Drug Dosage Forms II (PHR 312) Lecture 6 (Continued) Quality control (Q. C.) tests for tabletsQuality of tablets should fulfill certain specifications: 1.The tablet should include the correct doseof the drug (Weight uniformity and content uniformity test) . 2.The drug should be released from the tablet in a controlled and reproducible way(Dissolution test). 3.The tablet should show sufficient mechanical strengthto withstand fracture and erosion during manufacturing and handling (Hardness and friability test) . 4.The appearanc e of the tablet should be elegant and its weight, size and appearance should be consistent (Visual observation, weight variation, thickness and diameter of the tablet). 5.The tablet should be packed in a safe manner. Quality control tests and specifications for some of these properties are given in pharmaco poeias. The most important for these are; - Weight uniformity, - Dose uniformity, - The drug release in terms of tablet disintegration and drug dissolution, - Resistance of tablets to fracture in terms of friability and harness testing, and - The microbial quality of the product. These factors must be controlled during production (in-process control) and verified after producti on. Some test methods are described in the pharmacopeias; others are not and thus are referred to as "non-compendial " tests.
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Quality of tablets should fulfill certain specifications:1. The tablet should include the correct dose of the drug
(Weight uniformity and content uniformity test).
2. The drug should be released from the tablet in a controlledand reproducible way (Dissolution test).
3. The tablet should show sufficient mechanical strength towithstand fracture and erosion during manufacturing and
handling (Hardness and friability test).
4. The appearance of the tablet should be elegant and itsweight, size and appearance should be consistent (Visual
observation, weight variation, thickness and diameter of the
tablet).
5. The tablet should be packed in a safe manner.
Quality control tests and specifications for some of theseproperties are given in pharmacopoeias. The most important
for these are;- Weight uniformity,- Dose uniformity,- The drug release in terms of tablet disintegration and drug
dissolution,- Resistance of tablets to fracture in terms of friability and
harness testing, and- The microbial quality of the product.
These factors must be controlled during production (in-process
control) and verified after production. Some test methods aredescribed in the pharmacopeias; others are not and thus arereferred to as "non-compendial" tests.
Official Quality control tests for tablets (Compendialtests)British Pharmacopoeia (B.P.) & US Pharmacopoeia (USP) 1- Uniformity of content of active ingredient (Uniformity of weight
USP mentions some Q.C. tests before the powder is compressede.g. powder fineness, density,…
Non-Compandial tests There are many tests are frequently applied to tablets for whichthere are non-pharmacopoeial requirements but will form a partof manufacture's owner product specifications.
1- Tablet thickness.2- Tablet hardness.
I- Non-Compandial tests:
1. Tablet thickness Tablet thickness is important for tablet packaging; very thicktablets affect packaging either in blisters or plastic containers.
The tablet thickness is determined by the diameter of the die, theamount of fill permitted to enter the die and the force or pressureapplied during compression. The thickness of the tablet may be measured manually or by automatic equipment.
A part of Good Manufacturing Practice (GMP), the production run ismonitored under control chart. At regular intervals (10-15 min.)during the course of manufacturing, the operator must samplespecified number of tablets for testing (in-process control) e.g.weight of tablet, tablet thickness, friability, disintegration time, …
In general, tablets should be sufficiently hard to resist breakingduring normal handling, packaging and shipping, and yet softenough to disintegrate properly after swallowing.
Hardness of the tablet is controlled by (or is affected by) thedegree of the pressure applied during the compression stage.
Hardness is an important criterion, since it can affectdisintegration and dissolution.
Special hardness testers are used for this purpose (manually ormotor driven testers).
The test measures crushing strength property defined as thecompressional force applied diametrically to a tablet which justfracture (break) it. (The Figure below)
(N.B. In manual hardness testers, the strain rate depends on theoperator).
"Monsanto" Tablet hardness tester
A force of about 4 Kg (may be measured in Kg) is considered theminimum requirement for a satisfactory tablet.Certain tablets such as lozenges and buccal tablets that are intended to dissolve slowly intentionally are made hard; others
USP mentions some Q.C. tests before the powder is compressede.g. powder fineness, density, …
1- Uniformity of active ingredient:
(WHY?) To ensure a constant dose of drug between individualtablets. Traditionally, dose variation between tablets is tested in twoseparate tests;
1- Weight uniformity 2- Content uniformity
If the drug forms greater part of the tablet, any variation in thetablet weight obviously indicates a variation in the activeingredient. (Weight uniformity test)
If the drug is potent (USP specifies 50 mg of the active ingredientor less), the excipients form the greater part of the tablet weightand the correlation between the tablet weight and amount of theactive ingredient can be poor, in this case another test (Content uniformity ) must be performed.
A. Weight uniformity B.P. design:
- Weigh 20 tablets individually (i.e. determine the weight of eachtablet alone; X1, X2, X3… X20)
- Calculate the average weight of tablets ( = Total weight of tablets )
Number of tablets
Average weight of tablets (X) = (X1+X2 +X3+…+ X20)/20
Not more than two of the individual weights (for example, X1 andX7) deviate from the average weight ((((XXXX)))) by more than the %deviation shown in the table below and none deviates by morethan twice that %:
Pharmaceutical form Average tabletweight (X)
Percentage deviation
Tablets
80 mg or less 10
> 80- < 250 mg 7.5250 mg or more 5
(IMPORTANT) Example for Weight uniformity test (B.P. design):
% Error for a tablet=Difference between Actual tablet weight & Average tablet weight x 100
Average tablet weight
% error for tablet 1= 201.75 - 200/201.75 x 100= 0.86%% error for tablet 2= 202 - 201.75/201.75 x 100= 0.12%% error for tablet 3= 201.75 - 190/201.75 x 100= 5.82%% error for tablet 4= 205 - 201.75/201.75 x 100= 1.61%% error for tablet 5= ……………
Calculate % error for each tablet
Pharmacopoeial requirement:
Not more than two of the individual tablet weights deviate fromthe average weight (X) by more than 7.5% according to thefollowing table and none deviate by double this %:
Test result: Only one tablet (tablet number 12) deviated >7.5%,and this deviation (%error 9.04 %) is less than 15 %, i.e. tabletspassed this test successfully
B. Content uniformity USP defines content uniformity test for tablets containing 50 mgor less of drug substance in case of uncoated tablets and forall sugar coated tablets regardless to the drug content.
USP design:
Ten tablets are individually assayed for their content (accordingto the method described in the individual monograph) The requirements for content uniformity are met if the amount of the active ingredient in each tablet lies within the range of 85-115 % of the label claim.
(If one or more tablet does not meet these criteria, additional tests asprescribed in the USP are required)