Pharmaceutical Research

, Volume 30, Issue 7, pp 1915–1925 | Cite as

Functionalized Calcium Carbonate as a Novel Pharmaceutical Excipient for the Preparation of Orally Dispersible Tablets

  • Tanja Stirnimann
  • Nicola Di Maiuta
  • Daniel E. Gerard
  • Rainer Alles
  • Jörg Huwyler
  • Maxim PuchkovEmail author
Research Paper



To overcome the limitation of insufficient hardness during the production of rapidly disintegrating orally dispersible tablets (ODTs). Furthermore, we investigated the properties and usefulness of functionalized calcium carbonate (FCC) as a new pharmaceutical excipient for the production of ODTs.


A highly sensitive tensiometer-based method was developed to measure kinetics of weight loss during tablet disintegration. With this method we were able to determine the residence time of tablets placed on a basket immersed into a test medium. The shapes of tensiometer plots allowed us to categorize substances into four different types of disintegration.


At the same volume and hardness, the tablet formulations with FCC showed a significantly higher porosity (over 60%) than all other formulations. Residence time depended mainly on the tablet composition rather than on porosity. When combined with disintegrants, FCC formulations exhibited favorable disintegration properties, comparable to those of the marketed drug risperidone oro (disintegration time ca. 10 s).


Oral dosage forms - based on the new pharmaceutical excipient FCC - can be designed to have a short disintegration time combined with good mechanical strength. Due to these properties, FCC can be used for the preparation of ODTs.


disintegration ODT porosity residence time tensiometer 


Acknowledgments and Disclosures

Dr. Maxim Puchkov and Prof. Dr. Jörg Huwyler have contributed equally to the present work. Financial support for this PhD thesis was kindly provided by Omya limited. We would like to thank Mark Inglin for editorial assistance. Thanks also go to Daniel Mathys for his technical support in connection with electron microscopic examinations.


  1. 1.
    Kuchekar B, Badhan A, Mahajan H. Mouth dissolving tablets: a novel drug delivery system. Pharma Times. 2003;35:7–9.Google Scholar
  2. 2.
    Virely P, Yarwood R. Zydis - A novel, fast dissolving dosage form. Manuf Chem. 1990;61:36–7.Google Scholar
  3. 3.
    Corveleyn S, Remon JP. Formulation and production of rapidly disintegrating tablets by lyophilisation using hydrochlorothiazide as a model drug. Int J Pharm. 1997;152(2):215–25.CrossRefGoogle Scholar
  4. 4.
    Pebley W, Jager N, Thompson S. Rapidly disintegrating tablet. 1994.Google Scholar
  5. 5.
    Allen LV, Wang B. Process for making a particulate support matrix for making a rapidly dissolving tablet [Internet]. 1996 [cited 2012 Jun 14]. Available from:
  6. 6.
    Bhaskaran S, Narmada G. Rapid dissolving tablet a novel dosage form. Indian Pharmacist. 2002;1:9–12.Google Scholar
  7. 7.
    Dobetti L. Fast-melting tablets: developments and technologies. Pharm Tech Europe. 2000;12(9):32–42.Google Scholar
  8. 8.
    Sreenivas SA. Orodispersible tablets: new-fangled drug delivery system - a review. Indian J Pharm Educ Res. 2005;39(4):177–81.Google Scholar
  9. 9.
    Kumar VD, Sharma I, Sharma V. A comprehensive review on fast dissolving tablet technology. J App Pham Sci. 2011;1(5):50–8.Google Scholar
  10. 10.
    Bi Y, Sunada H, Yonezawa Y, Danjo K. Evaluation of rapidly disintegrating tablets prepared by a direct compression method. Drug Dev Ind Pharm. 1999;25(5):571–81.PubMedCrossRefGoogle Scholar
  11. 11.
    Pharmacopeia E. 7th ed. Strasbourg (France): Council of Europe; 2011.Google Scholar
  12. 12.
    Food and Drug Administration (FDA). Guidance for industry - orally disintegrating tablets [Internet]. 2008 [cited 2012 Nov 1]. Available from:
  13. 13.
    McLaughlin R, Banbury S, Crowley K. Orally disintegrating tablets: the effect of recent FDA guidance on ODT technologies and applications. Pharm Technol. 2009;33:18–25.Google Scholar
  14. 14.
    Bi Y, Sunada H, Yonezawa Y, Danjo K, Otsuka A, Iida K. Preparation and evaluation of a compressed tablet rapidly disintegrating in the oral cavity. Chem Pharm Bull. 1996;44(11):2121–7.PubMedCrossRefGoogle Scholar
  15. 15.
    Shukla D, Chakraborty S, Singh S, Mishra B. Mouth dissolving tablets II: an overview of evaluation techniques. Sci Pharm. 2009;77:327–41.CrossRefGoogle Scholar
  16. 16.
    Narazaki R, Harada T, Takami N, Kato Y, Ohwaki T. A new method for disintegration studies of rapid disintegrating tablet. Chem Pharm Bull. 2004;52(6):704–7.PubMedCrossRefGoogle Scholar
  17. 17.
    Ohta M, Hayakawa E, Ito K, Tokuno S, Morimoto K, Watanabe Y. Intrabuccally rapidly disintegrating tablet [Internet]. 2001 [cited 2012 Feb 1]. Available from:
  18. 18.
    Morita Y, Tsushima Y, Yasui M, Termoz R, Ajioka J, Takayama K. Evaluation of the disintegration time of rapidly disintegrating tablets via a novel method utilizing a CCD camera. Chem Pharm Bull. 2002;50(9):1181–6.PubMedCrossRefGoogle Scholar
  19. 19.
    Fu Y, Jeong S, Park K. Preparation of fast dissolving tablets based on mannose. ACS Symp Ser. 2006;924:340–51.CrossRefGoogle Scholar
  20. 20.
    Harada T, Narazaki R, Nagira S, Ohwaki T, Aoki S, Iwamoto K. Evaluation of the disintegration properties of commercial famotidine 20 mg orally disintegrating tablets using a simple new test and human sensory test. Chem Pharm Bull. 2006;54(8):1072–5.PubMedCrossRefGoogle Scholar
  21. 21.
    El-Arini S, Clas S. Evaluation of disintegration testing of different fast dissolving tablets using the texture analyzer. Pharm Dev Technol. 2002;7(3):361–71.PubMedCrossRefGoogle Scholar
  22. 22.
    Abdelbary G, Eouani C, Prinderre P, Joachim J, Reynier J, Piccerelle P. Determination of the in vitro disintegration profile of rapidly disintegrating tablets and correlation with oral disintegration. Int J Pharm. 2005;292(1–2):29–41.PubMedCrossRefGoogle Scholar
  23. 23.
    Kraemer J, Gajendran J, Guillot A, Schichtel J, Tuereli A. Dissolution testing of orally disintegrating tablets. J Pharm Pharmacol. 2012;64(7):911–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Massimo G, Catellani PL, Santi P, Bettini R, Vaona G, Bonfanti A, et al. Disintegration propensity of tablets evaluated by means of disintegrating force kinetics. Pharm Dev Technol. 2000;5(2):163–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Welch K, Strømme M. Simultaneous measurement of drug release and liquid uptake in pharmaceutical tablets. J Pharm Sci. 2003;92(6):1242–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Pabari RM, Ramtoola Z. Application of face centred central composite design to optimise compression force and tablet diameter for the formulation of mechanically strong and fast disintegrating orodispersible tablets. Int J Pharm. 2012;430(1–2):18–25.PubMedCrossRefGoogle Scholar
  27. 27.
    Ridgway CJ, Gane PAC, Schoelkopf J. Modified calcium carbonate coatings with rapid absorption and extensive liquid uptake capacity. Colloids Surf A. 2004;236(1–3):91–102.CrossRefGoogle Scholar
  28. 28.
    Rowe RC, Sheskey PJ, Quinn ME. Handbook of Pharmaceutical Excipients. 6th ed. London, UK: Pharmaceutical Press and American Pharmacist Association; 2009.Google Scholar
  29. 29.
    Gane PAC, Buri M, Blum RV, Karth B. Filler or pigment or processed mineral for paper, in particular a pigment containing natural CaCO3, its manufacturing process, preparations containing it and their applications [Internet]. 2004 [cited 2012 Oct 24]. Available from:
  30. 30.
    Fiedler HP. Fiedler Lexikon der Hilfsstoffe für Pharmazie, Kosmetik und angrenzende Gebiete. Aulendorf: Editio Cantor Verlag; 2002.Google Scholar
  31. 31.
    Krausbauer E. Contributions to a science based expert system for solid dosage form design. [Basel]: University of Basel, Faculty of Science; 2009.Google Scholar
  32. 32.
    Garboczi EJ, Snyder KA, Douglas JF, Thorpe MF. Geometrical percolation threshold of overlapping ellipsoids. Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics. 1995;52(1):819–28.PubMedCrossRefGoogle Scholar
  33. 33.
    Krausbauer E, Puchkov M, Betz G, Leuenberger H. Rational estimation of the optimum amount of non-fibrous disintegrant applying percolation theory for binary fast disintegrating formulation. J Pharm Sci. 2008;97(1):529–41.PubMedCrossRefGoogle Scholar
  34. 34.
    Ishikawa T, Mukai B, Shiraishi S, Utoguchi N, Fujii M, Matsumoto M, et al. Preparation of rapidly disintegrating tablet using new types of microcrystalline cellulose (PH-M series) and low substituted-hydroxypropylcellulose or spherical sugar granules by direct compression method. Chem Pharm Bull. 2001;49(2):134–9.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Tanja Stirnimann
    • 1
  • Nicola Di Maiuta
    • 2
  • Daniel E. Gerard
    • 2
  • Rainer Alles
    • 1
  • Jörg Huwyler
    • 1
  • Maxim Puchkov
    • 1
    Email author
  1. 1.Department of Pharmaceutical Science Division of Pharmaceutical TechnologyUniversity BaselBaselSwitzerland
  2. 2.Omya Development AG, R&D MicrobiologyOftringenSwitzerland

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