Experiment
4 Dosage Performance Tests
Objectives:
1. To study and evaluate the disintegration test for coated tablets
2. To study
and evaluate the dissolution test for tablets.
Date of
experiment: 12th December 2014
Introduction
Before an oral route drug being absorb
into the bloodstream via gastrointestinal (GI) tract, it has to undergo two
processes - disintegration and dissolution. Disintegration is where capsules, tablets and granules are break up to
powder particles to increase the surface area of the drug exposed to the gastrointestinal fluids, which is followed by absorption into the
systemic circulation. A tablet
that fails to disintegrate or disintegrates slowly will cause incomplete absorption or delay the onset of action of drug as the drug particle is too big to pass
through the membrane of GI tract .
Dissolution is define as the transfer of molecule and ions from a solid state
into solution. It involves the relocation of a solute molecule (eg. drug molecule) from an environment which is surrounded by it’s own identical molecules. These molecules would forms intermolecular attractions with other non-identical molecules in the
surrounding, and later depart from it’s
latter of identical molecules.
The size of the latter would decrease during dissolution. The small size drug
molecules or particles that has undergone dissolution will be able to be
absorbed into the GI membrane.
Dissolution and disintegration process in
tablets are critical and will determine it’s bioavailability and therapeutic
activity. Thus in this experiment on dosage performance test is carried out to
test the disintegration of film-coated tablets and dissolution of tablet
available in the market and to evaluate that whether these tablets comply with
the tests.
Experiment Method
A)Apparatus
Measuring cylinder 10ml, beaker 50ml, 10ml syringe, filter funnel, 50ml
volumetric flask, glass rod
B) Materials:
Buffer solution, tap water, distilled water, Mefenamic acid B.P. 500mg
film-coated tablets, Ibuprofen B.P. 200mg film-coated tablet, filter paper
C) Model of Analytical Equipments: Tablet
disintegration machine, tablet dissolution tester, spectrophotometer
D)Procedures
i) Disintegration test for coated
tablets
1. The apparatus for the disintegration test is set up according to it’s operation manual.
2. The temperature of the disintegration
medium (water) is ensure at 37 ±
2°C.
3. The time is set to 60 minutes. One tablet is introduced into each tube, the disk is added into each tube and the operation is started.
4. The tablet in each tube is checked at the end of the operation.
5. Tablets comply with the test if all 6
tablets disintegrate in 60 minutes. If there is any
tablet that does not disintegrate, the test is repeated using 6 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.
ii)Dissolution test for tablets
1. Each dissolution vessel is filled up with the buffer solution to 900 ml mark. The
temperature is set to 37°C.
2. The temperature of the dissolution medium is checked and ensure at 37 ±
0.5°C.
3. One Ibuprofen Tablet is placed into each dry basket assembly.
4. The stirring speed is set to 150 rpm. The basket is lowered to assembly into position in the vessel and the operation.
5. After 30 minutes, 10 ml samples of the
dissolution medium is
withdrawn from
each
vessel for analysis and the solution is filtered using suitable filter.Sampling is 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 aliquot withdrawn for
analysis is
replaced with an equal volume of same dissolution medium.
6. A standard solution of ibuprofen is prepared by diluting 10.0 mg of ibuprofen
reference standard to 50 ml with dissolution medium.
7. 2.0 ml of sample solution and 2.0 ml
of standard solution are
diluted to 25
ml with
dissolution medium in separate volumetric
flasks.
8. The absorption of both solutions in a 1 cm
cell at a wavelength of 221 nm is
measured.
9. The percentage amount of ibuprofen
dissolved is
calculated using the following formula:
A t /A s × W/50 × 2/25 × P × 900 × 25/2 × 100/200
Where A t = absorbance of sample solution
A s = absorbance of the standard solution
W = weight of ibuprofen reference
standard used.
P = purity of ibuprofen reference
standard.
10. From the results obtained, the
tablets are
determined whether it comply
with the
requirements of the United States
Pharmacopoeia.
USP limits: Not less than 75% of the
stated amount of C 13 H 18 O 2 dissolved in 30
minutes.
Result and Calculations
i) Disintegration test for coated tablets
All three Mefenamic acid B.P. 500mg film-coated
tablets disintegrate in the disintegration medium (water) within 60 minutes.
The tablets are completely disintegrated
in 9 minutes and 44 seconds.
ii) Dissolution test for tablets
|
Absorption of solution (ABS)
|
K*ABS
|
Standard Solution of Ibuprofen
|
3.436
|
3.4362
|
Sample Solution of Ibuprofen
|
1.872
|
1.872
|
The percentage amount of
ibuprofen dissolved
A t /A s × W/50 × 2/25 × P × 900 × 25/2 × 100/200
At = 1.872 AS= 3.436
W=10mg P= 0.98
Discussions
The disintegration test is a measure of the time required under a given set of conditions for a group of tablets to disintegrate into particles. The machine used in this test is the tablet disintegration machine. The disintegration medium is set around 37°C to mimic the temperature of human body. The up and down movement of the basket in the machine will mimic the agitation of gastric content when the tablet is inside the GI tract of human body.
In this experiment, the
Mefenamic acid 500mg B.P. film coated tablets managed to disintegrate less than
60 minutes. All the tablets disintegrate in 9 minutes 44 seconds. The Mefenamic acid tablets has passed the criteria of disintegration test. Film-coated tablets are compressed
tablets coated with a thin layer of polymer. This produces a skinlike film on
the tablet. The polymer has expanded film and will allow the penetration of water into the tablets which
induces relatively rapid disintegration.
Dissolution testing is a critical preformulation solubility analysis research tool in the process of drug discovery. This test measure the stability of the investigational product, achieving uniformity in production lots and determining its in vivo availability. From the dissolution test, it was found that the percentage of ibuprofen tablets dissolved is 48.05%. This is less than the U.S Pharmacopoiea limits, where not less than 75% of the stated amount of ibuprofen dissolved in 30 minutes. These tablets has failed it’s test. It could be due to various factors such as errors in formulation and chemical and physical properties of the solid oral dosage forms.
A few errors has occurred during the experiment. Firstly, the eye level is not
maintain perpendicular with the measuring scales of the apparatus. The eye level is also not in the same level with the meniscus while
measuring the amount of solutions. This could cause parallax error and will affect the
results. Besides that, while taking sample from the dissolution medium with a
syringe, air bubbles are formed inside the syringe. The air bubble will displace some amount of the liquid in the syringe. This will
reduce the amount of sample solution required to be taken and affect the result. During
spectrophotometric assay, same dropper is used while placing a small amount of
standard solution and sample solution into the cuvette. The dropper may not be
cleaned properly before applying with another solution. This would alter the
concentration of the active ingredient in the solution and affect the result.
To overcome these problems, a few precautions
are taken. Firstly make sure eye level is perpendicular to the measuring scale
and same level with the meniscus to prevent parallax error. While taking sample
solution with syringe, make sure no air bubble is formed. If air bubble is
formed, tap the syringe lightly till the air bubbles floats onto the surface
and burst. Make sure the dropper is cleaned thoroughly with buffer solution
before applying the sample or standard solution onto the cuvette.
Conclusion:
