Advertisement

AAPS PharmSciTech

, 20:332 | Cite as

Unmet Quality Needs in Oral Drug Delivery: Contrasts of Drug Content and Uniformity on Distinct Approaches for Achieving Individual Dosing

  • Jaqueline Kalleian Eserian
  • Márcia Lombardo
  • Jair Ribeiro Chagas
  • José Carlos Fernandes GaldurózEmail author
Research Article
  • 5 Downloads

Abstract

Individualized dosing is often required in pharmacotherapy, particularly for pediatric and geriatric patients and adjustment of drugs that demand dose adaptation. This study aimed to evaluate critical quality attributes (CQAs) of doses obtained by distinct approaches for achieving individual dosing. Approaches were evaluated as follows: subdivision of tablets by splitter and hand (haloperidol) and delivery by plastic dropper bottle (haloperidol), glass dropper bottle (clonazepam), dosing cup (sodium valproate), and dosing syringe (carbamazepine), including brand name, generic, and similar marketed products. Measuring devices were packaged with their respective product. Drug content uniformity was assessed to each substance according to pharmacopeial methods. Tablets subdivided by splitter had the poorest performance among all approaches, in which doses ranged around 60% of the labeled amount (Acceptance Value = 58.1 and RSD = 23.2%). The greatest performances were observed for the dosing syringe which fulfilled all the requirements for dose precision and for the glass dropper bottle. There were significant differences in dose delivery between manufacturers of the same medicine when measuring the same volume or number of drops. High drug content variability is extremely harmful to pharmacotherapy and may result in therapeutic failure or toxicity. It is crucial that measuring devices and scoring of tablets be checked for functionality and standardized for different manufacturers of the same medicine. Part of the approaches for achieving individual dosing did not meet the quality needs for drug content and uniformity. Yet, our findings show that more accurate and precise dosing can be accessed when using the dosing syringe and glass dropper bottle.

KEY WORDS

individualized medicines oral drug delivery quality control 

Notes

References

  1. 1.
    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(8):721–6.  https://doi.org/10.1007/s12603-012-0028-x.CrossRefPubMedGoogle Scholar
  2. 2.
    Eserian JK, Lombardo M, Chagas JR, Galduróz JCF. Actual versus expected doses of half tablets containing prescribed psychoactive substances: a systematic review. Prim Care Companion CNS Disord. 2018;20(1):17r02211.  https://doi.org/10.4088/PCC.17r02211.CrossRefPubMedGoogle Scholar
  3. 3.
    Wening K, Breitkreutz J. Oral drug delivery in personalized medicine: unmet needs and novel approaches. Int J Pharm. 2011;404(1–2):1–9.  https://doi.org/10.1016/j.ijpharm.2010.11.001.CrossRefPubMedGoogle Scholar
  4. 4.
    Elliott I, Mayxay M, Yeuichaixong S, Lee SJ, Newton PN. The practice and clinical implications of tablet splitting in international health. Tropical Med Int Health. 2014;19(7):754–60.  https://doi.org/10.1111/tmi.12309.CrossRefGoogle Scholar
  5. 5.
    Rosenberg JM, Nathan JP, Plakogiannis F. Weight variability of pharmacist dispensed split tablets. J Am Pharm Assoc (Wash). 2002;42(2):200–5.CrossRefGoogle Scholar
  6. 6.
    Berg C, Ekedahl A. Dosages involving splitting tablets: common but unnecessary? JPHSR. 2010;1:137–41.  https://doi.org/10.1111/j.1759-8893.2010.00020.x.CrossRefGoogle Scholar
  7. 7.
    McDevitt JT, Gurst AH, Chen Y. Accuracy of tablet splitting. Pharmacotherapy. 1998;18(1):193–7.PubMedGoogle Scholar
  8. 8.
    Polli JE, Kim S, Martin BR. Weight uniformity of split tablets required by a Veterans Affairs policy. J Manag Care Pharm. 2003;9(5):401–7.PubMedGoogle Scholar
  9. 9.
    Shah RB, Collier JS, Sayeed VA, Bryant A, Habib MJ, Khan MA. Tablet splitting of a narrow therapeutic index drug: a case with levothyroxine sodium. AAPS PharmSciTech. 2010;11(3):1359–67.  https://doi.org/10.1208/s12249-010-9515-8.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Zaid AN, Al-Ramahi RJ, Ghoush AA, Qaddumi A, Zaaror YA. Weight and content uniformity of lorazepam half-tablets: a study of correlation of a low drug content product. Saudi Pharm J. 2013;21(1):71–5.  https://doi.org/10.1016/j.jsps.2011.12.009.CrossRefPubMedGoogle Scholar
  11. 11.
    Hurst M. Oral medication dispensers in clinical research. J Clin Res Best Pract. 2006;2(9):1–3.Google Scholar
  12. 12.
    Ryu GS, Lee YJ. Analysis of liquid medication dose errors made by patients and caregivers using alternative measuring devices. J Manag Care Pharm. 2012;18(6):439–45.PubMedGoogle Scholar
  13. 13.
    Ph. Eur. 2.9.27. Uniformity of mass of delivered doses from multidose containers. In: Council of Europe, editor, 8th ed. Strasbourg, France; 2014.Google Scholar
  14. 14.
    Suárez-González J, Santoveña-Estévez A, Armijo-Ruíz S, Castillo A, Fariña JB. A high-demanding strategy to ensure the highest quality standards of oral liquid individualized medicines for pediatric use. AAPS PharmSciTech. 2019;20(5):208–11.  https://doi.org/10.1208/s12249-019-1432-x.CrossRefPubMedGoogle Scholar
  15. 15.
    Brazilian Pharmacopoeia. Brazilian Pharmacopoeia. 5th ed. Brazil: Brasilia; 2010.Google Scholar
  16. 16.
    United States Pharmacopeia (USP). The United States Pharmacopoeia 39—the National Formulary 34, 39th ed. Baltimore, United States; 2016.Google Scholar
  17. 17.
    Habib WA, Alanizi AS, Abdelhamid MM, Alanizi FK. Accuracy of tablet splitting: comparison study between hand splitting and tablet cutter. Saudi Pharm J. 2014;22(5):454–9.  https://doi.org/10.1016/j.jsps.2013.12.014.CrossRefPubMedGoogle Scholar
  18. 18.
    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(1):126–32.  https://doi.org/10.1208/s12249-009-9365-4.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Food and Drug Administration. Guidance for industry tablet scoring: nomenclature, labeling, and data for evaluation. 2013. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UCM269921.pdf. Accessed 28 Apr 2019.
  20. 20.
    United States Pharmacopeia (USP). <1221> Teaspoon. The United States Pharmacopoeia 29—the National Formulary 24, 29th ed. Rockville, United States; 2006.Google Scholar
  21. 21.
    Sobhani P, Christopherson J, Ambrose PJ, Corelli RL. Accuracy of oral liquid measuring devices: comparison of dosing cup and oral dosing syringe. Ann Pharmacother. 2008;42(1):46–52.CrossRefGoogle Scholar
  22. 22.
    United States Pharmacopeia (USP). The United States Pharmacopoeia 27—the National Formulary 22, 27th ed. Baltimore, United States; 2004.Google Scholar
  23. 23.
    Hill SW, Varker AS, Karlage K, Myrdal PB. Analysis of drug content and weight uniformity for half-tablets of 6 commonly split medications. J Manag Care Pharm. 2009;15(3):253–61.PubMedGoogle Scholar
  24. 24.
    Helmy SA. Tablet splitting: is it worthwhile? Analysis of drug content and weight uniformity for half tablets of 16 commonly used medications in the outpatient setting. J Manag Care Spec Pharm. 2015;21(1):76–86.PubMedGoogle Scholar
  25. 25.
    Eserian JK, Lombardo M. Potential dose adjustment implications resulting from clonazepam tablet splitting. Saúde (Santa Maria). 2017;43(3):1–7.Google Scholar
  26. 26.
    Tahaineh LM, Gharaibeh SF. Tablet splitting and weight uniformity of half-tablets of 4 medications in pharmacy practice. J Pharm Pract. 2012;25(4):471–6.  https://doi.org/10.1177/0897190012442716.CrossRefPubMedGoogle Scholar
  27. 27.
    van Riet-Nales DA, Doeve ME, Nicia AE, Teerenstra S, Notenboom K, Hekster YA, et al. The accuracy, precision and sustainability of different techniques for tablet subdivision: breaking by hand and the use of tablet splitters or a kitchen knife. Int J Pharm. 2014;466(1–2):44–51.  https://doi.org/10.1016/j.ijpharm.2014.02.031.CrossRefPubMedGoogle Scholar
  28. 28.
    Yin HS, Mendelsohn AL, Wolf MS, Parker RM, Fierman A, van Schaick L, et al. Parents’ medication administration errors: role of dosing instruments and health literacy. Arch Pediatr Adolesc Med. 2010;164(2):181–6.CrossRefGoogle Scholar
  29. 29.
    Yin HS, Parker RM, Sanders LM, Dreyer BP, Mendelsohn AL, Bailey S, et al. Liquid medication errors and dosing tools: a randomized controlled experiment. Pediatrics. 2016;138(4):e20160357.  https://doi.org/10.1001/archpediatrics.2009.269.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Food and Drug Administration. CFR - Code of Federal Regulations Title 21. 2018. https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfcfr/CFRSearch.cfm?fr=210.3. Accessed 16 Mar 2019.

Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Jaqueline Kalleian Eserian
    • 1
    • 2
  • Márcia Lombardo
    • 2
  • Jair Ribeiro Chagas
    • 1
  • José Carlos Fernandes Galduróz
    • 1
    Email author
  1. 1.Departamento de PsicobiologiaUniversidade Federal de São PauloSão PauloBrazil
  2. 2.Centro de Medicamentos, Cosméticos e SaneantesInstituto Adolfo LutzSão PauloBrazil

Personalised recommendations