Tablet Quality Control

-Raditya Weka Nugraheni-

Definitions of QC
• An aggregate of activities (such as design analysis and inspection for
defects) designed to ensure adequate quality especially in
manufactured products (Merriam-Webster)
• "A part of quality management focused on fulfilling quality
requirements" (ISO 9001)
Quality Control (Q.C.)
Quality control is concerned with:
1. sampling,
2. specifications for raw material, and
3. finished product,
4. testing,
5. documentation,
6. Analytical methodologies
7. good laboratory practice.
Universal Test for Drug Products
• 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).
Specific Test for Tablet Dosage Forms
• Volatile Content
• Disintegration
• Dissolution testing
• Tablet Friability
• Tablet Breaking Force
• Uniformity of Dosage Units
Disintegration
All tablets must pass a test for disintegration except Chewable tablets
and some Extended release tablets.

Procedure (USP):
- 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 deg. Celsius
- 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.
 The disintegration apparatus

A cylindrical disk of transparent plastic is also

used if specified in monograph.

Six tubes opened at the upper end and closed by a screen at the lower
Special cases
• Effervescent tablets
• 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.

Disintegration beaker Effervescent tablets

Dissolution testing
Purpose: To determine the suitability between monograph requirements and the
oral dosage forms.

Apparatus (FI V)
- Alat 1: Tipe Keranjang
- Alat 2: Tipe Dayung
- Alat 3: Silinder Kaca Bolak-balik
- Alat 4: sel yang dapat dialiri
Alat 1 Alat 2

Alat 3 Alat 4
Acceptance Criteria for immediate release
tablet
Friability Test
• 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 Test (2)
• 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.
Friability Tester
Tablet Breaking Force
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.
Apparatus
Uniformity of Dosage Units
• 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 Units
• Weight Uniformity
Applicable for: Hard capsules, uncoated tablets, or film-coated tablets,
containing 25 mg or more of a drug substance comprising 25% or more,
by weight, of the dosage unit.  relative standard deviation should not
more than 2%
• Content Uniformity
If the dosage containing < 25mg or <25% of drug in each units, the
content uniformity should be applied:
Acceptance Criteria:
Causes of weight variation
1. The size & distribution of the granules being compressed (presence of
too large or too fine granules).

2. Poor flow and high speed turret speed (incomplete filling of die),.

3. Poor mixing. (Sometimes the lubricants & glidants have not been
well distributed).

4. When lower punches are of unequal lengths, the fill of each die varies
because the fill is volumetric

5. Demixing or segregation of powder constituents of different

crystalinity, size and densities; in direct compression.
2. Content uniformity
USP defines content uniformity test for tablets containing less than < 25
mg or less than < 25% drug substance in case of coated or uncoated
tablets.

● 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%). If not comply,
repeat using 20 more tablets. No one should be 75 – 125% deviation.

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

not required.
Latihan Soal 1
Seorang apoteker di Industri melakukan pengujian disintegrasi tablet
ibuprofen. Spesifikasi tablet yang diharapkan adalah waktu hancur
tidak lebih dari 15 menit. Hasil pengujian sebagai berikut:

Nomor Waktu hancur

Sampel
I 2’13”
2 3’14”
3 4’18”
4 15’30”
5 25’13”
6 5’10”
Latihan Soal 2
Seorang apoteker melakukanpengujian tablet sefiksim. Persyaratan
Farmakope adalah dalam waktu 45 menit, harus larut tidak kurang dari
75% dari jumlah yang tertera pada etiket.

Nomor % terlarut
Sampel
I 74%
2 80%
3 85%
4 82%
5 78%
6 83%
Pengujian tahap II

Nomor % terlarut
Sampel
7 78%
8 83%
9 86%
10 87%
11 85%
12 82%
Latihan Soal 3
Pemeriksaan kerapuhan tablet sefadroksil diperoleh hasil sebagai
berikut:
Nomor Batch % kerapuhan
10023 1,35%
10024 0,75%
10025 Ada 2 tablet yang pecah
Keseragaman Sediaan
Kadar sefadroksil yang tertera di etiket sediaan tablet adalah 250
mg/tablet. Bobot tablet direncanakan 500 mg. Uji keseragaman apakah
yang harus dilakukan? Keseragaman bobot atau kandungan?
Hasil pengujian keseragaman bobot
Tablet Bobot
1 512
2 515
3 495
4 499
5 513
6 489
7 463
8 499
9 501
10 512
Keseragaman Sediaan 2
Kadar metilprednisolon yang tertera di etiket sediaan tablet adalah 8
mg/tablet. Bobot tablet direncanakan 100 mg. Uji keseragaman apakah
yang harus dilakukan? Keseragaman bobot atau kandungan?
Tablet Kandungan mg
1 7,2 mg
2 8,3 mg
3 8,5 mg
4 7,9 mg
5 8,1 mg
6 8,2 mg
7 8,4 mg
8 7,7 mg
9 7,2 mg
10 7,5 mg