EXPERIMENT NO. 5
OBJECT:To determine the disintegration time of enteric coated tablet of (Voren 50 mg)
Diclofenac Sodium.
APPARATUS:





Thermometer
Disintegration Apparatus
Stop Watch
Medium (0.1 N Hydrochloric Acid, Dihydrogen Phosphate Buffer)
Enteric coated TabletVoren 50 mg
THEORY:
Disintegration
The time required for a tablet to break up into granules of specified size (or smaller), under carefully
specified test conditions. The conditions of the laboratory test, in vitro, are set to simulate those which
obtain in vivo. Factors such as the kind and amount of tablet binders and the degree of compression
used in compacting the tablet ingredients help determine disintegration time. The active ingredients in a
disintegrated tablet are not necessarily found to be in solution and available for absorption. A long
disintegration time is incompatible with rapid drug absorption; a short disintegration time, by itself,
does not ensure rapid absorption.
Tablet disintegration testing is used as a quality-assurance measure. It is not a true predicter of how well
the dosage form will release its active ingredient in vivo. The United States Pharmacopea (USP) sets
standards for tablet disintegration testing.
Apparatus for Disintegration
The apparatus is relatively simple. It consists of a basket rack holding six plastic tubes open at the top
and bottom. The bottom is covered with a 10 mesh screen. The rack is immersed in a suitable liquid at
37 degrees C. It moves up and down at a specified rate. One tablet is placed into each tube and the time
to disintegrate and fall through the screen is noted.
BIOAVAILABILITY IN RELATION TO DISINTEGRATION TIME
Bioavailability of a drug depends in absorption of the drug, which is affected by solubility of the drug in
gastrointestinal fluid and permeability of the drug across gastrointestinal membrane. The drugs
solubility mainly depends on physical – chemical characteristics of the drug. However, the rate of drug
dissolution is greatly influenced by disintegration of the tablet.
FACTORS AFFECTING DISINTEGRATION TIME OF TABLET:
Disintegrants used to increase surface area of the tablet fragments and to overcome cohesive forces
that keep particles together in a tablet. However, there are several factors affecting disintegration
process in tablet, they are:


Effect of Fillers
Effect of Binder

Effect of Lubricants

Effect of Surfactant
Effect of fillers
The solubility and compression characteristics of fillers affect the rate and mechanism of disintegration
of tablet. If soluble fillers are used then it may cause increase in viscosity of the penetrating fluid which
tends to reduce effectiveness of strongly swelling disintegrating agents and as they are water soluble,
they are likely to dissolve rather than disintegrate. Insoluble diluents produce rapid disintegration with
adequate amount of disintegrants.
Effect of binder
As binding capacity of the binder increases, disintegrating time of tablet increases and this counteract
the rapid disintegration. Even the concentration of the binder can also affect the disintegration time of
tablet.
Effect of lubricants
Mostly lubricants are hydrophobic and they are usually used in smaller size than any other ingredient in
the tablet formulation. When the mixture is mixed, lubricant particles may adhere to the surface of the
other particles. This hydrophobic coating inhibits the wetting and consequently tablet disintegration.
Lubricant has a strong negative effect on the water uptake if tablet contains no disintegrants or even
high concentration of slightly swelling disintegrants. The disintegration time is hardly affected if there is
some strongly swelling disintegrants are present in the tablet. There is one exception, sodium starch
glycolate effect remains unaffected in the presence of hydrophobic lubricant.
Effect of surfactants
Surfactant
Remarks
Sodium lauryl sulfate
Good-various drugs
Poor - various drugs
Polysorbate 20
Good
Polysorbate 40 & 60
Poor
Polysorbate 80
Good
Tweens
Poor
Poly ethylene glycol
Poor
(Good – decrease in disintegration
time,
Poor
–
increase
in
disintegration
time)
Sodium lauryl sulphate increased absorption of water by starch or had a variable effect on water
penetration in tablets. Surfactants are only effective within certain concentration ranges. Surfactants are
recommended to decrease the hydrophobicity of the drugs because the more hydrophobic the tablet
the greater the disintegration time.
Medium Used are 0.1 N HCL and Phosphate Buffer or either Citro Phosphate Buffer can also be used
with pH 6.8, to know the disintegration of enteric coated tablet according to the different mediums
provided with their acidic and alkaline pH as similar to that of the physiological medium in the body.
BUFFERS (acid-base): “A buffer is a solution that can maintain a nearly constant pH if it is diluted, or if
relatively small amounts of strong acids or bases are added. Buffer solutions resist pH changes.”
Preparation of Citrophosphate Buffer & Dihydrogen phosphate Buffer
CITROPHOSPHATE BUFFER:
Reagents used are
A= Citric Acid 0.1 M (21.0 g/l)
B=Disodium Phosphate 0.2 M (35.6 g/l)
When mixed in different proportions so can maintain pH 2-8
For 100 ml
For 1000 ml
A= 27.9 ml (x);
A= 279 ml;
B= 100-x= 100-27.9= 72.1 ml
B= 721 ml
PHOSPHATE BUFFER:
Reagents used are
A= Dihydrogen Phosphate (27.8 g/l)
B= Dipotassium Hydrogen Phosphate (26.5 g/l)
For 2000 ml
A= 735 ml;
B= 265 ml & make up the volume upto 2000 ml with distilled water that is 735+265= 1000 ml
For 1000 ml calculation
PROCEDURE
I.
Place 1 dosage unit in each of the six tubes of the basket and add a disk in each tube with the
grooves of the disk placed downwards.
II.
Press the button of the heater on and heat the water bath in the tank upto 45 to 46 degree Celsius
so that inner temperature of the medium is maintained upto 37 + 2⁰ C as noted by thermometer.
III.
Fill the tank with the specified medium that is 0.1 N HCL as the immersion fluid maintained at 37 +
2⁰ C.
IV.
Dip the basket in the tank and as the run button is pressed on the system, switch on the stop watch
simultaneously.
V.
VI.
VII.
VIII.
IX.
X.
At the end of 90 minutes of operation, remove the basket-rack assembly from the fluid and gently
rinse with water.
Enteric coated tablets should not show any disintegration in gastric fluid, it fail the test if any now
show distinct evidence of disintegration.
Replace the 0.1 N HCL in the beaker with 600 ml of Intestinal Fluid that is Phosphate Buffer of pH
6.8.
Continue the test by setting the machine in motion.
Note down disintegration time for each tablet.
At the end of the time limit specified in the monograph that is 30 minutes, lift the basket from the
fluid, and observe the tablets:
a) All of the tablets have disintegrated completely.
b) If 1 or 2 tablets fail to disintegrate completely, repeat the test on 12 additional tablets.
c) The requirement is met if not less than 16 of the total 18 tablets tested are
disintegrated.
d) Enteric coated tablets pass the test if each of the six tablets disintegrates in not more
than 30 minutes in the Intestinal Fluid that is Phosphate Buffer of pH 6.8.
OBSERVATION
No. of Tablets (n)
Disintegration Time of Voren (mins) (x)
(x2)
1
90+17.20= 107.2
11,491.84
2
90+11.26= 101.26
10,253.588
3
90+14.12= 104.12
10,840.974
4
90+12.49= 102.49
10,504.2001
5
90+20.21= 110.21
12,146.2441
6
90+16.23= 106.23
11,284.8129
n=6
∑x = 631.51
∑x 2 =
66,521.6591
CALCULATION
FOR MEAN:
∑x/ n= 631.51/ 6= 105.252 mins
FOR STANDARD DEVIATION (SD):
RESULT & COMMENTS
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