In the December 2016/January 2017 issue of Chem 13 News, I explored the regulation of active ingredient content in pharmaceutical tablets. Recently, purchasing a bottle of Jamieson 400 IU1 (10 mg) Vitamin D tablets, I was surprised to see “Improved Smaller Tablets” boldly printed on the label in a blue rosette.1 Why make the small tablets even smaller? Tablets containing active ingredients in very low concentration, (e.g., Vitamin D or thyroid hormone) are typically very small. Having as high a concentration of the active ingredient as possible makes it less difficult to meet the regulatory requirement for content variability.
Vitamin D tablets were featured in my article noted above because the active ingredient is present in such low concentration. It requires special equipment and expertise to blend the active ingredient uniformly with the other powder ingredients, to dispense it into unit doses of equal amount, and to perform all necessary analysis, process control and quality control steps to meet the regulation requirement for content variability. The current fentanyl overdose crisis is an extremely tragic example of poor quality blending and unit dose dispensing of a highly potent powder-blend street drug.2
Jamieson is a Canadian company with a strong reputation for quality manufacturing. The parent company, Jamieson Wellness, recently became a publicly traded company on the Toronto Stock Exchange.3 Email queries to Jamieson’s Consumer Affairs Department about the size change of these tablets produced the following rationale — “Jamieson has recently introduced our IMPROVED, Smaller Tablets. They are improved because they are now smaller and easier to swallow.” — and the specifications of size and mass for both the former, larger tablets and the new, smaller tablets. These data has been used in Question 2 below.
In my judgement, the claim that the new tablet is easier to swallow is dubious. The former tablet was so small, that it could be difficult to see or handle, and the new tablet is worse. Far from being difficult to swallow, there is no sensation of having swallowed it, leaving you to wonder whether you put it in your mouth or dropped it on the floor. The new “improved smaller tablet” may be less costly to produce, since the smaller tablets have a higher proportion of Vitamin D and will be less difficult to bring to the required standard (see Question 2).
Student questions
- The IU or International Unit for each vitamin is different. Calculate the IU mass for Vitamin D, given that a 400 IU tablet contains nominally 10ug of Vitamin D. Answer: 25ng.
- The former, larger 400 International Unit tablet (10 ug) had a diameter of 8.7 mm and a mass of 0.230 g, and the proportion of the active ingredient was 0.0043 % by mass. The new tablet has a diameter of 7.5 mm. The new tablet is identical in shape to the old tablet, roughly lenticular (shaped like a lens or a circular, flat lentil bean).
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Calculate the fractional ratio of the new to the old diameter. Answer: 7.5/8.7 = 0.86
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Calculate the ratio of the volume of the new tablet to that of the old tablet, assuming the shapes are identical. Answer: (0.86)3 = 0.64
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Assume that the mass of the new tablet is in the same ratio to the old as is the ratio of the volume of the new tablet to the old tablet. Calculate the mass of the new tablet. Answer: 0.230 g*0.64 = 0.15 g
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Calculate the proportion (% by mass) of the Vitamin D in the new tablet. Answer: (0.000010 g/0.15 g)*100 % = 0.0067%
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Convert the two tablet concentrations from percent by mass to ppm (parts per million) by mass. Calculate the percentage increase in concentration. Answers: 43, 67 ppm; 56%
Notice that a 14% decrease in tablet diameter (Question 2) has produced a 56% increase in concentration.
References
- Vitamin D:Jamieson www.jamiesonvitamins.com/collections/vitamin-d.
- CBC News: www.cbc.ca/news/canada/british-columbia/victoria-fentanyl-testing-pharmacy-uvic-1.4023011.
- Toronto Globe and Mail Report on Business, July 8, 2017).
