Journal of the American Pharmaceutical Association (1996)
ResearchLack of Medication Dose Uniformity in Commonly Split Tablets
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)
- et al.
Breaking tablets in half
Lancet
(1984) 3 HMOs ask patients to save money by splitting pills
Baltimore Sun.
(23 March 2000)
Cited by (77)
Comparison of tablet splitting techniques for dosing accuracy of nebivolol tablets: Hand splitting versus tablet cutter and knife
2021, Saudi Pharmaceutical JournalPreparation and application of subdivided tablets using 3D printing for precise hospital dispensing
2020, European Journal of Pharmaceutical SciencesCitation Excerpt :Powdering involves crushing commercial tablets into fine powder and then visually dividing them into several parts, which also has problems of dose inaccuracy (Conroy, 2003). For drugs with narrow therapeutic windows such as aminophylline or phenobarbital, subdivision by milling may increase the incidence of poisoning events because of dose inaccuracy (Teng et al., 2002). In addition, the powder may have poor taste and poor patient compliance.
A systematic review of the use of dosage form manipulation to obtain required doses to inform use of manipulation in paediatric practice
2017, International Journal of PharmaceuticsCitation Excerpt :Splitting tablets into two or three parts was reproducible with relative standard deviations of 0.8–1.5%. The presence of a score line does not guarantee an even subdivision of tablets (Footitt, 1983; Hill et al., 2009; Polli et al., 2003; Rashed et al., 2003; Rosenberg et al., 2002; Teng et al., 2002; Zaid and Ghosh, 2011; Horn et al., 1999) (Table 3). Uniform splitting was related to the hardness, friability and shape of tablets (Zaid and Ghosh, 2011).
Tablet Splitting of Psychotropic Drugs for Patients with Dementia: A Pharmacoepidemiologic Study in a Brazilian Sample
2015, Clinical TherapeuticsCitation Excerpt :However, some experimental evaluations of pharmaceutical parameters of psychotropic drugs after tablet splitting have been published; most found no significant variations in the aspects assessed. Three studies of paroxetine and sertraline,21–23 2 of citalopram,21,24 and 1 each of donepezil,22 lorazepam,25 risperidone,22 and trazodone22 found no significant differences in weight uniformity between tablet halves. Conversely, 4 studies found significant negative effects on weight uniformity in half-tablets of phenobarbital,26,27 gabapentin,28 and venlafaxine.22
Accuracy of tablet splitting: Comparison study between hand splitting and tablet cutter
2014, Saudi Pharmaceutical JournalCitation Excerpt :As for policy implications, we concur with previous scientific recommendations (Teng et al., 2002) that manufacturers make it possible to avoid splitting, by introducing a wider range of tablet doses or liquid formulations.
See related articles on pages 160 and 200.
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.