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AAPS PharmSciTech

, 21:8 | Cite as

The Influence of Matrix Technology on the Subdivision of Sustained Release Matrix Tablets

  • Maira T. Teixeira
  • Livia Lira Sa-Barreto
  • Stephânia F. Taveira
  • Tais Gratieri
  • Guilherme M. Gelfuso
  • Ricardo N. Marreto
  • Izabel C. Silva
  • Marcilio Cunha-FilhoEmail author
Research Article

Abstract

The subdivision of sustained release tablets is a controversial issue, especially concerning its impact on dissolution profiles. The purpose of this study was to elucidate the behavior upon subdivision of this class of tablets. For this, three common sustained release matrices containing different technologies were selected, e.g., a tablet comprised of a multiple-unit particulate system (MUPS), a lipid matrix tablet, and a polymeric inert matrix tablet. These tablets were studied concerning their physicochemical performance, dissolution rate, and kinetic profile before and after their subdivision. When subdivision occurred in the scoreline, mass variation and mass loss were below the mean values described in the literature. The dissolution of tablets with inert matrices and some lipid tablets that had their matrices preserved along the dissolution was influenced directly by tablet surface area, which increased after the subdivision. Such a result implies possible clinical consequences, especially in the case of drugs with a narrow therapeutic window, such as clomipramine. Conversely, the subdivision of MUPS tablets did not interfere in the dissolution profile since the drug was released from the granules that resulted from tablet disintegration. Hence, MUPS technology is the most recommended to produce sustained release matrix tablets intended for dose adjustment upon subdivision.

KEY WORDS

tablet subdivision sustained release matrix tablet scoreline dissolution rate 

Notes

Funding information

This research was supported by Brazilian agencies FAP-DF, National Council for Scientific and Technological Development-CNPq and CAPES.

References

  1. 1.
    Quinzler R, Gasse C, Schneider A, Kaufmann-Kolle P, Szecsenyi J, Haefeli WE. The frequency of inappropriate tablet splitting in primary care. Eur J Clin Pharmacol. 2006;62(12):1065–73.  https://doi.org/10.1007/s00228-006-0202-3.CrossRefPubMedGoogle Scholar
  2. 2.
    Van Riet-Nales DA, Doeve ME, Nicia AE, 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
  3. 3.
    Araújo M, Sa-Barreto L, Gratieri T, Gelfuso G, Cunha-Filho M. The digital pharmacies era: how 3D printing technology using fused deposition modeling can become a reality. Pharmaceutics. 2019;11(3):128.  https://doi.org/10.3390/pharmaceutics11030128.CrossRefPubMedCentralGoogle Scholar
  4. 4.
    Gupta A, Hunt RL, Khan MA. Influence of tablet characteristics on weight variability and weight loss in split tablets. Am J Heal Pharm. 2008;65(24):2326–8.  https://doi.org/10.2146/ajhp080371.CrossRefGoogle Scholar
  5. 5.
    Teixeira MT, Sá-Barreto LCL, Silva DLM, Cunha-Filho MSS. Overview of regulatory aspects guiding tablet scoring. Rev Panam Salud Publica/Pan Am J Public Heal. 2016;39(6):372–377. https://www.ncbi.nlm.nih.gov/pubmed/27706433
  6. 6.
    Sovány T, Kása P, Pintye-Hódi K. Modeling of subdivision of scored tablets with the application of artificial neural networks. J Pharm Sci. 2010;99(2):905–15.  https://doi.org/10.1002/jps.21853.CrossRefPubMedGoogle Scholar
  7. 7.
    Teixeira MT, Sá-Barreto LCL, Gratieri T, Gelfuso GM, Silva ICR, Cunha-Filho MSS. Key technical aspects influencing the accuracy of tablet subdivision. AAPS PharmSciTech. 2017;18(4):1393–401.  https://doi.org/10.1208/s12249-016-0615-y.CrossRefPubMedGoogle Scholar
  8. 8.
    Pereira GRS, Taveira SF, Cunha-Filho M, Marreto RN. The effects of fillers and binders on the accuracy of tablet subdivision. AAPS PharmSciTech. 2018;19(7):2929–33.  https://doi.org/10.1208/s12249-018-1144-7.CrossRefPubMedGoogle Scholar
  9. 9.
    Arnet I, Hersberger KE. Misleading score-lines on tablets: facilitated intake or fractional dosing? Swiss Med Wkly. 2010;140(7-8):105–10.PubMedGoogle Scholar
  10. 10.
    Temer AC, Taveira SF, Cunha-Filho M, et al. Subdivision of tablets containing modified delivery technology: the case of orally disintegrating tablets. J Pharm Innov. 2018;13(3):261–9.  https://doi.org/10.1007/s12247-018-9323-3.CrossRefGoogle Scholar
  11. 11.
    Erramouspe J, Jarvi EJ. Effect on dissolution from halving methylphenidate extended-release tablets. Ann Pharmacother. 1997;31(10):1123–6.  https://doi.org/10.1177/106002809703101001.CrossRefPubMedGoogle Scholar
  12. 12.
    Sood A, Panchagnula R. Drug release evaluation of diltiazem CR preparations. Int J Pharm. 1998;175(1):95–107.  https://doi.org/10.1016/S0378-5173(98)00268-3.CrossRefGoogle Scholar
  13. 13.
    Wilczyński S, Koprowski R, Duda P, Banyś A, Błońska-Fajfrowska B. Microtomographic studies of subdivision of modified-release tablets. Int J Pharm. 2016;511(2):899–912.  https://doi.org/10.1016/j.ijpharm.2016.07.069.CrossRefPubMedGoogle Scholar
  14. 14.
    Vranic E, Uzunovic A. Influence of splitting on dissolution properties of metoprolol tablets. Bosn J Basic Med Sci. 2009;9(3):245–9.CrossRefGoogle Scholar
  15. 15.
    Zhao N, Zidan A, Tawakkul M, Sayeed VA, Khan M. Tablet splitting: product quality assessment of metoprolol succinate extended release tablets. Int J Pharm. 2010;401(1-2):25–31.  https://doi.org/10.1016/j.ijpharm.2010.09.004.CrossRefPubMedGoogle Scholar
  16. 16.
    Primrose WR, Clee MD, Moody JP, Hockings N. Alteration of pharmacokinetics after halving a slow-release theophylline tablet. Pharmatherapeutica. 1983;3(6):429–32 http://www.ncbi.nlm.nih.gov/pubmed/6622502.PubMedGoogle Scholar
  17. 17.
    Mandal TK. Effect of tablet integrity on the dissolution rate of sustained-release preparations. J Clin Pharm Ther. 1996;21(3):155–7.  https://doi.org/10.1023/A:1016442514205.CrossRefPubMedGoogle Scholar
  18. 18.
    USP 37/NF 32. Official monographs: carbamazepine extended-release tablets. In The United States Pharmacopeial Convention. 2014;27:2123–2124.Google Scholar
  19. 19.
    USP 37/NF 32. Official monographs: trazodone hydrochloride tablets. In The United States Pharmacopeial Convention. 2014;27:5026–5027.Google Scholar
  20. 20.
    Ansari M, Kazemipour M, Talebnia J. The development and validation of a dissolution method for clomipramine solid dosage forms. Dissolution Technol. 2004;11(3):16–24.  https://doi.org/10.14227/DT110304P16.CrossRefGoogle Scholar
  21. 21.
    Shah S, Tejas KG, Nirmal S, et al. Formulation and in vitro evaluation of sustained release tablets of clomipramine hydrochloride. Pharma Science Monit. 2012;3:2222–46.Google Scholar
  22. 22.
    Zhang Y, Huo M, Zhou J, Zou A, Li W, Yao C, et al. DDSolver: an add-in program for modeling and comparison of drug dissolution profiles. AAPS J. 2010;12(3):263–71.  https://doi.org/10.1208/s12248-010-9185-1.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Zar JH. Biostatistical analysis. 5th ed. Pearson Education Limited: United States; 2013.Google Scholar
  24. 24.
    Jaffer KY, Chang T, Vanle B, Dang J, Steiner AJ, Loera N, Abdelmesseh M, Danovitch I, Ishak WW. Trazodone for insomnia: a systematic review. Innov Clin Neurosci. 2017;14(7-8):24–34. http://www.ncbi.nlm.nih.gov/pubmed/29552421.
  25. 25.
    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.  https://doi.org/10.18553/jmcp.2009.15.3.253.CrossRefPubMedGoogle 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.
    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
  28. 28.
    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.  https://doi.org/10.18553/jmcp.2015.21.1.76.CrossRefPubMedGoogle Scholar
  29. 29.
    Cunha-Filho M, Teixeira MT, Santos-Rosales V, Sa-Barreto LL, Marreto RN, Martin-Pastor M, et al. The subdivision behavior of polymeric tablets. Int J Pharm. 2019;568:118554.  https://doi.org/10.1016/j.ijpharm.2019.118554.CrossRefPubMedGoogle Scholar
  30. 30.
    Rodenhuis N, De Smet PAGM, Barends DM. The rationale of scored tablets as dosage form. Eur J Pharm Sci. 2004;21(2-3):305–8.  https://doi.org/10.1016/j.ejps.2003.10.018.CrossRefPubMedGoogle Scholar
  31. 31.
    Abdul S, Chandewar AV, Jaiswal SB. A flexible technology for modified-release drugs: multiple-unit pellet system (MUPS). J Control Release. 2010;147(1):2–16.  https://doi.org/10.1016/j.jconrel.2010.05.014.CrossRefPubMedGoogle Scholar
  32. 32.
    Nollenberger K, Albers J. Poly (meth) acrylate-based coatings. Int J Pharm. 2013;457(2):461–9.  https://doi.org/10.1016/j.ijpharm.2013.09.029.CrossRefPubMedGoogle Scholar
  33. 33.
    Rowe RC, Sheskey PJ, Quinn ME. Handbook of Pharmaceutical 534 Excipients. 6th ed: Pharmaceutical Press; 2009.Google Scholar
  34. 34.
    Costa P, Sousa Lobo JM. Modeling and comparison of dissolution profiles. Eur J Pharm Sci. 2001;13(2):123–33.  https://doi.org/10.1016/S0928-0987(01)00095-1.CrossRefPubMedGoogle Scholar
  35. 35.
    de Alencar RG, de Oliveira AC, Lima EM, da Cunha-Filho MSS, Taveira SF, Marreto RN. Compacted multiparticulate systems for colon-specific delivery of ketoprofen. AAPS PharmSciTech. 2017;18(6):2260–8.  https://doi.org/10.1208/s12249-016-0700-2.CrossRefPubMedGoogle Scholar
  36. 36.
    Güres S, Siepmann F, Siepmann J, Kleinebudde P. Drug release from extruded solid lipid matrices: theoretical predictions and independent experiments. Eur J Pharm Biopharm. 2012;80(1):122–9.  https://doi.org/10.1016/j.ejpb.2011.10.002.CrossRefPubMedGoogle Scholar
  37. 37.
    Gram LF. Clomipramine dose-effect study in patients with depression: clinical end points and pharmacokinetics. Clin Pharmacol Ther. 1999;66(2):152–65.  https://doi.org/10.1016/S0009-9236(99)90053-X.CrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2019

Authors and Affiliations

  • Maira T. Teixeira
    • 1
  • Livia Lira Sa-Barreto
    • 2
  • Stephânia F. Taveira
    • 3
  • Tais Gratieri
    • 1
  • Guilherme M. Gelfuso
    • 1
  • Ricardo N. Marreto
    • 3
  • Izabel C. Silva
    • 2
  • Marcilio Cunha-Filho
    • 1
    Email author
  1. 1.Laboratory of Food, Drug, and Cosmetics (LTMAC), School of Health SciencesUniversity of BrasiliaBrasiliaBrazil
  2. 2.Faculty of CeilândiaUniversity of Brasília (UnB)BrasiliaBrazil
  3. 3.Laboratory of Nanosystems and Drug Delivery Devices (NanoSYS), School of PharmacyFederal University of GoiasGoiâniaBrazil

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