Blend uniformity is a function of both the formulation and mixing action. Once the formulation is optimized from a theoretical process standpoint, blend uniformity must be validated during piloting and scale-up. From a manufacturer’s perspective; poor uniformity generates unacceptable amounts of discarded products, resulting in significant loss of revenue. However, no method currently exists that detects uniformity during the blending process, and as a result the true optimum endpoint is realized rarely.
Various chemical and physical properties of drug substances are affected by their particle size distribution and shapes, also very fine materials are difficult to handle. When large difference in size exists between the active components and excipients, demixing effects can occur making thorough mixing difficult. This effect is greater when the diluents and active raw materials are of significantly different sizes. Not only size but shape too influences the flow and mixing efficiency of powders and granules. Fine materials are relatively more open to attack from atmospheric oxygen, heat, light, humidity and interacting excipients.
It is insufficient to show that adequate distribution of the drug is obtained in the final product; it must be demonstrated within the blend also.
The Acceptance criteria of Blend Uniformity Analysis is as follows,
• RSD (relative standard deviation) of all individual results ≤ 5.0 percent.
• All individual results are within 10.0 percent (absolute) of the mean of the results (90% to 110% of added amount of active drug substance- API).
The term “uniformity of dosage unit” is defined as the degree of uniformity in the amount of the drug substance among dosage units.
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 can be demonstrated by either of two methods,
- Content Uniformity or
- Weight Variation
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 USP criteria for content uniformity is that individual tablet (dosage unit) must contain 85%-115% (assay) of active drug substance - API added in it.