PHARMACEUTICAL PRODUCT DEVELOPMENT
NFNF2213
SEMESTER 1
SESSION 2016/2017
LAB REPORT 3
LECTURER : DR.MOHD HANIF BIN ZULFAKAR
GROUP A
GROUP 2 MEMBERS :
NISHAAL KORAN (A153334)
TAN MIN ANNE (A152663)
MUHAMMAD ROSMAN BIN JUNAIDI (A153262)
MUHAMAD HAZWAN BIN HARUN (A152983)
LEOW PUI MUN (A152593)
Objective
To test the quality of tablets and capsules based on uniformity of weight and content
Introduction
To test the quality of tablets and capsules based on uniformity of weight and content
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 are designed to ensure that a
tablet or a capsule exerts its full pharmacological actions. Those procedures are also done, to determine the
uniformity of the physical properties of the official tablet or capsule.
Those experiments are found in the British Pharmacopoeia
and United Pharmacopoeia. For example uniformity of diameter, uniformity
of weight (mass), content of active ingredient, uniformity of content,
friability, disintegration and dissolution.
Still 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.
Experiment 1 : Physical Appearance
Procedure
1. A tablet and capsule was selected from the provided samples. The sample was examined and the shape, colour, diameter, thickness and other physical characteristics were noted.
Results
Tablet
Shape : Compressed cylinder and circular
Colour : Light pink
Diameter : 12.5 mm
Thickness : 5 mm
Other physical characteristics : Has crafting of 250/APP on the
surface
Capsule
Shape : Cylinder with two parts a body and cap
Colour : Yellow body and blue cap
Diameter : 7 mm
Length : 20 mm
Other
physical characteristics : Word MEFA was written with a symbol.
Experiment 2 : Uniformity of diameter, thickness and hardness
Procedure
Procedure
1. 10 tablets were selected and the test for uniformity of diameter, thickness and hardness were carried out using the Tablet Testing Instrument (PHARMATEST PTB 311).
2. It was necessary to ensure that each individual unit did not deviate from the mean diameter by more than + 5% for tablets with diameter of less than 12.5 mm and + 3% for diameter of
12.5 mm or more.
Results and
discussion
Percentage of deviation : (Individual diameter - Average diameter / Average diameter) x 100%
Percentage of deviation : (Individual diameter - Average diameter / Average diameter) x 100%
No of Tablet
|
Diameter (mm)
|
Thickness (mm)
|
Hardness
(N)
|
Deviation (%)
|
1
|
5.45
|
13.12
|
139.30
|
-0.46
|
2
|
5.52
|
13.17
|
197.12
|
+0.82
|
3
|
5.52
|
13.13
|
129.88
|
+0.82
|
4
|
5.43
|
13.12
|
119.16
|
-0.82
|
5
|
5.49
|
13.14
|
191.58
|
+0.27
|
6
|
5.46
|
13.13
|
163.87
|
-0.27
|
7
|
5.44
|
13.13
|
142.07
|
-0.64
|
8
|
5.45
|
13.11
|
133.39
|
-0.46
|
9
|
5.50
|
13.12
|
150.01
|
+0.46
|
10
|
5.49
|
13.10
|
152.42
|
+0.27
|
Total =
54.75
Average
= 5.48
|
||||
In this experiment,
there are 10 tablets used to identify the uniformity of diameter, thickness and
hardness between the tablets. From the results, we can conclude that the
individual diameter and thickness between the tablets are slightly similar. The
range of the diameter of the tablets is 5.43 mm to 5.52 mm. For the thickness
of the tablets, it is in the range of 13.10 mm to 13.17 mm. The range of the
thickness is really close between them. This can show that the uniformity of
diameter and thickness of the tablets are achieved. If we look the result that
we obtained, the individual hardness between the tablets is different from each
other. The ranges of the hardness are really far. It prove that each tablets
have its own hardness which is slightly different compared to others.
The uniformity of the
diameter of the tablet can be proven by the following theory. Generally, the
individual unit of the tablets must have ± 5%
deviation from the average diameter for tablets with diameter less than 12.5 mm
while ± 3% deviation for tablets with diameter of 12.5 mm or more.
From the result, we can say that all tablets follow the deviation as they all
have deviation below ± 5%. The maximum deviation that we obtained is ± 0.82 %
while minimum deviation from the tablet is ± 0.27 %. This means that the
tablets pass the test and each of the tablets had obey the theoretical value of
standard diameter.
Prodecure
1. 10 tablets were selected and weighed.
2. All the tablets were put into the drum of the tablet abration and friability tester. The rate of the rotation was set to 100 rpm, timed to 10 minutes and the operation was started.
3. After the operation ended, all the tablets were removed and freedom from dust or powder was ensured by using the brush. The tablets were reweighed. The percentage loss of weight was determined.
Results and discussion
Results and discussion
Weight (g)
|
% of loss
|
||
Initial
|
End
|
Difference
|
(Wd/Wi) x 100 %
=(0.0216/5.7515)x 100%
= 0.3756 %
|
5.7515
|
5.7299
|
0.0216
|
|
This experiments are to measure the friability of a
tablet. Friability are tendency for a tablet to crumble, chips or break. Factor
that can affect friability of a tablet are such as poor tablet design (too sharp edges), low
moisture content, or insufficient binder.
In this experiment, 25 rpm tester machine are used
instead of 100 rpm. This will affect the result because the higher rotation per
minute the machine can provide the higher the friability of a tablet. The
laboratory can only provide two machine with 25 rpm and 65 rpm.
Dust and powder are brushed as clean as possible to
ensure the weight obtained after the test are exact. The tablets that are not
cleansed properly can altered the end weight of the tablets thus changing the %
of loss.
From the result, the tablets % of loss are less than
1% of initial weight, 0.3756%. this means the tablets have low friability and hard enough such that they do not
break up in the bottle but friable enough that they disintegrate in the
gastrointestinal tract
Experiment 4 : Uniformity of weight of tablets and capsules
Procedure
Procedure
Tablets
1. 20 tablets previously selected at random were weighed. The average weight was determined.
2. The tablets were individually weighed and the percentage of deviation of it's weight from the average weight were determined for each tablet.
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
± 20.0
|
Minimum 18
Maximum 2
|
80 mg to 250 mg
|
± 7.5
± 15.0
|
Minimum 18
Maximum 2
|
More than 250 mg
|
± 5.0
± 10.0
|
Minimum 18
Maximum 2
|
Percentage of deviation (%) = (Weight of each tablet - average weight of tablets/Average weight of tablets)× 100 %
Capsules
1. 20 capsules were selected at random.
2. Each capsule was weighed. A capsule was opened and all the contents were removed as completely as possible. The emptied shells were weighed. The net weight of its contents were determined by subtracting the weight of the shells from the weight of the intact capsule.
3. The procedure was repeated with the other 19 capsules.
4. The average net weight from the sum of the individual net weights was determined.
5. The percentage deviation from the average net weight for each capsule was determined. The deviation of individual net weight should not exceed the limits given below :
Average net weight of
capsules
|
Deviation
(%)
|
Number of capsules
|
Less than 300 mg
|
± 10.0
± 20.0
|
Minimum 18
Maximum 2
|
300 mg or more
|
± 7.5
± 15.0
|
Minimum 18
Maximum 2
|
Percentage of deviation (%) = (Net weight of capsules - average net weight of capsules/Average net weight of capsules)× 100 %
Results and discussion
Tablets
Tablets
|
Weight of one tablet (mg)
|
Deviation
|
1
|
660.8
|
- 0.257
|
2
|
657.6
|
- 0.740
|
3
|
654.0
|
- 1.283
|
4
|
655.7
|
- 1.026
|
5
|
680.4
|
2.702
|
6
|
664.9
|
0.362
|
7
|
685.6
|
3.487
|
8
|
672.4
|
1.494
|
9
|
675.3
|
1.932
|
10
|
678.3
|
2.385
|
11
|
669.0
|
0.981
|
12
|
645.8
|
- 2.521
|
13
|
641.4
|
- 3.185
|
14
|
663.9
|
0.166
|
15
|
660.6
|
- 0.287
|
16
|
642.1
|
- 3.079
|
17
|
662.5
|
0
|
18
|
680.0
|
2.642
|
19
|
655.1
|
- 1.117
|
20
|
650.0
|
- 1.887
|
Total weight of 20 tablets : 13.2493 g
Average weight of one tablet : 662.5 mg
Deviation of 5 % = 662.5 ± 5 %
= 662.5 to 695.6 mg
Deviation of 10 % = 662.5 ± 10 %
= 662.5 to 728.8 mg
Capsules
No
|
Capsule (mg)
|
Emptied capsule (mg)
|
Net Weight (mg)
|
Deviation (%)
|
1
|
369.8
|
62.8
|
307.0
|
+4.90
|
2
|
374.2
|
63.4
|
310.8
|
+6.20
|
3
|
371.6
|
63.1
|
308.5
|
+5.41
|
4
|
356.8
|
62.8
|
294.0
|
+0.46
|
5
|
345.9
|
63.1
|
282.8
|
-3.37
|
6
|
365.5
|
63.6
|
301.9
|
+3.16
|
7
|
362.2
|
63.7
|
298.5
|
+2.00
|
8
|
348.6
|
63.2
|
285.4
|
-2.48
|
9
|
361.3
|
62.3
|
299.0
|
2.17
|
10
|
355.7
|
64.5
|
291.2
|
-0.50
|
11
|
355.7
|
63.2
|
292.5
|
-0.06
|
12
|
346.8
|
64.9
|
281.9
|
-3.68
|
13
|
346.4
|
61.9
|
284.5
|
-2.79
|
14
|
351.1
|
64.5
|
286.6
|
-2.07
|
15
|
364.0
|
65.4
|
298.6
|
+2.03
|
16
|
357.2
|
64.2
|
293.0
|
+0.12
|
17
|
313.7
|
64.1
|
249.6
|
-14.71
|
18
|
356.5
|
65.3
|
291.2
|
-0.50
|
19
|
359.9
|
65.8
|
294.1
|
+0.49
|
20
|
366.3
|
64.2
|
302.1
|
+3.23
|
Total Net
Weight = 5853.2
|
||||
Average Net Weight = 292.7
|
||||
Deviation of 10% = 292.7 mg ± 10%
= 263.43 mg to
321.97 mg
Deviation of 20% = 292.7 mg ± 20%
= 234.16 mg to
351.24 mg
Uniformity
test of weight (mass) is carried out for tablets and capsules to ensure
accurate and consistent dosage form to be administered to patients. From experiment,
the average mass for 20 tablets is 662.5 mg that can be classified in the category of tablets with average mass greater than 250 mg, thus
minimum 18 tablets should not deviate from 662.5 mg by ±5%.can deviate. The maximum number of only two tablets can deviate by ±10% of the average mass. The uniformity of
weight of tablets is acceptable as all 20 tablets fall within the range limit
of mass (662.5 mg to 728.8 mg). We assume that the concentration of drug,
which is the weight of drug per weight of dosage form, is uniform.
On the other hand, the average net
weight of the capsule is 292.7 mg. We can classify this batch of capsules in
the class of ‘Less than 300 mg’ of the average net weight. For this category,
it must follow the percentage of deviation that has been fixed from the table.
This capsules should have minimum 18 capsules that deviate ± 10% from the
average net weight of the capsule. The capsules can only have maximum 2
capsules that deviate ± 20% from the average net weight of the capsule. From
the data that we obtained, 19 capsules have deviation of 10% while another one
capsule has deviation of 20% from the average net weight. The maximum deviation
from this experiment is -14.71% while the minimum deviation is -0.06%. We can
conclude that this batch of capsules have pass the test as they follow the
limits given from the table. The uniformity of the weight of the capsules are
acceptable.
Experiment 5 : Content of Ibuprofen (assay)
Procedure
Procedure
1. 20 Ibuprofen tablets previously selected at random were weighed and powdered.
2. A quantity of powder containing 0.5 g Ibuprofen was extracted with 20 ml chloroform for 15 minutes and it was filtered through a filter paper.
3. The residue was washed with 3.10 ml chloroform and the combined filtrate was gently evaporated just to dryness by using hair dryer. The residue was then dissolved in 100 ml of ethanol (96%) and few drops of phenolphthalein solution was added.
4. The solution was titrated with 0.1M sodium hydroxide to end point whereby phenolphthalein solution acted as a indicator. The content of Ibuprofen was calculated, if each ml of 0.1M sodium hydroxide was equivalent to 0.02063 g of C13H18O2.
Result and Calculation
1 tablet ibuprofen = 400mg ibuprofen
20 tablets = 8.0 g ibuprofen
Mass of 20 tablets (excipient +ibuprofen ) =
10.24 g
For 0.5 g ibuprofen :
10.24 g / 8 × 0.5= 0.69 g
Equation of titration :
C2H5OH + NaOH = C2H5ONa
+ H2O
Volume of NaOH used = 14.25ml
Number of mole of NaOH = 14.25×0.1÷1000
=
0.001425
Mass of ibuprofen = number of mole × RMM of ibuprofen
=0.001425×
(206)
=0.29g
Percentage deviation = ( 0.5 - 0.29 ) x 100 / 0.5
= 42%
Discussion
As we know, this experiment is to ensure the amount of
active ingredient, Ibuprofen is correct and sufficient in the tablets. From the
10.24g of powder which contains 8g of Ibuprofen, 6.69g of powder is obtained
which theoretically should contain 5g of Ibuprofen. The experiment is carried
out and we had obtained 0.29g of Ibuprofen which is more than half of the
theoretical value. Therefore, the deviation calculated is 58% which is very
unacceptable in real life.
During
the experiment, there are a few errors that contribute to the deviation.
Firstly, the content of the batch may not contain the correct amount of active
ingredient. Tritration of the powder after crushing 20 Ibuprofen tablets may
not be done properly where certain location of powder may have more active
ingredients. Besides that, during the extraction of Ibuprofen process, some may
stick on the filter paper, leaving behind Ibuprofen. The end point of
neutralization during titration method also may be inaccurate as the judgment
of pink colour differs from person to person.
Questions
1) What
are the objectives of the tests for uniformity of diameter and uniformity of
content?
The objectives for test
of uniformity of diameter of tablets and capsules are to beautify the product
to increase its’ appearance which indirectly can also increase patient’s
adherence as the product looked consistent to the patient. The objectives of
uniformity of content is to ensure that there is an equal less deviation on the
amount of active ingredient in the product to ensure efficacy of medication.
2) State
the types of tablets and capsules that must be tested for uniformity of
diameter and uniformity of content.
The types of tablets and capsules
needed to to be tested for uniformity of diameter tests involves all the
uncoated and coated tablets except for the enteric tablets, film-coated tablets
and sugar-coated tablets. For uniformity of content tests, it must involve all
tablets and capsules and is a very important step to ensure uniform
distribution of active ingredients.
3) Why is it important that tablets and capsules have uniform weight and content ?
It is important for the tablets and capsules to have uniform weight and content as both the factors have high degree of correlation and need to be considered before dispensing to patients. In situations, where one patient needs to take a whole tablet while another just needs half the tablet, content and weight uniformity plays a vital role to ensure that the right amount of drug is delivered to the patient's body.
4) Give reasons for the non-compliance to test for uniformity of weight.
One of the reason for the non-compliance to the test for uniformity of weight is an uneven feeding of the granules into the die. Next, the variation in capacity of die space also can make the tablets become non-compliance to the test for uniformity of weight. This might be happen when an irregular movement of the lower punch occur during manufacturing of the tablets. Besides that, the non-compliance also can be happen if we do not weight the correct amount of ingredients for the production of tablets and capsules.
5) Explain why is it beneficial for any tablets or capsules to have distinctive or identifying features.
There are many benefits for tablets and capsules to have distinctive or identifying features. One of the benefits is the patients that consume the medicine can know who’s the manufacture of their medicine. Patients can know the manufacture by seeing the imprint on their tablets. Next, it is also benefit for the patients that have many tablets and capsules that they need to take. For the example, when patient using medicine box organizer, they can identify which tablets or capsules that are responsible for certain disease that they experienced. Besides that, patients also can know the dosage strength of their tablets. Patients can know the strength by looking the size and colour of the tablets.
References
1. http://link.springer.com/article/10.1007/s40005-012-0030-72. http://www.uspbpep.com/ep50/2.9.40%20Uniformity%20of%20dosage%20units.pdf
3. http://www.fda.gov/downloads/drugs/guidancecomplianceregulatoryinformation/guidances/ucm377938.pdf
4. http://tmedweb.tulane.edu/pharmwiki/doku.php/dosage_forms
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