should be followed. From table 1, when the average weight of tablet is more
than 250mg (0.250g), there must be a minimum of 18tablets having deviation ±5.0
%and maximum 2 tablets having deviation ±10.0%.Based on the results, 20 tablets
tested follow the limits given .19 tablets are within the deviation of ±5.0%.Only
one tablet is out of deviation ±5% but it does not reached the deviation ±10%.Hence,
all the tested tablets have uniform weight and are acceptable.
The average net
weight of content for capsule is less than 300mg, so the individual net weight
of minimum 18 capsules should not exceed ±10% from its average net weight, and maximum 2
capsules should not exceed ±20% from its average
net weight. From the result of experiment of 20 amoxycillin capsules (250mg),
amoxicillin capsules pass the test of uniformity of weight of capsules. The
highest percentage deviation of capsule is -6.81% which is still under the
limit of ±10%. The high
percentage deviation is due to the leftover of content inside the capsule that
is unable to be removed completely. Therefore, the percentage deviation is not
accurate as the capsule may not be completely empty when weighing. 20 capsules
are tested to increase the accuracy of the test by finding their average
weight.
EXPERIMENT 5
Procedures:
1. 20 Ibuprofen
Tablets previously selected at random were weighed and powdered.
2. A quantity of
powder containing 0.5g ibuprofen was extracted with 20ml chloroform for 15
minutes and filtered through a sintered glass crucible (BS Porosity No. 1)
3. The residue
was washed with 3 · 10ml chloroform and the combined filtrate was gently
evaporated just to dryness in a current of air. The residue was dissolved in
100ml with ethanol (96%) previously neutralized to phenolphthalein solution.
4. The solution
was titrated with 0.1M sodium hydroxide to end point with phenolphthalein
solution as indicator. The content of ibuprofen was calculated provided each ml
of 0.1M sodium hydroxide is equivalent to 0.02063g of C13H18O2.
Results:
Given 20tablets
x 400mg = 8000mg
If 10.24g powder
contains 8g ibuprofen and 0.5g ibuprofen is needed, then
Powder required
= (0.5 x 10.24) / 8
= 0.64g
In this
experiment, each ml of 0.1M NaOH = 0.02063g of C13H18O2 and 19.7ml of
NaOH is required to titrate the residue dissolved in 100ml of ethanol to its
end point (phenolphthalein solution turns from colourless to pink), then
Ibuprofen
content = (0.02063 x 19.7 ) / 1
= 0.4064g
Uniformity of
content = 0.4064 X 100%
= 81.28%
Uniformity of
content refers to a method of pharmaceutical analysis to determine the actual
content of tablets and capsules at which the tablets and capsules are randomly
chosen.
Theoretically,
the content of the ibuprofen in solution should be 0.5000 g. However, the experimental
value of ibuprofen content in solution is 0.4064 g. This shows that the
experimental value is actually lower than the theoretical value. The percentage
deviation value calculated is 81.28%, which is not compliance with the
experiment. In fact, the percentage deviation should be within 85%-115%,
according to British Pharmacopeia. Any
value outside the range of the standard is considered as a failed formulation
in the B.P test for content of active ingredient. The experimental percentage deviation
value is 3.72% lesser in order to achieve the compliance value. On top of that,
19.7 mL of 0.1 M sodium hydroxide is used in titration upon reaching the end
point where the colourless solution turns pink. In fact, for the 0.5g content
of tablets, the volume of 0.1 M sodium hydroxide solution expected should be
24.24 ml but not 19.7 mL of sodium hydroxide upon reaching the end point.
The deviations
happened as there might be some errors happen during the experiment. One of the
errors that might happen is when weighing the ibuprofen powder. The Ibuprofen might be weighed less or
more during weighing session. Besides, the Ibuprofen powder may not transferred
completely from one apparatus to another. Upon transferred, some of the
Ibuprofen may remained in the weighing boat and conical flask, therefore there
may be lesser Ibuprofen present in the solution. Thus, precautions step should
be taken such as rinsing the apparatus thoroughly in order to ensure that there
are no residues left in the apparatus. Another
possible error is we used filter funnel and filter paper instead of sintered
glass crucible to filter the solution. As a result, alteration of the powder uniformity
might be happened. Incomplete drying of the solution can also be another source
of error which leads to inaccurate results.
The determination
end point of titration can be one of the sources of error during titration.
Firstly, the amount of phenolphthalein added is small in quantity causing the
colour change cannot be seen precisely. Next, the titration might be done too
fast until we missed the end point where the colourless solution turns pink. In
fact, the correct technique of titration is the titrate should be added drop by
drop to the analyte in order to obtain an accurate result.
QUESTIONS
1. What are the
objectives of the tests for uniformity of diameter and uniformity of content?
The aim of tests
for uniformity of diameter is to ensure the uniformity of the size and
appearance of tablets. On the other hand, the objective of measuring the uniformity
of content is to ensure the uniformity of the active ingredient in the tablets
or capsules.
2.State the
types of tablets and capsules that must be tested for the uniformity of
diameter and uniformity of content.
All the tablets and
capsules including coated and uncoated tablet.
3.Why it is
important that tablets and capsules have uniform weight and content?
The test for the
uniformity of weight and content of tablets and capsules is to ensure the
quality of tablets and capsules being marketed are under controlled. The
importance of measuring the uniformity of content is to ensure that the active
ingredient in the tablets or capsule is in a therapeutic range and do not cause
any toxicity.
4.Give
reasons for the non-compliance to test for uniformity of weight.
Firstly, there may
be uneven feeding of granules into the die during tablet manufacturing at the
tablet press. The powders may also not be mixed properly before the tablets are
manufactured. The granules may be exposed to air during the compression
process, where excess air is trapped inside the tablet causing uneven
distribution of granules in the tablet. For capsules, they may not be filled
completely or are overfilled. Distortion of the tablets and capsules due to
heat, chemical or environment factors can also occur which causes loss of
content. Human error is also possible where a mistake in procedure may happen
due to fatigue or systematic error due to error in the apparatus.
5.Explain why is it
beneficial for any tablets or capsules to have distinctive or identifying
features.
It is easy for identification. The
patients will be able to differentiate the tablets easily though its
distinctive features such as colour and markings. Besides, the identifying
features such as trademark markers can help a person to identify the pill. Some
markers are codes which function as a legal requirement for pill
identification. The distinctive features also give the tablets and capsules an
attractive appearance, which will in turn help in improving patient compliance.
No comments:
Post a Comment