Skip to main content
SpringerLink
Log in

Recent Progress in Roll Compaction Process Development for Pharmaceutical Solid Dosage Form Manufacture

  • Chapter
  • First Online:
Continuous Pharmaceutical Processing

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 42))

Abstract

Roll compaction technologies have advanced substantially over the past decade and are increasingly adapted by formulation scientists as a preferred means of granulation. This chapter presents recent progress in pharmaceutical roll compaction with respect to the following three key aspects: formulation development, process modeling, and equipment. On the modeling front, we outline various continuum-based modeling efforts and their role in furthering the fundamental, mechanistic understanding of the process. Here, we discuss the significant body of work that has been derived from the rolling theory for granular solids, focusing on both the quantities that that model predicts accurately and the reasons it recurrently falls short in predicting various process outcomes, as well as the rise of high-fidelity computational simulations and their potential to overcome the shortcomings of the rolling theory. With regard to the formulation development aspects of the process, common pharmaceutical excipients and their impact on the resulting ribbon and granule qualities are discussed. Lastly, we present the current state of the art in equipment design and process control that enable the processing of a wide variety of pharmaceutical powders. Emphases are placed on different roll compactor options and their ability to precisely control the roll force and roll gap, perform efficient deaeration, and minimize powder leakage.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 99.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 129.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 199.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Acevedo D, Muliadi A, Giridhar A, Litster JD, Romanach RJ. Evaluation of three approaches for real-time monitoring of roller compaction with near-infrared spectroscopy. AAPS PharmSciTech. 2012;13:1005–12. https://doi.org/10.1208/s12249-012-9825-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Allesø M, Holm R, Holm P. Roller compaction scale-up using roll width as scale factor and laser-based determined ribbon porosity as critical material attribute. Eur J Pharm Sci. 2016;87:69–78.

    Article  PubMed  CAS  Google Scholar 

  • am Ende MT, et al. Improving the content uniformity of a low-dose tablet formulation through roller compaction optimization. Pharm Dev Technol. 2007;12:391–404. https://doi.org/10.1080/10837450701369253.

    Article  CAS  Google Scholar 

  • Bi M, Alvarez-Nunez F, Alvarez F. Evaluating and modifying Johanson’s rolling model to improve its predictability. J Pharm Sci. 2014;103:2062–71.

    Article  CAS  PubMed  Google Scholar 

  • Bindhumadhavan G, Seville JPK, Adams MJ, Greenwood RW, Fitzpatrick S. Roll compaction of a pharmaceutical excipient: experimental validation of rolling theory for granular solids. Chem Eng Sci. 2005;60:3891–7.

    Article  CAS  Google Scholar 

  • Boersen N, Belair D, Peck GE, Pinal R. A dimensionless variable for the scale up and transfer of a roller compaction formulation. Drug Dev Ind Pharm. 2016;42:60–9.

    Article  CAS  PubMed  Google Scholar 

  • Crowley ME, et al. Near-infrared monitoring of roller compacted ribbon density: investigating sources of variation contributing to noisy spectral data. Eur J Pharm Sci. 2017;102:103–14. https://doi.org/10.1016/j.ejps.2017.02.024.

    Article  CAS  PubMed  Google Scholar 

  • Csordas K, Kleinebudde P. Evaluation of the performance of different types of roll compactors. Powder Technol. 2017; https://doi.org/10.1016/j.powtec.2017.04.009.

  • Cunningham JC. Experimental studies and modeling of the roller compaction of pharmaceutical powders. PhD thesis, Drexel University; 2005.

    Google Scholar 

  • Cunningham JC, Winstead D, Zavaliangos A. Understanding variation in roller compaction through finite element-based process modeling. Comput Chem Eng. 2010;34:1058–71.

    Article  CAS  Google Scholar 

  • Dawes J, Gamble JF, Greenwood R, Robbins P, Tobyn M. An investigation into the impact of magnesium stearate on powder feeding during roller compaction. Drug Dev Ind Pharm. 2012;38:111–22.

    Article  CAS  PubMed  Google Scholar 

  • Dec RT. Study of compaction process in roll press. Proc Inst Briquet Agglomerat. 1991;22:207–18.

    CAS  Google Scholar 

  • Dec RT, Zavaliangos A, Cunningham JC. Comparison of various modeling methods for analysis of powder compaction in roller press. Powder Technol. 2003;130:265–71.

    Article  CAS  Google Scholar 

  • Deshmukh AR, Sundararajan T, Dube RK, Bhargava S. Analysis of cold densification rolling of a sintered porous metal strip. J Mater Process Technol. 1998;84:56–72.

    Article  Google Scholar 

  • Fahmy R, et al. Quality by design I: application of failure mode effect analysis (FMEA) and Plackett-Burman design of experiments in the identification of “main factors” in the formulation and process design space for roller-compacted ciprofloxacin hydrochloride immediate-release tablets. AAPS PharmSciTech. 2012;13:1243–54. https://doi.org/10.1208/s12249-012-9844-x.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gago AP, Reynolds G, Kleinebudde P. Impact of roll compactor scale on ribbon density. Powder Technol. 2018; 337:92–103.

    Google Scholar 

  • Guigon P, Simon O. Roll press design—influence of force feed systems on compaction. Powder Technol. 2003;130:41–8. https://doi.org/10.1016/S0032-5910(02)00223-1.

    Article  CAS  Google Scholar 

  • Gun GY, Stebunov SA, Katashinskii VP. Computer modeling and investigation of the metal powder rolling processes. Powder Metall Metal Ceram. 1986;25:8–11.

    Article  Google Scholar 

  • Gupta A, Peck GE, Miller RW, Morris KR. Effect of the variation in the ambient moisture on the compaction behavior of powder undergoing roller-compaction and on the characteristics of tablets produced from the post-milled granules. J Pharm Sci. 2005;94:2314–26. https://doi.org/10.1002/jps.20414.

    Article  CAS  PubMed  Google Scholar 

  • Gurson AL. Continuum theory of ductile rupture by void nucleation and growth: Part 1–yield criteria and flow rules for porous ductile media. ASME J Eng Mater Technol. 1977;99:2–15.

    Article  Google Scholar 

  • Hancock BC, Vendola TA. The effect of mill type on two dry-granulated placebo formulations. AAPS PharmSciTech. 2008;32

    Google Scholar 

  • Hancock B, Colvin JT, Mullarney MP, Zinchuk AV. The relative densities of pharmaceutical powders, blends, dry granulations, and immediate-release tablets. Pharm Technol. 2003;27:64–80.

    CAS  Google Scholar 

  • He X, Secreast PJ, Amidon GE. Mechanistic study of the effect of roller compaction and lubricant on tablet mechanical strength. J Pharm Sci. 2007;96:1342–55.

    Article  CAS  PubMed  Google Scholar 

  • Inghelbrecht S, Paul Remon J. The roller compaction of different types of lactose. Int J Pharm. 1998a;166:135–44. https://doi.org/10.1016/S0378-5173(98)00022-2.

    Article  CAS  Google Scholar 

  • Inghelbrecht S, Paul Remon J. Roller compaction and tabletting of microcrystalline cellulose/drug mixtures. Int J Pharm. 1998b;161:215–24.

    Article  CAS  Google Scholar 

  • Iyer RM, Hegde S, DiNunzio J, Singhal D, Malick W. The impact of roller compaction and tablet compression on physicomechanical properties of pharmaceutical excipients. Pharm Dev Technol. 2014;19:583–92.

    Article  CAS  PubMed  Google Scholar 

  • Johanson JR. A rolling theory for granular solids. J Appl Mech. 1965;32:842–8.

    Google Scholar 

  • Katashinskii VP. Analytical determination of specific pressure during the rolling of metal powders. Powder Metall Metal Ceram. 1986;5:765–72.

    Google Scholar 

  • Katashinskii VP, Shtern MB. Stress-strain state of powder being rolled in the densification zone–II. Distribution of density, longitudinal strain, and contact stress in the densification zone. Powder Metall Metal Ceram. 1983a;22:972–6.

    Article  Google Scholar 

  • Katashinskii VP, Shtern MB. Stress-strain state of powder being rolled in the densification zone–I. mathematical model of rolling in the densification zone. Powder Metall Metal Ceram. 1983b;22:882–5.

    Article  Google Scholar 

  • Kleinebudde P. Roll compaction/dry granulation: pharmaceutical applications. Eur J Pharm Biopharm. 2004;58:317–26. https://doi.org/10.1016/j.ejpb.2004.04.014.

    Article  CAS  PubMed  Google Scholar 

  • Krok A, Peciar M, Fekete R. Using the DPIV optical technique to measure the velocity of powder material in the space between the rollers in a roll compactor. Powder Technol. 2014;262:131–41. https://doi.org/10.1016/j.powtec.2014.04.067.

    Article  CAS  Google Scholar 

  • Kushner J, Langdon BA, Hiller JI, Carlson GT. Examining the impact of excipient material property variation on drug product quality attributes: a quality-by-design study for a roller compacted, immediate release tablet. J Pharm Sci. 2011;100:2222–39.

    Article  CAS  PubMed  Google Scholar 

  • LaMarche K, Buckley D, Hartley R, Qian F, Badawy S. Assessing materials’ tablet compaction properties using the Drucker–Prager Cap model. Powder Technol. 2014;267:208–20.

    Google Scholar 

  • Liu Y, Wassgren C. Modifications to Johanson’s roll compaction model for improved relative density predictions. Powder Technol. 2016;297:294–302. https://doi.org/10.1016/j.powtec.2016.04.017.

    Article  CAS  Google Scholar 

  • Liu Z, et al. Scale-up of a pharmaceutical roller compaction process using a joint-Y partial least squares model. Ind Eng Chem Res. 2011;50:10696–706.

    Article  CAS  Google Scholar 

  • Mazor A, Perez-Gandarillas L, de Ryck A, Michrafy A. Effect of roll compactor sealing system designs: a finite element analysis. Powder Technol. 2016;289:21–30. https://doi.org/10.1016/j.powtec.2015.11.039.

    Article  CAS  Google Scholar 

  • Mazor A, Orefice L, Michrafy A, de Ryck A, Khinast JG. A combined DEM & FEM approach for modelling roll compaction process. Powder Technol. 2017; https://doi.org/10.1016/j.powtec.2017.04.053.

  • McCann R, Muliadi A, Paaso J, Litster JD, Pinal R. On-line monitoring of roller compaction ribbon density using NIR spectroscopy. Paper presented at the AIChE annual meeting, Salt Lake City, UT, 7–12 November 2010.

    Google Scholar 

  • Metzler C, et al. A rapid, materials-sparing approach to the exploration of a roller compaction process design space. Paper presented at the AIChE annual meeting, San Francisco, CA, 13–18 November 2016.

    Google Scholar 

  • Michrafy A, Diarra H, Dodds JA, Michrafy M. Experimental and numerical analyses of homogeneity over strip width in roll compaction. Powder Technol. 2011;206:154–60. https://doi.org/10.1016/j.powtec.2010.04.030.

    Article  CAS  Google Scholar 

  • Miguelez-Moran AM, Wu C-Y, Seville JP. The effect of lubrication on density distributions of roller compacted ribbons. Int J Pharm. 2008;362:52–9.

    Article  CAS  PubMed  Google Scholar 

  • Miguelez-Moran AM, Wu CY, Dong H, Seville JP. Characterisation of density distributions in roller-compacted ribbons using micro-indentation and X-ray micro-computed tomography. Eur J Pharm Biopharm. 2009;72:173–82. https://doi.org/10.1016/j.ejpb.2008.12.005.

    Article  CAS  PubMed  Google Scholar 

  • Miller RW. Roller compaction technology. In Parikh DM, editor. In Handbook of pharmaceutical granulation technology. Marcel Dekker; New York, NY. 1997.

    Google Scholar 

  • Miller T, York P. Pharmaceutical tablet lubrication. Int J Pharm. 1988;41:1–19.

    Article  CAS  Google Scholar 

  • Mosig J, Kleinebudde P. Critical evaluation of root causes of the reduced compactability after roll compaction/dry granulation. J Pharm Sci. 2015;104:1108–18.

    Article  CAS  PubMed  Google Scholar 

  • Muliadi AR, Litster JD, Wassgren CR. Modeling the powder roll compaction process: comparison of 2-D finite element method and the rolling theory for granular solids (Johanson’s model). Powder Technol. 2012;221:90–100.

    Article  CAS  Google Scholar 

  • Muliadi AR, Litster JD, Wassgren CR. Validation of 3-D finite element analysis for predicting the density distribution of roll compacted pharmaceutical powder. Powder Technol. 2013;237:386–99. https://doi.org/10.1016/j.powtec.2012.12.023.

    Article  CAS  Google Scholar 

  • Nesarikar VV, et al. Roller compaction process development and scale up using Johanson model calibrated with instrumented roll data. Int J Pharm. 2012a;436:486–507.

    Article  CAS  PubMed  Google Scholar 

  • Nesarikar VV, et al. Instrumented roll technology for the design space development of roller compaction process. Int J Pharm. 2012b;426:116–31. https://doi.org/10.1016/j.ijpharm.2012.01.032.

    Article  CAS  PubMed  Google Scholar 

  • Omar CS, et al. Roller compaction: effect of morphology and amorphous content of lactose powder on product quality. Int J Pharm. 2015;496:63–74.

    Article  CAS  PubMed  Google Scholar 

  • Otsuka M, Yamane I, Matsuda Y. Effects of lubricant mixing on compression properties of various kinds of direct compression excipients and physical properties of the tablets. Adv Powder Technol. 2004;15:477–93.

    Article  Google Scholar 

  • Perez-Gandarillas L, et al. Effect of roll-compaction and milling conditions on granules and tablet properties. Europ J Pharm Biopharm. 2016;106:38–49. https://doi.org/10.1016/j.ejpb.2016.05.020.

    Article  CAS  Google Scholar 

  • Reimer HL, Kleinebudde P. Hybrid modeling of roll compaction process with the Styl’One evolution. Powder Technol. 2019;341:66–74.

    Article  CAS  Google Scholar 

  • Reynolds G, Ingale R, Roberts R, Kothari S, Gururajan B. Practical application of roller compaction process modeling. Comput Chem Eng. 2010;34:1049–57.

    Article  CAS  Google Scholar 

  • Rowe JM, et al. Mechanistic insights into the scale-up of the roller compaction process: a practical and dimensionless approach. J Pharm Sci. 2013;102:3586–95.

    Article  CAS  PubMed  Google Scholar 

  • Sakwanichol J, Puttipipatkhachorn S, Ingenerf G, Kleinebudde P. Roll compaction/dry granulation: comparison between roll mill and oscillating granulator in dry granulation. Pharm Dev Technol. 2012;17:30–9. https://doi.org/10.3109/10837450.2010.508078.

    Article  CAS  PubMed  Google Scholar 

  • Samanta AK, Ng KY, Heng PW. Cone milling of compacted flakes: process parameter selection by adopting the minimal fines approach. Int J Pharm. 2012;422:17–23. https://doi.org/10.1016/j.ijpharm.2011.10.015.

    Article  CAS  PubMed  Google Scholar 

  • Sheskey P, Pacholke K, Sackett G, Maher L, Polli J. Effect of process scale-up on robustness of tablets, tablet stability, and predicted in vivo performance. Pharm Technol. 2000;24:30–52.

    CAS  Google Scholar 

  • Shi W, Hajedemos D, Sprockel O. An energetic approach of powder mixing by manipulating cohesive interaction in a magnetic field. Powder Technol. 2013;235:400–4.

    Article  CAS  Google Scholar 

  • Shima S, Yamada M. Compaction of metal powder by rolling. Powder Metall. 1984;27:39–44.

    Article  CAS  Google Scholar 

  • Simon O, Guigon P. Correlation between powder-packing properties and roll-press compact heterogeneity. Powder Technol. 2003;130:257–64.

    Article  CAS  Google Scholar 

  • Sommer K, Hauser G. Flow and compression properties of feed solids for roll-type presses and extrusion presses. Powder Technol. 2003;130:272–6. https://doi.org/10.1016/s0032-5910(02)00204-8.

    Article  CAS  Google Scholar 

  • Souihi N, et al. A quality by design approach to investigate the effect of mannitol and dicalcium phosphate qualities on roll compaction. Int J Pharm. 2013a;447:47–61.

    Article  CAS  PubMed  Google Scholar 

  • Souihi N, Josefson M, Tajarobi P, Gururajan B, Trygg J. Design space estimation of the roller compaction process. Ind Eng Chem Res. 2013b;52:12408–19. https://doi.org/10.1021/ie303580y.

    Article  CAS  Google Scholar 

  • Souihi N, et al. Roll compaction process modeling: transfer between equipment and impact of process parameters. Int J Pharm. 2015;484:192–206. https://doi.org/10.1016/j.ijpharm.2015.02.042.

    Article  CAS  PubMed  Google Scholar 

  • Sun CC, Himmelspach MW. Reduced tabletability of roller compacted granules as a result of granule size enlargement. J Pharm Sci. 2006;95:200–6. https://doi.org/10.1002/jps.20531.

    Article  CAS  PubMed  Google Scholar 

  • Sun CC, Kleinebudde P. Mini review: mechanisms to the loss of tabletability by dry granulation. Eur J Pharm Biopharm. 2016;106:9–14.

    Article  CAS  PubMed  Google Scholar 

  • Teng Y, Qiu Z, Wen H. Systematical approach of formulation and process development using roller compaction. Eur J Pharm Biopharm. 2009;73:219–29. https://doi.org/10.1016/j.ejpb.2009.04.008.

    Article  CAS  PubMed  Google Scholar 

  • Tezyk M, Jakubowska E, Milanowski B, Lulek J. Implementation of quality by design approach in manufacturing process optimization of dry granulated, immediate release, coated tablets – a case study. Drug Dev Ind Pharm. 2017;43:1626–36. https://doi.org/10.1080/03639045.2017.1328431.

    Article  CAS  PubMed  Google Scholar 

  • von Eggelkraut-Gottanka SG, Abed SA, Muller W, Schmidt PC. Roller compaction and tabletting of St. John’s wort plant dry extract using a gap width and force controlled roller compactor. II. Study of roller compaction variables on granule and tablet properties by a 3×3 factorial design. Pharm Dev Technol. 2002;7:447–55.

    Article  CAS  Google Scholar 

  • Vromans H, Bolhuis G, Lerk C, Van de Biggelaar H, Bosch H. Studies on tableting properties of lactose. VII. The effect of variations in primary particle size and percentage of amorphous lactose in spray dried lactose products. Int J Pharm. 1987;35:29–37.

    Article  CAS  Google Scholar 

  • Wang W, Cunningham JC, Zavaliangos A. The effect of side constraint in rolling compaction of powders. Paper presented at the international conference on powder metallurgy and particulate materials, Las Vegas, NV, 8-12 June 1998.

    Google Scholar 

  • Wang J, Wen H, Desai D. Lubrication in tablet formulations. Eur J Pharm Biopharm. 2010;75:1–15.

    Article  PubMed  CAS  Google Scholar 

  • Wu SJ, Sun C. Insensitivity of compaction properties of brittle granules to size enlargement by roller compaction. J Pharm Sci. 2007;96:1445–50. https://doi.org/10.1002/jps.20929.

    Article  CAS  PubMed  Google Scholar 

  • Yu S. Roll compaction of pharmaceutical excipients. Ph.D. thesis, University of Birmingham; 2012.

    Google Scholar 

  • Yu S, et al. The effects of lubrication on roll compaction, ribbon milling and tabletting. Chem Eng Sci. 2013;86:9–18.

    Article  CAS  Google Scholar 

  • Yusof YA, Smith AC, Briscoe BJ. Roll compaction of maize powder. Chem Eng Sci. 2005;60:3919–31.

    Article  CAS  Google Scholar 

  • Zavaliangos A, Dec RT, Komarek RK. Analysis of powder processing in the roller press using finite element modeling. Paper presented at the XXII international mineral processing congress, Cape Town, South Africa, 29 September – 3 October 2003.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Genentech Inc., Small Molecule Pharmaceutical Sciences, Research and Early Development (gRED), South San Francisco, CA, USA

    Ariel R. Muliadi, Alamelu Banda & Chen Mao

Authors
  1. Ariel R. Muliadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alamelu Banda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Chen Mao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ariel R. Muliadi .

Editor information

Editors and Affiliations

  1. Davidson School of Chemical Engineering, Purdue University, West Lafayette, IN, USA

    Zoltan K Nagy

  2. Faculty of Pharmacy, Cairo University, Cairo, Egypt

    Arwa El Hagrasy

  3. Department of Chemical and Biochemical Engineering, The University of Sheffield, Sheffield, UK

    Jim Litster

Rights and permissions

Reprints and permissions

Copyright information

© 2020 American Association of Pharmaceutical Scientists

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Muliadi, A.R., Banda, A., Mao, C. (2020). Recent Progress in Roll Compaction Process Development for Pharmaceutical Solid Dosage Form Manufacture. In: Nagy, Z., El Hagrasy, A., Litster, J. (eds) Continuous Pharmaceutical Processing. AAPS Advances in the Pharmaceutical Sciences Series, vol 42. Springer, Cham. https://doi.org/10.1007/978-3-030-41524-2_7

Download citation

Publish with us

Policies and ethics

Search

Navigation