DPP1 ASSESSMENT 3 : Quality of
Tablets And Capsules
KOO BAO YI (A162843)
MUHAMMAD SYAKIR BIN MOHD
SHAHRIZAN (A162715)
AKMAL HADAWIAH BINTI ISMAIL
YATIM (A162694)
Introduction:
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, friability, 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,
and hardness.
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.
Friability is the ability of
solid substance break into smaller pieces under mechanical shock, friction and
rubbing between solid substances and wall of machine. Substances are said to be
friable if small particles are easily dislodged and become airborne and hence
become respirable. Friability testing is a laboratory technique used to test
the durability of tablets during transit. A sample of tablets is repeatedly
dropped over a fixed time by using friability tester so that we can measure about the
percentage loss of weight of tablet through chipping. Friability test is
essential to evaluate the capability of tablet to withstand abrasion or
friction in packaging, handling or shipping. The repeatedly dropped tablet
should not lose more than 1% of its weight or else the tablets within the batch
will be rejected. This step is carried out in order to produce physical stable
and good tablet which is resistant to abrasion.
Uniformity of weight is a
pharmaceutical analysis parameter for the quality control of capsules or
tablets. It is an important quality assessment to ensure that each of the
tablet and capsule produced meets the requirement of pharmacopoeia standard and
also manufacturing standard. Multiple capsules or tablets are selected at
random and a suitable analytical method is applied to assay the individual
content of the active ingredient in each capsule or tablet.
Uniformity of weight of tablets and capsules are
important in order to ensure that the patient will get accurate dose of drug in
tablet or capsule form to prevent the toxic effect or getting no therapeutic
effect. Therefore, uniformity test of weigh of tablets and capsules is carried
out in manufacturing process to make sure those produced tablets and capsules
fit the requirements.
Questions:
1. What are the objectives of the tests for uniformity of
diameter and uniformity of content?
The objectives of the tests for uniformity of diameter and uniformity of
content is to determine the
consistency in weight, size, and appearance of tablets to increase the patient compliance, consumer
acceptance of the product, and to facilitate packaging Objectives oo
test for uniformity of content are to ensure similar amounts of all active
ingredients and excipients are well distributed in the tablets which increases
potency and efficacy of the drugs.
2. State the types of tablets and capsules that must be
tested for uniformity of diameter and uniformity of content.
The uniformity of diameter is tested for all uncoated and coated tablets
except enteric tablets, film-coated tablets and sugar-coated tablets. For
uniformity of content, it involves uncoated and coated tablets and also hard
and soft capsules.
3. Why is it important that tablets and capsules have
uniform weight and content?
It is important that tablets and capsules have uniform weight and
content to ensure that the tablet contains the proper amount of drug so that the
patients take a precise pharmaceutical dose. This is because non-uniform amount
of active ingredients in the capsule or tablets might lead to lethal effects
towards patients.
4. Give reasons for the non-compliance to test for
uniformity of weight.
The reasons for the non-compliance to test for uniformity of weight are
uneven feeding of granules into the die and also due to irregular movement of
the lower punch that cause variation in capacity die space.
5. Explain why it is beneficial for any tablets or
capsules to have distinctive or identifying features.
It is beneficial for any tablets and capsules to have distinctive or
identifying features so that the patient can identify and recognize the
medication that they take by looking at the shape, pattern, colours and size of
the tablets or capsules. So, this can prevent confusion among patients towards the
medications and reduce the possibility of medication errors.
Experiment 1: Physical
Appearance
Objective:
To determine the physical appearance of the tablet from different
aspects.
Procedure:
1. Select any tablet or capsule from the provided
samples. For the sample assigned to you, examine and note its shape, colour,
diameter, thickness and/or other physical characteristics.
Apparatus and Materials:
Tablet
Results:
|
|
Tablet
|
|
Shape
|
Circle
|
|
Colour
|
Light Pink
|
|
Diameter
|
1.1cm
|
|
Thickness
|
0.5cm
|
|
Surface
|
Dim surface
|
Experiment 2: Uniformity of
diameter, thickness and hardness
Objective:
To study the uniformity of diameter, thickness and hardness of tablet by
using the Tablet Testing Instrument (PHARMATEST PTB 311).
Apparatus and Materials:
10 tablets, Tablet Testing Instrument (PHARMATEST PTB 311), weighing
boat
Procedure:
- 10 tablets
were selected and tests for uniformity of diameter, thickness and hardness
were carried out using the Tablet Testing Instrument (PHARMATEST PTB 311).
- 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.
Results:
|
Tablet
|
Thickness (mm)
|
Diameter (mm)
|
Hardness (N)
|
Diameter Deviation (±mm)
|
Individual Unit Deviation (%)
|
|
1
|
3.81
|
11.19
|
179.7
|
0.006
|
7.5
|
|
2
|
3.97
|
11.20
|
220
|
0.004
|
5
|
|
3
|
4.00
|
11.19
|
169.8
|
0.006
|
7.5
|
|
4
|
3.96
|
11.21
|
174.7
|
0.014
|
17.5
|
|
5
|
3.98
|
11.19
|
215.1
|
0.006
|
7.5
|
|
6
|
3.87
|
11.18
|
198.6
|
0.016
|
20
|
|
7
|
3.87
|
11.20
|
227.4
|
0.004
|
5
|
|
8
|
3.98
|
11.19
|
191.2
|
0.006
|
7.5
|
|
9
|
3.97
|
11.20
|
216.7
|
0.004
|
5
|
|
10
|
3.97
|
11.21
|
190.4
|
0.014
|
17.5
|
Total diameter : (11.19 + 11.20 + 11.19 + 11.21 + 11.19 +
11.18 + 11.20 + 11.19 + 11.20 + 11.21) mm = 111.96mm
Mean of diameter: 
Discussion:
This experiment was conducted to test for the uniformity of diameter,
thickness and hardness of tablets. The objectives of the tests for uniformity
of diameter are to ensure the consistency of tablets so tablets won’t deviate
much in their size in terms of appearance. High tablet consistency in terms of
appearance may facilitate in packaging process and also enhance patient
compliance to the medicine. Objectives to test for uniformity of content are to
ensure the even distribution of active ingredient in the medicine which
increases potency and efficacy of the drugs. For such the active ingredient
will be released evenly at correct target site and in right amount. Coated and
uncoated tablets and capsule should be tested for uniformity of diameter and
uniformity of content.
The thickness and diameter of tablets were measured to analyse the
consistency of tablets. Tablets thickness should be within ±5% variation of the
standard value while 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. By
comparing the results, the tablets which show the high consistency in their
diameter and thickness because their percentage of deviation is less than 3%
for diameter of 12.5mm or more which obey with the consistency stated. It’s
important to analyse in term of diameter and thickness because the variation in
tablets is not obvious to human naked eye thus it must be tested with Tablet
Testing Instrument so the products can exhibit higher consistency.
The tablets were also tested for the hardness to for their resistance to
chipping, abrasion or breakage during transport, storage or handling before
use. The tablets tested in this experiment showed some variation in terms of
hardness but still considered uniform. This may influence their ability to
withstand shock of handling, packaging and transporting and also the solubility
of the tablets. This is because if a tablet product is very hard, it may make
it hard to disintegrate and solubilise in vivo which eventually will interrupt
with its efficacy and fail to produce desire therapeutic effect. An appropriate
hardness of tablets will ensure the stability of the product before it reaches
the target site to produce effect.
Conclusion:
The 10 tablets have uniform diameter, thickness and hardness which are
said to comply with the pharmacopeia standard.
Experiment 3: Tablet
Friability
Objective:
1. To determine the tendency of tablet to
break into smaller pieces after exposure to mechanical impact and attrition.
2. To determine the percentage loss of weight
of tablet after being put into the drum of tablet aberration and friability
tester.
Material/apparatus:
10 tablets weighing boat, drum of the table aberration and friability tester
friability tester
Procedures:
- 10
tablets were selected and weighed.
- All the
10 tablets were put into the drum of the tablet aberration and friability
tester. The rate of rotation was set to 60rpm, time to 10 minutes and the
operation was started.
- At the
end of the operation, all the tablets were removed. The freedom from dust
or powder ensured by using brush. The tablets were reweighed and
percentage loss of weight of 10 tablets was determined.
- Compressed
tablet should not lose more than 1% of its weight.
Result and calculations:
|
Initial
weight of 10 tablets before abrasion (mg)
|
Final
weight of 10 tablets after abrasion (mg)
|
|
2989.2
|
2962.1
|
Rate of rotation: 40rpm
Wight difference:
2989.2mg - 2962.1mg = 27.1mg
Percentage loss of weight:
27.1/2989.2 x 100%= 0.91%
Discussion:
From the experiment, the percentage loss of tablet weight is 0.91% which
does not exceed 1% means that the batch of tablets are good tablets that can
resistant to abrasion and mechanical shock.
If capping occurs, friability values are not calculated. A thick tablet
may have less tendency to cap whereas thin tablets of large diameter often show
extensive capping, thus indicating that tablets with greater thickness have
reduced internal stress.
Effervescent tablets and chewable tablets may have different
specifications as far as friability is concerned. In the case of hygroscopic
tablets, an appropriate humidity-controlled environment is required for
testing.
Conclusion:
In conclusion, the weight loss of the tablets is 0.91% which mean that
the tablets are strong and hard enough to withstand from breaking easily during
the packing, handling and also shipping.
Experiment 4 : Uniformity of weight of tablets and capsules.
Objective:
To test the
uniformity of weight of tablets and capsules.
Materials
and apparatus:
20 tablets, 20
capsules, weighing balance
Procedure:
Tablets
- 20
tablets that were previously selected at random were weighed. The average
weight of the tablet was determined.
- The
tablets were weighed individually and the percentage deviation of its
weight was determined from the average weight.
- 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
|
Capsules
- 20
capsules were selected at random.
- One
capsule was weighed. The capsule was opened and the contents of the
capsules were removed as completely as possible. The emptied shells were
weighed. Then, the net weight of its contents was determined by
subtracting the weight of the shells from the weight of the intact
capsule.
- The
procedure was repeated with other 19 capsules.
- The
average net weight was determined from the sum of the individual net
weights.
- The
percentage deviation was then 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
tablets
|
|
Less than 300
mg.
|
± 10.0
|
Minimum 18
|
|
|
± 20.0
|
Maximum 2
|
|
300 mg or more
|
± 7.5
|
Minimum 18
|
|
|
± 15.0
|
Maximum 2
|
|
|
|
|
Results:
Tablets
|
Tablets
|
Weight of the
tablet (mg)
|
Percentage
Deviation (%)
|
|
1
|
290.3
|
-0.79
|
|
2
|
287.0
|
-1.92
|
|
3
|
286.7
|
-2.02
|
|
4
|
284.4
|
-2.81
|
|
5
|
296.5
|
+1.33
|
|
6
|
283.4
|
-3.15
|
|
7
|
287.5
|
-1.75
|
|
8
|
291.0
|
+0.55
|
|
9
|
281.1
|
-3.93
|
|
10
|
281.4
|
-3.83
|
|
11
|
312.5
|
+6.80
|
|
12
|
323.5
|
+10.56
|
|
13
|
286.3
|
-2.16
|
|
14
|
292.3
|
-0.11
|
|
15
|
289.5
|
-1.06
|
|
16
|
287.0
|
-1.92
|
|
17
|
292.0
|
-0.21
|
|
18
|
292.6
|
-0.003
|
|
19
|
287.5
|
-1.75
|
|
20
|
293.4
|
+0.27
|
Total weight of 20 tablets =
5852.1 mg
Average weight of the tablet = Total weight of 20 tablets / 20
= 5852.1 mg / 20
= 292.61mg
= 5852.1 mg / 20
= 292.61mg
Percentage deviation (%) = (weight of individual tablet – average
weight of tablet) x 100
Average weight of tablet
Average weight of tablet
Capsules
|
Capsules
|
Weight of
intact capsules (mg)
|
Weight of capsule
shells (mg)
|
Net weight
of contents (mg)
|
Percentage
Deviation (%)
|
|
1
|
477.5
|
81.2
|
396.3
|
+1.99
|
|
2
|
476.4
|
80.2
|
396.2
|
+1.97
|
|
3
|
470.0
|
76.9
|
393.1
|
+1.17
|
|
4
|
464.6
|
84.8
|
379.8
|
-2.25
|
|
5
|
448.1
|
78.2
|
369.9
|
-4.80
|
|
6
|
469.5
|
81.6
|
387.9
|
-0.16
|
|
7
|
466.2
|
76.0
|
390.2
|
+0.43
|
|
8
|
470.9
|
79.6
|
391.3
|
+0.71
|
|
9
|
460.8
|
76.8
|
384.0
|
-1.17
|
|
10
|
468.7
|
85.5
|
383.2
|
-1.37
|
|
11
|
458.8
|
71.2
|
387.6
|
-0.24
|
|
12
|
448.9
|
80.4
|
368.5
|
-5.16
|
|
13
|
449.9
|
76.4
|
373.5
|
-3.87
|
|
14
|
463.3
|
75.4
|
387.9
|
-0.16
|
|
15
|
468.5
|
72.7
|
395.8
|
+1.87
|
|
16
|
478.0
|
73.5
|
404.5
|
+4.11
|
|
17
|
467.3
|
68.6
|
398.7
|
+2.61
|
|
18
|
473.4
|
78.8
|
394.6
|
+1.56
|
|
19
|
462.4
|
72.0
|
390.4
|
+0.48
|
|
20
|
473.7
|
76.4
|
397.3
|
+2.25
|
Total weight of 20 capsules =
7770.7 mg
Average weight of the capsules = Total weight of 20 capsules / 20
= 7770.7 mg / 20
= 388.54mg
= 7770.7 mg / 20
= 388.54mg
Percentage deviation (%) = (net
weight of individual capsule – average weight of capsule)
x 100
Average weight of capsule
x 100 Average weight of capsule
DISCUSSION
This experiment was conducted
to study the uniformity of weight of tablets and capsules. The uniformity of
weight was determined by calculating the percentage deviation of the tablets
and capsules in order to make sure that the dosage units is consistent. For the
uniformity of weight, the totals of 20 tablets and 20 capsules were used and
the weights were recorded.
The percentage deviation (%)
of tablets from the average weight of tablets can be calculated by this formula
:
Percentage deviation (%)
= (weight of individual tablet –
average weight of tablet) x 100
Average weight of tablet
Average weight of tablet
Whereas, for the calculation
of deviation (%) of capsule, this formula was used :
Percentage deviation (%) = (net
weight of individual capsule – average weight of capsule) x 100
Average weight of capsules
Average weight of capsules
In this experiment, since the
average mass obtained for 20 tablets is 292.61mg which is greater than 250mg,
thus minimum 18 tablets should not deviate from 292.61mg by ±5% and maximum 2
tablets should not deviate from 292.61mg by ±10% . All tablets were considered
passed the test, because the percentage deviation of 20 tablets fall within the
range. This shows that all tablets used is this experiment are uniform in the
aspect of weight.
For the capsules, the average
mass obtained for 20 capsules is 388.54mg which is greater than 300mg, thus
minimum 18 tablets should not deviate from 388.54mg by ±7.5% and maximum 2
tablets should not deviate from 388.54mg by ±15%. All capsules were considered
passed the test, because the percentage deviation of 20 capsules fall within
the range. This shows that all capsules used is this experiment are uniform in
the aspect of weight.
Even though the results showed
that all tablets and capsules passed the test,
the results of the test may not be accurate as there might be some
inaccuracy in the measurement of weight especially for the capsules. The errors
might arise when measuring the weight of these tablets and capsules. Some
powders might still get stuck inside the capsule shells and the powders are not
completely removed, thus cause the measurement of emptied shells may not
accurate.
CONCLUSION
The uniformity of weight of tablets and capsules
test is useful in quality control during the production of tablets and
capsules. In this experiment, it is found that all of the tablets and capsules
are uniform in the form of weight. Therefore, the tablets and capsules are all
passed the test and follow the standard of uniformity of weight.
Experiment 5: Content of
ibuprofen
Objective:
To determine the content of
ibuprofen from ibuprofen drugs that has been formulated into tablets.
Material/apparatus:
Ibuprofen
tablets, mortar and pestle, measuring cylinder, conical flask, burette, retort
stand, filter paper, chloroform, ethanol, phenolphthalein solution, 0.1M sodium
hydroxide.
Procedures:
1. 20 Ibuprofen tablets selected at random and the
tablets were weighed and powdered.
2. A quantity of powder containing 0.5 g ibuprofen with
20 ml chloroform for 15 minutes was extracted and filtered through a conical
flask.
3. The residue was washed with 10 ml chloroform three
times and gently evaporated using water bath.
4. The evaporated residue was dissolved in 100 ml of
ethanol and phenolphthalein solution was added.
5. The solution was titrated with 0.1M sodium hydroxide
to end point with phenolphthalein solution as the indicator.
6. The result was calculated and recorded.
Results & Calculation:
Weight
of 20 tablets = 11.31g
Content
of ibuprofen in 20 tablets = 400mg x 20 = 8000mg or 8g
Weight
of powder containing 0.5g ibuprofen = 11.31g/8g x 0.5g = 0.707g
The
endpoint of titration = 15.2ml
Given
that each ml of 0.1M sodium
hydroxide is equivalent to 0.02063g of C13H18O2,
Therefore,
Amount
of ibuprofen at the end of experiment = 15.2 x 0.02063 = 0.314g
The
percentage of ibuprofen content = 0.314g/0.5g x 100 = 62.8%
Discussion:
The ibuprofen tablets were checked
its uniformity in content to see whether those tablets were subjected to those
phamacopoeial standards or not. The Ibuprofen tablets should contain 85% - 115%
of the labelled ibuprofen content in accordance British Pharmacopoeia.
According to the result obtained in the experiment, the content of ibuprofen
obtained is 62.8% which mean the ibuprofen tablets being tested was considered
to have failed the B.P. test for content of active ingredient. However, we can
really say that the ibuprofen tablets that were tested did not really comply
with the pharmacopoeial standard because there were a few other factors that
might lead to the error of the result obtained.
One of the errors that might
happened during the experiment was failure to fully extract the ibuprofen with
20ml of chloroform. This might happen due to time constraint. Another
possibility is spillage of materials used especially the drug or even failure
to completely emptying the weighing boat when the drug was transferred into the
conical flask. Other than that, some ibuprofen might also stick at the filter
paper when filration technique was done. Improper titration technique also
might contribute to the error of the result. Nevertheless, all those factors
can be corrected to get a more accurate result. Among the things that are need
to be done are being extra careful and cautious while handling the material,
making sure that the drug is being transferred completely, washing the residue
that might stick at the filter paper with chloroform and also properly do the
titration technique without any rush.
Conclusion:
The
content of ibuprofen obtained was 0.314g and the percentage of ibuprofen was
62.8% which outside the limit percentage set by pharmacopoeial standard (85% -
115%). Therefore, the ibuprofen tablets have failed the B.P test of content.
