Tablet Quality Control
Tablet Quality Control
Raditya Weka Nugraheni
Dyah Rahmasari
Merriam- Webster
GMP
An aggregate of activities (such as design analysis and
inspection for defects) designed to
ensure adequate quality especially in
manufactured products
QC is concerned with sampling, specifications
and testing, and with the organization, documentation and release procedures”. In
essence, QC is a sampling, testing,
monitoring and checking activity.
DEFINITION OF QUALITY CONTROL (QC)
DEFINITION OF QUALITY CONTROL (QC)
ISO
A part of quality 9001
management focused on fulfilling quality
requirements
Quality Control (Q.C.) Quality Control (Q.C.)
Quality control is concerned with:
★ Sampling
★ Specifications for raw material and finished product
★ Testing
★ Documentation
★ Analytical methodologies
★ Good laboratory practice
Product quality attributes for oral dosage forms are important
to ensure that commercialized products meet minimum quality
requirements. Universal tests should be applied to all oral
dosage forms and include Description, Identification,
Strength (assay test), and Impurities (organic, inorganic,
and residual solvents).
Universal
Test for Drug Products
Universal
Test for Drug
Products
Physical tests applicable to tablet formulation
Physical tests applicable to tablet formulation
★ Bulk density / tapped density of powder
★ Powder fineness
★ Loss on drying
★ Size, shape and thickness of tablet
★ Organoleptic properties
★ Disintegration test
★ Dissolution test
★ Tablet friability
★ Hardness test
★ Uniformity of dosage unit
★ Drug release testing
★ Container permeation test
★ Labeling of inactive ingredients
Bulk
Density / Tapped
Density of Powder
Bulk
Density / Tapped
Density of Powder
01 01
TAPPED
DENSITY OF POWDER
TAPPED
DENSITY OF POWDER
The tapped density is an
increased bulk density attained after mechanically tapping a container containing the
powder sample. Tapped density is obtained by mechanically tapping a graduated measuring cylinder or vessel containing a powder sample. After observing the initial powder volume or weight, the measuring cylinder or vessel is mechanically
tapped, and volume or weight
readings are taken until little
further volume or weight
change is observed.
TAPPED DENSITY OF POWDER TAPPED DENSITY OF POWDER
Proceed as described above for the determination of the bulk volume (V0). Secure the cylinder in the holder.
Carry out 10, 500, and 1250 taps on the same powder sample and read the corresponding volumes V10, V500, and V1250 to the nearest graduated unit. If the difference between V500 and V1250 is less than or equal to 2
mL, V1250 is the tapped volume. If the difference between V500 and V1250 exceeds 2 mL, repeat in increments such as 1250 taps, until the difference between succeeding measurements is less than or equal to 2 mL. Fewer taps may be appropriate for some powders, when validated. Calculate the tapped density (g/mL) using the formula m/VF, in which VF is the final tapped volume
Powder Fineness Powder Fineness
02 02
POWDER FINENESS POWDER FINENESS
For practical reasons, sieves are commonly used to measure powder fineness. Sieving is most suitable where a majority of the particles are larger than about 75 µm, although it can be used for some powders having smaller particle sizes where the method can be validated. Light diffraction is also a widely used
technique for measuring the size of a wide range of particles.
Loss on Drying Loss on
Drying
03 03
LOSS ON DRYING LOSS ON DRYING
Unless otherwise directed in the individual monograph, conduct the determination on a 1- to 2-g test specimen. Mix the substance to be tested and, if it is in the form of large particles, reduce the particle size to about 2 mm by quickly crushing before weighing out the test specimen. Tare an appropriate glass-stoppered, shallow weighing bottle that has been dried for about 30 minutes under the same conditions to be employed in the determination and cooled to room temperature in a desiccator. Put the test specimen in the bottle, replace the cover, and accurately weigh the bottle and the contents.
By gentle, sidewise shaking, distribute the test specimen as evenly as practicable to a depth of about 5 mm generally, and not more than 10 mm in the case of bulky materials. Place the loaded bottle in the drying chamber, removing the stopper and leaving it also in the chamber. Dry the test specimen at the temperature and for the time specified in the monograph. When “dry to constant weight” is specified in a monograph, drying shall be continued until two consecutive weighings do not differ by more than 0.50 mg per g of substance taken, the second weighing following an additional hour of drying. Upon opening the chamber, close the bottle promptly, and allow it to come to room
temperature in a desiccator before weighing. If the substance melts at a lower temperature than that specified for the determination of Loss on Drying, maintain the bottle with its contents for 1 to 2 hours at a temperature 5° to 10° below the melting temperature, then dry at the specified temperature.
Size,
Shape, and Thickness
of Tablet Size,
Shape, and Thickness
of Tablet
04 04
Size, Shape and Thickness Size, Shape and Thickness
This is important to facilitate packaging and to decide
which tablet compressing machine to use
Organolepti c
Properties Organolepti
c
Properties
05 05
Organoleptic Properties Organoleptic Properties
Which include color and odor of the tablets
- All tablets must pass a test for disintegration except Chewable tablets and some Extended release tablets.
Procedure:
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°C ± 2 °C
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.
- All tablets must pass a test for disintegration except Chewable tablets and some Extended release tablets.
Procedure:
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°C ± 2 °C
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 Test
Disintegration Test
06
Disintegration Test Apparatus
Disintegration Test
Apparatus
Place 1 tablet in a beaker containing 200 ml of water at (15-25°C;
the tablet should evolve bubbles and when the evolution of gas around the tablet stops, the tablet has disintegrated. The same procedures are performed for other 5 tablets. The tablets comply
with the test if each of the six tablets used disintegrated within 5 min or as justified.
Special Case – Effervescent Tablet
Special Case – Effervescent Tablet
Disintegration vessel Effervescent tablets
Purpose: To determine the
suitability between monograph requirements and the oral
dosage forms.
Apparatus
Type 1: Basket Apparatus Type 2: Paddle Apparatus
Type 3: Reciprocating Cylinder Type 4: Flow-through Cell
Purpose: To determine the
suitability between monograph requirements and the oral
dosage forms.
Apparatus
Type 1: Basket Apparatus Type 2: Paddle Apparatus
Type 3: Reciprocating Cylinder Type 4: Flow-through Cell
Dissolution Test Dissolution Test 07
Type 2 Type 1
Type 4 Type 3
Acceptance Criteria
Acceptance Criteria
The test procedure is applicable to most compressed, uncoated tablets. Friability
determines the ability of tablets to withstand mechanical stresses and their
resistance to chipping and surface abrasion.
The test procedure is applicable to most compressed, uncoated tablets. Friability
determines the ability of tablets to withstand mechanical stresses and their
resistance to chipping and surface abrasion.
Tablet Friability
Tablet Friability 08
Tablet Friability Tablet Friability
Procedure:
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.
Requirements:
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.
Procedure:
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.
Requirements:
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.
A measure of the mechanical integrity, which is the force required to cause them to fail (i.e., break) in a specific plane. The tablets are generally placed between two platens, one of which moves to apply sufficient force
to the tablet to cause fracture. For conventional, round (circular cross- section) tablets, loading occurs across their diameter (sometimes referred
to as diametral loading), and fracture occurs in that plane.
A measure of the mechanical integrity, which is the force required to cause them to fail (i.e., break) in a specific plane. The tablets are generally placed between two platens, one of which moves to apply sufficient force
to the tablet to cause fracture. For conventional, round (circular cross- section) tablets, loading occurs across their diameter (sometimes referred
to as diametral loading), and fracture occurs in that plane.
Hardness Test Tablet Breaking Force
Hardness Test Tablet Breaking Force
09
Purpose: To ensure the consistency of dosage units, each unit in a batch should have a drug substance content within a
narrow range around the label claim. Dosage units are
defined as dosage forms containing a single dose or a part of a dose of drug substance in each unit.
Purpose: To ensure the consistency of dosage units, each unit in a batch should have a drug substance content within a
narrow range around the label claim. Dosage units are
defined as dosage forms containing a single dose or a part of a dose of drug substance in each unit.
Uniformity of Dosage Unit
Uniformity of Dosage Unit
10
*If content uniformity test is required, the weight variation
test is not required.
Uniformity of Dosage Unit
Uniformity of Dosage
Unit
Weight Variation and Content Uniformity
Weight Variation and Content Uniformity
Weight Variation:
Select not fewer than 30 dosage units, and proceed as follows for the dosage form designated.
Accurately weigh 10 tablets individually. Calculate the content, expressed as percentage of label claim, of each tablet from the weight of the individual tablet and the result of the Assay. Calculate the acceptance value
Content Uniformity:
● Determining the amount of drug in a sample of tablets (10)
● The average drug content is calculated
● The content of the individual tablets should fall within specified limits in terms of % deviation from the mean (85 – 115%)
Acceptance value:
Weight Variation:
Select not fewer than 30 dosage units, and proceed as follows for the dosage form designated.
Accurately weigh 10 tablets individually. Calculate the content, expressed as percentage of label claim, of each tablet from the weight of the individual tablet and the result of the Assay. Calculate the acceptance value
Content Uniformity:
● Determining the amount of drug in a sample of tablets (10)
● The average drug content is calculated
● The content of the individual tablets should fall within specified limits in terms of % deviation from the mean (85 – 115%)
Acceptance value:
Acceptance Criteria Acceptance Criteria
The requirements for dosage uniformity are met if the acceptance value of the first 10 dosage units is less than or equal to L1%. If the acceptance value is >
L1%, test the next 20 units, and calculate the acceptance value. The
requirements are met if the final acceptance value of the 30 dosage units
is L1%, and no individual content of any dosage unit is less than [1 (0.01)(L2)]M
nor more than [1 + (0.01)(L2)]M as specified in the Calculation of Acceptance
Value under Content Uniformity or under Weight Variation. Unless otherwise
specified, L1 is 15.0 and L2 is 25.0
Drug
Release Testing
Drug
Release Testing
11 11
Drug Release Testing Drug Release Testing
Which related to dissolution testing
Container Permeation
Test
Container Permeation
Test
12 12
Container Permeation Test Container Permeation Test
See USP <671> CONTAINERS—PERFORMANCE
TESTING
Labeling of Inactive
Ingredients Labeling of
Inactive Ingredients
13 13
Labeling of Inactive Ingredients Labeling of Inactive Ingredients
See USP <1091> LABELING OF INACTIVE
INGREDIENTS
