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“MCC SANAQ®burst”—A New Type of Cellulose and its Suitability to Prepare Fast Disintegrating Pellets

  • Cornelia Krueger
  • Markus Thommes
  • Peter Kleinebudde
Research Article

Abstract

Introduction

Microcrystalline cellulose (MCC) is the commonly used pelletization aid in wet extrusion-spheronization processes. MCC has the structure of cellulose I and is denoted as MCC I. Recently, MCC II, a different polymorphic type of MCC, became commercially available, known under the name MCC SANAQ®burst. Due to the fact, that MCC II can be used as a filler and a disintegrant in tableting, MCC SANAQ®burst was investigated as new pelletization aid with the goal to prepare disintegrating pellets.

Materials

MCC II pellets were compared to the corresponding conventional pellets, manufactured on the basis of MCC I, namely Avicel® PH 102. Formulations with 10%, 20%, and 50% of either MCC I or MCC II as pelletization aids were produced.

Methods

One series of binary mixtures, contained lactose monohydrate as filler and a second series chloramphenicol as model drug. All pellets were characterized by their yield, aspect ratio, equivalent diameter, water content, tensile strength, disintegration behavior and—if applicable—drug release.

Results and Discussion

The production of pellets with sufficient quality properties by addition of 10%, 20%, and 50% of MCC II as pelletization aid was possible. In contrast to MCC I pellets, MCC II-based pellets showed disintegration resulting in a much faster drug release.

Conclusion

MCC SANAQ®burst is a promising pelletization aid providing disintegrating and fast-dissolving pellets.

Keywords

Extrusion-spheronization Pellet Cellulose II MCC SANAQ®burst Pelletization aid Disintegration Fast dissolving 

Notes

Acknowledgment

The authors acknowledge the financial support and the gift of MCC SANAQ®burst from Pharmatrans SANAQ Ltd, Basel, Switzerland. Furthermore, the authors are grateful to SciConcept for their support regarding crystal structure analyses.

References

  1. 1.
    Thommes M, Kleinebudde P. Use of κ-carrageenan as alternative pelletisation aid to microcrystalline cellulose in extrusion/spheronisation. I. Influence of type and fraction of filler. Eur J Pharm Biopharm. 2006;63:59–67.CrossRefPubMedGoogle Scholar
  2. 2.
    Okada S, Nakahara H, Isaka H. Adsorption of drugs on microcrystalline cellulose suspended in aqueous solutions. Chem Pham Bull. 1987;35:761–8.Google Scholar
  3. 3.
    Bornhöft M, Thommes M, Kleinebudde P. Preliminary assessment of carrageenan as excipient for extrusion/spheronisation. Eur J Pharm Biopharm. 2005;59:127–31.CrossRefPubMedGoogle Scholar
  4. 4.
    Tho I, Sande SA, Kleinebudde P. Pectinic acid, a novel excipient for production of pellets by extrusion/spheronisation: preliminary studies. Eur J Pharm Biopharm. 2002;54:95–9.CrossRefPubMedGoogle Scholar
  5. 5.
    Liew CV, Gu L, Soh JLP, Heng PWS. Functionality of cross-linked polyvinylpyrrolidone as a spheronisation aid: a promising alternative to microcrystalline cellulose. Pharm Res. 2005;22(8):1387–98.CrossRefPubMedGoogle Scholar
  6. 6.
    Dukic´-Ott A, Thommes M, Remon JP, Kleinebudde P, Vervaet C. Production of pellets via extrusion—spheronisation without the incorporation of microcrystalline cellulose: a critical review. Eur J Pharm Biopharm 2009; 71 (1) 38–46.Google Scholar
  7. 7.
    Kumar V, Reus-Medina M, Yang D. Preparation, characterization, and tabletting properties of a new cellulose-based pharmaceutical aid. Int J Pharm. 2002;235:129–40.CrossRefPubMedGoogle Scholar
  8. 8.
    Reus-Medina M, Lanz M, Kumar V, Leuenberger H. Comparative evaluation of the powder properties and compression behavior of a new cellulose-based direct compression excipient and Avicel PH-102. J Pharm Pharmacol. 2004;56:951–6.CrossRefPubMedGoogle Scholar
  9. 9.
    Lanz M, Pharmaceutical powder technology: towards a science based understanding of the behavior of powder systems, Dissertation, University of Basel, 2006.Google Scholar
  10. 10.
    Phadnis NV, Suryanarayanan R. Polymorphism in anhydrous theophylline—implications on the dissolution rate of theophylline tablet. J Pharm Sci. 1997;86:1256–63.CrossRefPubMedGoogle Scholar
  11. 11.
    Chemburkar SR, Bauer J, Deming K, Spiwek H, Patel K, Morris J, et al. Dealing with the impact of ritonavir polymorphs on the late stages of bulk drug process development. Org Process Res Dev. 2000;4:413–17.CrossRefGoogle Scholar
  12. 12.
    Listionhadi Y, Hourigan JA, Sleigh RW, Stelle RJ. Moisture sorption, compressibility and caking of lactose polymorphs. Int J Pharm. 2008;359:123–34.CrossRefGoogle Scholar
  13. 13.
    Burger A, Henck JO, Hetz S, Rollinger JM, Weissnicht AA, Stottner H. Energy/temperature diagram and compression behavior of the polymorphs of D-mannitol. J Pharm Sci. 2000;89:457–68.CrossRefPubMedGoogle Scholar
  14. 14.
    Kono H, Numata Y, Erate T, Takai M. 13C and 1H resonance assignment of mercerized cellulose II by two-dimensional MAS NMR spectroscopies. Macromolecules. 2004;37:5310–16.CrossRefGoogle Scholar
  15. 15.
    Kroon-Batenburg LMJ, Kroon J. The crystal and molecular structures of cellulose I and II. Glycoconj J. 1997;14:677–90.CrossRefPubMedGoogle Scholar
  16. 16.
    El-Sabawi D, Price R, Edge S. Novel temperature controlled surface dissolution of excipient particles for carrier based dry powder inhaler formulations. Drug Dev Ind Pharm. 2006;32:243–51.CrossRefPubMedGoogle Scholar
  17. 17.
    Merck Index “Different Monographs” in: The Merck Index—an Encyclopedia of Chemicals, Drugs and Biologicals; Merck & Co Rahway, NJ, USA 1989.Google Scholar
  18. 18.
    Sanderson H, Thomsen M. Comparative analysis of pharmaceuticals versus industrial chemicals acute aquatic toxicity classification according to the United Nations classification system for chemicals. Assessment of the (Q)SAR predictability of pharmaceuticals acute aquatic toxicity and their predominant acute toxic mode-of-action. Toxicol Lett. 2009;187:84–93.CrossRefPubMedGoogle Scholar
  19. 19.
    Shipway PH, Hutchings IM. Fracture of brittle spheres under compression and impact loading I. Elastic stress distributions. Philos Mag A. 1993;67:1389–404.CrossRefGoogle Scholar
  20. 20.
    Schröder M, Kleinebudde P. Structure of disintegrating pellets with regard to fractal geometry. Pharm Res. 1995;12(11):1694–700.CrossRefPubMedGoogle Scholar
  21. 21.
    Langguth P, Fricker G, Wunderli-Allenspach H. Biopharmazie. Weinheim: Wiley; 2004.Google Scholar
  22. 22.
    Korsmeyer RW, Peppas NA. Effect of the morphology of hydrophilic polymeric matrices on the diffusion and release of water soluble drugs. J Memb Sci. 1981;9:211–27.CrossRefGoogle Scholar
  23. 23.
    Höpner T, Jayme G, Ulrich JC. Bestimmung des Wasserrückhaltevermögens (Quellwertes) von Zellstoffen. Das Papier. 1955;19/20:476–82.Google Scholar
  24. 24.
    Thommes M, Ely DR, Kleinebudde P. The water binding behaviour of κ-Carrageenan determined by three different methods. Pharm Dev Tech. 2009;14(3):249–58.CrossRefGoogle Scholar
  25. 25.
    Brittain HG, Lewen G, Newman AW, Fiorelli K, Bogdanowich S. Changes in material properties accompanying the national formulary (NF) identity test for microcrystalline cellulose. Pharm Res. 1993;10(1):61–7.CrossRefPubMedGoogle Scholar
  26. 26.
    Kleinebudde P. Shrinking and swelling properties of pellets containing microcrystalline cellulose and low substituted hydroxypropylcellulose: I. shrinking properties. Int J Pharm. 1994;109:209–19.CrossRefGoogle Scholar
  27. 27.
    Reynolds AD. A new technique for the production of spherical particles. Manuf Chemist. 1970;41:40–3.Google Scholar
  28. 28.
    Kleinebudde P. The crystallite-gel-model for microcrystalline cellulose in wet-granulation, extrusion, and spheronisation. Pharm Res. 1997;14(6):804–9.CrossRefPubMedGoogle Scholar
  29. 29.
    Krässig HA. Cellulose: structure, accessibility and reactivity. Yverdon: Gordon and Breach Science Publisher; 1993.Google Scholar
  30. 30.
    Cambridge Structural Database (CSD), The Cambridge Crystallographic Data Centre; 12 Union Road, Cambridge, UK.Google Scholar
  31. 31.
    Nishiyama Y, Langan P, Chanzy H. Crystal structure and hydrogen-bonding system in cellulose Iβ from synchrotron X-ray and neutron fiber diffraction. J Am Chem Soc. 2002;124(31):9074–82.CrossRefPubMedGoogle Scholar
  32. 32.
    Nishiyama Y, Sugiyama J, Chanzy H, Langan P. Crystal structure and hydogen bonding system in cellulose Iα from synchrotron X-ray and neutron fiber diffraction. J Am Chem Soc. 2003;125(47):14300–6.CrossRefPubMedGoogle Scholar
  33. 33.
    Zimm KR, Schwartz JB, O’Connor RE. Drug release from a multiparticulate pellet system. Pharm Dev Techn. 1995;1:37–42.CrossRefGoogle Scholar
  34. 34.
    O’Connor RE, Schwartz JB. Drug release mechanism from a microcrystalline cellulose pellet system. Pharm Res. 1993;10(3):356–61.CrossRefPubMedGoogle Scholar
  35. 35.
    Nishiyama Y. Structure and properties of the cellulose microfibril. J Wood Sci 2009 (in press).Google Scholar
  36. 36.
    Langan P, Nishiyama Y, Chanzy H. A revised structure and hydrogen-bonding system in cellulose II from a neutron fiber diffraction analysis. J Am Chem Soc. 1999;121:9940–6.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Cornelia Krueger
    • 1
  • Markus Thommes
    • 1
  • Peter Kleinebudde
    • 1
  1. 1.Institute of Pharmaceutics and BiopharmaceuticsHeinrich Heine UniversityDuesseldorfGermany

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