Transcript tab Eval

Tablet Evaluation
Pharmacopoeial tests (USP)
1- Disintegration
2- Dissolution
3- Weight uniformity
4- Content uniformity
5- Friability
I-Disintegration
This test is provided to determine whether tablets
or capsules disintegrate within the prescribed
time when placed in a liquid medium at the
experimental conditions presented below.
Compliance with the limits on Disintegration
stated in the individual monographs is required
except where the label states that the tablets or
capsules are intended for use as troches, or
are to be chewed, or are designed as extendedrelease dosage forms or delayed-release
dosage forms. Determine the type of units under
test from the labeling and from observation,
and apply the appropriate procedure to 6 or more
dosage units
PROCEDURE
• Uncoated Tablets— Place 1 dosage unit in each of the six
tubes of the basket and, if
• prescribed, add a disk. Operate the apparatus, using water or
the specified medium as the
• immersion fluid, maintained at 37 ± 2 . At the end of the time
limit specified in the
• monograph, lift the basket from the fluid, and observe the
tablets: all of the tablets have
• disintegrated completely. If 1 or 2 tablets fail to disintegrate
completely, repeat the test on 12
• additional tablets. The requirement is met if not fewer than
16 of the total of 18 tablets tested
• are disintegrated.
Disintegration apparatus. (All
dimensions are expressed in mm.)
II-Dissolution
Definition• Dissolution is a process in which a solid substance
solubilizes in a given solvent i.e. mass transfer from
the solid surface to the liquid phase.
• Rate of dissolution is the amount of drug substance
that goes in solution per unit time under
standardized conditions of liquid/solid interface,
temperature and solvent composition.
• The rate of dissolution is given by Noyes and
Whitney:
dc
dt
=
k (Cs- Cb)
Where,
dc/dt= dissolution rate of the drug
K= dissolution rate constant
Cs= concentration of drug in stagnant layer
Cb= concentration of drug in the bulk of the
at time t
solution
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Dissolution rate under non-sink and
sink conditions.
zero order dissolution
under sink condition
Conc. of dissolved drug
first order dissolution under
non-sink condition
Time
7
Dissolution test
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Introduce the stated volume of the dissolution medium, free from dissolved air, into
the vessel of the apparatus.
Warm the dissolution medium to between 36.5° and 37.5°. Unless otherwise stated
use one tablet or capsule.
When Apparatus I is used, place the tablet or capsule in a dry basket at the beginning
of each test. Lower the basket into position before rotation.
When Apparatus II is used, allow the tablet or capsule to sink to the bottom of the
vessel prior to the rotation of the paddle. A suitable device such as a wire or glass
helix is used to keep tablets or capsules that would otherwise float horizontal at the
bottom of the vessel.
Care should be taken to ensure that air bubbles are excluded from the surface of the
tablet or capsule.
Operate the apparatus immediately at the speed of rotation specified in the individual
monograph.
Take samples at the prescribed time. Withdraw the samples from a point half-way
between the surface of the dissolution medium and the top of the rotating basket or
blade, not less than 10 mm from the wall of the vessel. Add a volume of dissolution
medium equal to the volume of the samples withdrawn or compensate by calculation.
Filter the samples at 36.5° to 37.5° and determine the amount of active ingredient
present by the method prescribed in the individual monograph. .
Repeat the complete operation five times.
Rotating Basket Apparatus (Apparatus
1)
 It is basically a closed-compartment, beaker type
apparatus.
 It comprising of a cylindrical glass vessel with
hemispherical bottom of one litre capacity partially
immersed in a water bath.
 A cylindrical basket made of #22 mesh is located
centrally in the vessel at a distance of 2 cm from the
bottom and rotated by a variable speed motor
through a shaft.
9
Contd…..
All metal parts like basket and shaft are made
of stainless steel 316.
Apparatus 1
Rotating Paddle Apparatus
(Apparatus 2)
 Here, basket is replaced with a stirrer.
 A small, loose, wire helix may be attached to the
dosage form that would otherwise float.
 The position and alignment of the paddle are
specified in the official books.
Appratus2
Acceptance table
stage Numb
er
tested
Acceptance criteria
S1
6
Each unit is not less than Q + 5%
S2
6
1- Average of the12 units (S1+ S2) is equal to or greater
than Q
2- No unit is less than Q – 15%
S3
12
1. average of the 24units (S1+ S2+ S3) is equal to or
greater than Q
2. not more than 2 units are less than Q – 15%
3. no unit is less than Q – 25%
Weight and Hardness Variation:
• Weight and hardness variation are common
problems experienced when tableting. Tablet
weight is mainly affected by factors such as
powder variation, tablet press condition and
tooling, and flow of powder on the tablet
press.
• Inconsistent powder or granulate density and
particle size distribution are common sources
of weight variation during tablet compression.
Problems related to the density of the powder
or granulate are often associated with
overfilling of the die and recirculation of the
product on the tablet press. A variation of
particle size distribution of the powder or
granulate can be the result of segregation due
to transfer or static electricity
• Weight variation can arise as a result of a
poorly prepared or operated tablet press.
• Inspection of the critical dimensions of tablet
press tools is recommended
• During the course of a compression operation
it is also important to not neglect the level of
the product in the hopper. Head pressure is a
critical factor related to the amount of
product in the hopper
III – uniformity of dosage units
1- Content uniformity test:
• it is required for the:
Uncoated tablets containing
less than 50 mg of an active
ingredient comprising less
than 50% of the weight of
one dosage unit.
2-Weight variation test:
• it is required for the:
Uncoated tablets containing 50
mg or more of an active
ingredient comprising 50%
or more of the weight of
one dosage unit.
1- Content uniformity test
• Method
•
1- Select not less than 30 units
•
2-Assay 10 units individually as directed in the assay
in the individual monograph.
• 3- From the assay, calculate the content of active
ingredient in each unit.
• 4- Calculate Xi = (content/L.C)*100
• 5- Calculate X¯ = ∑ Xi / n ( NO. of tablets tested)
• 6- Calculate standard deviation (S) = [(Xi - X¯)2 / (n – 1)]½
• 7- Calculate (Relative standard deviation)
RSD = (S / X¯)*100
2-Weight variation test
• Method:
• weigh accurately 10 tablets individually
• From the assay, calculate the average content % then calculate the
content of active ingredient in each capsule.
• Calculate Xi = (content/L.C)*100
• Calculate X¯ = ∑ Xi / n ( NO. of tablets tested)
• Calculate standard deviation (S) = [(Xi - X¯)2 / (n – 1)]½
• Calculate RSD ( Relative standard deviation) = ( S / X¯)*100
Criteria:
• Accepted if:
• the amount of Xi of the 10 tablets lies within the range of 85% to
115%
• And RSD of the 10 tablets is less than or equal to 6%.
• Suspected if:
• One Xi is outside the range 85% to 115% but not outside the range
of 75% to 125%.
• Or RSD is greater than 6%
• Or both conditions.
Test 20 another 20 tablets
• Accepted if:
– Not more than one Xi of 30 Xi are outside the range of 85% to 115%
– None outside the range of 75% to 125%.
– RSD of the 30 tablets is less than or equal to 7.8 %.
IV- Friability (measure of tablet
resistance to abrasion)
Reasons of tablet friability
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•
•
Hardness variation
Capping and lamination
Low moisture content in tablets
Low binder efficiency
• For tablets with a unit weight equal to or less than 650 mg, take
a sample of whole tablets corresponding as near as possible to
6.5 g. For tablets with a unit weight of more than 650 mg,take a
sample of 10 whole tablets. The tablets should be carefully
dedusted prior to testing.
• Accurately weigh the tablet sample, and place the tablets in the
drum. Rotate the drum 100 times, and remove the tablets.
Remove any loose dust from the tablets as before, and
accurately weigh.
• Generally, the test is run once. If obviously cracked, cleaved, or
broken tablets are present in the tablet sample after tumbling,
the sample fails the test. If the results are difficult to interpret
or if the weight loss is greater than the targeted value, the test
should be repeated twice and the mean of the three tests
determined. A maximum mean weight loss from the three
samples of not more than 1.0% is considered acceptable for
most products