Tablets and capsules are
types of dosage form which are widely used. About 70% of all ethical
pharmaceutical preparations used tablet as dosage form. There are several types
of tablet which are delayed release, coated tablet and immediate release. The
British Pharmacopoeia defines tablets as being circular in shape with either
flat or convex faces and prepared by compressing the medicaments, usually with
added substances. For the capsule, it has two types which are soft and hard.
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. There are specific equipment that may help in
determining some of the standards.
Experiment 1: Physical appearance
Aim
To determine the physical appearance of provided tablet
and capsule.
Procedure
1. Any
tablet and capsule were selected from the provided samples.
2. The tablet and capsule selected was examined
and the shape, colour, diameter, thickness, and other physical characteristics
were recorded.
Result
Tablet:
·
Colour – White
·
Shape – Circular, convex face
·
Diameter – 1 cm
·
Thickness – 0.2 cm
·
Physical characteristic – odorless, RMB
written on tablet
Capsule:
·
Colour – White (body), red (cap)
·
Shape – Rod
·
Size – 0.5 cm width, 2.2 cm length
·
Physical characteristics – odorless
Discussion
The
tablet selected was Metronidazole tablet while the capsule selected was
Gempibrozil capsule. The colour of tablets and capsules play an important role as
tablets and capsules are meant to be swallow by patient. The colour will
determines the patient acceptance toward the drug and may also help in
adherence to the medicines. The colour also can be used to easily identify the
drug as used in capsules. Other than colour, the smell of the medicine also
important as it will affect the patient’s acceptance. Usually medicines are
odorless but some may have orange smell and sweet smell. Some capsules have
something written on it or in tablet have carved on it, usually they are
indicating the company that manufactures the medicine. The shape may vary for
tablet, some tablets have oval shape, some are circular and even rectangle
shape but for capsule, the shape is usually rod.
Conclusion
As a
conclusion, the physical appearance of the tablets and capsules must be done
appropriately to get a nice and accepted tablet and capsule since the physical
appearance is the first thing patients will see on the tablets they have been
prescribed. It really gives a big contribution to patient adherence.
Experiment 2: Uniformity of diameter,
thickness and hardness
Aim
To determine the uniformity of diameter, thickness and
hardness of tablets.
Procedure
1. 10
tablets were selected.
2. Test
for uniformity of diameter, thickness and hardness were carried out for each of
the tablet using Tablet Testing Instrument (PHARMTEST PTB 311)
3. The
deviations of each individual unit were calculated and the mean diameter should
not exceed ± 5% for the tablets with the diameter of less than 12.5 mm and ± 3%
for the diameter of 12.5 mm or more.
Result
Tablet
|
D1 (Diameter,
mm)
|
T1 (Thickeness,
mm)
|
HA
(Hardness, N)
|
1
|
12.81
|
5.58
|
105.68
|
2
|
12.81
|
5.54
|
138.01
|
3
|
12.80
|
5.58
|
123.04
|
4
|
12.80
|
5.48
|
141.70
|
5
|
12.81
|
5.52
|
125.81
|
6
|
12.82
|
5.58
|
125.44
|
7
|
12.82
|
5.47
|
143.18
|
8
|
12.82
|
5.54
|
126.74
|
9
|
12.80
|
5.53
|
121.01
|
10
|
12.82
|
5.57
|
137.82
|
Average
|
12.81
|
||
Discussion
This
experiment was conducted to test the uniformity of diameter, thickness, and
hardness of the tablets. The measurement that obtained can be used to determine
the uniformity of the tablet. Based on the result, the thickness of tablets
shown lies in uniform in between the range of 5.47 mm to 5.58 mm. The varied
values may arise due to the difference during the granulation process and
pressure applied to the tablets, the wear, tear on the length of punches and
the speed of tablet during compression process. The uniformity of thickness of
the tablets are important in packaging process. Since they will be packed in a
blister pack, the thickness of the tablet must uniform for all tablets so that
it can fit into the blister pad. Besides, the thickness of the tablets also
contribute to patient compliance.
For
the hardness of the tablets, all of the tablets are in uniform ranges which are
from 105.68 N to 143.18 N. The hardness of tablets is important to withstand
the mechanical shocks during the tablets manufacturing, packaging and
transport. At the same time, if the tablet is too hard, it may not disintegrate
in required location and time. Hardness also relates to friability property of
the tablets. Friability evaluates the tablets ability to withstand the abrasion
in packaging, handling and shipping rather than measuring the force required to
break the tablets.
For
diameter of the tablets, from the result we can see the diameter is in uniform
ranges which are from 12.80 mm to 12.82 mm. The average diameter of the tablet
is 12.81 mm. Since the average diameter exceeds the given range which is 12.5
mm and therefore the percentage deviation shall not be more than ± 3%. The
diameter of tablets is determine by the die and punches used in compression
process. The less concave the punches, the flatter the tablets and conversely,
the more concave the punches, the more convex the tablets. A slightly changes
in the tablets diameter may due to the uneven surface of punch and die during
compression or due to less precise measurement of tablet testing instrument.
The importance of getting the uniform diameter of tablets are same as getting
uniformity of the thickness. In addition, the uniform size of tablet also
indicate the precise dose of the drug. The drug will consist of correct
proportion of active ingredient as well as excipients. With that, it may help in achieving desired
therapeutic effects.
Conclusion
The
diameter, thickness and hardness of the tablets are three important aspects
need to consider during the manufacture of the tablets as to produce the
quality tablets and also produce higher therapeutic effect. The diameter,
thickness, and hardness of the tablets are in uniform range.
Experiment
3 : Tablet friability
Aim
To check
the strength of tablet so that can give the right therapeutic effects.
Procedures :
1. 10
tablets are selected and are weighed.
2. All the
tablets are put into the drum of the tablet abration and friability tester. The
rotation is set to 60 rpm, 10 minutes and the operation is started.
3. At the
end of the operation, the tablets are removed and the drum is cleaned from dust
or powder by using brush. The tablets are reweighed and the percentage loss of
the weight is calculated.
4.
Compressed tablet should not lose more than 1% of its weight.
Result :
Weight before using machine
|
Weight after using machine
|
Calculation
|
Percentage loss
|
5.7283
|
5.0546
|
5.7283-5.0546
5.7283
= 0.1176 x 100
=11.76
|
11.76%
|
Discussion :
This
experiment is to determine the mechanical strength of tablet through friability
test. This is to ensure that the tablets are not easily break or crumble so
that it is compliance to the patients and can give its best therapeutic
effects.
From the
result we can know that these tablets are not suitable to use anymore. This is
because these tablets are exensive breakableness. Due this condition, it may
cause the tablets to damage during the packing, handling and shipping and may
not compliance to the patients. The patient may not gain benefit because the
tablets are not giving the therapeutic effects to the patient. This is because
the active ingredients may decrease due to the crumbliness. Other than that, the
tablets may have expired because it is easily damage. In this experiment, we
only used the 60 rpm for tablet abration and friability tester. If we increase
the rotation, these tablets may increase their percentage loss. These tablets
should not loss more than 1% of its weight to show that these tablets can give
therapeutic effects to the patients.
Conclusion ;
Theses
tablets are not suitable to use as it loss 11.76% of its weight. They might
break during packing, handling and shipping.
Experiment 4 :
Uniformity of weight of tablets and capsules.
Objective: To determine the
uniformity of weigh of tablets and capsules.
Introduction:
Uniformity of weight is one of the
Pharmacopoeial test which acts as test parameter to ensure the consistency of
dosage units. Variation between tablets and capsules with respect to dose and
weight must be reduced to a minimum. This is because the safety and efficacy of
drug products can be guaranteed when the quality of the drug products are
reliable. There are a number of procedures which apply specifically to tablets and capsules, and which
are designed to ensure they exerts its full pharmacological actions and to
determine the uniformity of physical properties which can be found in the
British Pharmacopoeia and United Pharmacopoeia.
Materials and
apparatus
Weighing boat
20 capsules
20 tablets
Weighing balance
Spatula
Procedure
Tablets
- 20 tablets were weighed previously selected at random and the
average weigh was determined.
- The tablets were weighed individually and determined for each
tablet, the percentage deviation of its weigh was determined from the
average weigh.
- 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 randomly.
- One capsule was
weighed. The capsule was opened and its contents were removed as
completely as possible. The emptied shell was weighed. The net weigh of
its contents was determined, that is by subtracting the weight of the
shells from 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 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
The formula used in calculating
deviation(%) was:
Total weight of 20 tablets: 11513.40mg
Average weight: 11513.40mg ÷ 20
= 575.67mg
NO.
|
WEIGHT OF TABLET(mg)
|
DEVIATION(%)
|
1.
|
561.6
|
±2.4441
|
2.
|
568.3
|
±1.2802
|
3.
|
585.8
|
±1.7597
|
4.
|
577.2
|
±0.2658
|
5.
|
570.4
|
±0.9155
|
6.
|
569.0
|
±1.1586
|
7.
|
579.2
|
±0.6132
|
8.
|
572.2
|
±0.6028
|
9.
|
579.4
|
±0.6479
|
10.
|
575.3
|
±0.0643
|
11.
|
583.5
|
±1.3601
|
12.
|
579.3
|
±0.6306
|
13.
|
563.9
|
±2.0446
|
14.
|
578.5
|
±0.4916
|
15.
|
571.7
|
±0.6896
|
16.
|
576.0
|
±0.0573
|
17.
|
603.5
|
±4.8344
|
18.
|
583.8
|
±1.4123
|
19.
|
566.0
|
±1.6798
|
20.
|
568.8
|
±1.1934
|
Capsules
Average weight of capsule: total weight of
capsule with contents- total weight without content/ 20
= (12118.9-1952.6)mg / 20
= 508.32mg
Deviation %: { (weight of capsule with
contents – weight without contents)-average weight/average weight } x 100
%
Weight of capsule with contents / mg
|
Weight of capsule without contents/mg
|
Deviation / %
|
604.8
|
95.1
|
0.2754
|
606.3
|
94.3
|
0.7279
|
606.0
|
95.8
|
0.3738
|
603.5
|
92.1
|
0.6099
|
603.3
|
93.9
|
0.2164
|
607.4
|
92.7
|
1.2591
|
605.2
|
94.3
|
0.5115
|
606.2
|
95.3
|
0.5115
|
610.2
|
93.0
|
1.7509
|
605.9
|
96.7
|
0.1771
|
606.7
|
95.6
|
0.5509
|
609.8
|
90.7
|
2.1247
|
606.2
|
94.9
|
0.5902
|
605.2
|
94.4
|
0.4918
|
606.7
|
96.5
|
0.3738
|
609.2
|
93.8
|
1.3968
|
607.0
|
95.0
|
0.7279
|
605.6
|
95.3
|
0.3935
|
614.4
|
94.9
|
2.2034
|
606.6
|
95.6
|
0.5312
|
Discussion
For
tablets, since our average weight was is 575.67mg, the deviation of individual
net weight should not exceed the limits given below:
Deviation
of ±5.0% = 575.67mg ±5.0%
= 546.89mg to 604.45mg
From
the results above, all our tablets are having a deviation of ±5.0%, which means
that all tablets have uniform weights. This may indicate the uniformity of the
tablets production. The uniformity of tablets may be caused by the uniformity
in particle size distribution and bulk densities during compression of the
tablets. At the same time, this uniformity may also be caused by the usage of a
good weighing balance. The weighing balance used for measuring the weight of
tablet is more accurate as it is a more advanced balance.
If
the weight variation in tablet exceeds the limit, means the tablet does not
pass the uniformity test. And this may be explained by the following factors
such as, the speed of tableting machine, the flowing properties of the powder,
the pressure used in compression and the type of machine used in tableting may
affect the weight of tablet. However the two most common causes of weight
variation are the particle size distribution during compression and the
differences in bulk densities.
For
capsules, since the average mass obtained is 508.3mg, which is more than 300mg,
thus minimum 18 capsules must not deviate from the average net mass by ±10 %. Based on the
experiment, the deviation is within the range of ±10 %, thus the uniformity of
the capsule used is acceptable. In other words, all the 20 capsules pass the
uniformity test.
However, there are some errors contribute to the inaccurate experimental
results. Other errors that can contribute to ununiformed weights of the tablets
may be the systemic error caused by the inaccuracy of the weighing balance.
Environmental factors such as wind from the air conditioner also can affect the
reading of the weighing balance a little bit. Sometimes, during weighing the
tablets, they may be the fragment of tablets or dust on the tablets or weighing
balance that can caused an error to occur.
Conclusion:
All the tablets and capsules have passed the test
of weigh uniformity. All of the weight of the tablets and capsules fall within
the acceptable range of percentage deviation.
Experiment 5
Content of ibuprofen (assay)
INTRODUCTION
Ibuprofen is an organic compound which is
widely used as a nonsteroidal anti-inflammatory drug applied in fever,
arthritis, and as a pain reliever. Ibuprofen is known to have an antiplatelet
effect, though it is relatively mild and somewhat short-lived when compared
with aspirin. The content of ibuprofen assay is carried out to determine and
verify the exact content of ibuprofen as an active ingredient in a tablet for
the standardization in the manufacturing process. This test is designed to
ensure that a tablet can exert its full pharmacological action as well as
maintaining it uniformity of its physical properties irrespective of the
manufacturers.
RESULTS AND
CALCULATIONS
1 tablet of Ibuprofen is 400 mg.
20 tablets of Ibuprofen after crushed is 20 x 400 mg = 8000 mg = 8 g
20 tablets of Ibuprofen after crushed is 20 x 400 mg = 8000 mg = 8 g
10.97 g
of total weight contains 8 g of ibuprofen powder and other excipients.In order to obtain 0.5 g content of Ibuprofen;
x = 0.5 g
10.97 g 8.0 g
X = 0.6856 g
So theoretically, the total weight of powder
required is 0.6856 g which contains 0.5 g of ibuprofen.
The end point of titration volume of 0.1 M
sodium hydroxide is 19.0 ml.
Thereby, 19.0 ml x 0.02063 g of C13H802
= 0.39197 g.
To calculate for the standard deviation of the
experiment, we can use the formula below :
Standard deviation = (Theoretical
- Experimental value) x 100 %
(Theoretical
value)
= (0.5 - 0.39197) × 100%
0.5
= 21.606 %
DISCUSSION
Based on the British Pharmacopoeia, the range of the standard deviation is within 85% to 115%. The preparation fails to comply with the test if more than 3 individual contents are outside the limits of 85 per cent to 115 per cent of the average content or if one or more individual contents are outside the limits of 75 per cent to 125 per cent of the average content. As our result has a deviation that is 21.606 %, this means that more than 3 individual contents are outside the limits. To be exact is 4.3212 individual contents are out of the range. Even if our experiment is closed to be considered successful, but our preparation does not comply with the test. There are maybe several errors and reasons due to the deviation of the test.
The possibility of the errors is the quality
and expiry date of the sample of ibuprofen. The ibuprofen sampled may have
expired and this may greatly affected the loss of active ingredients in the
tablets as the active ingredients might have decomposed. Therefore, to increase
the accuracy of the experiment, we should use ibuprofen tablets that are not
expired. On the other hand, during weighing out the crushed tablets, the weight
is not accurately measured. Another error is the solutions are filtered by
using filter funnel and filter paper that can cause some of the powder that are
not dissolved in the chloroform will pass through into the conical flask. To counter this problem is by using a
sintered glass crucible which filtered thoroughly rather than the filter paper.
Lastly, the error might happen due to the titration of the solution with sodium
hydroxide. The actual end-point of the solution to turn from colourless to pale
pink in colour might be missed.
The technique used in acquire the content of
ibuprofen is by solid-liquid extraction. The process for isolating ibuprofen from an
ibuprofen-containing solid comprising a combination of the said solid with
chloroform at a temperature of at least about 35° C, whereby chloroform is used
to dissolve ibuprofen and form an ibuprofen-containing solution. The filtering
of the solution is to remove the residue (other excipients). The evaporation of
the filtrate is said to crystallize the ibuprofen from the solution. As the
weight of the crystallization of ibuprofen is small, and cannot be measured, it
is dissolve in ethanol (weak acid) and titrates with 0.1M sodium hydroxide
(weak base) to produces salt. The end point of the sodium hydroxide is
equivalent to the weight of 0.02063 g of ibuprofen. This is an acid-base
extraction.
CONCLUSION
In a conclusion, the ibuprofen content
obtained from the experiment is 0.39197 g. The percentage of deviation is
21.606 % which means that the content of ibuprofen is 78.394 % of the labelled
content. This concludes that our preparation does not comply with the test and
how uniformity of content per tablet is essential in the assessment of
designing dosage form.
QUESTIONS
1. What are the objectives of the tests
for uniformity of diameter and uniformity of content?
The test of
uniformity is to determine the consistency of weight, size, and appearance of
the tablets. The test for uniformity of content is to know the uniformity of
active ingredients in each tablet.
2.
State the types of tablets and capsules that must be tested for uniformity of
diameter and uniformity of content.
All
uncoated and coated tablets must be tested for uniformity of diameter except
enteric tablet, film-coated tablet and sugar-coated tablet. All types of capsules
must be tested for uniformity of diameter. All types of tablets and capsules
must be test for uniformity of content except liquid-filled soft capsules and
solids packaged in single-unit containers.
3.
Give reasons for the non-compliance to test for
uniformity of weight.
There are
some reasons for the non-compliance to test for uniformity of weight, one of
that are because due to inconsistency feeding of granules into the die that be
pressed by the lower punch and form a tablets. The other reasons are due to
irregular movement of lower punch that cause variation in capacity die space.
4.
Why is it important that tablets and capsules
have uniform weight and content?
The
uniformity of weigh of tablets and capsules is very important as it is closely
related to the dosage of drugs delivered to the patients. If the weigh is too
less and the low dose may not reach the therapeutic index and affect the
efficacy of the drug. On the other hand, if the weigh is excessive, the higher
dose may exceed the therapeutic range and may results in toxicity. Hence, the
weigh variation of tablets and capsules may decrease the patient compliance and
bring the side effects as well.
5.
Explain why it is beneficial for any tablets or capsules to have distinctive or
identifying features.
The most important
for any tablets or capsules to have an identifying feature is to make it easier
for patient or consumers to recognize and distinguish different medicines.
Tablets are often stamped with symbols, letters, and numbers, which enable them
to be identified. In the other hand, it can enhance the product by helping
positively impact patient preference, differentiating product's visual
appearance, as well as improving the ability to swallow and masking
objectionable tastes or odours.
REFERENCES :
1. http://www.pharmainfo.net/friability-test
2. http://www.pharmatron.com/newsroom/news/article/key-factors-influencing-measured-tablet-hardness/
3. http://pharmlabs.unc.edu/labs/tablets/evaluation.htm
REFERENCES :
1. http://www.pharmainfo.net/friability-test
2. http://www.pharmatron.com/newsroom/news/article/key-factors-influencing-measured-tablet-hardness/
3. http://pharmlabs.unc.edu/labs/tablets/evaluation.htm
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