💊 Uniformity of dosage units
In short
Determination of uniformity of active substance content in individual dosage units (tablets, capsules). The test is performed according to European Pharmacopoeia 2.9.40; Method: Content Uniformity (CU) or Mass Variation (MV). The procedure comprises 5 steps (about 2 h 50 min–3 h 50 min in total); it is used for: Quality control of tablets and capsules — batch release, Drug registration — stability testing, Tableting process control (in-process control).
At a glance
- Standard: European Pharmacopoeia 2.9.40
- Category: Pharma
- Procedure steps: 5
- Total time of stages: 2 h 50 min–3 h 50 min
- Method: Content Uniformity (CU) or Mass Variation (MV)
- Number of units L1: 10
- Number of units L2: 30 (if L1 not met)
Overview
Uniformity of dosage units (UDU) is a key test ensuring that each tablet or capsule contains a similar amount of active substance. Ph.Eur. 2.9.40 defines two methods: (1) content uniformity (CU, individual HPLC/UV determination in 10 units) and (2) mass variation (MV, weighing 10 units).
Acceptance criterion: acceptance value (AV) ≤ 15.0 (level L1, 10 units). If AV > 15.0, test is extended to 30 units (L2, AV ≤ 25.0). AV = |M − X̄| + k × s, where M = reference value, X̄ = mean, s = standard deviation, k = 2.4 (n=10) or 2.0 (n=30).
Method principle
Content uniformity: 10 tablets are individually analyzed — each is dissolved/extracted and determined (HPLC or UV-VIS). Mean, standard deviation, and acceptance value AV are calculated. Mass variation: 10 tablets are individually weighed, and substance content is calculated proportionally to mass (requires prior batch assay determination). MV method allowed for tablets ≥25 mg active substance comprising ≥25% of tablet mass.
Applications
- Quality control of tablets and capsules — batch release
- Drug registration — stability testing
- Tableting process control (in-process control)
- Bioequivalence testing of generic drugs
- Quality control of dietary supplements
Key parameters
| Parameter | Value |
|---|---|
| Method | Content Uniformity (CU) or Mass Variation (MV) |
| Number of units L1 | 10 |
| Number of units L2 | 30 (if L1 not met) |
| AV criterion (L1) | ≤ 15.0 |
| AV criterion (L2) | ≤ 25.0 |
Standard
- Standard number
- European Pharmacopoeia 2.9.40
- Title (PL)
- Jednorodność zawartości substancji czynnej w jednostkach dawkowania
- Title (EN)
- Uniformity of dosage units
Step-by-step procedure
-
Sample selection
Randomly select 10 tablets from production batch (10 + 20 spare for L2).
-
Weighing (MV) or extraction (CU)
MV: weigh each tablet individually (0.01 mg). CU: dissolve each tablet separately in solvent.
-
HPLC/UV analysis (for CU)
Determine active substance content in each of 10 tablets by HPLC or UV per monograph.
-
AV calculation
Calculate X̄ (mean), s (std. dev.), M (98.5–101.5% or 101.5% if X̄<98.5%). AV = |M − X̄| + 2.4 × s.
-
Result evaluation
L1: AV ≤ 15.0 → PASSES. AV > 15.0 → proceed to L2 (30 units, k=2.0). L2: AV ≤ 25.0 → PASSES.
Required equipment and apparatus
| Equipment | Example | Indicative price |
|---|---|---|
| HPLC with UV/DAD detector | Agilent 1260, Shimadzu Nexera, Waters Alliance | 200 000–400 000 PLN |
| UV-VIS spectrophotometer | Agilent Cary 60, Shimadzu UV-1900i | 25 000–60 000 PLN |
| Analytical balance (0.01 mg) | Mettler Toledo XPR206DR, Sartorius Cubis II | 15 000–40 000 PLN |
| Ultrasonic bath | Bandelin Sonorex RK 510 | 3 000–8 000 PLN |
| Volumetric flask 100–200 mL | Class A, calibrated | 20–50 PLN/pc |
Reagents, media and consumables
| Reagent | CAS | Details |
|---|---|---|
| Active substance standard (CRM) | — | Ph.Eur. Reference Standard, certified |
| Solvent (methanol/water/buffer) | — | Dependent on product monograph |
| HPLC mobile phase | — | Per monograph (e.g., phosphate buffer + acetonitrile) |
Health and safety (OHS)
- Organic solvents (methanol, ACN) — toxic, flammable. Fume hood.
- Active substances — pharmacologically active, gloves and mask
- Volumetric glassware — cut risk, caution
Frequently asked questions
Which standard describes this test?
The test is performed according to European Pharmacopoeia 2.9.40 — “Uniformity of dosage units”.
How does this method work?
Content uniformity: 10 tablets are individually analyzed — each is dissolved/extracted and determined (HPLC or UV-VIS). Mean, standard deviation, and acceptance value AV are calculated.
What is the measuring range and accuracy?
Method: Content Uniformity (CU) or Mass Variation (MV); Number of units L1: 10; Number of units L2: 30 (if L1 not met); AV criterion (L1): ≤ 15.0.
How long does the test take?
The times given for the individual stages add up to approximately 2 h 50 min–3 h 50 min. The procedure comprises 5 steps.
What equipment is required?
HPLC with UV/DAD detector, UV-VIS spectrophotometer, Analytical balance (0.01 mg), Ultrasonic bath, Volumetric flask 100–200 mL. Indicative cost of the core instrument (HPLC with UV/DAD detector): 200 000–400 000 PLN.
Where is this test used?
Quality control of tablets and capsules — batch release; Drug registration — stability testing; Tableting process control (in-process control); Bioequivalence testing of generic drugs; Quality control of dietary supplements.
What safety precautions apply?
Organic solvents (methanol, ACN) — toxic, flammable. Fume hood.; Active substances — pharmacologically active, gloves and mask; Volumetric glassware — cut risk, caution.
Which laboratory can perform this test?
The test is performed by laboratories accredited to ISO/IEC 17025. On LabCoda you can find them by the standard number Ph.Eur. 2.9.40.