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Tablets & Capsules October 2017 25 covalent compounds, which would make the electrostatic charge have a greater effect on the motion of their parti- cles. As a result, they would be more likely to adhere to the spatula's surface [1]. In order to verify the effects of the sampling error, we conducted content uniformity tests on the tablets. Table 2 shows the results of that testing. According to USP-38, if the calculated acceptance value of the active ingredient—based on 10 dosage units—is less than or equal to 15.0, then the product is considered to meet the USP's quality standard [4]. The test results in Table 2 show that all the acceptance values are less than 15.0, indicating that the vitamin B 12 , folic acid, vitamin D 3 , chromium, and zinc in the MVM tablet product meet the USP's quality standard. Based on the results for tablet content uniformity, we believe that each of the five ingredients (vitamin B 12 , folic acid, vitamin D 3 , chromium chloride, and zinc oxide) was uniform in the final blend. As explained above, the higher RSDs of the vitamin B 12 and vitamin D 3 results in the final blend, as shown in Table 1, may reflect sampling errors during lab analysis. Table 3 lists the weight, thickness, hardness, and disinte- gration time of the tablets taken from the three lots. Table 4 shows the assay test results of the finished products. All test results in tables 3 and 4 meet the product spec- ifications, demonstrating that both the formulation and the manufacturing process are robust enough for com- mercial production. All results in Table 4 appear to sup- port our assumption that if the lower-content active ingredients are uniform in the final blend of an MVM tablet, then each active ingredient in the MVM tablet is likewise homogenous. According to this study, for a low-content ingredient (less than 0.7 percent), RSD may be considered to relax to 7.2 percent from 5.0 percent (the pharmaceutical stan- dard). However, further studies are needed to confirm this change and to demonstrate that uniformity of low- content ingredients can be used as an indicator to verify the uniformity of the other active ingredients. T&C Acknowledgements The authors thank Victor Ramos for manufacturing the three pilot batches and conducting the weighing, blending, sampling, tabletting, and physical testing. We also thank Bill Shultz, Piya Vong, Alice Carbajal, and Johanna Maligaya in Pharmavite's analytical group for conducting all the chemical tests. References 1. Zeng W, Wang D, Roper, D (2016). Effect of sam- pling methods on vitamin D blending uniformity. Tablets & Capsules: 14(7): 17-20. 2. Guidance for Industry (1999). ANDAs: Blend Uniformity Analysis, Draft Guidance. US Department of Health and Human Services, FDA, Center for Drug Evaluation and Research. 3. Muselik I, Franc A, Dolezel P, Gonec R, Krondlova A, Lukasova I (2014). Influence of process parameters on content uniformity of a low dose active pharmaceutical ingredient in a tablet formulation according to GMP. Acta Pharm 64(3): 355-67. 4. General Chapter <905> Uniformity of Dosage Units (2015). USP-38: 675-79. Wenming Zeng, PhD, is a senior formulator of research and development; Dan Wang, PhD, is a scientist of research and development; and Doug Roper is director of quality and product development at Pharmavite, 28310 Livingston Avenue, Valen- cia, CA. Tel. 818 602 0159. Website: www.pharmavite.com. Table 3 Average tablet weight, thickness, hardness, and disintegration time Table 4 Assay test data for active ingredients Weight (mg) (n = 20) Thickness (inch) (n = 20) Hardness (Strong- Cobb) (n = 20) Disintegration time (min) (n = 6) Lot 1 900 0.238 29.5 15.3 Lot 2 901 0.244 27.8 14.9 Lot 3 900 0.251 27.1 9.4 Lot 1 Lot 2 Lot 3 Vitamin A (g) 300.0 303.0 308.0 Vitamin B 1 (mg) 6.6 6.5 6.7 Riboflavin (mg) 5.3 5.3 5.2 Pyridoxine (mg) 2.6 2.7 2.5 Vitamin B 12 (g) 3.6 3.5 3.6 Vitamin C (mg) 41.1 41.7 41.3 Vitamin D 3 (g) 3.5 3.5 3.6 Vitamin E (mg) 4.7 4.7 4.8 Vitamin K 1 (g) 26.6 27.1 26.0 Pantothenic acid (mg) 4.7 4.8 4.8 Niacinamide (mg) 3.6 3.8 3.7 Biotin (g) 31.0 31.2 27.2 Folic acid (g) 109.6 104.7 100.1 Calcium (mg) 216.0 201.0 200.0 Selenium (g) 24.3 25.5 25.7 Iron (mg) 4.9 4.9 5.0 Zinc (mg) 5.0 5.0 5.1 Chromium (g) 12.0 11.8 11.8