microsoft word - lecture 6 cont 09-10

8/7/2019 Microsoft Word - Lecture 6 Cont 09-10

http://slidepdf.com/reader/full/microsoft-word-lecture-6-cont-09-10 1/9

Drug Dosage Forms II (PHR 312)

Lecture 6 (Continued)

Quality control (Q. C.) tests for tablets

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

& Content uniformity)2- Disintegration test.3- Dissolution test.4- Friability test.

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, …



2. Hardness test

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.

Micrometer (tablet thickness) (Tablet thickness & diameter)

Tablet packaging in blisters Tablet packaging in plastic containe



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

such as immediate-release tablets are made soft.



The Electronics Tablet Hardness, Thickness and Diameter Tester

II- Official standards (Q. C. tests) for tablets(Compendial tests):

British Pharmacopoeia (B.P.) & US Pharmacopoeia (USP) 1- Uniformity of content of active ingredient

(Uniformity of weight & Content uniformity)2- Disintegration test.3- Dissolution test.4- Friability test.

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):

- Weigh 20 tablets individually(X1, X2, X3… X20)For example;

(200, 202, 190, 205, 201, 200, 198, 190, 199, 203, 210, 220, 210, 201, 202,199, 190, 195, 200, 200 mg)

- Calculate the average weight of tablets

X = Total weight of tabletsNumber of tablets

Average weight of tablets ( X) = (200+202+190+205+201+200+198+190+199+ 203+210+220+210+ 201+202+ 199+190+195+200+200)/20 = 201.75 mg



% 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)

2019181716151413121110987654321Tablet

no

0.86 0.86 3.34 5.82 1.36 0.12 0.37 4.08 9.04 4.08 0.6 1.36 5.82 1.85 0.86 0.37 1.61 5.82 0.12 0.86 %

error

Pharmaceutical form Average tabletweight (X)

Percentage deviation

Tablets80 mg or less 10

> 80- < 250 mg 7.5

250 mg or more 5



If content uniformity test is required, the weight uniformity test is notrequired

I- Match:

II- Put Write or Wrong:

1- Tablet thickness and hardness test are non-compendial quality control tests

2- Tablet thickness is important for tablet packaging

3- Hardness does not affect disintegration or dissolution of the tablet

4- If content uniformity test is required, the weight uniformity test is not required

5- 1 Kg is a suitable hardness value for a satisfactory buccal tablet

6- Disintegration test is a Pharmacopoeial Requirement for chewable tablets

7- Content uniformity test is essential for all sugar coated tablets regardless totheir drug content

8- In weight uniformity test, tablets are individually assayed for their content

III- What is the only suitable Quality Control Test forDexamethasone tablet (0.5 mg/Tab), to ensure a constant dose of drug between individual tablets

- Friability test

- Dissolution test

- Hardness test

- Weight uniformity

- Content uniformity

1- USP quality control test performed for tablets containing20mg drug to ensure that each include the correct dose

2- Quality control test performed for tablets to ensure thateach shows sufficient mechanical strength

3- Quality control test performed for tablets to ensure that

the drug is released in a controlled and reproducible way



IV- During the in-process quality control testing of tablethardness, many tablet samples were found to be very hard (10 Kg)

What are the possible reasons?What are your suggestions?What are the expected problems with these hard tablets?

Remember

No Quizzes will be held next week during lab sessions (16, 18/11/2009)

Next Quiz (in lab 23, 25/11/2009)

Tablet coating and Quality control tests for tablets

Uxáà j|á{xá Uxáà j|á{xá Uxáà j|á{xá Uxáà j|á{xá

microsoft word - lecture 6 cont 09-10

Documents