The term ‘uniformity of dosage unit' is defined as the degree of uniformity in the amount of the active substance among dosage units. To ensure the consistency of dosage units, each unit in a batch should have an active substance content within a narrow range around the label claim.
Application of Content Uniformity (CU) and Mass Variation (MV) test for dosage forms
Dosage units are defined as dosage forms containing a single dose or a part of a dose of an active substance in each dosage unit.
Unless otherwise stated, the uniformity of dosage units specification is not intended to apply to solutions, suspensions, emulsions or gels in single-dose containers intended for local action following cutaneous administration.
The test for content uniformity is not required for multivitamin, single-vitamin and trace-element preparations.
As per BP/EP, the test for mass variation is applicable for the following dosage forms:
(1) Solutions enclosed in single-dose containers and in soft capsules;
(2) Solids (including powders, granules and sterile solids) that are packaged in single-dose containers and contain no added active or inactive substances;
(3) Solids (including sterile solids) that are packaged in single-dose containers, with or without added active or inactive substances, that have been prepared from true solutions and freeze-dried in the final containers and are labelled to indicate this method of preparation;
(4) Hard capsules, uncoated tablets, or film-coated tablets, containing 25 mg or more of an active substance comprising 25 per cent or more, by mass, of the dosage unit or, in the case of hard capsules, the capsule contents, except that uniformity of other active substances present in lesser proportions is demonstrated by meeting content uniformity requirements.
The test for content uniformity is required for all dosage forms not meeting the above conditions for the mass variation test. Alternatively, products that do not meet the 25 mg/25 per cent threshold limit may be tested for uniformity of dosage units by mass variation instead of the content uniformity test on the following condition:
- The concentration Relative Standard Deviation (RSD) of the active substance in the final dosage units is not more than 2 per cent, 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 (m/m or m/V), where concentration per dosage unit equals the assay result per dosage unit divided by the individual dosage unit mass.
RSD and Acceptance Value Calculation formula for Uniformity of Dosage Unit Measurement
Content Uniformity Test Procedure
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 (i.e., Tablet, Capsule)
Assay 10 units individually using an appropriate analytical method. Calculate the acceptance value.
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. Express the results as delivered dose. Calculate the acceptance value.
Mass Variation Test Procedure
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 active substance content, expressed as percentage of label claim, of each tablet from the mass of the individual tablets and the result of the assay. Calculate the acceptance value (mentioned above table).
Hard capsules
Accurately weigh 10 capsules individually, taking care to preserve the identity of each capsule. Remove the contents of each capsule by suitable means. Accurately weigh the emptied shells individually, and calculate for each capsule the net mass of its contents by subtracting the mass of the shell from the respective gross mass. Calculate the active substance content in each capsule from the mass of product removed from the individual capsules and the result of the assay. Calculate the acceptance value (mentioned above table).
Soft capsules
Accurately weigh 10 intact capsules individually to obtain their gross masses, 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 min, taking precautions to avoid uptake or loss of moisture. Weigh the individual shells, and calculate the net contents. Calculate the active substance content in each capsule from the mass of product removed from the individual capsules and the result of the assay. Calculate the acceptance value (mentioned above table).
Solid dosage forms other than tablets and capsules
Proceed as directed for hard capsules, treating each unit as described therein. Calculate the acceptance value (mentioned above table).
Liquid or semi-solid dosage forms
Accurately weigh the amount of liquid or semi-solid 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 active 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 (mentioned above table).
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