CoChat
Sign Up
Cited by 6Pharmacy and Medical PracticesPatient Safety and Medication ErrorsPharmaceutical studies and practices

Does splitting a tablet obtain an accurate dose? A systematic review and meta‐ analysis

Open access
Chaudhri, Kanika, Kearney, Madeleine, Di Tanna, Gian Luca, Gnanenthiran, Sonali R., Day, Richard O., Rodgers, Anthony, Atkins, Emily R.·2022·Journal of Pharmacy Practice and Research
DOI 10.1002/jppr.1843
Open this paper in CoChat — free accountOpen PDF

Abstract

Background: Tablet splitting is a widely prevalent practice resulting from the need to alter doses into two or more parts and optimise medicine in individual patients. If a tablet is split unequally problems may arise. Aim: The aim of the study was to summarise the literature measuring the effect of tablet splitting on dose accuracy. Method: MEDLINE, EMBASE, CINAHL and Cochrane were searched and studies published prior to January 2020 investigating the effect of splitting tablets on dose accuracy were included. Studies investigating any drug, where the tablet was split, were potentially eligible. Two independent reviewers conducted the screening and extracted the data. Meta‐analyses assessing the effect of tablet splitting on dose accuracy were performed. (Study registration: PROSPERO CRD42018106252). Results: Of 25 included studies, 16 examined the effect of tablet splitting on weight of the tablet, one on drug concentration and eight examined both. Meta‐analysis found small variation between split tablets (0.87% weight variation, 95% confidence interval 0.63%–1.11% and 0.24% drug content variation, 95% confidence interval 0.06%–0.43%). There was some inconsistency across trial results for weight but not for drug content variation (I2 50% and I2 1%, respectively). Splitting method and tablet characteristics were predictors of accuracy. Conclusion: Although tablet splitting may influence dose accuracy, this analysis suggests that the weight and drug content variation is minimal, regardless of method and tablet characteristics. Additional studies, such as those examining drug plasma concentrations and effect on patient health outcomes for example blood pressure and cholesterol levels, are needed to better understand the role of tablet splitting on dose accuracy.

AI snapshot

Written from the paper’s full text.

TL;DR

This systematic review and meta-analysis of 25 laboratory-based studies found that tablet splitting produced small overall variation in split-tablet weight and drug content. Method of splitting and tablet characteristics influenced accuracy, but clinical outcomes and patient satisfaction were largely unmeasured.

Key findings

  • Pooled mean weight variation among split tablets was 0.87% (95% CI 0.63–1.11%; I² = 50%), and pooled mean drug content variation was 0.24% (95% CI 0.06–0.43%; I² = 1%).
  • By splitting method, manual splitting had the least weight variation (0.44%, 95% CI 0.00–1.00%), while a tablet splitter had the least drug content variation (0.13%, 95% CI 0.00–0.36%); sharp tools had greater weight variation (1.43%, 95% CI 0.74–2.11%).
  • Scored tablets had less variation than unscored tablets (weight 0.72% vs 1.09%; drug content 0.29% vs 0.87%), and oval tablets had less variation than round tablets (weight 0.54% vs 0.99%; drug content 0.48% vs 2.36%).
  • No included papers reported health outcomes from ingesting split tablets; one study noted almost three-quarters of patients had plasma drug concentrations outside the optimal range, and another reported 96.8% of volunteers would prefer a lower-dose formulation rather than splitting.

Methods

  • Systematic review and meta-analysis registered with PROSPERO (CRD42018106252), reported per PRISMA 2020; MEDLINE, EMBASE, CINAHL, and Cochrane were searched from database start to January 2020, with reference-list and citation searches.
  • Eligible studies investigated any drug where tablets were split, cut, or broken, with the whole unbroken tablet as comparator; 25 studies were included, all laboratory-based, covering 6670 split tablets and 116 different drugs.
  • Meta-analyses of proportions used fixed- and random-effects models with a binomial distribution, continuity correction of 0.5 for zero numerators, Wilson Score 95% CIs, subgroup analyses by splitting method and tablet characteristics, and Stata 15 with the metaprop function.

Limitations

  • The authors state that requiring dose accuracy by weight or drug content for inclusion may have omitted studies relevant to secondary outcomes; variation in splitting methods and user experience could add unaccounted variance, though subgroup analyses were performed; and they were limited by eligible-study quality, including no randomised trials, limited patient-satisfaction reporting, and few drug-content studies.
  • Evident from the text: all included studies were laboratory-based, no randomised controlled trials met eligibility, and none reported health outcomes or patient satisfaction/tolerability of ingesting split tablets.
  • Evident from the text: weight-variation results showed some inconsistency across trials (I² = 50%), and the paper reports differing counts of studies assessing weight versus drug content in the abstract versus results.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1002/jppr.1843

Cites

41 of 41 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

4 of 10 cited sources checked · 1 supported · 0 flagged · accuracy not yet measured

  • Premisecitation

    There is limited literature summarising the evidence available on obtaining the correct dose upon splitting tablets.

    “currently there is limited literature summarising the evidence available on obtaining the correct dose upon splitting tablets.”
    Quote in the paperSubstantial claim1 of 2 sources checked
    • cites [13] source
    • cites [14] source

      The General Discussion (page unavailable) says there is a dearth of evidence about dosage-form manipulation in children, and the dose-accuracy section reviews studies of split-tablet weight and drug content. It does not establish that literature *summarising* tablet-splitting dose accuracy is limited generally; its stated evidence gap is specifically about paediatric practice. (LLM, conf=0.78)

      Experimental — accuracy not yet measured
  • Findingown data

    Manual splitting had the least weight variation (0.44%, 95% CI 0.00-1.00%) compared with a tablet splitter (0.58%, 95% CI 0.35-0.82%) or a sharp tool (1.43%, 95% CI 0.74-2.11%).

    “Manually splitting had the least weight variation (0.44%, 95% CI 0.00-1.00%)compared to splitting the drug using a tablet splitter (0.58%, 95% CI 0.35-0.82%)or sharp tool (1.43%, 95% CI 0.74-2.11%).”
    Quote in the paperSubstantial claim
  • Findingown data

    Coated tablets had greater weight variation (1.15%, 95% CI 0.38-1.91%) than uncoated tablets (0.65%, 95% CI 1.16-1.15%).

    “coated tablets had greater weight variation (1.15%, 95% CI 0.38-1.91%)than uncoated tablets (0.65%, 95% CI 1.16-1.15%).”
    Quote in the paperNot a substantial claim
  • Findingown data

    The mean drug content variation of a split tablet was 0.24% (95% CI 0.06-0.43%).

    “The mean drug content variation of a split tablet was 0.24% (95% CI 0.06-0.43%,I 2 1%, Figure 2b).”
    • Also stated in: § Abstract · plain
      “and 0.24% drug content variation, 95% confidence interval 0.06%-0.43%”
    Quote in the paperSubstantial claim
  • Findingown data

    Oval shaped tablets had less weight variation (0.54%, 95% CI 0.25-0.83%) than round shaped tablets (0.99%, 95% CI 0.45-1.52%).

    “oval shaped tablets had less variation (weight variation 0.54%, 95% CI 0.25-0.83%;drug content variation 0.48%, 95% CI 0.51-1.48%)than round shaped (weight variation 0.99%, 95% CI 0.45-1.52%;drug content variation 2.36%, 95% CI 0.66-4.06%)tablets.”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim. 15
  • May combine two claims. 6

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The data extraction form was piloted and iteratively optimised by two investigators using three of the included studies.

    “The data extraction form was piloted and iteratively optimised by two investigators (KC, MK) using three of the included studies.16”
    Quote in the paperNot a substantial claim1 of 1 sources checked
    • cites [16] source

      The Methods section (Data collection process) says two reviewers would pilot and optimise the data extraction form. It specifies five randomly selected eligible studies, not three, and describes a plan rather than a completed pilot; it does not say the optimisation was iterative. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Risk of bias of included studies was assessed independently by two investigators using appropriate risk of bias tools.

    “Risk of bias of included studies was assessed independently by two investigators using appropriate risk of bias tools.16”
    Quote in the paperSubstantial claim1 of 1 sources checked
    • cites [16] source

      The Methods section (‘Risk of bias in individual studies’) says two reviewers will assess RCTs in parallel using the Cochrane Risk of Bias Tool and describes a separate quality appraisal tool for other studies. But this paper is a protocol: it proposes those assessments rather than reporting that two investigators assessed the included studies. (LLM, conf=0.88)

      Experimental — accuracy not yet measured

  • Classified as probably not a substantial claim.

    Premisecitation

    Prior research suggested that tablet-splitting processes caused drug and content variation.

    “Prior research suggested that tablet-splitting processes caused drug and content variation, 21”
    Quote in the paperSubstantial claim1 of 1 sources checked

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    In one included study, given the choice, 96.8% of volunteers would prefer a lower-dose formulation rather than splitting a tablet.

    “given the choice, 96.8% of volunteers would prefer a lower-dose formulation rather than splitting a tablet.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] source

  • May combine two claims.

    Findingown data

    There was some inconsistency across trial results for weight (I2 50%) but not for drug content variation (I2 1%).

    “There was some inconsistency across trial results for weight but not for drug content variation (I 2 50% and I 2 1%, respectively).”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    The final analysis included 25 studies.

    “The final analysis included 25 studies.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingnone given

    All included studies were laboratory-based, and no randomised controlled trials met the eligibility criteria.

    “All included studies were laboratory-based studies, but no randomised controlled trials met the eligibility criteria.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingcitation

    In one included study, over three-quarters of participants stated they would pay more for a lower dosage strength, with the median amount being 20% over the original prescription price.

    “over three-quarters of participants interviewed within this study stated that they would pay more for a lower dosage strength, with the median amount being 20% over the original price of the prescription.26”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [26] source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    Small changes in drug content for some drugs, such as warfarin, could conceivably influence outcomes.

    “It is conceivable that small changes in drug content for some drugs, such as warfarin, could influence outcomes.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    A review conducted in 2012 did not focus on a specific population, drug, or disease, but a meta-analysis was not undertaken and an update is needed.

    “A review conducted in 2012 did not focus on a specific population, drug, or disease, but a meta-analysis was not undertaken and an update is needed.15”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [15] source

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The review protocol was registered with PROSPERO (Registration Number: CRD42018106252).

    “The review protocol was registered with PROSPERO (Registration Number: CRD42 018106252).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationown data

    Splitting method and tablet characteristics were determinants (predictors) of dose accuracy, although the differences were marginal.

    “Splitting method and tablet characteristics were predictors of accuracy.”
    • Also stated in: § raising concerns · boosted
      “The meta-analysis demonstrated that the method of splitting and tablet characteristics were determinants of dose accuracy, although the differences were marginal.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Studies were not excluded from analysis because of methodological flaws if they otherwise met inclusion criteria.

    “Studies were not excluded from analysis because of methodological flaws if they otherwise met inclusion criteria.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based). May combine two claims.

    Premisenone given

    Splitting extended-release tablets may result in toxicity due to uncontrolled, rapid release of the active ingredient, or may render the drug ineffective.

    “splitting of extended-release tablets may result in toxicity due to uncontrolled, rapid release of the active ingredient or rendering the drug ineffective.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    Subgroup analyses were conducted to minimise any systematic effects of variation in splitting methods and user experience.

    “subgroup analyses were conducted to minimise any systematic effects of these factors.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Two independent reviewers conducted the screening and extracted the data.

    “Two independent reviewers conducted the screening and extracted the data.”
    • Also stated in: § Study Selection · plain
      “Two researchers (KC, MK) independently screened abstracts and full texts for eligibility according to predefined inclusion and exclusion criteria.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    The data extracted from each study were independently verified by a second investigator.

    “The data extracted from each study were independently verified by a second investigator.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    This systematic review is reported in accordance with the 2020 PRISMA statement.

    “This systematic review is reported in accordance with the 2020 PRISMA statement.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Arnet and Hersberger reported that the majority of scored tablets contained no explicit information on tablet splitting in official sources.

    “Arnet and Hersberger reported the majority of scored tablets contained no explicit information on tablet splitting in official sources.5”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [5] source
19 of 19

  • The paper relies on this without support.

    Weight and drug content variation of split tablets are adequate measures of dose accuracy, so that minimal variation implies acceptable dose accuracy.

    “The primary outcome was the dose accuracy of the split drug either by weight or drug content as a proportion of the tablet.”
1 of 1

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Conflicting confidence intervals for manual splitting

    Major

    The text and Table 2 give different 95% confidence intervals for the same 1.56% drug-content variation estimate.

  • Oval-tablet estimate falls outside its confidence interval

    Minor

    The reported drug-content variation of 0.48% is below its stated 95% confidence interval, which starts at 0.51%.

  • Tablet-splitter drug-content estimate differs between text and table

    Minor

    The text reports 0.13% drug-content variation for tablet splitters, while Table 2 reports 0.12% for the same subgroup.

  • Nidanapu study has conflicting reference numbers

    Minor

    The study is numbered 26 in the study table but 24 in the reference list.

  • Uncoated-tablet confidence interval excludes its estimate

    Minor

    The reported weight variation of 0.65% is outside its stated 95% confidence interval. The interval's bounds are also reversed: 1.16% to 1.15%.

5 of 5

Cites

Flagged first, then by citations

Research works printed but not linked: 1

  1. British Pharmacopoeia Commission, 2001, British Pharmacopoeia

Cited by

Sorted by citations

Related

Authors
Chaudhri, K., Kearney, M., Di Tanna, G. L., Gnanenthiran, S. R., Day, R. O., Rodgers, A., & Atkins, E. R.
Affiliations
  • UNSW Sydney (AU)
  • The George Institute for Global Health UNSW Sydney Australia
  • The University of Sydney (AU)
Corresponding author
Chaudhri, Kanika
ORCID
Venue
Journal of Pharmacy Practice and Research
Publisher
Wiley
Published
2022-12
Volume
52
Issue
6
Pages
411-421
ISSN
  • 0310-6810 (ISSN-L)
  • 1445-937X
  • 2055-2335
DOI
10.1002/jppr.1843
OpenAlex
W4319975563
Semantic Scholar
53e4f690307eadfd752333058be180cdafc2958e
Cited by
6
References
41
Citations by year
2026: 2 · 2025: 3 · 2024: 1
FWCI
0.33
Type
journal article
Language
en
Open access
Licence
Locations
Journal of Pharmacy Practice and Research (publishedVersion, cc-by-nc-nd)
Funders
  • Australian Government
  • University of New South Wales
Topics
  • Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacy and Medical Practices
  • Health Sciences › Health Professions › Emergency Medical Services › Patient Safety and Medication Errors
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
Keywords
tablet splitting, dose accuracy, drug dosing, operator splitting, individualized dosing

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-12.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-12.

Cited sources are checked by gpt-6-sol.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review