Introduction:
Tablets and
capsules are like other dosage forms which are subjected to those pharmacopoeial
standards which deals with “added substances” respective to their toxicity,
interference with analytical methods, etc. However, some procedures are apply
specifically to tablets and capsules which are designed not only to ensure that
the tablet or capsules achieve its full pharmacological actions, but also to
determine the uniformity of the physical properties of the official
tablet/capsule, irrespective of the manufacturer.
Standards can be
found in the British Pharmacopoeias and United Pharmacopoeia which include the
uniformity of diameter, uniformity of weight, content of active ingredients,
uniformity of content, disintegration and dissolution. Besides, there are a few
number of quality control which are widely applied but not defined in the
pharmacopoeias such as thickness, hardness and friability.
The experiments
below demonstrate the application of a number of selected physical and dosage
performance test on samples of commercially available tablets and capsules.
Official pharmacopoeias are required to be refer for more detailed description
of other test which is not carried out in this practical session.
Procedure:
Experiment
1- Uniformity of diameter, thickness and hardness
1. 10
tablets were selected and test was carried out for uniformity of diameter,
thickness and hardness using the Tablet Testing Instrument ( PHARMATEST PTB
311)
2. The
deviation of individual unit were measured. The mean diameter shall not exceed
±5% for tablet with diameter less than 12.5 and 3± for diameter of 12.5mm or
more.
Experiment
2- Tablet friability
1. 10
Tablets were selected and weighted.
2. All
tablets were placed into the drum of tablet abration and friability tester. The
rate of rotation were set at 100rpm, time to 10minutes and operation were
start.
3. At
the end of operation, all tablets were removed and the tablets were ensured to
be free from dust and powder by using a brush. The tablets were reweigh. The
percentage loss of weight were determine.
4. The
compressed tablet weight should not loss more than 1% of its initial weight.
Friability tester
Experiment
3- Uniformity of weight of tablets and capsule
Tablet
1. 20
tablets were selected randomly and weighted. The average weight were determine.
2. Tablets
were weigh individually. Each tablet’s percentage deviation of it’s weight from
the average weight were measured.
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 80mg
|
±10.0
±20.0
|
Minimum 18
Maximum 2
|
80mg to 250mg
|
±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 randomly
2. One
capsule were weighed. The capsule was open and the contents were removed as
completely as possible. The emptied shell were weighed and the net weight of
the content were determined by subtracting the weight if 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 was determine 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
±20.0
|
Minimum 18
Maximum 2
|
300mg or more
|
±7.5
±15.0
|
Minimum 18
Maximum 2
|
Experiment
4- Dosage performance tests
Disintegration
test for sugar-coated tablets
1. Apparatus
were set up for the disintegration test according to its operation manual.
2. The
temperature of the disintegration medium ( water) was ensure to be at 37±2
°C.
3. The
time was set to 60 minutes. One tablet was introduce into each tube, the disk
was added into each tube and the operation was started.
4. The
tablet was check in each tube at the end of the operation.
5. If
all the 6 tablets disintegrate in 60 minutes, the tablets will comply with the
test. If the tablet does not disintegrate, the test will be repeated using 6
new tablets but replace the medium with 0.1M hydrochloric acid. The tablets
will be comply with the test if all 6 tablets disintegrate in the acidic
medium.
Dissolution
test for tablets
1. Dissolution
vessel was fill up with buffer solution to 900 ml mark. The temperature was set
up to 37°C.
2. The
temperature of the dissolution medium were checked. The temperature was ensure
to be at 37±0.5°C.
3. One
Ibuprofen Tablet were placed into each dry basket assembly.
4. The
stirring speed was set up to 150 rpm. The basket was lower to assembly into
positon in the vessel and the operation were started.
5. After
30 minutes, 10 ml samples of dissolution medium were withdraw from each vessel
for analysis and the solution were filter using suitable filter. The sampling
was done from a point half-way between the surface of the dissolution medium
and the top of the rotating basket, and not less than 10mm from the wall of the
vessel. The volume of aliquot withdrawn for analysis were replaced with an
equal volume of the same dissolution medium.
6. A
standard solution of ibuprofen were prepared by diluting 10.0mg of ibuprofen
reference standard to 50 ml of dissolution medium.
7. 2.0ml
of sample solution and 2.0ml of standard solution were diluted to 25ml of
dissolution medium in separate volumetric flasks.
8. The
absorption of both solution were measured in a 1cm cell at a wavelength of
221nm.
9. The
percentage amount of ibuprofen dissolved was calculated using the formula
below.
At/As ·W/50·2/25·P·900·25/2·100/200
Where
At = absorbance of sample
solution
AS=
absorbance of the standard solution
W= Weight of ibuprofen reference
standard used
P = Purity of ibuprofen reference
standard
10. According
to the results above, the tablets were determined to see whether do they
complied with the requirements of the British Pharmacopoeia ( Assume Q= 75%)
Experiment
5- Content of ibuprofen( Assay)
1. 20
Ibuprofen Tablets were selected randomly. They were then weigh and powder.
2. A
quantity of powder containing 0.5 g of Ibuprofen were extracted with 20 ml
chloroform for 15 minutes and were filtered through a sintered glass crucible (
BS Porosity No.1)
3. The
residue was wash with 3·10 ml chloroform. The filtrate was gently evaporated in
a current of air. The residue is again dissolve in 100ml of ethanol (96%) which
was previously neutralised to phenolphthalein solution.
4. The
solution was titrate with 0.1M sodium hydroxide to end point with
phenolphthalein solution as the indicator. The content of ibuprofen was
calculated whereby 0.1M sodium hydroxide is equivalent to 0.02063g of C13H1802.
Results:
Experiment
1- Uniformity of diameter, thickness and hardness
Tablet
|
Thickness (mm)
|
Diameter (mm)
|
Hardness (N)
|
Deviation of diameter
(%)
|
1
|
4.02
|
12.76
|
264.74
|
0.05
|
2
|
4.21
|
12.79
|
255.87
|
0.28
|
3
|
4.18
|
12.74
|
273.05
|
0.11
|
4
|
4.00
|
12.74
|
229.27
|
0.11
|
5
|
3.98
|
12.74
|
250.52
|
0.11
|
6
|
4.02
|
12.74
|
274.52
|
0.11
|
7
|
3.96
|
12.75
|
255.50
|
0.03
|
8
|
4.01
|
12.74
|
229.46
|
0.11
|
9
|
4.09
|
12.77
|
254.77
|
0.16
|
10
|
4.10
|
12.77
|
278.23
|
0.16
|
Mean:
|
4.06
|
12.75
|
256.593
|
Discussion (Exp 1):
During tablet
manufacture, the thickness of tablets is depending on the force used to
compress the powder. The larger the force applied, the more thinner and more
compact the tablet. Meanwhile, a compact tablet takes longer time to
disintegrate, dissolve and be absorbed by our body. On the other hand, thick
tablet can break very easily and might not survive the manufacture, packaging,
transport and usage process. Therefore, a medium thickness for a tablet is
essential.
In this
experiment, tablets were tested for their thickness, diameter and hardness by
using the Tablet Testing Instrument (PHARMATEST PTB 311). The mean thickness of
tablets in this experiment is 4.06 which is a medium range for tablet’s
thickness. Besides, the mean diameter for the tablets in this experiment is
12.75mm, so the tolerance for these tablets is the deviation of individual unit
from the mean diameter should not exceed ±
3%. The table above shows that the
deviation of the individual unit does not exceed ±
3%, at most only 0.28%. Therefore, we can conclude that the tablets have uniform diameters.
Experiment
2- Tablet friability
Discussion (Exp 2):
A test on table
friability was conducted. Friability is the tendency for a tablet to chip,
crumble or break following compression. It can be caused by a number of factors
such as poor tablet design, insufficient binder, etc. Tablets need to be hard
enough so that they do not break easily in the bottle but friable enough to
disintegrate in the gastrointestinal tract. Based on the experiment, the tablet
only loss 0.9% of its initial weight after the test( by using a friabilator).
This shows that the friability of the tablets are acceptable.
Experiment
3- Uniformity of weight of tablets and capsule
Capsules
Discussion (Exp 3-Capsules):
As the average
net weight of capsules is 0.302g or 302mg which is more than 300mg, we use the
deviation ±7.5% (Minimum 18) and ±15.0% (Maximum 2) as standard.
None of the
capsules exceed ±7.5%, the magnitude of highest percentage deviation is 2.52%
while the lowest percentage deviation is 0.07%.
The capsules
pass the test.
Tablets
Discussion (Exp 3-Tablets):
As the average net weight of these 20 tablets is 0.5723g or
572.3mg which is more than 300mg, we use ±7.5%
(Minimum 18) and ±15.0 (Maximum 2) as standard.
None of the
tablet exceeds the range of ±7.5%. The magnitude of highest percentage
deviation is 4.11% while the lowest is ±0.12%.
Thus, those
tablets pass the test.
Experiment
4- Dosage performance tests
1. Disintegration
test for sugar-coated tablets
After an hour, all the six
sugar-coated tablets were disintegrated completely in the water, left only the
sugar coatings on the discs.
Discussion (Exp 4-Disintegration test for sugar-coated
tablets):
Disintegration test is
widely used in the evaluation of the disintegration capability of different
formulations as well as quality control of different dosage forms. In this
experiment, six sugar-coated tablets were used to determine whether the tablets
can disintegrate within the prescribed time when placed in a liquid medium that
is water under at the temperature same as our body temperature. Although the
time assigned for the experiment is an hour, through observation, all the
tablets had disintegrated when the time passed 30 minutes, this shows that the
tablets have high disintegration capability. Water is used as the liquid medium
because it is closely resemble to the environment in our digestive track in
which high proportion is made up of water. However, the pH of the stomach as
well as small intestine have not yet take in to account. The high
disintegration capability of the tablets may be due to the appropriate
proportion of disintegrate agent like starch and microcrystalline cellulose in
the tablets. The disintegrate agents absorb the water in the surrounding and
expand, hence push the powder outwards, help the disintegration of the tablets.
2. Dissolution
test for tablets
Result
Absorbance
of sample solution, At
|
0.654
|
Absorbance
of standard solution, As
|
3.612
|
% amount of
ibuprofen dissolved
= At/As × W/50 × 2/25 × P × 900 × 25/2 × 100/200
= 0.654/3.612 × 10mg/50 × 2/25 × 0.98 × 900 × 25/2 × 100/200
= 15.97%
Discussion
(Exp4-Dissolution test for tablets):
After
conducting the experiment, we obtain only 15.97% dissolved ibuprofen. This
shows that the ibuprofen tablet is not comply with the requirement of British
Pharmacopoeia, as the acceptance criteria is not less than (Q + 5)%, where Q =
75%. 15.97% dissolved ibuprofen shows that there are too little ibuprofen
dissolved in the dissolution medium due to some error occurs.
One
of the errors is that the sample solution and standard solution of the
ibuprofen prepared in the volumetric flask are not shaked well before measuring
the absorbance of both solutions. In addition to that, the physicochemical
properties of the ibuprofen may be altered due to instability. Change in
physicochemical properties will directly affect the solubility of ibuprofen.
While
conducting the experiment of dissolution test, many precaution steps need to be
taken. Firstly, the temperature of dissolution medium have to be at 37 ± 0.5°C, as this may affect the amount
of dissolved ibuprofen. Besides, we must be careful while diluting the
ibuprofen solution. Make sure the solution accurately reach the calibration mark
of the volumetric flask. In addition to that, parallax error must be avoided as
it will affect the final result. Make sure the eyes are always perpendicular to
the plane of measuring cylinder and syringe, and the calibration mark of the
volumetric flask.
Conclusion:
Experiment 1 - Tablets in this experiment have diameter larger than 12.55mm, deviations of individual unit from mean diameter of these tablets do not exceed ± 3%. Hence, we can conclude that the tablets passed the test the uniformity test.
Experiment 2 - The tablets only loss 0.9% of its initial weight after the test by using a friabilator, this shows that the friability of the tablets can be accepted.
Experiment 3 - The consistency and accuracy of content in a tablet or capsule can be tested by weighing the individual weight of sample tablet or capsule and compare with the average weight of sample tablet or capsule.
Experiment 4 - The amount
of active compound in the tablets must be accurate and consistent in order to
have the therapeutic effect on the body. Tests are carried out to determine the
amount of active compounds in the tablets before the batch of tablets being
dispensed. If the average amount of active compound is not within the range,
then the tablets cannot be dispensed.
References:
- United States Pharmacopeia, General Chapter. Disintegration (701).
- http://www.who.int/medicines/publications/pharmacopoeia/TabletFriability_QAS11-414_FINAL_MODIFIED_March2012.pdf
- https://www.academia.edu/4110379/Quality_Controlling_of_Tablets
Questions:
1. What
are the objectives of the tests for uniformity of diameter and uniformity of
content?
The objectives
of the test for uniformity of diameter is to increase the patient compliances
by increasing by improving the product appearance and to prevent confusion
among patients towards the dosage of the medications. On the other hand, the
objectives if the uniformity of content is to ensure that no overdose cases
occur in patient because non-uniform amount of active ingredients in the
capsule or tablets might lead to lethal effects towards patients.
2. States
the types of tablets and capsules that must be tested for uniformity of
diameter and uniformity of content.
Test for uniformity of
diameter involve uncoated and coated tablets but does not apply on enteric
tablets, film-coated tablets and sugar coated tablets. However, it involve all
tablets in uniformity of content test.
3. Give
reasons for the non-compliance to test for uniformity of weight.
The reasons where
non-compliance occur while testing the uniformity of weight is due to uneven
feeding of granules into the die. Another reasons might be due to irregular
movement of the lower punch that cause variation in capacity die space.
4. Why
is dissolution test suitable to be used for batch to batch quality control?
After oral
administration, drug absorption depends on the release of the drug from the
product, dissolution rate under physiological conditions and the permeability
across the gastrointestinal tract. Therefore, dissolution rate of tablets and
capsules are important as it will affect their performance. Therefore, in vitro
dissolution test are important for immediate release solid oral dosage forms (
eg: tablets and capsule) which is used to assess the batch to batch drug
quality control.
5. Describe
other apparatus that you can use to conduct dissolution test apart from the one
found in the laboratory.
Another dissolution
test for Ibuprofen can be conducted by Sotax CE70 flow through cell. 2 cells
with different diameter were used, which is 12mm and 26mm respectively. The
small cell was packed with a rubin bead at the bottom, a meatal filter and a
glass fiber on which 4 grams of glass beads and drug was placed. In the top pf
the cell, a glass fiber filter was place to prevent particles to leave the cell
with the eluat. The cell with larger
diameter was packed in the same way, just that small cell lack of the lower
metal-glass fiber filter. The purpose of glass bead was to produce a laminar
flow of the medium. The flow of medium was either 8 or 16 ml/min. All the
experiment were conducted at the temperature of 37°C.
