Skip to main content
SpringerLink
Log in

High-Molecular-Weight Hypromellose from Three Different Suppliers: Effects of Compression Speed, Tableting Equipment, and Moisture on the Compaction

  • Research Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

Use of higher tableting speeds is gaining increasing importance for pharmaceutical industry. There is a profound lack of new studies of mechanical properties of hypromellose, and none of them evaluate different suppliers. Thus, the objective of this study was to investigate flow and compaction properties of different grades of hypromellose (type 2208) from three different suppliers, with particular focus on the effect of the compression speed. The flow properties were determined using flow time, shear cell, Carr index, and constant B from initial part of Heckel profile. Compaction properties were quantified using “out-of-die” Heckel, Walker, and Kuentz-Leuenberger models; two tensile strength profiles (tabletability and compactibility); and elastic recovery. Compaction was performed by both an instrumented single-punch press and a high-speed rotary press simulator. Due to larger, rounder, and smoother particles, both Methocel™ DC grades together with Benecel™ K4M showed better flow properties compared with other materials, with Metolose® K100M having the worst flow. Overall, Benecel™ K100M and Metolose® K100M showed the best compaction properties, closely followed by Metolose® K4M. Heckel analysis showed the highest compressibility of Benecel™ K100M, followed by both Methocel™ DC grades. Kuentz-Leuenberger model showed to have no practical superiority in comparison with Heckel model in the compression pressure range used. Results of strain rate sensitivity showed that Methocel™ K4M DC was the least susceptible to change of tableting speed, followed by Methocel™ K100M DC and both grades of Benecel™, and in contrast, both grades of Metolose® were the most sensitive. Effect of moisture on compaction was also studied.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10

Similar content being viewed by others

References

  1. Roger TL. Hypromellose. In: Rowe RC, Sheskey PJ, Quinn ME, editors. Handbook of pharmaceutical excipients. 6th ed. London: Pharmaceutical Press; 2009. p. 326–9.

    Google Scholar 

  2. Grdešič P, Vrečer F, Ilić I. Flow and compaction properties of hypromellose: new directly compressible versus the established grades. Drug Dev Ind Pharm. 2016;42(11):1877–86.

    Article  Google Scholar 

  3. Devjak Novak S, Šporar E, Baumgartner S, Vrečer F. Characterization of physicochemical properties of hydroxypropyl methylcellulose (HPMC) type 2208 and their influence on prolonged drug release from matrix tablets. J Pharm Biomed Anal. 2012;66:136–43.

    Article  CAS  Google Scholar 

  4. Gustafsson C, Bonferoni MC, Caramella C, Lenholm H, Nystrom C. Characterisation of particle properties and compaction behavior of hydroxypropylmethylcellulose with different deegres of methoxy/hydroxypropyl substitution. Eur J Pharm Sci. 1999;9:171–84.

    Article  CAS  Google Scholar 

  5. Gustafsson C, Nyström C, Lennholm H, Bonferoni MC, Caramella MC. Characteristics of hydroxypropyl methylcellulose influencing compactibility and prediction of particle and tablet properties by infrared spectroscopy. J Pharm Sci. 2003;92:494–504.

    Article  CAS  Google Scholar 

  6. Nokhodchi A, Ford JL, Rowe P, Rubinstein MH. The effects of compression rate and force on the compaction properties of different viscosity grades of hydroxypropylmethylcellulose. Int J Pharm. 1996;129:21–31.

    Article  CAS  Google Scholar 

  7. Nokhodchi A, Ford JL, Rowe P, Rubinstein MH. The influence of moisture content on the consolidation properties of hydroxypropylmethylcellulose K4M (HPMC 2208). J Pharm Pharmacol. 1996;48:1116–21.

    Article  CAS  Google Scholar 

  8. Nokhodchi A, Ford JL, Rubinstein MH. Studies on the interaction between water and (hydroxypropyl)methylcellulose. J Pharm Sci. 1997;86:608–15.

    Article  CAS  Google Scholar 

  9. Malamataris S, Karidas T, Goidas P. Effect of particle size and sorbed moisture on the compression behaviour of some hydroxypropyl methylcellulose (HPMC) polymers. Int J Pharm. 1994;103:205–15.

    Article  CAS  Google Scholar 

  10. Sinko CM, Smith DP, Nixon PR. Mechanical characterization of hydroxypropyl methylcellulose: modulus determination from indentation loading profiles. Int J Pharm. 1992;81:243–52.

    Article  CAS  Google Scholar 

  11. European Pharmacopoeia. Edition 9, 2017.

  12. Heckel RW. Density-pressure relationship in powder compaction. Trans Metall Soc AIME. 1961;221:671–5.

    CAS  Google Scholar 

  13. Walker EE. The properties of powder VI: the compressibility of powders. Trans Faraday Soc. 1923;19:73–82.

    Article  Google Scholar 

  14. Sonnergaard JM. Quantifiaction of the compactibility of pharmaceutical powders. Eur J Pharm Biopharm. 2006;63:270–7.

    Article  CAS  Google Scholar 

  15. Kuentz M, Leuenberger H. Pressure susceptibility of polymer tablets as a critical property: a modified Heckel equation. J Pharm Sci. 1999;88:174–9.

    Article  CAS  Google Scholar 

  16. Fell JT, Newton JM. Determination of tablet strength by the diametral compression test. J Pharm Sci. 1970;59:688–91.

    Article  CAS  Google Scholar 

  17. Armstrong NA, Haines-Nutt RF. Elastic recovery and surface area changes in compacted powder systems. J Pharm Pharmacol. 1972;24:135–6.

    Article  Google Scholar 

  18. Malamataris S, BibBaie S, Pilpel N. Plasto-elasticity and tableting of paracetamol. J Pharm Pharmacol. 1984;36:616–7.

    Article  CAS  Google Scholar 

  19. Sonnergaard JM. Investigation of a new mathematical model for compression of pharmaceutical powders. Eur J Pharm Sci. 2001;14:149–57.

    Article  CAS  Google Scholar 

  20. Sonnergaard JM. A critical evaluation of the Heckel equation. Int J Pharm. 1999;193:63–71.

    Article  CAS  Google Scholar 

  21. Ilić I, Govedarica B, Šibanc R, Dreu R, Srčič S. Deformation properties of pharmaceutical excipients determined using an in-die and out-die method. Int J Pharm. 2013;446:6–15.

    Article  Google Scholar 

  22. Egart M, Ilić I, Janković B, Lah N, Srčič S. Compaction properties of crystalline pharmaceutical ingredients according to the Walker model and nanomechanical attributes. Int J Pharm. 2014;472:347–55.

    Article  CAS  Google Scholar 

  23. Ilić I, Kasa P Jr, Dreu R, Pintye-Hodi K, Srčič S. The compressibility and compactibility of different types of lactose. Drug Dev Ind Pharm. 2009;35:1271–80.

    Article  Google Scholar 

  24. Šantl M, Ilić I, Vrečer F, Baumgartner S. A compressibility and compactibility study of real tableting mixtures: the impact of wet and dry granulation versus direct tableting mixture. Int J Pharm. 2011;414:131–9.

    Article  Google Scholar 

  25. Nokhodchi A, Ford JL, Rubinstein MH. The effect of particle size and viscosity grade on the compaction properties of K grade of hydroxypropylmethylcellulose. Int J Pharm. 1995;126:189–97.

    Article  CAS  Google Scholar 

  26. Roberts RJ, Rowe RC. The effect of punch velocity on the compaction of a variety of materials. J Pharm Pharmacol. 1985;37(6):377–84.

    Article  CAS  Google Scholar 

  27. Tye CK, Sun C, 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. 2004;94:465–72.

    Article  Google Scholar 

  28. Natoli D, Liu L, Levin M, Tsygan L. Chapter 32 – development, optimization, and scale-up of process parameters: tablet compression. In: Developing Solid Oral Dosage Forms. 2009; 725–759.

Download references

Acknowledgments

The authors wish to express sincere gratitude to KRKA, d.d., Novo mesto and Faculty of Pharmacy, University of Ljubljana, for providing us the opportunity and resources to develop and complete this work. The authors would like to thank Prof. Odon Planinšek from the Faculty of Pharmacy, University of Ljubljana, for his assistance in conducting the SEM analysis.

Funding

The research was supported by Krka, d.d., Novo mesto.

Author information

Authors and Affiliations

  1. Krka, d.d., Novo mesto, Šmarješka cesta 6, 8501, Novo mesto, Slovenia

    Peter Grdešič

  2. Research Center Pharmaceutical Engineering GmbH, Inffeldgasse 13, 8010, Graz, Austria

    Amrit Paudel

  3. Institute of Process and Particle Engineering, Graz University of Technology, Inffeldgasse 13, 8010, Graz, Austria

    Amrit Paudel

  4. Department of Pharmaceutical Technology, Faculty of Pharmacy, University of Ljubljana, Aškerčeva 7, 1000, Ljubljana, Slovenia

    Ilija German Ilić

Authors
  1. Peter Grdešič
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Amrit Paudel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ilija German Ilić
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ilija German Ilić.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Grdešič, P., Paudel, A. & German Ilić, I. High-Molecular-Weight Hypromellose from Three Different Suppliers: Effects of Compression Speed, Tableting Equipment, and Moisture on the Compaction. AAPS PharmSciTech 21, 203 (2020). https://doi.org/10.1208/s12249-020-01688-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1208/s12249-020-01688-y

KEY WORDS

Search

Navigation