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Cited by 23Analytical Methods in PharmaceuticalsPharmaceutical Quality and CounterfeitingPharmaceutical studies and practices

Dose Uniformity of Scored and Unscored Tablets: Application of the FDA Tablet Scoring Guidance for Industry

Ciavarella, A. B., Khan, M. A., Gupta, A., Faustino, P. J.·2016·PDA Journal of Pharmaceutical Science and Technology
DOI 10.5731/pdajpst.2016.006411
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Abstract

PURPOSE: This U.S. Food and Drug Administration (FDA) laboratory study examines the impact of tablet splitting, the effect of tablet splitters, and the presence of a tablet score on the dose uniformity of two model drugs. METHODS: Whole tablets were purchased from five manufacturers for amlodipine and six for gabapentin. Two splitters were used for each drug product, and the gabapentin tablets were also split by hand. Whole and split amlodipine tablets were tested for content uniformity following the general chapter of the United States Pharmacopeia (USP) Uniformity of Dosage Units <905>, which is a requirement of the new FDA Guidance for Industry on tablet scoring. The USP weight variation method was used for gabapentin split tablets based on the recommendation of the guidance. RESULTS: All whole tablets met the USP acceptance criteria for the Uniformity of Dosage Units. Variation in whole tablet content ranged from 0.5 to 2.1 standard deviation (SD) of the percent label claim. Splitting the unscored amlodipine tablets resulted in a significant increase in dose variability of 6.5-25.4 SD when compared to whole tablets. Split tablets from all amlodipine drug products did not meet the USP acceptance criteria for content uniformity. Variation in the weight for gabapentin split tablets was greater than the whole tablets, ranging from 1.3 to 9.3 SD. All fully scored gabapentin products met the USP acceptance criteria for weight variation. CONCLUSION: Size, shape, and the presence or absence of a tablet score can affect the content uniformity and weight variation of amlodipine and gabapentin tablets. Tablet splitting produced higher variability. Differences in dose variability and fragmentation were observed between tablet splitters and hand splitting. These results are consistent with the FDA's concerns that tablet splitting can have an effect on the amount of drug present in a split tablet and available for absorption. LAY ABSTRACT: Tablet splitting has become a very common practice in the United States and throughout the world. Tablets are often split to modify dose strength, make swallowing easier, and reduce cost to the consumer. To better address product quality for this widely used practice, the U.S. Food and Drug Administration (FDA) published a Guidance for Industry that addresses tablet splitting. The guidance provides testing criteria for scored tablets, which is a part of the FDA review process for drugs. The model drugs selected for this study were amlodipine and gabapentin, which have different sizes, shapes, and tablet scores. Whole and split amlodipine tablets were tested for drug content because of a concern that the low-dose strength may cause greater variability. Whole and split gabapentin tablets were tested for weight variation because of their higher dosage strength of 600 mg. All whole tablets met the acceptance criteria for the Uniformity of Dosage Units based on the guidance recommendations. When unscored amlodipine tablets were split by a splitter, all formulations did not meet the acceptance criteria. When fully scored gabapentin tablets were split by hand and by splitter, they met the acceptance criteria. The findings of this FDA study indicated physical characteristics such as size, shape, and tablet score can affect the uniformity of split tablets.

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Crossref · 10.5731/pdajpst.2016.006411

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Authors
Ciavarella, A. B., Khan, M. A., Gupta, A., & Faustino, P. J.
Affiliations
United States Food and Drug Administration (US)
ORCID
Venue
PDA Journal of Pharmaceutical Science and Technology
Publisher
Parenteral Drug Association, Inc.
Published
2016-11-01
Volume
70
Issue
6
Pages
523-532
ISSN
1079-7440 (ISSN-L)
DOI
10.5731/pdajpst.2016.006411
OpenAlex
W2473996994
Semantic Scholar
0ec855aaba9896557d316d926e4f315d2a70c16f
Cited by
23
References
24
Citations by year
2026: 3 · 2025: 3 · 2024: 2 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 2 · 2019: 4 · 2018: 5
FWCI
2.30
Type
journal article
Language
en
Open access
closed
Locations
  • PDA Journal of Pharmaceutical Science and Technology (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Physical Sciences › Chemistry › Analytical Chemistry › Analytical Methods in Pharmaceuticals
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Pharmaceutical Quality and Counterfeiting
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
Keywords
tablet splitting, scored tablets, dose homogeneity, content uniformity, weight variation, amlodipine, gabapentin, dose variation, model drugs, pharmaceutical quality control, generic tablets
MeSH terms
Body Weight, Drug Compounding, Industry, Tablets, United States, United States Food and Drug Administration

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