• LAKSHMI NARASIMHA RAO KATAKAM Department of Analytical Chemistry, Analytical Research and Development, Saptalis Pharmaceuticals LLC, Hauppauge, New York 11788, USA.


A solid oral dosage form (as a tablet) which is an immediate or extended-release dosage form which necessitates the scoring bisect of the tablet. This review discusses the quality attributes and interpretations for the split studies of the various tablet formulations using the analytical techniques. Each method of analysis for the evaluation of split-half tablets in terms of its critical quality attributes discusses in detail explanation of analytical methodology and challenges in formulation development. The results for quantitative analytical evaluation in terms of finished product/stability testing and release of the split-half drug product against the acceptance criterion and also discusses the flowchart guidance for the investigation of out of specification results. The present article provides an insight into the complete analytical evaluation of split-half drug product testing according to the requirements of tablet scoring as per US food and drug administration.

Keywords: Split-half tablet, Analytical testing, Calculation formulae, Acceptance criteria, Investigation of results


1. Ekedahl AB. Patients’ experiences of splitting tablets. Clin Med Res 2013;2:58-62.
2. van Santen E, Barends DM, Frijlink HW. Breaking of scored tablets: A review. Eur J Pharm Biopharm 2002;53:139-45.
3. Dormuth CR, Schneeweiss S, Brookhart AM, Carney G, Bassett K, Adams S, et al. Frequency and predictors of tablet splitting in statin prescriptions: A population-based analysis. Open Med 2008;2:e74-82.
4. Directive 2001/83/EC of the European Parliament and of the Council of 6 November 2001 on the Community Code Relating to Medicinal Products for Human Use. Document European Union; 2001. p. 1-129.
5. Quinzler R, Gasse C, Schneider A, Kaufmann-Kolle P, Szecsenyi J, Haefeli WE, et al. The frequency of inappropriate tablet splitting in primary care. Eur J Clin Pharmacol 2006;62:1065-73.
6. van der Steen KC, Frijlink HW, Schipper CM, Barends DM. Prediction of the ease of subdivision of scored tablets from their physical parameters. AAPS PharmSciTech 2010;11:126-32.
7. Shah RB, Collier JS, Sayeed VA, Bryant A, Habib MJ, Khan MA, et al. Tablet splitting of a narrow therapeutic index drug: A case with levothyroxine sodium. AAPS PharmSciTech 2010;11:1359-67.
8. Mehuys E, Dupond L, Petrovic M, Christiaens T, Van Bortel L, Adriaens E, et al. Medication management among home-dwelling older patients with chronic diseases: Possible roles for community pharmacists. J Nutr Health Aging 2012;16:721-6.
9. Freeman MK, White W, Iranikhah M. Tablet splitting: A review of the clinical and economic outcomes and patient acceptance. Second of a 2-part series. Part 1 was published in may 2012 (Consult pharm 2012;27:239-53). Consult Pharm 2012;27:421-30.
10. Quinzler R, Schmitt SP, Pritsch M, Kaltschmidt J, Haefeli WE. Substantial reduction of inappropriate tablet splitting with computerised decision support: A prospective intervention study assessing potential benefit and harm. BMC Med Inform Decis Mak 2009;9:1-5.
11. Rodenhuis N, De Smet PA, Barends DM. The rationale of scored tablets as dosage form. Eur J Pharm Sci 2004;21:305-8.
12. Guidance for Industry Tablet Scoring: Nomenclature, Labeling, and Data for Evaluation, US Department of Health and Human Services, FDA, Center for Drug Evaluation and Research; 2011. Available from: http://www. fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/ Guidances/UCM269921.pdf. [Last assessed on 2013 Oct 10; Last accessed on 2018 Aug 08].
13. Brown WE. Quality Attributes of Tablets Labeled as Having a Functional Score. Vol. 4., Ch. 705. USP 41-NF 36; 2018. p. 586-8.
14. Freeman MK, White W, Iranikhah M. Tablet splitting: A review of weight and content uniformity. Consult Pharm 2012;27:341-52.
15. Tahaineh LM, Gharaibeh SF. Tablet splitting and weight uniformity of half-tablets of 4 medications in pharmacy practice. J Pharm Pract 2012;25:471-6.
16. Brown WE. Tablet Friability. Vol. 5., Ch. 1216. USP41-NF36; 2018. p. 7634-5.
17. Botros LL. Physical Tests-Water Determination. Vol. 4., Ch. 921. USP41-NF36; 2018. p. 6687-92.
18. Hernandez-Cardoso A. Loss on Drying. Vol. 4., Ch. 731. USP41-NF36; 2018. p. 6485-6.
19. Margareth RC. Marques. Physical Tests-Dissolution. Vol. 4., Ch. 711. USP41-NF36; 2018. p. 6455-7.
20. Brown WE. Disintegration. Vol. 4., Ch. 701. USP41-NF36; 2018. p. 6455-7.
21. Brown WE. Uniformity of Dosage Units. Vol. 4., Ch. 905. USP41-NF36; 2018. p. 6673-7.
22. Ciavarella AB, Khan MA, Gupta A, Faustino PJ. Dose uniformity of scored and unscored tablets: Application of the FDA tablet scoring guidance for industry. PDA J Pharm Sci Technol 2016;70:523-32.
23. Rao KL, Reddy KP. Simultaneous estimation of fluticasone propionate, azelastine hydrochloride, phenylethyl alcohol and benzalkonium chloride by RP-HPLC method in nasal spray preparations. Int J Res Pharm Sci 2010;1:473-80.
24. Rao KL, Reddy KP. Development and validation of a stability-indicating LC method for simultaneous determination of related compounds of guaifenesin, terbutaline sulfate and ambroxol HCl in cough syrup formulation. J Saudi Chem Soc 2014;18:593-600.
25. Dongala T, Katari NK, Palakurthi AK, Jonnalagadda SB. Stability indicating HPLC method for simultaneous quantification of 14 impurities in excedrin tablet formulations and identification of new impurity by LC-MS in accelerated stability studies. Biomed Chromatogr 2019. Doi.org/10.1002/bmc.4608.
26. Thirupathi D, Palakurthi AK, Vytla Y, Katari NK. A novel UPLC-PDA isocratic method for the quantification fulvestrant in oil-based pre-filled syringe injection matrix formulations. J Anal Sci Technol 2019;10:12.
27. Rao KL, Reddy KP. Stability-indicating liquid chromatographic method for the simultaneous determination of ascorbic acid, citric acid, butylated hydroxyanisole, simvastatin and related compounds in pharmaceutical solid dosage form. Int J Anal Pharm Biomed Sci 2014;3:1-10.
28. Rao KL, Reddy KP. Stability-Indicating method for simultaneous determination of polar and non-polar related compounds of zidovudine in drug substance and drug product tablet form. Int J Res Pharm Sci 2015;6:5-14.
29. Rao KL, Rao KP. Development and validation of a stability-indicating LC method for determination of bexarotene in softgel dosage formulation. Chromatographia 2017;80:1211-24.
30. Basha SS, Manikanta S, Jahnavi T. UV spectrophotometric determination of rupatadine fumarate in bulk and tablet dosage form by using single point standardization method. Int J Pharm Pharm Sci 2019;11:120-4.
31. Thota B, Adepu GS, Galla R. Method development, validation and stability studies for the determination of lurasidone hydrochloride in bulk and tablet dosage form by rp-hplc. Int J Pharm Pharm Sci 2018;10:58-63.
32. Sharma D, Singh G, Kumar D, Singh M. Development and validation of spectroscopic method for simultaneous estimation of salbutamol sulphate, ambroxol hydrochloride and cetirizine hydrochloride in combined pharmaceutical tablet formulation: A novel technique for In vitro dissolution studies. Int J Pharm Pharm Sci 2014;6:446-52.
33. Biba E. Residual Solvents. Vol. 4. Ch. 467. USP41-NF36; 2018. p. 6222-37.
34. Impurities Guideline for Residual Solvents, International Conference on Harmonization; 2016. p. 1-34.
35. Tirumalai RS. Microbiological Examination of Non-sterile Products: Microbial Enumeration Tests. Vol. 4., Ch. 61. USP41-NF36; 2018. p. 5965-71.
36. Tirumalai RS. Microbiological Examination Of Non-sterile Products: Tests for Specified Microorganisms. Vol. 4., Ch. 62. USP41-NF36; 2018. p. 5971-8.
37. Zaidi K. Elemental Impurities-Limits. Vol. 4., Ch. 232. USP41-NF36; 2018. p. 6147-51.
38. Zaidi K. Elemental Impurities-Procedure. Vol. 4., Ch. 233. USP41-NF36; 2018. p. 6151-5.
39. Guidelines for Elemental Impurities, International Conference on Harmonization; 2014. p. 1-73.
93 Views | 30 Downloads
How to Cite
LAKSHMI NARASIMHA RAO KATAKAM. “SPLIT-HALF TABLETS: A COMPLETE REVIEW FOR ANALYTICAL TESTING”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 12, no. 9, July 2019, pp. 27-38, https://innovareacademics.in/journals/index.php/ajpcr/article/view/34601.
Review Article(s)