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Predictive Approach to Understand and Eliminate Tablet Breakage During Film Coating

  • Research Article
  • Theme: Modeling and Simulations of Drug Product Manufacturing Unit Operations
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Abstract

Pharmaceutical tablets can be susceptible to damage such as edge chipping or erosion of the core during the tablet coating process. The intersection of certain process parameters, equipment design, and tablet properties may induce more significant tablet damage such as complete tablet fracture. In this work, a hybrid predictive approach was developed using discrete element method (DEM) modeling and lab-based tablet impact experiments to identify conditions that may lead to tablet breakage events. The approach was extended to examine potential modifications to the coating equipment and process conditions in silico to mitigate the likelihood of tablet breakage during future batches. The approach is shown to enhance process understanding, identify optimal process conditions within development constraints, and de-risk the manufacture of future tablet coating batches.

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References

  1. Seo K-S, Bajracharya R, Lee SH, Han H-K. Pharmaceutical application of tablet film coating. Pharmaceutics. 2020;12(9):853.

    Article  CAS  Google Scholar 

  2. Zaid AN. A Comprehensive review on pharmaceutical film coating: past, present, and future. Drug Des Devel Ther. 2020;14:4613–23.

    Article  CAS  Google Scholar 

  3. Ghadiri M, Zhang Z. Impact attrition of particulate solids. Part 1: a theoretical model of chipping. Chem Eng Sci. 2002;57(17):3659–69.

    Article  CAS  Google Scholar 

  4. Hutchings I. Mechanisms of wear in powder technology: a review. Powder Technol. 1993;76(1):3–13.

    Article  CAS  Google Scholar 

  5. Evans A, Wilshaw T. Dynamic solid particle damage in brittle materials: an appraisal. J Mater Sci. 1977;12(1):97–116.

    Article  CAS  Google Scholar 

  6. Podczeck F. Methods for the practical determination of the mechanical strength of tablets—from empiricism to science. Int J Pharm. 2012;436(1):214–32.

    Article  CAS  Google Scholar 

  7. Shafer EGE, Wollish EG, Engel CE. The “Roche” Friabilator. J Am Pharm Assoc. 1956;45(2):114–6.

    Article  CAS  Google Scholar 

  8. Osei-Yeboah F, Sun CC. Validation and applications of an expedited tablet friability method. Int J Pharm. 2015;484(1):146–55.

    Article  CAS  Google Scholar 

  9. Bharadwaj R, Ketterhagen WR, Hancock BC. Characterization of tablet attritional forces in a friability tester and film coating pan using DEM. AIChE Annual Meeting; November 8, 2010; Salt Lake City, UT.

  10. Yuregir KR, Ghadiri M, Clift R. Impact attrition of sodium chloride crystals. Chem Eng Sci. 1987;42(4):843–53.

    Article  CAS  Google Scholar 

  11. Zhang Z, Ghadiri M. Impact attrition of particulate solids. Part 2: experimental work. Chem Eng Sci. 2002;57(17):3671–86.

    Article  CAS  Google Scholar 

  12. Hare C, Bonakdar T, Ghadiri M, Strong J. Impact breakage of pharmaceutical tablets. Int J Pharm. 2018;536(1):370–6.

    Article  CAS  Google Scholar 

  13. Sabri AH, Hallam CN, Baker NA, Murphy DS, Gabbott IP. Understanding tablet defects in commercial manufacture and transfer. J Drug Deliv Sci Technol. 2018;46:1–6.

    Article  CAS  Google Scholar 

  14. Thornton C, Ciomocos M, Adams M. Numerical simulations of agglomerate impact breakage. Powder Technol. 1999;105(1-3):74–82.

    Article  CAS  Google Scholar 

  15. Moreno R, Ghadiri M, Antony S. Effect of the impact angle on the breakage of agglomerates: a numerical study using DEM. Powder Technol. 2003;130(1-3):132–7.

    Article  CAS  Google Scholar 

  16. Tye CK, Sun CC, Amidon GE. Evaluation of the effects of tableting speed on the relationships between compaction pressure, tablet tensile strength, and tablet solid fraction. J Pharm Sci. 2005;94(3):465–72.

    Article  CAS  Google Scholar 

  17. Cundall PA, Strack OD. A discrete numerical model for granular assemblies. Geotechnique. 1979;29(1):47–65.

    Article  Google Scholar 

  18. Zhu HP, Zhou ZY, Yang RY, Yu AB. Discrete particle simulation of particulate systems: theoretical developments. Chem Eng Sci. 2007;62(13):3378–96.

    Article  CAS  Google Scholar 

  19. Ketterhagen WR. Process modeling in the pharmaceutical industry using the discrete element method. J Pharm Sci. 2009;98(2):442–70.

    Article  CAS  Google Scholar 

  20. Yeom SB, Ha ES, Kim MS, Jeong SH, Hwang SJ, Choi DH. Application of the discrete element method for manufacturing process simulation in the pharmaceutical industry. Pharmaceutics. 2019;11(8).

  21. Zhu H, Zhou Z, Yang R, Yu A. Discrete particle simulation of particulate systems: a review of major applications and findings. Chem Eng Sci. 2008;63(23):5728–70.

    Article  CAS  Google Scholar 

  22. EDEM 2019.1 User Guide. DEM Solutions Ltd.; 2019.

  23. Bharadwaj R, Smith C, Hancock BC. The coefficient of restitution of some pharmaceutical tablets/compacts. Int J Pharm. 2010;402(1-2):50–6.

    Article  CAS  Google Scholar 

  24. Ketterhagen WR. Modeling the motion and orientation of various pharmaceutical tablet shapes in a film coating pan using DEM. Int J Pharm. 2011;409(1-2):137–49.

    Article  CAS  Google Scholar 

  25. Stern PW. Effects of film coatings on tablet hardness. J Pharm Sci. 1976;65(9):1291–5.

    Article  CAS  Google Scholar 

  26. Alexander A, Shinbrot T, Muzzio FJ. Scaling surface velocities in rotating cylinders as a function of vessel radius, rotation rate, and particle size. Powder Technol. 2002;126(2):174–90.

    Article  CAS  Google Scholar 

  27. Pandey P, Turton R. Movement of different-shaped particles in a pan-coating device using novel video-imaging techniques. AAPS PharmSciTech. 2005;6(2):E237–E44.

    Article  Google Scholar 

  28. Pandey P, Song Y, Kayihan F, Turton R. Simulation of particle movement in a pan coating device using discrete element modeling and its comparison with video-imaging experiments. Powder Technol. 2006;161(2):79–88.

    Article  CAS  Google Scholar 

  29. Pandey P, Katakdaunde M, Turton R. Modeling weight variability in a pan coating process using Monte Carlo simulations. AAPS PharmSciTech. 2006;7(4):E2–E11.

    Article  Google Scholar 

  30. Kalbag A, Wassgren C. Inter-tablet coating variability: tablet residence time variability. Chem Eng Sci. 2009;64(11):2705–17.

    Article  CAS  Google Scholar 

  31. Chen W, Chang S-Y, Kiang S, Marchut A, Lyngberg O, Wang J, et al. Modeling of pan coating processes: prediction of tablet content uniformity and determination of critical process parameters. J Pharm Sci. 2010;99(7):3213–25.

    Article  CAS  Google Scholar 

  32. Toschkoff G, Just S, Knop K, Kleinebudde P, Funke A, Djuric D, et al. Modeling of an active tablet coating process. J Pharm Sci. 2015;104(12):4082–92.

    Article  CAS  Google Scholar 

  33. Boehling P, Toschkoff G, Knop K, Kleinebudde P, Just S, Funke A, et al. Analysis of large-scale tablet coating: modeling, simulation and experiments. Eur J Pharm Sci. 2016;90:14–24.

    Article  CAS  Google Scholar 

  34. Vogel L, Peukert W. Breakage behaviour of different materials—construction of a mastercurve for the breakage probability. Powder Technol. 2003;129(1-3):101–10.

    Article  CAS  Google Scholar 

  35. Vogel L, Peukert W. From single particle impact behaviour to modelling of impact mills. Chem Eng Sci. 2005;60(18):5164–76.

    Article  CAS  Google Scholar 

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Acknowledgements

The authors would like to acknowledge the assistance of Alex Ramirez to conduct the tablet drop test experiments and useful discussions with Maxx Capece and Alex Russell. The authors are also grateful for the support of Ruth Aquino, Amarillys De Jesus Vazquez, and Efrain Ruiz Machado during the experimental coating trials. Finally, Soumojeet Ghosh, David O’Brien, Ken Chong, Brendon Ricart, Mike Hoffman, and Juergen Zeidler are also acknowledged for their support of this work.

All authors and contributors are employees of AbbVie and may own AbbVie stock. AbbVie sponsored and funded the study; contributed to the design; participated in the collection, analysis, and interpretation of data, and in writing, reviewing, and approval of the final publication.

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Authors and Affiliations

  1. Drug Product Development, AbbVie Inc., R4SW, Bldg. AP31-4, 1 N Waukegan Road, North Chicago, Illinois, 60064, USA

    William R. Ketterhagen & Jeffery Larson

  2. Operations Science & Technology, AbbVie Inc., North Chicago, Illinois, USA

    Kevin Spence & Jared A. Baird

Authors
  1. William R. Ketterhagen
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  2. Jeffery Larson
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  3. Kevin Spence
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  4. Jared A. Baird
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Correspondence to William R. Ketterhagen.

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Guest Editors: Alexander Russell and Maxx Capece

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Ketterhagen, W.R., Larson, J., Spence, K. et al. Predictive Approach to Understand and Eliminate Tablet Breakage During Film Coating. AAPS PharmSciTech 22, 178 (2021). https://doi.org/10.1208/s12249-021-02061-3

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  • DOI: https://doi.org/10.1208/s12249-021-02061-3

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