Content Uniformity (CU) or Uniformity of Dosage Units

“Uniformity of Dosage Units” or Content Uniformity (CU) is defined as the degree of uniformity in the amount of the drug substance among dosage units.

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.

The uniformity of dosage units can be demonstrated by either of two methods, Content Uniformity or  Weight Variation (Mass Variation)

Following table describe Application of Content uniformity (CU) and weight variation (WV) tests for Dosage forms.

Dosage form	Type	Drug Substance More than 25 mg or 25 %	Drug Substance Less than 25 mg 25 %
Tablets	Uncoated	WV	CU
	Film Coated	WV	CU
	Other coated	CU	CU
Capsules	Hard	WV	CU
	Soft (Suspension, Emulsion or gel)	CU	CU
	Soft (Solution)	WV	WV
Solid Power		WV	WV
Solution		WV	WV

Content uniformity (CU)

Uniformity of content is an important aspect when it comes to the manufacturing of tablets, powders for parenteral use, ophthalmic inserts, and suspension for injection. It ensures that each dosage form contains the correct amount of active pharmaceutical ingredients (APIs).

To carry out the content uniformity test, a sample of ten tablets or ten single dose units is taken. The assay of each individual unit is then conducted to determine the content of the APIs. The assay value of each unit is recorded, and the target value is set at 100%.

Testing of Content uniformity (CU)

1. Select not fewer than 30 units
2. Perform Assay for 10 units individually using an appropriate analytical method.
3. Calculate the Acceptance value (AV)

How to calculate Acceptance value (AV value ) in content uniformity ?

Calculate the Acceptance value (AV) by following formula:

Acceptance value (AV) = | M – x̅ | + ks

M  — Reference value

• If x̅ <98.5%, then M =  98.5%, 
• If x̅ >101.5%, then M = 101.5%,
• If 98.5% ≤  x̅ ≤ 101.5%, then M = x̅

x̅  — Mean of individual contents

k — Acceptability constant 

• If n = 10, then k = 2.4,
• If n = 30, then k = 2.0

s— standard deviation

WEIGHT VARIATION (WV)

1. Select not fewer than 30 units
2. Accurately weigh 10 tablets individually
3. Calculate the content, expressed as % of label claim, of each tablet from the weight of the individual tablet and the result of the Assay. 
4. Calculate the Acceptance value (AV) by following formula:

Acceptance value (AV) = | M – x̅ | + ks

M : Reference value

• If x̅ <98.5%, then M = 98.5%
• If x̅ >101.5%, then M = 101.5%
• If 98.5% ≤  x̅ ≤ 101.5%, then M = x̅

x̅ : Mean of individual estimated contents

• Xi = individual estimated contents = wi × A / W
• wi = individual weights of the units tested
• A = content of drug substance
• W= mean of individual weights

k : Acceptability constant 

• If n = 10, then k = 2.4,
• If n = 30, then k = 2.0

s:  standard deviation

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. (L1 is 15.0 and L2 is 25.0.)

Conclusion

In conclusion, the uniformity of content test is crucial in ensuring that tablets, powders for parenteral use, ophthalmic inserts, and suspension for injection contain the correct amount of APIs. By following the guidelines set by the European Pharmacopoeia and Indian Pharmacopoeia, manufacturers can maintain the quality and effectiveness of these dosage forms.

Related article : Blend uniformity (BU) analysis