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Tablets & Capsules October 2016 19 Zinc sulfate has a much smaller particle size than vita- min D (Table 2) but has better blending uniformity (Table 1). According to the study [4] cited above, zinc sulfate should have poor uniformity due to its smaller par- ticle size, while vitamin D, calcium carbonate, and mag- nesium oxide should have better uniformity because of their larger particle sizes. Why doesn't the electrostatic charge affect the unifor- mity of calcium carbonate, magnesium oxide, and zinc sulfate? Because those minerals are ionic compounds that have both positive and negative charges in their mole- cules, which limits the electrostatic charge generated dur- ing blending and thus its impact on blending uniformi- ties. However, vitamin D is a covalent compound, like warfarin. The electrostatic charge may thus have a greater effect on the motion of vitamin D particles. Therefore, it's likely that some vitamin D molecules adhered to the wall of the sampling thief's cells, which led to a poor uniformity of vitamin D. Taking larger samples from a discharge stream may reduce the effect of electrostatic charge on the uniformity of vitamin D. Table 3 shows the uniformity results from samples collected from discharge streams. The RSDs of blending uniformity for calcium, magnesium, zinc, and vitamin D are less than 5 percent and thus meet the FDA guideline. Furthermore, during discharge, the force of gravity may greatly exceed the electrostatic force, which may explain why the electrostatic charge (force) doesn't affect the blending uniformity of vitamin D. This sampling method is very useful and practicable for pharmaceuticals and dietary supplements. To further verify the effects of the two sampling meth- ods, we conducted content uniformity tests on tablets. We collected a composite sample from each lot and then randomly chose 10 tablets from the sample for testing. Calcium, magnesium, and zinc were analyzed by using an inductively coupled plasma instrument (Optima 5300DV from Perkin Elmer, Waltham, MA), and vitamin D was analyzed using a high-performance liquid chromatogra- phy instrument (Alliance HPLC from Waters Corp., Milford, MA) according to Pharmavite's standard meth- ods. Table 4 shows tablet content uniformity results based on individual tablet tests. All RSDs of the tablet content uniformity were less than 6 percent, which meets the USP standard [5]. These results demonstrate that thief sampling has a big negative impact on the blending uniformity of vitamin D. Weight, thickness, hardness, and disintegration time of the tablets taken from three lots are presented in Table 5. Table 6 shows the assay test results of the finished products. All test results in tables 5 and 6 meet the product spec- ifications, demonstrating that both the formulation and the manufacturing process are robust enough for com- mercial production. Conclusions This blending uniformity study demonstrates that tak- ing samples from discharge streams can more accurately measure the blending uniformity of vitamin D granules, and that the formulation and manufacturing process at Pharmavite can produce a high-quality CaMgZnD tablet that meets the USP standard. T&C Table 3 RSDs of samples taken from the discharge stream of final blends (n=6) Lot number 15060200 15060201 15060202 Calcium 1.00% 3.12% 3.12% Magnesium 1.45% 3.77% 2.25% Zinc 3.87% 0.40% 2.25% Vitamin D 1.75% 1.91% 2.10% Table 4 RSDs of tablet content uniformity (n=10) Lot number 15060200 15060201 15060202 Calcium 2.89% 1.16% 1.56% Magnesium 2.81% 3.80% 2.02% Zinc 3.28% 2.91% 2.25% Vitamin D 5.80% 5.93% 5.70% Table 5 Average tablet weight, thickness, hardness, and disintegration time Lot number Weight (mg) (n=20) Thickness (inch) (n=20) Hardness (Strong-Cobb) (n=20) Disintegration time (min) (n=6) 15060200 1,268.8 0.266 22.0 13.2 15060201 1,262.0 0.271 20.2 11.2 15060202 1,257.8 0.270 21.0 13.0 Table 2 Sieve analysis: Percentages retained on each sieve Mesh size (#) Calcium Magnesium Zinc Vitamin D MCC 14 0% 0% 0% 0% 0% 20 0% 0% 0% 0% 0% 40 20% 36% 0% 5% 0% 60 22% 44% 7% 61% 3% 80 21% 14% 8% 32% 8% 100 8% 2% 5% 2% 7% Pan 29% 5% 80% 1% 82% Total 100% 100% 100% 100% 100%