AAPS PharmSciTech

, Volume 12, Issue 3, pp 834–853 | Cite as

A Quantitative Correlation of the Effect of Density Distributions in Roller-Compacted Ribbons on the Mechanical Properties of Tablets Using Ultrasonics and X-ray Tomography

  • Ilgaz Akseli
  • Srinivas Iyer
  • Hwahsiung P. Lee
  • Alberto M. Cuitiño
Research Article Theme: Quality by Design: Case Studies and Scientific Foundations


Enabling the paradigm of quality by design requires the ability to quantitatively correlate material properties and process variables to measureable product performance attributes. In this study, we show how heterogeneities in compacted ribbon densities quantitatively correlate to tablet mechanical properties. These density variations, which have been purposely modulated by internal and external lubrications, are characterized longitudinally and transversally by nondestructive ultrasonic and X-ray micro-computed tomography measurements. Subsequently, different transversal regions of the compacted ribbon are milled under the same conditions, and granules with nominally the same particle size distribution are utilized to manufacture cylindrical tablets, whose mechanical properties are further analyzed by ultrasonic measurements. We consider three different ribbon conditions: no lubrication (case 1); lubricated powder (case 2); and lubricated tooling (hopper, side sealing plates, feed screws, and rolls) (case 3). This study quantitatively reveals that variation in local densities in ribbons (for case 1) and process conditions (i.e., internal case 2 and external lubrication case 3) during roller compaction significantly affect the mechanical properties of tablets even for granules with the same particle size distribution. For case 1, the mechanical properties of tablets depend on the spatial location where granules are produced. For cases 2 and 3, the ribbon density homogeneity was improved by the use of a lubricant. It is demonstrated that the mechanical performances of tablets are decreased due to applied lubricant and work-hardening phenomenon. Moreover, we extended our study to correlate the speed of sound to the tensile strength of the tablet. It is found that the speed of sound increases with the tensile strength for the tested tablets.

Key words

density distribution elastic properties nondestructive ultrasonic technique roller compaction tensile strength x-ray micro-computed tomography 


  1. 1.
    Miller RW. Roller compaction technology. In: Parikh DM, editor. Handbook of pharmaceutical granulation technology. New York: Marcel Dekker; 1997. p. 100–49.Google Scholar
  2. 2.
    Adeyeye MC. Roller compaction and milling pharmaceutical unit processes: part I. Am Pharm Rev. 2000;3:37–42.Google Scholar
  3. 3.
    Sheskey PJ, Hendren J. The effects of roll compaction equipment variables granulation technique and HPMC polymer level on a controlled-release matrix model drug formulation. Pharm Technol. 1999;23:90–106.Google Scholar
  4. 4.
    Simon O, Guigon P. Correlation between powder-packing properties and roll press compact heterogeneity. Powder technol. 2003;130:257–64.CrossRefGoogle Scholar
  5. 5.
    Kleinebudde P. Roll compaction/dry granulation: pharmaceutical applications. Eur J Pharm Biopharm. 2004;58:317–26.PubMedCrossRefGoogle Scholar
  6. 6.
    Zinchuk AV, Mullarney MP, Hancock BC. Simulation of roller compaction using a laboratory scale compaction simulator. Int J Pharm. 2004;269:403–15.PubMedCrossRefGoogle Scholar
  7. 7.
    Weyenberg W, Vermeire A, Vandervoort J, Remon JP, Ludwig A. Effects of roller compaction settings on the preparation of bioadhesive granules on ocular minitablets. Eur J Pharm Biopharm. 2005;59:527–36.PubMedCrossRefGoogle Scholar
  8. 8.
    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.CrossRefGoogle Scholar
  9. 9.
    Xiaorong H, Pamela JS, Gregory EA. Mechanistic study of the effect of roller compaction and lubricant on tablet mechanical strength. J Pharm Sci. 2007;96:1342–55.CrossRefGoogle Scholar
  10. 10.
    Farber L, Hapgood KP, Michaels JN, Fu XY, Meyer R, Johnson MA, et al. Unified compaction curve model for tensile strength of tablets made by roller compaction and direct compression. Int J Pharm. 2008;346:17–24.PubMedCrossRefGoogle Scholar
  11. 11.
    Miguélez-Morán AM, Wu CY, Dong H, Seville JPK. 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.PubMedCrossRefGoogle Scholar
  12. 12.
    Mitchell SA, Reynolds TD, Dasbach TP. A compaction process to enhance dissolution of poorlywatersoluble drugs using hydroxypropyl methylcellulose. Int J Pharm. 2003;250:3–11.PubMedCrossRefGoogle Scholar
  13. 13.
    Funakoshi Y, Asogawa T, Satake E. Use of a novel roller compactor with a concavo-convex roller pair to obtain uniform compacting pressure. Drug Dev Ind Pharm. 1977;6:555–73.CrossRefGoogle Scholar
  14. 14.
    Malkowska S, Khan KA. Effect of recompression on the properties of tablets prepared by dry granulation. Drug Dev Ind Pharm. 1983;9:331–47.CrossRefGoogle Scholar
  15. 15.
    Roberts RJ, Rowe RC. Relationships between the modulus of elasticity and tensile strength for pharmaceutical drugs and excipients. J Pharm Pharmacol. 1999;51:975–7.PubMedCrossRefGoogle Scholar
  16. 16.
    Podczeck F, Drake KR, Newton JM, Haririan I. The strength of bilayered tablet. Eur J Pharm Sci. 2006;29:361–6.PubMedCrossRefGoogle Scholar
  17. 17.
    Akseli I, Mani G, Cetinkaya C. Non-destructive acoustic defect detection in drug tablets. Int J Pharm. 2008;360:65–76.PubMedCrossRefGoogle Scholar
  18. 18.
    Hein S, Picker-Freyer KM. Simulation of roller compaction with subsequent tableting and characterization of lactose and microcrystalline cellulose. Pharm Dev Technol. 2008;13:523–32.PubMedCrossRefGoogle Scholar
  19. 19.
    Sheskey PJ, Cabelka TD, Robb RT, Boyce BM. Use of roller compaction in the preparation of controlled-release hydrophilic matrix tablets containing methylcellulose and hydroxypropyl methylcellulose polymers. Pharm Technol. 1994;9:133–50.Google Scholar
  20. 20.
    Sun CC, Himmelspach MW. Reduced tabletability of roller compacted granules as a result of granule size enlargement. J Pharm Sci. 2006;95:200–6.PubMedCrossRefGoogle Scholar
  21. 21.
    Alderborn G, Nystrom C. Studies on direct compression of tablets. III. The effect on tablet strength of changes in particle shape and texture obtained by milling. Acta Pharm Suec. 1982;19:147–56.PubMedGoogle Scholar
  22. 22.
    Luangtana-Anan M, Fell JT. Bonding mechanisms in tabletting. Int J Pharm. 1990;60:197–202.CrossRefGoogle Scholar
  23. 23.
    Kadiri MS, Michrafy A, Dodds JA. Pharmaceutical powders compaction: experimental and numerical analysis of the density distribution. Powder Technol. 2005;157:176–82.CrossRefGoogle Scholar
  24. 24.
    Hancock BC, Clas SD, Christensen K. Micro-scale measurement of the mechanical properties of compressed pharmaceutical powders. 1: The elasticity and fracture behaviour of microcrystalline cellulose. Int J Pharm. 2000;209:27–35.PubMedCrossRefGoogle Scholar
  25. 25.
    Eichhorn SJ, Young RJ. The Young’s modulus of microcrystalline cellulose. Cellulose. 2001;8:197–207.CrossRefGoogle Scholar
  26. 26.
    Akseli I, Libordi C, Cetinkaya C. Real-time acoustic elastic property monitoring of compacts during compaction. J Pharm Innov. 2008;3:134–40.CrossRefGoogle Scholar
  27. 27.
    Akseli I, Becker DC, Cetinkaya C. Ultrasonic determination of Young’s Moduli’s of the coat and core of a drug tablet. Int J Pharm. 2009;370:17–25.PubMedCrossRefGoogle Scholar
  28. 28.
    Akseli I, Hancock BC, Cetinkaya C. Anisotropic mechanical property testing for the development of pharmaceutical dosage forms. Int J Pharm. 2009;377:35–44.PubMedCrossRefGoogle Scholar
  29. 29.
    Akseli I, Dey D, Cetinkaya C. Mechanical property characterization of bilayered tablets using nondestructive air-coupled acoustics. AAPS PharmSciTech. 2010;11:90–102.PubMedCrossRefGoogle Scholar
  30. 30.
    Busignies V, Leclerc B, Porion P, Evesque P, Couarraze G, Tchoreloff P. Quantitative measurements of localized density variations in cylindrical tablets using X-ray microtomography. Eur J Pharm Biopharm. 2006;64:38–50.PubMedCrossRefGoogle Scholar
  31. 31.
    Sinka IC, Burch SF, Tweed JH, Cunningham JC. Measurement of density variations in tablets using X-ray computed tomography. Int J Pharm. 2004;271:215–24.PubMedCrossRefGoogle Scholar
  32. 32.
    Hancock BC, Mullarney MP. X-ray microtomography of solid dosage forms. Pharmaceut Tech. 2005;2:92–100.Google Scholar
  33. 33.
    Kak AC. Computerized tomography with X-ray, emission and ultrasound sources. Proc IEEE. 1979;67:1245–72.CrossRefGoogle Scholar
  34. 34.
    Hancock BC, Colvin JT, Mullarney PM, Zinchuk AV. The relative densities of pharmaceutical powders, blends, dry granulations, and immediate-release tablets. Pharm Technol. 2003;27:64–80.Google Scholar
  35. 35.
    Heckel RW. Density–pressure relationships in powder compaction. Trans Metall Soc AIME. 1961;221:671–5.Google Scholar
  36. 36.
    Denny PJ. Compaction equations: a comparison of the Heckel and Kawakita equations. Powder Technol. 2002;127:162–72.CrossRefGoogle Scholar
  37. 37.
    Hersey, J.A. and Rees, J.E., 1970. The effect of particle size on the consolidation of powders during compaction. Particle Size Analysis Conference, 2nd edn. University of Bradford: Bradford, UKGoogle Scholar
  38. 38.
    Fell JT, Newton JM. Determination of tablet strength by the diametral-compression test. J Pharm Sci. 1970;59:688–91.PubMedCrossRefGoogle Scholar
  39. 39.
    Krycer I, Pope DV, Hersey JA. An evaluation of the techniques employed to investigate powder compaction behavior. Int J Pharm. 1982;12:113–34.CrossRefGoogle Scholar
  40. 40.
    Johansson B, Alderborn G. Degree of pellet deformation during compaction and its relationship to the tensile strength of tablets formed of microcrystalline cellulose pellets. Int J Pharm. 1996;132:207–20.CrossRefGoogle Scholar
  41. 41.
    Aulton ME, Tebby HG, White PJ. Indentation hardness testing of tablets. J Pharm Pharmacol. 1974;26(Suppl):59P–60P.PubMedCrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2011

Authors and Affiliations

  • Ilgaz Akseli
    • 1
  • Srinivas Iyer
    • 1
  • Hwahsiung P. Lee
    • 1
  • Alberto M. Cuitiño
    • 1
  1. 1.Department of Mechanical and Aerospace EngineeringRutgers UniversityPiscatawayUSA

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