TENGKU NUR EQHWANA BINTI KU JAYA
A139454
YAP SHI YUN
A139856
SHERON TAPA
A140146
NG KHAI SHIH
A140228
LOH JIA SHIN
A140275
RAUHAH BINTI AB RASHID
A139654
Monday, 30 December 2013
Thursday, 26 December 2013
Practical 6: Experiment 1 and 2
Procedures:
Experiment 1: Uniformity of diameter, thickness and hardness
1.
10 tablets were selected and tests for
uniformity of diameter, thickness and hardness were tested using the Tablet
Testing Instrument (PHARMATEST PTB 311).
2.
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 12.5mm or more.
Experiment 2: Tablet friability
1.
10 tablets are selected and weighed.
2.
All tablets are put into the drum of the
tablet abrasion and friability tester. The rate of rotation is set to 40 rpm,
time to 10 minutes, and the operation is started.
3.
At the end of the operation, all the
tablets are removed and the dust or powder is freed using a brush. The tablets
are weighed. The percentage loss of weight is determined.
4.
Compressed tablets are not more than 1%
of its weight.
Results and
calculations:
Experiment 1
Tablet
|
Thickness
(mm)
|
Diameter
(mm)
|
Deviation
|
Hardness
|
1
|
5.44
|
13.13
|
-0.01
|
150.17
|
2
|
5.37
|
13.12
|
-0.02
|
139.87
|
3
|
5.46
|
13.13
|
-0.01
|
145.37
|
4
|
5.40
|
13.19
|
+0.05
|
141.29
|
5
|
5.51
|
13.14
|
0
|
132.04
|
6
|
5.46
|
13.11
|
-0.03
|
126.89
|
7
|
5.44
|
13.12
|
-0.02
|
130.80
|
8
|
5.48
|
13.16
|
+0.02
|
177.90
|
9
|
5.38
|
13.14
|
0
|
137.38
|
10
|
5.51
|
13.10
|
-0.04
|
130.09
|
Average
|
5.45
|
13.14
|
141.18
|
Average diameter = 13.14mm
13.14mm x 3% =0.39mm
±3% of 13.14mm = 12.75mm - 13.53mm
Experiment
2
Before abrasion
Weight (g)
|
After abrasion
|
||
Weight (g)
|
Weight loss(g)
|
Weight loss(%)
|
|
6.8170
|
6.7963
|
0.0207
|
0.30
|
Compressed tablets lost 0.30% of their weight, which
is not more than 1% of its weight. Hence, all the 10 tablets have passed the
friability test.
Discussion
One of the pharmacopoeial standards
that should be followed by oral dosage forms is the test of uniformity of
diameter. Based on the result obtained, the average diameter of tablet is 13.14mm.
So, the deviation of individual unit from the mean diameter should not exceed 3%
for tablets with diameter of more than 12.5mm. The result shows that all the
tablets do not exceed the limit of standard percentage deviation, thus they are
all acceptable. For the non-pharmacopoeial standards, we have tests for
hardness and thickness of oral dosage forms. The tablet thickness depends on
the diameter of the die, the amount of powder permitted to flow into the die
and also the force exerted during compression process. Meanwhile, the hardness
test measures the strength of pressure required to crush the tablet. Degree of
hardness of tablets is determined by the strength of force applied during compression.
Tablets should possess sufficient hardness to resist breaking during normal
handling, packaging and transporting. At the same time they should also be soft
enough to disintergrate after administered orally.
Physical instability in terms of friability
is often related to various forces applied on tablets. Friction and shock are
the most common forces that cause tablet to break or cap. Transportation and
packaging of tablets often exposed tablets to these forces. In this experiment,
the rotation of tablets in the tablet abrasion and friability tester subjects
them to frictional forces. These frictions result in the tablets to being
abraded, hence, loss some materials as well as weight
In this experiment, compressed tablets
lost 0.30% of their weight, which is not more than 1% of its weight. Hence,
these 10 tablets have passed the friability test. A thick tablet may have
tendency to cap whereas thin tablets of large diameter often show extensive
capping, thus indicating that tablets with greater thickness have reduced
internal stress. (http://www.pharmainfo.net/tablet-evaluation-tests/mechanical-strength-tablets/friability)
Hence, the 10 experimental tablets achieve appropriate thickness which gives
them a higher friability.
Tablets
which are too friable may cause undesirable effects, such as inaccurate dose,
instability and wastage of money as well as resources. To prevent all these,
friability test which is closely related to tablet hardness, is designed to
evaluate the ability of the tablet to withstand abrasion in packaging, handling
and transportation. During tablet manufacture, friability test should be
correlated with actual stress experience. Packaged tablets also should
subjected to cross-country shipping tests as well as to various drop tests.
Tuesday, 24 December 2013
practical 6: experiment 4 DOSAGE PERFORMANCE TEST
A) DISINTEGRATION TEST FOR SUGAR COATED TABLETS
MATERIAL AND APPARATUS: Tablet Disintegration Test Apparatus,
3 Ibuprofen tablet and water for disintegration medium.
Method:
The apparatus was set up for disintegration test according
to its operation manual and the temperature of disintegration medium was
ensured at 37±2°C. The apparatus was set for 60 minutes and then one
tablet was added into each tube and was allowed to sink at bottom of tube.
Next, before the operation was started the disked was added to each tube. After
60 minutes, the tablet in each tube is checked to know it’s disintegrated or
not. If all the tablets disintegrated in 60 minutes that’s means the tablet
comply with the test. Next, if there was
any tablet that did not disintegrated, the experiment was repeated using new
tablets but the disintegration medium was replaced with 0.1M hydrochloric acid.
The tablets were considered comply with the test if all tablets disintegrated
in acidic medium.
Results:
All the 3 tablets disintegrate after the test. When the test
ended, there still have solid particle in the tube but when we presses the
solid particle by using hand it was disintegrate. In this situation the tablet
are still considered to pass the disintegration test.
Discussion:
For a drug to be absorbed from a solid dosage form after
oral administration, it must first be in solution, and the first important step
toward this condition is usually the break-up of the tablet; a process known as
disintegration.
The disintegration test determines whether tablets or
capsules disintegrate within the prescribed time when placed in a liquid medium
in the experimental conditions prescribed above. Disintegration is considered
to be achieved when:
a) No residue remains in the tube, or
b) If there is a residue, it consists of a soft mass having
no palpably firm, unmoistened core, or
c) Only fragments of coating (tablets) or only fragments of shell
(capsules) remain in the tube; if a disc has been used (capsules), fragments of
shell may adhere to the lower surface of the disc.
In this experiment, Ibuprofen tablet passes the
disintegration test because no residue left after 60 minutes. The possible
errors that occur during the experiment are the temperature is less than 37°C
so the tablet does not disintegrate according to the body temperature. Other
than that, the tablet use has already reached its expiry date and does not
disintegrated properly.
Conclusion:
Ibuprofen tablet disintegrated at 37±2°C after 60 minutes.
MATERIAL AND APPARATUS: Tablet Dissolution Test Apparatus, 1
tablet of Ibuprofen, 25 ml volumetric flask, syringe and spectrophotometer.
Method:
Firstly, the dissolution vessel was filled up with the
buffer solution to 900ml mark and the temperature was set to 37°C.
The dissolution medium temperature was ensured at 37±0.5°C. Next, one tablet of
Ibuprofen was placed into the dry basket assembly and before start the
operation, the stirring speed was set to 150rpm and the basket assembly was
then lowered into position in the vessel. The operation was left for 30 minutes
and after that, 10 ml of sample was withdrawn from dissolution medium using
syringe for analysis. Sampling should be done from a point half away between
the surface of dissolution medium and top of rotating basket and not less than
10 mm from the wall of vessel. The volume of aliquot withdrawn was replaced
with an equal volume of same dissolution medium.
Next, the standard solution of Ibuprofen was prepared by
diluting 10mg of Ibuprofen reference standard to 50 ml with dissolution medium.
After that, 2.0ml sample solution and 2.0 ml standard solutions was diluted to
25ml with dissolution medium in separated volumetric flask. The sample then analyzed for absorbance in 1
cm cell at a wavelength of 221 nm using spectrophotometer.
The percentage amount of ibuprofen dissolved was calculated
using the following formula:
.png)
Where:
At
=absorbance of sample solution
As
=absorbance at standard solution
W
=weight of ibuprofen reference standard used
P
=purity of ibuprofen reference standard
The result obtained was determined whether the tablets
comply with the requirement of United State Pharmacopoeia.
USP limits: not less than 75% of stated amount of ibuprofen
dissolve in 30 minutes.
Result:
ABS
|
K*ABS
|
|
Standard
|
3.215
|
3.2148
|
Sample solution
|
0.697
|
0.6969
|
W=0.01g
P=0.98
So, the percentage amount of ibuprofen dissolved using the
formula are:
.png){kind=small}
Discussion:
The release of drug from the tablet into
the solution per unit time under standardize condition is called dissolution
test. In this experiment, we using USP apparatus I that using basket.
In vitro dissolution testing of solid
dosage forms is important because:
Dissolution studies in the early stages
of a product’s development allow differentiation between formulations and
correlations identified with in vivo bioavailability data. The conduct of such
testing from early product development through approval and commercial
production ensures control of any variables of materials and processes that
could affect dissolution and quality standards. Consistent in vitro dissolution
testing ensures bioequivalence from batch to batch. It is a requirement for
regulatory approval of marketing for products registered with the FDA and
regulatory agencies of other countries.
In this experiment by using the formula,
the percentage of ibuprofen dissolve is 23.9%. This amount is does not achieved
USP limit that stated that not less than 75% of stated amount of
ibuprofen dissolve in 30 minutes. The possible errors that may occur during the
experiment are the temperature is less than 37°C so the tablet does not
dissolve properly. Other than that, the tablet use has already reached its
expiry date and does not dissolve to get it optimum percentage concentration.
In order to reduce error, the method of dissolution testing must be controlled
to minimize important variables such as basket rotational speed, vibration, and
disturbances by sampling probes.
In addition to method of dissolution, formulation and
manufacturing controls also play important role why the tablet does not achieved
USP dissolution unit. A number of formulation and manufacturing factors can
affect the disintegration and dissolution of a tablet, including particle size
of the drug substance; solubility and hygroscopicity of the formulation; type
and concentration of the disintegrant, binder, and lubricant; manufacturing
method, particularly the compactness of the granulation and compression force
used in tableting.
Conclusion:
The percentage amount of Ibuprofen dissolve is 23.9%. The
dissolution test on Ibuprofen at 37±0.5°C does not reach USP limit that
is not less than 75% of Ibuprofen must dissolve in 30 minutes. The method of
dissolution, manufacture and formulation play important role in order for
tablet to dissolve.
2. State the type of
tablet and capsules that must be tested for uniformity of diameter and
uniformity of content.
-uncoated and coated
tablet
-suspension in soft
capsule
practical 6: experiment 3 Uniformity of weight of tablets and capsules
Title
Uniformity of
weight of tablets and capsule
Objective
Determine whether the uniformity of weight of tablets
and capsules studied comply with the standard of British Pharmacopoeia or not.
Introduction
Uniformity of weight of tablets and capsules 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. Uniformity of weight test is not applicable to tablets and capsules
required to comply with the test for uniformity of content. Uniformity of
tablets and capsules ensure that 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.
Apparatus
Weighing balance, weighing boat
Material
20 Tablets and 20 capsules
Procedures
Tablets
1)
20 tablets previously selected at random
were weighed. The average weight was determined.
2)
The tablets were weighed individually
and for each tablet, the percentage deviation of its weight from the average
weight was determined.
3)
The deviation of individual weight from
the average 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
|
80-250
mg
|
±7.5
±15.0
|
Minimum 18
Maximum 2
|
More
than 250 mg
|
±5.0
±10.0
|
Minimum 18
Maximum 2
|
Capsules
1)
20 capsules were selected at random.
2)
One capsule was weighed. The capsule was
opened and the contents were removed as completely as possible. The emptied
shells were then weighed. The net weight of its content was determined by
subtracting the weight of the shells from the weight of the intact capsule.
3)
The procedure was repeated with other 19
capsules.
4)
The average net weight was determined
from the sum of the individual net weights.
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
capsule
|
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
|
Results and Calculations
Paralgin tablets:
Tablet
|
Individual
weight (g)
|
Difference
between individual weight and average weight (g)
|
%
of deviation
|
1
|
0.6376
|
0.0101
|
1.48
|
2
|
0.7115
|
0.0278
|
4.07
|
3
|
0.6921
|
0.0084
|
1.23
|
4
|
0.7057
|
0.0220
|
3.22
|
5
|
0.7053
|
0.0216
|
3.16
|
6
|
0.7163
|
0.0326
|
4.77
|
7
|
0.6636
|
0.0201
|
2.94
|
8
|
0.6701
|
0.0136
|
1.99
|
9
|
0.6811
|
0.0026
|
0.38
|
10
|
0.6810
|
0.0027
|
0.39
|
11
|
0.6706
|
0.0131
|
1.92
|
12
|
0.6900
|
0.0063
|
0.92
|
13
|
0.6745
|
0.0092
|
1.35
|
14
|
0.6594
|
0.0243
|
3.55
|
15
|
0.7102
|
0.0265
|
3.88
|
16
|
0.6992
|
0.0155
|
2.27
|
17
|
0.7147
|
0.0310
|
4.53
|
18
|
0.7021
|
0.0185
|
2.71
|
19
|
0.6583
|
0.0254
|
3.72
|
20
|
0.6558
|
0.0279
|
4.08
|
i.
Average weight = 13.6736g =
0.68368g
20
ii.
Since the average weight is 683.68mg which is more than 250mg, so the
deviation are ±5% and ±10% ,
a.
% deviation ±5% =
95% ≤ X ≤ 105%
= 649.50 mg ≤ X ≤ 717.86 mg
b.
% deviation ±10% = 90%
≤ X ≤ 110%
= 615.31 mg ≤ X ≤ 752.05 mg
iii.
No tablets deviate from the weight so
this product passed the uniformity of weight test.
Mefenamic Acid Capsules:
Capsules
|
Individual weight (g)
|
Weight of the emptied shells (g)
|
Net weight of the contents (g)
|
Difference between individual weight and
average weight (g)
|
% of deviation
|
1
|
0.4608
|
0.0766
|
0.3842
|
0.0031
|
0.80
|
2
|
0.4547
|
0.0733
|
0.3814
|
0.0059
|
1.52
|
3
|
0.4528
|
0.0704
|
0.3824
|
0.0049
|
1.27
|
4
|
0.4752
|
0.0786
|
0.3966
|
0.0093
|
2.40
|
5
|
0.4675
|
0.0710
|
0.3965
|
0.0092
|
2.38
|
6
|
0.4610
|
0.0782
|
0.3828
|
0.0045
|
1.16
|
7
|
0.4567
|
0.0751
|
0.3816
|
0.0057
|
1.47
|
8
|
0.4578
|
0.0732
|
0.3846
|
0.0027
|
0.70
|
9
|
0.4690
|
0.0739
|
0.3951
|
0.0078
|
2.01
|
10
|
0.4706
|
0.0793
|
0.3913
|
0.0040
|
1.03
|
11
|
0.4684
|
0.0756
|
0.3928
|
0.0055
|
1.42
|
12
|
0.4094
|
0.0718
|
0.3376
|
0.0497
|
12.83
|
13
|
0.4709
|
0.0752
|
0.3957
|
0.0084
|
2.17
|
14
|
0.4728
|
0.0826
|
0.3902
|
0.0029
|
0.75
|
15
|
0.4680
|
0.0728
|
0.3952
|
0.0079
|
2.04
|
16
|
0.4756
|
0.0740
|
0.4016
|
0.0143
|
3.70
|
17
|
0.4662
|
0.0716
|
0.3946
|
0.0073
|
1.89
|
18
|
0.4620
|
0.0749
|
0.3871
|
0.0002
|
0.05
|
19
|
0.4492
|
0.0695
|
0.3797
|
0.0076
|
1.96
|
20
|
0.4682
|
0.0732
|
0.3950
|
0.0077
|
1.99
|
i.
Average net
weight of content = 7.7460 g =
0.3873 g
20
ii.
Since the average weight is 387.30 mg which is more than 300mg, so the
deviation are ±7.5% and ±15% ,
a.
% deviation ±7.5% =
92.5% ≤ X ≤ 107.5%
= 358.25 mg ≤ X ≤ 416.35 mg
b.
% deviation ±15% = 85%
≤ X ≤ 115%
= 329.21 mg ≤ X ≤ 445.40mg
iii.
Only one tablet deviates from the weight
so this batch of products still considers to pass the uniformity of weight
test.
Discussion
According to the results obtained, the average weight of the tablet Paralgin
tablets is 0.68368 g (683.68 mg) which
means the range of more than 250 mg is the suitable range chosen from the table
of the deviation limits. From the data obtained, it is found that all tablets
follow the limits. This shows that almost all tablets tested in this experiment
are uniform in the aspect of weight.
According to the
results obtained, the average weight of the capsules is 0.3873 g ( 387.3 mg) which
means the range of 300 mg and more is the suitable range chosen from the table
of the deviation limits. From the data obtained, it is found that only one
capsule has deviation from the weight. This shows that almost all capsules
tested in this experiment are uniform in the aspect of weight.
Furthermore, errors might also due to the air flow or
wind around the weighing balance to influence the reading of weighing balance.
All these errors will lead to inaccuracies of measurement of weight.
The lid of weighing balance should be closed to
minimize the error occurred.
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 tablets and capsules used are uniform.
References
Florence E. Eichie, Ikhuoria M. Arhewoh and Oliver C.
Ezeobi, 13 August 2009. In- vitro evaluation of the pharmaceutical quality of
some ibuprofen tablets dispensed in Nigeria.
African Journal of Pharmacy
and Pharmacology Vol. 3 (10).
Questions:
1 3. Give reasons for
the non-compliance to test for uniformity of weight.
The reasons included poor in-process control during manufacturing of tablet and capsule as well as inaccurate weighing and mixing during preparation. During manufacturing, granules may fed unevenly into the die or/ and lower punch moves irregularly which cause variation in capacity of die space, resulting in different weight of tablets or capsules.
4.
Why does
dissolution test suitable to be used for batch to batch quality control?
Dissolution test is used to assess the in vivo
performance of products. Biopharmaceutical aspects are as important for
stability concerns as they are for batch release after production, in vitro
dissolution being of high relevance in quality control and quality assurance.
In vitro dissolution data will be of great importance when assessing changes in
production site, manufacturing process or formulation and assist in decisions
concerning the need for bioavailability studies. Thus, dissolution test is suitable
to be used for batch to batch quality control.
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