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Uniformity of Content for Solid & Liquid Dosage forms

This article outlines the uniformity of content for Solid & Liquid dosage forms

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Description

Importance

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 unit’s specification is not intended to apply to suspensions, emulsions, or gels in unit-dose containers intended for external, cutaneous administration.

Definition

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 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 sinunit containers, with or without active or inactive added substances, that have been prepared from true solutions and freeze-dried in the final containers and are labeled to indicate this method of preparation;

(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 uniformity of other drug substances present in lesser proportions is demonstrated by meeting the requirements for Content Uniformity.

Table 1

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

Dosage form

Type

Subtype

Dose & ratio of drug substance

 

25 mg and 25%

<25 mg or <25%

Tablets

Uncoated

 

WV

CU

Coated

Film

WV

CU

Others

CU

CU

Capsules

Hard

 

WV

CU

Soft

Suspensions, emulsion, or gel

CU

CU

Solutions

WV

WV

Solids in single unit containers

Single component

 

WV

WV

Multiple components

Solution freeze dried in final container

WV

WV

Others

CU

CU

Solutions in unit dose containers and into soft capsules

 

 

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:

  | M- X | + ks

In which the terms are as defined in Table 2.

Table 2

Variable

Definition

Conditions

Value

X

Mean of individual contents (c1, c2, ¼ , cn), expressed as a percentage of the label claim

 

 

c1, c2, ¼ , cn

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

 

(n                           1/2 

Σ ( - X)2

i=1         / n-1)

 

RSD

Relative standard deviation (the

sample standard deviation expressed

as a percentage of the

mean)

 

100s/X

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

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:

| M- X | + ks

(Calculations are specified above

for the different cases.)

L1

Maximum allowed acceptance value

 

L1 = 15.0 unless otherwise specified

L2

 

Maximum allowed range for deviation

of each dosage unit

tested from the calculated of M

On the low side, no dosage unit result can be less than value [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

 

 

 

T Target content per dosage unit at

the time of manufacture, expressed

as a percentage of the label claim

 

 

Tags

Uniformity of content, acceptability constant, weight variation, uniformity of dosage unit

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