Weight Variation in Pharmaceutical Analysis
To ensure the consistency of dosage units, it is crucial that each unit in a batch contains a drug substance content that falls within a narrow range around the label claim. Dosage units are dosage forms that hold a single dose or a portion of a dose of the drug substance in each unit. Testing the weight variation is one way to ensurce consistency of dosage units.
Weight variation is applicable to the following:
Reference: USP <905> Uniformity of Dosage Units
How to test for weight variation:
Perform an assay on a representative sample of the batch to analyze the drug substance using an appropriate analytical method. This test will yield result A, expressed as a percentage of the label claim (refer to Calculation of Acceptance Value). It is assumed that the concentration or the weight of drug substance per weight of dosage unit is consistent throughout. Ensure that at least 30 dosage units are selected, and follow the instructions below for the designated dosage form.
Uncoated or Film-Coated Tablets
Weigh 10 tablets individually.
Calculate the content as % of label claim of each tablet from the weight of the individual tablet and assay result.
Calculate the acceptance value.
Hard Capsules
Weigh 10 capsules individually, making sure to preserve the identity of each capsule.
Remove the contents of each capsule.
Individually weigh the empty shells, and determine the net weight of each capsule's contents by subtracting the shell weight from the corresponding gross weight.
Calculate the drug substance content of each capsule from the net weight of the individual capsule content and the assay result.
Calculate the acceptance value.
Soft Capsules
Weigh 10 intact capsules individually to obtain their gross weights, making sure to preserve the identity of each capsule.
Cut open the capsules using 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 naturally at room temperature for approximately 30 minutes, while taking precautions to prevent moisture absorption or loss.
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 assay result.
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
Weigh the amount of liquid 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 assay result.
Calculate the acceptance value.
How to calculate the acceptance value: The acceptance value is |M-X| + ks, except that the individual contents of the units are replaced with the individual estimated contents below.
Reference: USP <905> Uniformity of Dosage Units
Requirement to pass:
Acceptance value must be less than or equal to L1%
If acceptance value > L1%, test additonal 20 units and calculate 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
Feeling overwhelmed? Simplify the process with our weight variation calculator. Quickly perform these calculations and make your life easier!
Preview of Weight Variation Calculator
Simply input the gross and shell weights of the 10 dosage units, along with the % Label Claim result for the assay of a representative sample. The template will automatically calculate the net weight and the estimated % label claim for each dosage unit. These values will then be used to determine the acceptance value, and the template will indicate whether the test has passed or failed.
Read related article on Content Uniformity in Pharmaceutical Analysis.
