[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 topical 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 in the individual monograph.

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 is based on the assay of the individual content of drug substance(s) in a number of individual 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 Content Uniformity is required for those dosage forms described in (C1)–(C6) below:

The test for Weight Variation is applicable for the following dosage forms:

The test for Content Uniformity is required for all dosage forms not meeting the above conditions for the Weight Variation test. Where compliance with the Content Uniformity test is required, then, by application of the provision for use of alternative methods provided in the General Notices section of this Pharmacopeia, it is possible for manufacturers to ensure this compliance by application of the Weight Variation test where the concentration relative standard deviation (RSD) of the drug substance in the final dosage units is not more than 2%. This RSD determination may be based on the manufacturer's process validation and product development data. 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. Where the Weight Variation test is used in this way, the product must, if tested, nevertheless comply with the official compendial test for Content Uniformity.

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

Select not fewer than 30 units, and proceed as follows for the dosage form designated. Where the amount of drug substance in a single dosage unit differs from that required in the Assay, adjust the degree of dilution of the solutions and/or the volume of aliquots so that the concentration of the drug substances in the final solution is of the same order as that obtained in the Assay procedure; or, in the case of a titrimetric assay, use a titrant of a different concentration, if necessary, so that an adequate volume of titrant is required (see Titrimetry 541); see also Procedures under Tests and Assays in the General Notices and Requirements. If any such modifications are made in the Assay procedure set forth in the individual monograph, make the appropriate corresponding changes in the calculation formula and titration factor.

Where a special Procedure for content uniformity is specified in the test for Uniformity of dosage units in the individual monograph, make any necessary correction of the results obtained as follows.

Variable	Definition	Conditions	Value
X	Mean of individual contents (1, 2, … , n), expressed as a percentage of the label claim
1, 2, … , n	Individual contents of the units tested, 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 sample standard deviation expressed as a percentage of the mean)
M (case 1) to be applied when T 101.5	Reference value	If 98.5% X 101.5%, then	M = X (AV = ks)
		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 >101.5	Reference value	If 98.5 X T, then	M = X (AV = ks)
		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 value		L1 = 15.0 unless otherwise specified in the individual monograph
L2	Maximum allowed range for deviation of each dosage unit tested from the calculated value of M	On the low side, no dosage unit result can be less than [1 – (0.01)(L2)]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.)	L2 = 25.0 unless otherwise specified in the individual monograph
T	Target content per dosage unit at the time of manufacture, expressed as a percentage of the label claim. For purposes of this Pharmacopeia, unless otherwise specified in the individual monograph, T is the average of the limits specified in the potency definition in the individual monograph.

Select not fewer than 30 dosage units, and proceed as follows for the dosage form designated. The result of the Assay, obtained as directed in the individual monograph, is designated as result A, expressed as % of label claim (see Calculation of Acceptance Value). Assume that the concentration (weight of drug substance per weight of dosage unit) is uniform. [note—Specimens other than these test units may be drawn from the same batch for assay determinations.]

1, 2, ... , n	=	individual estimated contents of the units tested, wherei = wi × A / W ,
w1, w2, ... , wn	=	individual weights of the units tested, for weight variation,
A	=	content of drug substance (% of label claim) determined as described in the Assay, and
W	=	mean of individual weights (w1, w2, ... , wn) of the units used in the Assay.

Apply the following criteria, unless otherwise specified in the individual monograph.

Limit A (if the average of the limits specified in the potency definition in the individual monograph is 100.0 percent or less)—Unless otherwise specified in the individual monograph, the requirements for dosage uniformity are met if the amount of the drug substance in each of the 10 dosage units as determined from the Content Uniformity method lies within the range of 85.0% to 115.0% of the label claim, and the RSD is less than or equal to 6.0%.

Limit B (if the average of the limits specified in the potency definition in the individual monograph is greater than 100.0 percent)—

Limit A (if the average of the limits specified in the potency definition in the individual monograph is 100.0 percent or less)—Unless otherwise specified in the individual monograph, the requirements for dosage uniformity are met if the amount of the drug substance in not fewer than 9 of the 10 dosage units as determined from the Content Uniformity method (or, in the case of solutions for inhalation packaged in glass or plastic ampuls and intended for use in nebulizers, from either the Content Uniformity or the Weight Variation method) lies within the range of 85.0% to 115.0% of label claim, and no unit is outside the range of 75.0% to 125.0% of label claim, and the RSD of the 10 dosage units is less than or equal to 6.0%.

Limit B (if the average of the limits specified in the potency definition in the individual monograph is greater than 100.0 percent)—