Pharmaceutical Research

, Volume 18, Issue 11, pp 1562–1569 | Cite as

Microcrystalline Cellulose-Water Interaction—A Novel Approach Using Thermoporosimetry

  • Pirjo Luukkonen
  • Thad Maloney
  • Jukka Rantanen
  • Hannu Paulapuro
  • Jouko Yliruusi


Purpose. To study the physical state of water in microcrystalline cellulose (MCC) and in silicified microcrystalline cellulose wet masses and the effect of granulation on different water fractions.

Methods. Thermoporosimetry, together with the solute exclusion technique, was used to measure different water fractions and pore size distributions of wet granules. To understand the effect of granulation on the physical state of water, both ungranulated and granulated wet masses were studied. In addition, dynamic and isothermal step melting procedures were compared.

Results. Four distinct fractions of water (nonfreezing, freezing bound, free, and bulk water) could be detected in MCC wet masses. Granulation decreased the volume of bulk water and increased the volume of freezing bound and free water. Consequently, granulated wet masses were able to hold more water inside the particles compared to ungranulated wet masses. Thus, granulation had a similar effect on MCC as beating has on cellulose fibers in the papermaking process.

Conclusions. Thermoporosimetry and solute exclusion increased the understanding of MCC-water interaction and showed how the physical state of water in MCC wet masses changes during granulation.

thermoporosimetry isothermal step melting microcrystalline cellulose pore structure effect of granulation physical state of water 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Y. Nakai, E. Fukuoka, S. Nakajima, and J. Hasegawa. Crystallinity and physical characteristics of microcrystalline cellulose. Chem. Pharm. Bull. 25:96-101 (1977).Google Scholar
  2. 2.
    G. Hollenbeck, G. Peck, and D. Kildsig. Application of immersional calorimetry to investigation of solid-liquid interactions: microcrystalline cellulose-water system. J. Pharm. Sci. 67:1599-1606 (1978).Google Scholar
  3. 3.
    G. Zografi, M. Kontny, A. Y. S. Yang, and G. S. Brenner. Surface area and water vapor sorption of microcrystalline cellulose. Int. J. Pharm. 18:99-116 (1984).Google Scholar
  4. 4.
    S. Delwiche, R. Pitt, and K. Norris. Examination of starch-water and cellulose-water interactions with near infrared (NIR) diffuse reflectance spectroscopy. Starch/Stärke 43:422-427 (1991).Google Scholar
  5. 5.
    K. E. Fielden, J. M. Newton, P. O'Brien, and R. C. Rowe. Thermal studies on the interaction of water and microcrystalline cellulose. J. Pharm. Pharmacol. 40:674-678 (1988).Google Scholar
  6. 6.
    P. Luukkonen, J. Rantanen, K. Mäkelä, E. Räsänen, J. Tenhunen, and J. Yliruusi. Characterization of silicified microcrystalline cellulose and α-lactose monohydrate wet masses using near infrared spectroscopy. Pharm. Dev. Technol. 6:1-9 (2001).Google Scholar
  7. 7.
    G. Zografi and M. Kontny. The interactions of water with cellulose-and starch-derived pharmaceutical excipients. Pharm. Res. 3:187-194 (1986).Google Scholar
  8. 8.
    G. Zografi. States of water associated with solids. Drug Dev. Ind. Pharm. 14:1905-1926 (1988).Google Scholar
  9. 9.
    K. Nakamura, T. Hatakeyama, and H. Hatakeyama. Studies on bound water of cellulose by differential scanning calorimetry. J. Text. Inst. 72:607-613 (1981).Google Scholar
  10. 10.
    T.-Q. Li. Interactions Between Water and Cellulose Fibers: Application of NMR Techniques, Doctoral Thesis, Royal Institute of Technology, Stockholm, 1991.Google Scholar
  11. 11.
    J. Mousseri, M. P. Steinberg, A. I. Nelson, and L. S. Wei. Bound water capacity of corn starch and its derivatives by NMR. J. Food Sci. 39:114-116 (1974).Google Scholar
  12. 12.
    R. Nelson. The determination of moisture transitions in cellulosic materials using differential scanning calorimetry. J. Appl. Polym. Sci. 21:645-654 (1977).Google Scholar
  13. 13.
    T. Yamauchi and K. Murakami. Differential scanning calorimetry as an aid for investigating the wet state of pulp. J. Pulp Pap. Sci. 17:J223-J226 (1991).Google Scholar
  14. 14.
    K. Ishikiriyama and M. Todoki. Pore size distribution measurements of silica gels by means of differential scanning calorimetry. II. Thermoporosimetry. J. Colloid Interface Sci. 171:103-111 (1995).Google Scholar
  15. 15.
    J. E. Stone and A. M. Scallan. A structural model for the cell wall of water swollen wood pulp fibres based on their accessibility to macromolecules. Cellulose Chem. Technol. 2:343-358 (1968).Google Scholar
  16. 16.
    A. M. Scallan and J. E. Carles. The correlation of water retention value with fiber saturation point. Svensk Papperstidn. 75:699-703 (1972).Google Scholar
  17. 17.
    T. C. Maloney, H. Paulapuro, and P. Stenius. Hydration and swelling of pulp fibers measured with differential scanning calorimetry. Nord. Pulp Pap. Res. J. 13:31-36 (1998).Google Scholar
  18. 18.
    H. N. Joshi and T. D. Wilson. Calorimetric studies of dissolution of hydroxypropyl methylcellulose E5 (HPMC E5) in water. J. Pharm. Sci. 82:1033-1038 (1993).Google Scholar
  19. 19.
    T. C. Maloney. Thermoporosimetry by Isothermal Step Melting, ISWPC Pre-Symposium, Seoul, 1999 pp. 245-253.Google Scholar
  20. 20.
    J. Berthold. Water Adsorption and Uptake in the Fibre Cell Wall as Affected by Polar Groups and Structure, Doctoral Thesis, Royal Institute of Technology, Stockholm (1996).Google Scholar
  21. 21.
    M. Froix and R. Nelson. The interaction of water with cellulose from nuclear magnetic resonance relaxation times. Macromol. 8:726-730 (1975).Google Scholar
  22. 22.
    T. C. Maloney and H. Paulapuro. The formation of pores in the cell wall. J. Pulp Pap. Sci. 25:430-436 (1999).Google Scholar
  23. 23.
    H. W. Emerton. The preparation of pulp fibres for papermaking. In H. F. Rance (eds.), Handbook of Paper Science, Vol. 1, The Raw Materials and Processing of Papermaking, Elsevier Scientific Publishing Company, The Netherlands, 1980 pp. 139-164.Google Scholar
  24. 24.
    R. Ek and J. M. Newton. Microcrystalline cellulose as a sponge as an alternative concept to the crystallite-gel model for extrusion and spheronization. Pharm. Res. 15:509-510 (1998).Google Scholar
  25. 25.
    P. Kleinebudde. The crystallite-gel-model for microcrystalline cellulose in wet-granulation, extrusion and spheronization. Pharm. Res. 14:804-809 (1997).Google Scholar
  26. 26.
    P. Kleinebudde, M. Jumaa, and F. El Saleh. Influence of degree of polymerization on behavior of cellulose during homogenization and extrusion/spheronisation. AAPSPharmsci 2(3) article 21 (htpp:// (2000).Google Scholar
  27. 27.
    C. Schmidt and P. Kleinebudde. Influence of the granulation step on pellets prepared by extrusion/spheronization. Chem. Pharm. Bull. 47:405-412 (1998).Google Scholar
  28. 28.
    D. M. Newitt and J. M. Conway-Jones. A contribution to the theory and practise of granulation. Trans. Inst. Chem. Eng. 36:422-442 (1958).Google Scholar
  29. 29.
    S. Wissing, D. Craig, S. Barker, and W. Moore. An investigation into the use of stepwise isothermal high sensitivity DSC as a means of detecting drug-excipient incompatibity. Int. J. Pharm. 199:141-150 (2000).Google Scholar
  30. 30.
    S. Deodhar and P. Luner. Measurement of bound (nonfreezing) water by differential scanning calorimetry. In S.P. Rowland (eds.), Water in Polymers, American Chemists Society, Washington, 1980 pp. 273-286.Google Scholar

Copyright information

© Plenum Publishing Corporation 2001

Authors and Affiliations

  • Pirjo Luukkonen
    • 1
  • Thad Maloney
    • 3
  • Jukka Rantanen
    • 4
  • Hannu Paulapuro
    • 3
  • Jouko Yliruusi
    • 1
  1. 1.Pharmaceutical Technology Division, Department of PharmacyUniversity of HelsinkiFinland
  2. 2.AstrZeneca R&D MölndahMölndalSweden
  3. 3.Laboratory of Paper TechnologyHelsinki University of TechnologyHUT, Finland
  4. 4.Viiki Drug Discovery Technology Center (DDTC), Pharmaceutical Technology DivisionUniversity of HelsinkiFinland

Personalised recommendations