Using low-content active ingredients as an indicator of overall blend and tablet uniformities
Blending uniformity studies are becoming more important during product development within the dietary supplement industry . A multivitamin and mineral (MVM) dietary supplement product usually contains more than 15 active ingredients. How do you know if each ingredient in the final blend of the MVM product is uniform? So far, data are scarce, if not absent, to answer this question.
In the pharmaceutical industry, if an active ingredient of a drug product is greater than or equal to 50 milligrams (mg) per dosage form unit or the active ingredient is greater than or equal to 50 percent of the dosage form unit by weight, a blending uniformity study is not required . Among the FDA’s acceptance criteria for blending uniformity of generic drug products are that an active ingredient should be in the range of 90.0 percent to 110.0 percent of the amount specified, and relative standard deviation (RSD) must be no more than 5.0 percent (usually based on testing six to 10 samples) .
Most drug products contain one active ingredient, and some incorporate two or three active ingredients. Whatever the case, the amount of the active ingredient(s) in a pharmaceutical dosage form (tablet or capsule) by weight is usually 2 percent or more . In the dietary supplement industry, however, an MVM tablet may contain more than 15 active ingredients, some of which may account for less than 0.2 percent of the dosage form’s weight. Indeed, some supplement ingredients are present in amounts of less than 0.05 percent. At the other end of the spectrum, the active ingredients used in the highest amounts rarely exceed 50 percent of the dosage form. If we follow the pharmaceutical industry’s standards, our blending uniformity studies must test for nearly all the active ingredients. In this study, the MVM tablet contains 18 active ingredients, in which only calcium carbonate— since its use level exceeds 50 percent by weight—need not be tested. The other 17 active ingredients must be tested. But doing so would take a long time and cost a lot of money, an expense that would eventually be borne by consumers. But we can simplify blending uniformity studies of MVM tablets by making a reasonable assumption: If the active ingredients present in lower amounts are uniform in the final blend, then each active ingredient in the MVM tablet can also be considered to be uniform.Therefore, we only need to test several lower-content vitamin
and mineral active ingredients in the final blend.