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 that 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.
Experiment 1:
Uniformity Of Diameter, Thickness
And Hardness
Experimental Methods:
Analytical
Equipment: Tablet Testing Instrument (PHARMATEST PTB 311)
Procedures:
1.
10 tablets are
selected and the tests are carried out for the uniformity of diameter,
thickness and hardness using the Tablet Testing Instrument(PHARMATEST PTB 311)
2.
The deviation
of individual unit from the mean diameter are made sure to not exceed ±5% for
tablets with diameter of less than 12.5 and ±3% for diameter of 12.5mm or more.
Results and Calculations:
Tablet
|
Thickness (mm)
|
Diameter(mm)
|
Hardness(N)
|
Deviation of diameter(mm)
|
Percentage deviation of diameter(%)
|
1
|
4.77
|
11.89
|
179.30
|
±0.00
|
±0.00
|
2
|
4.66
|
11.93
|
153.80
|
+0.04
|
+0.34
|
3
|
4.61
|
11.91
|
166.20
|
+0.02
|
+0.17
|
4
|
4.71
|
11.90
|
163.80
|
+0.01
|
+0.08
|
5
|
4.73
|
11.91
|
203.00
|
+0.02
|
+0.17
|
6
|
4.72
|
11.87
|
184.80
|
-0.02
|
+0.17
|
7
|
4.59
|
11.87
|
182.40
|
-0.02
|
+0.17
|
8
|
4.71
|
11.88
|
169.60
|
-0.01
|
+0.08
|
9
|
4.76
|
11.86
|
163.40
|
-0.03
|
+0.25
|
10
|
4.62
|
11.88
|
187.50
|
-0.01
|
+0.08
|
Mean
|
4.69
|
11.89
|
175.38
|
||
Mean
of thickness = (4.77+4.66+4.61+4.71+4.73+4.72+4.59+4.71+4.76+4.62) ÷10
= 4.69mm
Mean
of diameter = (11.89+11.93+11.91+11.90+11.91+11.87+11.87+11.88+11.86+11.88) ÷10
= 11.89mm
Mean
of hardness = (179.30+153.80+166.20+163.80+203.00+184.80+182.40+169.60+163.40
+187.50) ÷ 10
=175.38mm
Discussions:
10
tablets of Uphamol Cold &Flu(brand name) have been used for this experiment. The following are the active
ingredients contain in each tablet used:
Paracetamol.B.P.
500mg
Chlorpheniramine
Maleate B.P. 4mg
Phenylpropanolamine
HCL B.P. 25mg
The mean diameter of the tablets is 11.89mm. All the deviations of individual unit
(diameter of less than 12.5mm) from the mean diameter are less than 5% which is
0.5945mm. Hence, all the results are acceptable as all the tablets are comply
with test for uniformity of diameter.
Generally, the tablet thickness should also be
controlled within a ± 5% variation of standard value. The thickness of the tablets
depends on the coating of the tablet which is an important feature in
pharmaceutical manufacturing. In this experiment, all
the deviations of individual unit from the mean thickness are less than 5%
which is 0.2345mm. All thickness is also in the standard range of thickness of
tablet which is 0 - 15 mm. Therefore,
this test is also acceptable. Uniformity of thickness of tablet is very
important to minimize appearance problems, to assure that tablets will fit into
the container and to assure that they can be accurately counted by the filling
equipment. Some filling equipments depends on the uniform thickness of the
tablets as a counting mechanism.
This experiment also tests the
uniformity of hardness of the tablets to determine the crushing strength of the
tablets. This is because tablet requires a
certain amount of strength or hardness and resistance to friability to
withstand mechanical shakes of handling in manufacture, packaging and shipping. However, the strength of tablet
obtained in this experiment maybe lower
than before as the tablets are expired after 4 years of production
(Manufactured date: 12/1999 and Expiry date: 12/2003)as the quality of the
tablet may reduce. In this experiment, all values of hardness of tablets are
within the standard range of up to 400N. Hence,
this test is acceptable.
The variation of values for the diameter, thickness and
hardness of all tablets and the deviations of individual unit from the standard
values may be due to the errors occurring during manufacturing process. Coating
process can influence the diameter and thickness of the tablet to be different
from one another. Besides, thickness may differ if there is a difference in the
granulation and pressure applied to the tablets, wear and tear on length of punches
as well as on the speed of tablet compression. The slight variations in
diameter of the tablets may also due to uneven surfaces of punch and die or due
to the less precise measurement with the micrometer screw gauge.
The errors that may occur to influence
the hardness of the tablet are the speed of
compression, solid state structure, particle size, mechanical interlocking,
solid bridges, distance forces, bonding mechanisms, volume reduction mechanisms
of powder during the process of compression or the surface area change during
compression.
Conclusions
Diameter examination of these
tablets showed a slight variations in diameter (11.86-11.91 mm) which is within
the B.P. limits of ± 5% and hence negligible. For the thickness of the tablet,
the results show a slight variation from 4.61-4.77mm but still within the B.P.
limits of. ± 5% thus also negligible.
The hardness of the tablets are from 163.40-203.00N which is still below the
maximum value of 400N.
References:
2.
Mark D Mowery, Robert Sing, John Kirsch, Amir Razaghi, Simon Béchard,Robert A Reed, Journal
of Pharmaceutical and Biomedical Analysis, Merck
Research Laboratories, Pharmaceutical Research and Development, West Point, PA
19486, USA.
5.
Linda
M. Tahaineh, Journal of Pharmacy Practice Irbid, Department of Clinical
Pharmacy, College of Pharmacy, Jordan University of Science and Technology,
22110, Jordan.
Experiment 2: Tablet
Friability
Methods:
1. 10 tablets
of mefenamic acid was selected and weighed.
2. All tablets
was placed into the drum of the tablet abration and friability tester. The rate
of rotation was set up at 25 rpm for 10
minutes. Then, operation was started.
3. At the end
of the operation, all tablets was removed. The tablets was cleaned from dust
using brush and reweighed again. The percentages loss of weight was determined.
Results:
Initial weight
of tablets = 5.8315g
After operation
= 5.7920g
Calculations:
Loss of weight
= 5.8315g – 5.7920g
= 0.0395g
Percentages
loss of weight = 0.0395g/5.8315g x 100%
= 0.68%
Discussions:
One of the testing criteria of mechanical strength of tablets
tablet friability testing. Tablets must be able to withstand mechanical
stresses during their manufacturing, distribution and handling by the end-user.
During the process of coating, transportation, packing and processing tablet,
tablet will lose some weight. Because of that, the friability test is performed
in the pharmaceutical industry to test the tendency of a tablet breaking into
smaller pieces during transit. It includes repeatedly dropping a sample of
tablets over a fixed time by using friability tester and then checking whether
any tablets are broken, and calculate the percentage of loss weight of tablets.
A good compressed tablet should not loss more than 1% of its weight.
Based on this experiment, after the operation ended, the weight
loss of tablets is 0.0395g which is equivalent to 0.68% loss from its weight.
This means, those tablets are good quality and strong tablets which then can
endure the stresses. There are may be some error during handling the experiment
that can lead to incorrect results. After operation ended, the tablets are not
fully cleaned from dust which is affecting the result. When finished, the
samples have to be de-dusted first before weigh again.
Conclusion:
The percentage
loss of weight of samples is 0.68%. The samples are good quality tablets
because the percentage loss of weight is not more than 1%.
References:
Experiment 3:
Uniformity of weight of tablets and capsules
Experimental
methods:
Tablets
1.
20
tablets are selected at random and weighed. The average weight is determined
that is 0.6828g.
2.
Then,
the tablets are weight individually and the percentage of deviation of its
weight from the average weight is 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
|
Capsules
1.
20
capsules are selected at random.
2.
One
capsule is weight. The capsule is opened and the contents are removed
completely as possible. The emptied shell is weight. The net weight of its
contents is determined 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
that is 298.4 mg.
5.
The
percentage deviation from the average net weight for each capsule is
determined. The deviation of individual net weight should not exceed the limits
given below:
Average
net weight of capsule
|
Deviation
(%)
|
Number
of capsule
|
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:
Tablets
Total weight of 20 tablets: 13.6552
g
Average weight of one tablet: 0.6828 g
Percentage of deviation =
(weight of individual tablet - average of weight tablet) / (average weight of tablet) x 100%
=
0.6828 g to 0.7169g
Deviation of 10% = 0.6828 g ±
10%
=
0.6828 g to 0.7568 g
Tablets
|
Weight
of one tablet (mg)
|
X (x10-3)
|
Deviation
(%)
|
1
|
684.8
|
+2
|
+0.293
|
2
|
683.5
|
+0.7
|
+0.103
|
3
|
687.8
|
+5
|
+0.732
|
4
|
661.7
|
-21.1
|
-3.090
|
5
|
696.2
|
+13.4
|
+1.963
|
6
|
672.4
|
-10.4
|
-1.523
|
7
|
687.0
|
+4.2
|
+0.615
|
8
|
677.1
|
-5.7
|
-0.835
|
9
|
689.9
|
+7.1
|
+1.040
|
10
|
680.3
|
-2.5
|
-0.366
|
11
|
682.2
|
-0.6
|
-0.088
|
12
|
673.1
|
-9.7
|
-1.421
|
13
|
687.1
|
+4.3
|
+0.630
|
14
|
694.7
|
+11.9
|
+1.743
|
15
|
681.5
|
-1.3
|
-0.190
|
16
|
694.0
|
+11.2
|
+1.640
|
17
|
675.2
|
-7.6
|
-1.113
|
18
|
684.0
|
+1.2
|
+1.744
|
19
|
678.9
|
-3.9
|
-0.571
|
20
|
677.7
|
-5.1
|
-0.747
|
X=
difference between weight of one tablet and average weight of one tablet.
Capsule
Total net weight of capsule: 5968.1
mg
Average net content of the capsule: 298.4 mg
Percentage of deviation
=
(net content of capsule – average net content of capsule) / (average net
content of capsule) x 100%
Deviation of 10% = 298.4 mg ± 10%
=
298.4 mg to 328.24 mg
Deviation of 20% = 298.4 mg ± 20%
=
298.4 mg to 358.08 mg
Capsule
|
Weight
of capsule (mg)
|
Emptied
shell (mg)
|
Net
weight of content (mg)
|
1
|
370.6
|
61.9
|
308.7
|
2
|
365.2
|
62.6
|
302.3
|
3
|
369.6
|
61.9
|
307.7
|
4
|
356.6
|
64.2
|
292.4
|
5
|
348.1
|
62.7
|
285.4
|
6
|
339.7
|
63.9
|
275.8
|
7
|
363.7
|
65.1
|
298.6
|
8
|
364.1
|
64.3
|
299.8
|
9
|
353.5
|
62.0
|
291.5
|
10
|
357.3
|
62.4
|
294.9
|
11
|
352.3
|
62.6
|
289.7
|
12
|
367.2
|
62.2
|
305.0
|
13
|
365.7
|
65.5
|
300.2
|
14
|
369.9
|
62.7
|
307.2
|
15
|
362.8
|
63.9
|
298.9
|
16
|
366.5
|
63.2
|
303.3
|
17
|
370.6
|
64.9
|
305.7
|
18
|
376.7
|
63.9
|
312.8
|
19
|
349.4
|
62.6
|
286.8
|
20
|
362.9
|
61.5
|
301.4
|
Total
|
5968.1
|
||
Average
net of content in one capsule = 298.4 mg
Capsules
|
X
(x10-3)
|
Deviation
(%)
|
1
|
+10.3
|
+3.452
|
2
|
+3.9
|
+1.307
|
3
|
+9.3
|
+3.117
|
4
|
-6.0
|
-2.011
|
5
|
-13.0
|
-4.357
|
6
|
-22.6
|
-7.574
|
7
|
+0.2
|
+0.067
|
8
|
+1.4
|
+0.469
|
9
|
-6.9
|
-2.312
|
10
|
-3.5
|
-1.173
|
11
|
-8.7
|
-2.916
|
12
|
+6.6
|
+2.212
|
13
|
+1.8
|
+0.603
|
14
|
+8.8
|
+2.949
|
15
|
+0.5
|
+0.168
|
16
|
+4.9
|
+1.642
|
17
|
+7.3
|
+2.446
|
18
|
+14.4
|
+4.826
|
19
|
-11.6
|
-3.887
|
20
|
+3.0
|
+1.005
|
X= difference
between individual net weight and average net of content.
Discussions:
Test
of uniformity of weight (mass) is carried out to tablets and capsules to ensure
accurate and consistent dosage form to be administered by patients. However
uniformity of weight test is not applicable to tablets and capsules required to
comply with test for uniformity of contents as drug substances present in
lesser proportion is demonstrated by content variation. Procedures in this
experiments follow procedure in appendix XII C, BO 2011. Limit is the
acceptable range of value of uniform weight.
In the experiment, since the average
mass obtained for 20 tablets is 0.6828g that is greater than 250mg, thus
minimum 18 tablets should not deviate from 0.6828 g by ±5%. The uniformity of
weight of tablets is acceptable as all 20 tablets fall within the range limit
of mass (0.6828 g to 0.7169g).
For capsule, the average mass obtained is 298.4 mg,
that is less than 300mg, thus minimum 18 capsules must not deviate from average
mass by ± 10%. The uniformity of capsule is acceptable as all the 20 capsules
fall within the range limit (298.4
mg to 328.24 mg). We assume
that the concentration of drug, which is the weight of drug per weight of
dosage form, is uniform.
The results of
the test of uniformity of weight may not be accurate as there is always
substance left in the capsules when they are emptied from the shells. The shell
of capsule should be completely emptied before weight. Besides, the balance
should calibrated first before doing the experiment.
Conclusion:
All the tablets and capsules follow
the standard of uniformity of weight as not more than two of the individual
masses deviate from the average mass by more than the percentage deviation
stated
References:
Experiment 4: Dosage Performance Test
Material/Apparatus:
Basket, paddle,
reciprocating cylinder, flow-through cell, cylindrical vessel 1000 ml, water
bath (36.5-37.5°C.), Ibuprofen tablets and motor to regulate
basket or paddle speed.
A) Disintegration
test for sugar-coated tablets
Methods:
1. The
apparatus for the disintegration test according to its operation manual were
set up.
2. The
temperature of the disintegration medium (water) was ensured at 37 ± 2°C.
3. The time was
set to 60 minutes. One tablet was introduced into each tube, the disk was add
into each tube and the operation was
started.
4. The tablet
in each tube was check at the end of the operation.
5. Tablets
comply with the test if all 3 tablets disintegrate in 60 minutes. If there is
any tablet that
does not disintegrate, repeat the test
using 3 new tablets but replacing the disintegration
medium (water) with 0.1M hydrochloric acid.
Tablets comply with the test if all 6 tablets
disintegrate
in the acidic medium.
Results:
During the experiment, we had used Paralgin Tablets which are
uncoated tablets. The tablets disintegrated at first trial after 22 minutes and
48 seconds.
Each tablet
contains:
·
Paracetamol
BP 500mg
·
Codeine
Phosphate 8 mg
·
½ H2O
BP
Discussion:
In definition, disintegration is the state in which no residue of
the tablet or capsule, except fragments of undissolved coating or capsule
shell, remains on the screen of the test apparatus or, if any other residue remains,
it consists of a soft mass having no palpably firm, unmoistened core. 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 is to
determine whether tablets and capsules disintegrate within a prescribed time
when placed in an immersion fluid under prescribed experimental conditions. The
disintegration test are applicable to uncoated tablets, coated tablets,
enteric-coated tablets, soluble tablets, dispersible tablets, hard capsules,
soft capsules and enteric capsules. While not applicable to modified-released
tablets, modified-release capsules, chewable tablets and tablets or capsules
that must comply with the dissolution test.
Conclusions:
Based on the experiment, the disintegration process is important
for the tablets in order for the active ingredient to be absorbed at the target
areas. We had used Paralgin Tablets which are uncoated tablets. The tablets
disintegrated at first trial after 22minutes and 48 seconds in water. If the
tablets not disintegrated or still rigid after 60 minutes mean that the rate of
disintegration was low and the experiment was not succeed.
References:
B) Dissolution test for tablets
Procedures:
1.
Each
of the dissolution vessel was filled up with the buffer solution up to 900 ml
mark. The temperature was set to 37
.
2.
The
temperature of the dissolution medium was checked. It was ensured that it was
at 37
.
3.
One
Ibuprofen tablet was placed into each dry basket assembly.
4.
The
stirring speed was set to 150 rpm. The basket assembly was lowered into
position in the vessel and the operation was started.
5.
After
30 minutes had passed, 10 ml samples of the dissolution medium from each vessel
was withdrawn for analysis and the solution was filtered using a suitable
filter. Sampling should be done from a point half-way between the surface of
the dissolution medium and the top of the rotating basket, and not less than 10
mm from the wall of the vessel. The volume of the aliquot withdrawn for
analysis was replaced with an equal volume of same dissolution medium.
6.
A
standard solution of ibuprofen was prepared by diluting 10.0 mg of ibuprofen
reference standard to 50 ml with dissolution medium.
7.
2.0
ml of sample solution and a 2.0 ml of standard solution to 25 ml were diluted
with dissolution medium in separate volumetric flask.
8.
The
absorption of both solutions in a 1 cm cell at a wavelength of 221 nm were
measured.
9.
The
percentage amount of ibuprofen dissolved was calculated by using the formula
stated at the calculation part below.
10. From the results obtained, the tablets
were determined whether they complied with the requirements of the United
States Pharmacopoeia.
Results:
Absorbence of
sample solution
(At) = 0.667
Absorbence of the
standard solution
(As) = 3.436
Weight of ibuprofen
reference standard used (W) = 10mg
Purity of ibuprofen
reference standard (P) = 0.98
Calculations:
Thus, the percentage amount of ibuprofen dissolved is 17.12%.
According to the results obtained, the tablets did not comply with the
requirements of the United States Pharmacopoeia standard. This is because the
stated amount of
C13H18O that was dissolved in 30 minutes is less than
75% of the United States Pharmacopoeia limits.
Discussions:
Based on the results obtained, some
calculations have been done to determine the percentage amount of ibuprofen
dissolved. The percentage amount of ibuprofen dissolved is 17.12%. According to
the results obtained, the tablets do not comply with the requirements of the
United States Pharmacopoeia standard. This is because the stated amount of
ibuprofen dissolved is less than 75%, which is the United States Pharmacopoeia
limits. Even though, through observation, the tablet has dissolved completely
in the dissolution medium, the results shows that the active ingredient of
Ibuprofen does not dissolved completely in the dissolution medium. This is
because the active ingredient may require longer time to dissolve in the dissolution
medium completely.
Moreover, there are several errors which may cause the
inaccuracy of the results obtained in this experiment. Firstly, the temperature
of the water bath falls below 37 ±0.5 ºC when the experiment is carried out. Secondly,
the drug is not expected to dissolve in water within the time given. Thirdly,
the stirrer that has been used in this operation is of the slow rotation speed.
There are several precautions that must be taken in order to
minimize the errors happened during the operation. Firstly, the temperature of
the water bath must be ensured that it is fall in the range of 36.5-37.5 ºC throughout the operation by using
thermometer. This is because the temperature of the water bath is reflecting
the body temperature. Make sure that the water bath is clean and does not have
any chemical contamination as the normal pH of the body is 5-7. The pH of the
water is 7, therefore, it reflecting the pH off the body. If the drug is not
expected to dissolve in the water, a small amount of solubilizing agent should
be added to the water bath. This is to ensure the solubility of the tablet in
the aqueous phase. The rotation speed of the stirrer must be increased so that
the active ingredients of the drug can dissolve completely within the time
given. An inert filter with a suitable pore size must be used to filtrate the
removed fluid.
Conclusion
In conclusion, the percentage amount of ibuprofen
dissolved in the dissolution medium is 17.12%. The result failed to comply with
the requirements of the United States Pharmacopoeia. This is due to the several
errors that arise during the operation. Several precaution steps must be taken
in order to improve the accuracy of results in the dissolution testing.
References
Experiment
5: Content of Ibuprofen (assay)
Methods:
Materials
1.007g of
ibuprofen powder, chloroform, ethanol (96%), phenolphthalein solution, 0.1 M
sodium hydroxide
Apparatus
100mL beaker,
100mL measuring cylinder, mortar and pestle, weighing boat, weighing
machine, 250ml conical flasks, filter
paper, filter funnel, hair dryer, burette, retort stand and separating funnel
Procedures:
1.
20
Ibuprofen Tablets previously selected at random were weighed and powdered.
2.
A quantity
of powder containing 0.5 g ibuprofen (1.0071g) was extracted with 20 ml
chloroform was extracted for 15 minutes and filtered through a sintered glass
crucible.
3.
The
residue was washed with 3 × 10 ml chloroform and gently the combined filtrate
was allowed to evaporate just to dryness in a current of air. The residue was
dissolved in 100 ml 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 the indicator. The content of ibuprofen was
calculated that if each ml of 0.1M sodium hydroxide is equivalent to 0.02063 g
of C13H18O2.
Results and calculations:
Weight of weighing boat + powder
(20 ibuprofen tablet)
|
11.2867g
|
Weight of weighing boat
|
3.2301g
|
Weight of powder (20 ibuprofen
tablet)
|
8.0566g
|
1 ibuprofen tablet contains 200mg of active
ingredients and expicients.
Hence, 20 tablets contain 4000mg
(4g) ibuprofen.
Thus, 1,0071g of powder contain 0.5g of ibuprofen. It is then
weighed and dissolved in 20ml chloroform.
In titration,
Initial reading of 0.1M sodium hydroxide
|
1mL
|
Final reading of 0.1M sodium hydroxide
|
9.5mL
|
Volume of 0.1M sodium hydroxide used
|
8.5mL
|
Given that 1 mL of 0.1M sodium hydroxide is equivalent to 0.02063g
C13H1802,
So, the weight of ibuprofen in the tablet is 8.5 x 0.02063g =
0.1754g.
Percentage of ibuprofen content that we get is
= 0.1754g/0.5000g x100%
=35.08%
Number of mole of sodium hydroxide
needed to react with ibuprofen,
NNaOH = Volume x Molar Concentration
= (8.5mL/1000ml) x 0.1M
= 0.00085 mol
From the chemical equation,
Number of mole of ibuprofen
Number of mole of sodium
hydroxide used
NIbuprofen = 0.00085 mol
Mass of ibuprofen,
MassIbuprofen = Number of mole x Molar mass of C13H18O2
=
0.00085 mol x (13x12.01 + 18x 1.008 + 2x16.00)g mol-1
= 0.00085 mol x 206.274 g mol-1
=
0.1753 g
From the experiment, 0.1753g of C13H18O2
was neutralized by 8.5ml of 0.1M NaOH.
This experiment aim to analyze the
content of Ibuprofen in tablet dosage form. Based on information from British
Pharmacopoeia (B.P) each tablet should have 90% to 110% of the labelled
Ibuprofen. However, from the experimental results, each tablet of ibuprofen
only contain 35.08% of active ingredient which have a great deviation from the
theoretical value. The value should in compliance with the standard to ensure
that the uniformity of content is achieved.
The percentage of deviation in this experiment was 64.94% which is a
high value.
Some errors might occur during the
experiment and should be avoided to reduce the great deviation with the
theoretical value. Firstly, when making the 20 tablet of ibuprofen into powder,
some of the fine powder may escape as they are too light. Some of the active
ingredients may be lost during this process.
Since powder easily dispersed in the air, when crushing the tablets into
powder we should close the fan and air conditioner to prevent the air flow and
escape of fine powder. Besides, some of the fine powder may be lost during the
transferring and weighing process. Some of the fine powder will stick to the
weighing boat and thus cause the lost of active ingredients. Moreover, parallax
error can be eliminated by placing the eye at the position perpendicular to the
scale on measuring cylinder or burette. Several experiments can be repeated
until we get the accurate and consistent result. In addition instead of expired
ibuprofen provided, a new batch of ibuprofen should be use because active
ingredient in tablets may degraded or spoiled. This may affects the result of
the experiment.
Conclusion:
1.0071g of fine powder contain 0.5g
of the ibuprofen active ingredients. The volume of 0.1M sodium hydroxide used
to titrate to end point is 8.5mL. Percentage of ibuprofen content that
we get is 35.08%. The content of active
ingredient is not tally with the theoretical dosage expected. Percentage of
deviation is 64.94%
References:
Questions:
1. What are the objectives of the tests for uniformity of diameter
and uniformity of content?
The objective of the tests for uniformity of diameter is to ensure
that all tablets have same size therefore have same amount of active
ingredient. If the diameter of tablet is not uniform, it could lead to
different amount of drug in tablet. The content uniformity test is used to
ensure that every tablet contains the amount of drug substance intended with
little variation among tablets within a batch.
2. State the
types of tablets and capsules that must be tested for the uniformity of
diameter and uniformity of content.
Types of tablets that must be tested for the uniformity of diameter
are uncoated and coated tablets. Whereas, the types of capsules that must be
tested for the uniformity of diameter are soft, hard and modified-release
capsules (including delayed-release capsules (gastro-resistant/enteric
capsules) and sustained-release capsules (extended-/prolonged-release
capsules). On the other hand, for tablets or capsules which contain less than
50 mg of any active ingredient, they must be tested for the uniformity of
content.
3. Give reasons for the non-compliance to test for the uniformity of
weight.
Uneven
feeding of granules into the die by hopper shoe due to uneven powder flow could
affect its weight uniformity. Irregular movement of the lower punch will cause
variation in capacity of die space.
4. Why does dissolution test
suitable to be used for batch to batch quality control?
a) Dissolution test is a testing that
is essential in the product development to ensure that the active ingredients
can dissolved completely at the given time in the patients’ body.
b)
Dissolution
test is used to test whether the particular batch meet the requirements set by
the United States Pharmacopoeia before placing the batch in the market.
c)
The
test is used to identify any potential problem that may occur in the
bioavailability of the product over a period of time.
d) The test is used to obtain clinical
results for the support of the product specification in the product quality
control and to obtain information on the ability of test batches to dissolve in
the bioequivalence studies.
5. Explain the differences found in
the procedures for dissolution test in the United States Pharmacopoiea and the
British Pharmacopoiea.
Dissolution
is defined as the process by which solid substance enters in solvent to yield a
solution. Three types of apparatus are now described in the British and
European Pharmacopoeias; the basket, the paddle and the flow-through cell. The
descriptions are concordant with those published in the United States
Pharmacopeia (USP). Of the two established apparatus (basket and paddle) the
paddle is now the apparatus of choice for many preparations. Pharmacopoeial
tests using either the basket or the paddle are based on the principle of
operating under 'sink conditions', that is, in a manner such that material
already in solution does not exert a modifying effect on the rate of
dissolution of the remainder. 'Sink conditions' normally occur in a volume of
dissolution medium that is at least 5 to 10 times the saturation volume. The
revised standardised BP conditions for published tests using either the basket
or the paddle are: rotation speed:100 rpm (basket), 50 rpm (paddle),
dissolution medium volume: 900 ml, dissolution medium composition: aqueous,
commonly 0.1M HCl or phosphate buffers
of pH 6.8 to 7.6, number of units tested: 6. The standardised BP criteria for
published tests using either the basket or the paddle are that, for each unit
tested, not less than 70% of the active ingredient or ingredients dissolves
within 45 minutes. If one unit fails to meet this requirement, a retest may be
carried out using the same number of units; all units in the retest must
comply.
