Research
Lack of Medication Dose Uniformity in Commonly Split Tablets

https://doi.org/10.1331/108658002763508489Get rights and content

Objective

To divide 11 commonly split tablets and evaluate the resulting half-tablets for content uniformity.

Design

Pre-post comparison.

Setting

Laboratory. Interventions: A trained individual split tablets of 11 products using a single-edged razor blade and 3 products by hand alone.

Main Outcome Measures

The Uniformity of Dosage Units test published in the United States Pharmacopeia 24 (USP), which applies to whole tablets, was adapted liberally to assess the dose uniformity of the resulting split tablets.

Results

Of the 11 razor-split products, 8 failed the liberal adaptation of the USP uniformity test. No visible tablet features (e.g., scoring) predisposed a product's split tablets to pass or fail the uniformity test. All three hand-split tablets failed the uniformity test and yielded worse results than did razor-split tablets.

Conclusion

The majority of the 11 drug products we tested, when assessed for their ability to be split into half-tablets of equal dose, failed a liberally interpreted USP uniformity test. The practice of dividing tablets to save costs or to improve a dosage regimen may not cause problems for patients using drugs with low toxicity and relatively flat dose-response relationships, but it is not recommended for patients using drugs with more substantial toxicity and steep dose-response efficacy curves.

Section snippets

Objectives

The objective of this study was to divide 11 commonly split tablets and evaluate whether the resulting half-tablets provided equal doses, based on a liberal adaptation of the USP Uniformity of Dosage Units test.

Selection of Tablet Products for Splitting

Eleven tablet products identified through anecdotal reports of which products are commonly split were selected and subjected to splitting:

  • Paxil 40 mg (lot 9258B13) (paroxetine—GlaxoSmithKline).

  • Zestril 40 mg (lot CTB671) (lisinopril—AstraZeneca).

  • Zoloft 100 mg (lot 9JP040A) (sertraline—Pfizer).

  • Glucophage 850 mg (lot MAH93) (metformin—Bristol-Myers Squibb).

  • Glyburide 5 mg (lot 109257A) (Novopharm).

  • HydroDIURIL 50 mg (lot D6811) (hydrochlorothiazide—Merck).

  • Lipitor 20 mg (lot 09609V) and 40 mg (lot

Results

Tables 1 and 2 summarize the performance of the 11 products in the uniformity test when they were split using a razor blade. Table 3 reports the performance of three products that were split by hand.

Of the 11 tablet products evaluated, only 3 (Paxil 40 mg, Zestril 40 mg, and Zoloft 100 mg) passed the uniformity test (Table 1). Splitting these products produced no half-tablets with weights outside the target range of 85% to 100%. Each product also exhibited RSD less than 10%; Paxil 40 mg

Discussion

The old pharmacy adage “right drug, right patient, right dose” articulates a basic goal of pharmacy practice. From a drug product quality perspective, selecting the right dose of a commercially available product is generally as simple as reading the strength on a product label, allowing pharmacists to concentrate their efforts on more complex clinical questions rather than questions of product quality. Pharmacists and patients expect—and rely on—high public health standards with regard to the

Limitations

Our study was subject to two principal limitations. First, only one individual performed tablet splitting. Different results might be obtained if tablets were split by several individuals, and future research might focus on what individual factors contribute to successful tablet splitting. However, the individual who split the tablets in our study was a 25-year-old pharmacy student who had been specially trained to split tablets efficiently. Further, she performed this task in the presence of

Conclusion

The majority of the 11 drug products we tested, when assessed for their ability to be split into half-tablets of equal dose, failed a liberally interpreted USP uniformity test. No visible tablet features (e.g., scoring) indicated whether a product's split tablets would pass or fail the uniformity test. The practice of dividing tablets to save costs or to improve a dosage regimen may not cause problems for patients using drugs with low toxicity and relatively flat dose-response relationships,

References (5)

  • M. Stimpel et al.

    Breaking tablets in half

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  • 3 HMOs ask patients to save money by splitting pills

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    (23 March 2000)
There are more references available in the full text version of this article.

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The authors declare no conflicts of interest or financial interests in any product or service mentioned in this article, including grants, employment, gifts, stock holdings, or honoraria.

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