Pharmaceutical Research

, Volume 30, Issue 5, pp 1300–1310 | Cite as

Understanding the Effect of Environmental History on Bilayer Tablet Interfacial Shear Strength

  • Gerard Klinzing
  • Antonios ZavaliangosEmail author
Research Paper



To understand the effect of post production environmental conditions on the interfacial strength of bilayer tablets.


Bilayer tablets of microcrystalline cellulose/dicalcium phosphate were exposed to several humidity conditions higher/lower than production conditions and tested in shear to assess interfacial strength. Specific failure mechanisms were observed using x-ray microtomography and scanning electron microscopy.


Transients in moisture diffusion of bilayer tablets with significant differential moisture absorption characteristics are responsible for the reduction of strength in both high and low moisture environments. X-ray microtomography and SEM experiments have shown that two different mechanisms of interfacial crack formation are present. For low moisture exposure, interfacial cracks close to the surface were produced, whereas at high moisture conditions, internal interfacial cracks were created. In both cases the fracture modes are consistent with the tensile stresses that develop locally due to the volumetric strains induced by moisture absorption.


The insight gained from this work will be useful for material selection and packaging of bilayer tablet systems. While additional work is needed to develop specific guidelines for the optimization of bilayer strength, the results presented here provide a rational basis upon which such work can be conducted.


bilayer tablets cracking humidity interfacial strength transient diffusion 



The authors would like to acknowledge the NSF GOALI project #0900476 for funding and Merck Inc & Co for the use of the compaction simulator.

Supplementary material


(MOV 2069 kb)


(MOV 9961 kb)


  1. 1.
    Wiseman EH, Federici NJ. Development of a sustained-release aspirin tablet. J Pharm Sci. 1968;57(9):1535–9.PubMedCrossRefGoogle Scholar
  2. 2.
    Shiyani B, Gattani S, Surana S. Formulation and evaluation of bi-layer tablet of metoclopramide hydrochloride and ibuprofen. AAPS PharmSciTech. 2008;9(3):818–27.PubMedCrossRefGoogle Scholar
  3. 3.
    Conte U, Maggi L, Colombo P, La Manna A. Multi-layered hydrophilic matrices as constant release devices (GeomatrixTM Systems). J Control Release. 1993;26(1):39–47.CrossRefGoogle Scholar
  4. 4.
    Chaudhary A, Tiwari N, Jain V, Singh R. Microporous bilayer osmotic tablet for colon-specific delivery. Eur J Pharm Biopharm. 2011;78(1):134–40.PubMedCrossRefGoogle Scholar
  5. 5.
    Karehill PG, Glazer M, Nyström C. Studies on direct compression of tablets. XXIII. The importance of surface roughness for the compactability of some directly compressible materials with different bonding and volume reduction properties. Int J Pharm. 1990;64(1):35–43.CrossRefGoogle Scholar
  6. 6.
    Inman SJ, Briscoe BJ, Pitt KG. Topographic characterization of cellulose bilayered tablets interfaces. Chem Eng Res Des. 2007;85(A7):1005–12.CrossRefGoogle Scholar
  7. 7.
    Inman SJ, Briscoe BJ, Pitt KG, Shiu C. The non-uniformity of microcrystalline cellulose bilayer tablets. Powder Technol. 2009;188(3):283–94.CrossRefGoogle Scholar
  8. 8.
    Wu CY, Seville JPK. A comparative study of compaction properties of binary and bilayer tablets. Powder Technol. 2009;189(2):285–94.CrossRefGoogle Scholar
  9. 9.
    Anuar MS, Briscoe BJ. Interfacial elastic relaxation during the ejection of bi-layered tablets. Int J Pharm. 2010;387(1–2):42–7.PubMedCrossRefGoogle Scholar
  10. 10.
    Podczeck F. Theoretical and experimental investigations into the delamination tendencies of bilayer tablets. Int J Pharm. 2011;408(1–2):102–12.PubMedCrossRefGoogle Scholar
  11. 11.
    Emery E, Oliver J, Pugsley T, Sharma J, Zhou J. Flowability of moist pharmaceutical powders. Powder Technol. 2009;189(3):409–15.CrossRefGoogle Scholar
  12. 12.
    Khan F, Pilpel N. An investigation of moisture sorption in microcrystalline cellulose using sorption isotherms and dielectric response. Powder Technol. 1987;50(3):237–41.CrossRefGoogle Scholar
  13. 13.
    Khan F, Pilpel N, Ingham S. The effect of moisture on the density, compaction and tensile-strength of microcrystalline cellulose. Powder Technol. 1988;54(3):161–4.CrossRefGoogle Scholar
  14. 14.
    Sun CC. Mechanism of moisture induced variations in true density and compaction properties of microcrystalline cellulose. Int J Pharm. 2008;346(1–2):93–101.PubMedCrossRefGoogle Scholar
  15. 15.
    Malamataris S, Goidas P, Dimitriou A. Moisture sorption and tensile-strength of some tableted direct compression excipients. Int J Pharm. 1991;68(1–3):51–60.CrossRefGoogle Scholar
  16. 16.
    Elamin AA, Alderborn G, Ahlneck C. The effect of pre-compaction processing and storage conditions on powder and compaction properties of some crystalline materials. Int J Pharm. 1994;108(3):213–24.CrossRefGoogle Scholar
  17. 17.
    Miyazaki T, Sivaprakasam K, Tantry J, Suryanarayanan R. Physical characterization of dibasic calcium phosphate dihydrate and anhydrate. J Pharm Sci. 2009;98(3):905–16.PubMedCrossRefGoogle Scholar
  18. 18.
    Cunningham JC, Sinka IC, Zavaliangos A. Analysis of tablet compaction. I. Characterization of mechanical behavior of powder and powder/tooling friction. Journal of Pharmaceutical Sciences. 2004;93(8):2022–39.PubMedCrossRefGoogle Scholar
  19. 19.
    Eiliazadeh B, Pitt K, Briscoe B. Effects of punch geometry on powder movement during pharmaceutical tabletting processes. International Journal of Solids and Structures. 2004;41(21):5967–77.CrossRefGoogle Scholar
  20. 20.
    Dietrich P, Cremer K, Bauer-Brandl A, Schubert R. Adhesion strength in two-layer tablets. Pharm Res. 1997;14(11):S429.Google Scholar
  21. 21.
    Sexton M, Procopio A, Zavaliangos A. Strength characterization of Bilayer compacts. Advances in powder metallurgy & particulate materials – 2008, Editors Roger Lawcock; Alan Lawley; Patrick J McGeehan : Proceedings of the 2008 World Congress on Powder Metallurgy & Particulate Materials: World Congress PM 2008, June 8‐12, Washington.Google Scholar
  22. 22.
    Radebaugh GW, Babu SR, Bondi JN. Characterization of the viscoelastic properties of compacted pharmaceutical powders by a novel nondestructive technique. Int J Pharm. 1989;57(2):95–105.CrossRefGoogle Scholar
  23. 23.
    Welch K, Mousavi S, Lundberg B, Stromme M. Viscoelastic characterization of compacted pharmaceutical excipient materials by analysis of frequency-dependent mechanical relaxation processes. Eur Phys J E. 2005;18(1):105–12.PubMedCrossRefGoogle Scholar
  24. 24.
    Cespi M, Bonacucina G, Misici-FalZi M, Golzi R, Boltri L, Palmieri GF. Stress relaxation test for the characterization of the viscoelasticity of pellets. European Journal of Pharmaceutics and Biopharmaceutics. 2007;67(2):476–84.PubMedCrossRefGoogle Scholar
  25. 25.
    Klinzing GR. PhD Thesis: Aspects into the structural integrity of pharmaceutical bilayer tablets: Drexel University; 2012.Google Scholar
  26. 26.
    Busignies V, Porion P, Leclerc B, Evesque P, Tchoreloff P. Application of PGSTE-NMR technique to characterize the porous structure of pharmaceutical tablets. Eur J Pharm Biopharm. 2008;69(3):1160–70.PubMedCrossRefGoogle Scholar
  27. 27.
    Evans AG, Rühle M, Dalgleish BJ, Charalambides PG. The fracture energy of bimaterial interfaces. Mater Sci Eng, A. 1990;126(1–2):53–64.Google Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Drexel UniversityPhiladelphiaUSA

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