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〈905〉 UNIFORMITY OF DOSAGE UNITS

This general chapter is harmonized with the corresponding texts of the European Pharmacopoeia and the Japanese Pharmacopoeia. Portions of the general
chapter text that are national USP text, and are not part of the harmonized text, are marked with symbols (⧫⧫) to specify this fact.
[NOTE—In this chapter, unit and dosage unit are synonymous.⧫]
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. The uniformity of dosage units specification is
not intended to apply to suspensions, emulsions, or gels in unit-dose containers intended for external, cutaneous administration.
The term “uniformity of dosage unit” is defined as the degree of uniformity in the amount of the drug substance among dosage units. Therefore, the
requirements of this chapter apply to each drug substance being comprised in dosage units containing one or more drug substances, unless otherwise
specified elsewhere in this Pharmacopeia.
The uniformity of dosage units can be demonstrated by either of two methods, Content Uniformity or ⧫Weight⧫Variation (see Table 1). The test for Content
Uniformity of preparations presented in dosage units is based on the assay of the individual content of drug substance(s) in a number of dosage units to
determine whether the individual content is within the limits set. The Content Uniformity method may be applied in all cases.
The test for ⧫Weight⧫Variation is applicable for the following dosage forms:

(W1) Solutions enclosed in unit-dose containers and into soft capsules;

(W2) Solids (including powders, granules, and sterile solids) that are packaged in
single-unit containers and contain no active or inactive added substances;

(W3) Solids (including sterile solids) that are packaged in single-unit containers,
with or without active or inactive added substances, that have been pre-
pared from true solutions and freeze-dried in the final containers and are la-
beled to indicate this method of preparation; and

(W4) 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 or, in the case of hard capsules, the capsule contents, except that uni-
formity of other drug substances present in lesser proportions is demon-
strated by meeting the requirements for Content Uniformity.

The test for Content Uniformity is required for all dosage forms not meeting the above conditions for the ⧫Weight⧫Variation test.1

Table 1. Application of Content Uniformity (CU) and Weight Variation (WV) Tests for Dosage Forms

Dose & Ratio of Drug Substance

Dosage Form Type Subtype ≥25 mg and ≥25% <25 mg or <25%

Tablets Uncoated WV CU

Coated Film WV CU

Others CU CU

Capsules Hard WV CU

Soft Suspension, emulsion, or

gel CU CU

Solutions WV WV

Solids in single-unit contain- Single component WV WV

ers
Multiple components Solution freeze-dried in final
container WV WV

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Dose & Ratio of Drug Substance

Dosage Form Type Subtype ≥25 mg and ≥25% <25 mg or <25%

Others CU CU

Solutions in unit-dose con-

tainers ⧫and into soft cap-
sules⧫ WV WV

Others CU CU

CONTENT UNIFORMITY
Select not fewer than 30 units, and proceed as follows for the dosage form designated.
Where different procedures are used for assay of the preparation and for the Content Uniformity test, it may be necessary to establish a correction factor to be
applied to the results of the latter.
Solid Dosage Forms

Assay 10 units individually using an appropriate analytical method. Calculate the acceptance value (see Table 2).
Liquid or Semi-Solid Dosage Forms

Assay 10 units individually using an appropriate analytical method. Carry out the assay on the amount of well-mixed material that is removed from an
individual container in conditions of normal use, and express the results as delivered dose. Calculate the acceptance value (see Table 2).
Calculation of Acceptance Value

Calculate the acceptance value by the formula:

in which the terms are as defined in Table 2.

Table 2

Variable Definition Conditions Value

Mean of individual contents (χ1, χ2,

…, χn), expressed as a percentage of
X the label claim

χ1, χ2, …, χn Individual contents of the units test-

ed, expressed as a percentage of
the label claim

n Sample size (number of units in a

sample)

k Acceptability constant If n = 10, then k = 2.4

If n = 30, then k = 2.0

s Sample standard deviation

RSD Relative standard deviation (the 100s/X

sample standard deviation ex-
pressed as a percentage of the
mean)

M (case 1) to be applied when T Reference value If 98.5% ≤X ≤101.5%, then M = X (AV = ks)
≤101.5

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Variable Definition Conditions Value

If X <98.5%, then M = 98.5% (AV = 98.5 – X + ks)

If X >101.5%, then M = 101.5% (AV = X – 101.5 + ks)

M (case 2) to be applied when T Reference value If 98.5 ≤X ≤T, then M = X (AV = ks)
>101.5
If X <98.5%, then M = 98.5% (AV = 98.5 – X + ks)

If X >T, then M = T% (AV = X – T + ks)

Acceptance value (AV) General formula:

(Calculations are specified above

for the different cases.)

L1 Maximum allowed acceptance val- L1 = 15.0 unless otherwise speci-

ue fied

L2 Maximum allowed range for devia- On the low side, no dosage unit re- L2 = 25.0 unless otherwise speci-
tion of each dosage unit tested sult can be less than [1– (0.01)(L2)] fied
from the calculated value of M M, while on the high side, no dosage
unit result can be greater than [1 +
(0.01) (L2)]M. (This is based on an
L2 value of 25.0.)

T Target content per dosage unit at

the time of manufacture, expressed
as a percentage of the label claim.
Unless otherwise stated, T is
100.0%, or T is the manufacturer's
approved target content per dosage
unit.

⧫WEIGHT
⧫ VARIATION
Carry out an assay for the drug substance(s) on a representative sample of the batch using an appropriate analytical method. This value is result A, expressed
as percentage of label claim (see Calculation of Acceptance Value). Assume that the concentration (weight of drug substance per weight of dosage unit) is
uniform. Select not fewer than 30 dosage units, and proceed as follows for the dosage form designated.
Uncoated or Film-Coated Tablets

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.
Hard Capsules

Accurately weigh 10 capsules individually, taking care to preserve the identity of each capsule. Remove the contents of each capsule by a suitable means.
Accurately weigh the emptied shells individually, and calculate for each capsule the net ⧫weight⧫ of its contents by subtracting the ⧫weight⧫ of the shell from the
respective gross ⧫weight⧫. Calculate the drug substance content of each capsule from the ⧫net weight⧫ of the individual capsule ⧫content⧫ and the result of the
Assay. Calculate the acceptance value.
Soft Capsules

Accurately weigh 10 intact capsules individually to obtain their gross ⧫weights⧫, taking care to preserve the identity of each capsule. Then cut open the
capsules by means of a suitable clean, dry cutting instrument such as scissors or a sharp open blade, and remove the contents by washing with a suitable
solvent. Allow the occluded solvent to evaporate from the shells at room temperature over a period of about 30 minutes, taking precautions to avoid uptake or
loss of moisture. Weigh the individual shells, and calculate the net contents. Calculate the drug substance content in each capsule from the ⧫weight⧫ of product
removed from the individual capsules and the result of the Assay. Calculate the acceptance value.
Solid Dosage Forms Other Than Tablets and Capsules

Proceed as directed for Hard Capsules, treating each unit as described therein. Calculate the acceptance value.
Liquid Dosage Forms

Accurately weigh the amount of liquid that is removed from each of 10 individual containers in conditions of normal use. If necessary, compute the equivalent
volume after determining the density. Calculate the drug substance content in each container from the mass of product removed from the individual containers
and the result of the Assay. Calculate the acceptance value.
Calculation of Acceptance Value

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Calculate the acceptance value as shown in Content Uniformity, except that the individual contents of the units are replaced with the individual estimated
contents defined below.

χ1, χ2, …, χn = individual estimated contents of the units tested,

where χi = wi × A/W

w1, w2, …, wn = individual ⧫weights⧫ of the units tested

A = content of drug substance (% of label claim) ob-

tained using an appropriate analytical method

W = mean of individual ⧫weights⧫ (w1, w2, …, wn)

CRITERIA
Apply the following criteria, unless otherwise specified.
Solid, Semi-Solid, and Liquid Dosage Forms

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.

1 ⧫
European Pharmacopoeia and Japanese Pharmacopoeia text not accepted by the United States Pharmacopeia: Alternatively, products listed in item (4) above that do not meet the 25 mg/25% threshold limit may be tested for
uniformity of dosage units by Mass Variation instead of the Content Uniformity test if the concentration relative standard deviation (RSD) of the drug substance in the final dosage units is not more than 2%, based on process
validation data and development data, and if there has been regulatory approval of such a change. The concentration RSD is the RSD of the concentration per dosage unit (w/w or w/v), where concentration per dosage unit equals
the assay result per dosage unit divided by the individual dosage unit weight. See the RSD formula in Table 2.⧫

Auxiliary Information- Please check for your question in the FAQs before contacting USP.

Topic/Question Contact Expert Committee

<905> UNIFORMITY OF DOSAGE UNITS William E. Brown GCDF2015 General Chapters-Dosage Forms 2015
Senior Scientific Liaison
+1 (301) 816-8380

Most Recently Appeared In:

Pharmacopeial Forum: Volume No. 35(3)

Page Information:

USP42-NF37 - 7079
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