AAPS PharmSciTech

, Volume 15, Issue 1, pp 131–139 | Cite as

Influence of Starting Material Particle Size on Pellet Surface Roughness

  • Srimanta Sarkar
  • Bee Hwee Ang
  • Celine Valeria Liew
Research Article

Abstract

The purpose of this study was to investigate the effect of pelletization aids, i.e., microcrystalline cellulose (MCC) and cross-linked polyvinyl pyrrolidone (XPVP), and filler, i.e., lactose, particle size on the surface roughness of pellets. Pellets were prepared from powder blends containing pelletization aid/lactose in 1:3 ratio by extrusion–spheronization. Surface roughness of pellets was assessed quantitatively and qualitatively using optical interferometry and scanning electron microscopy, respectively. Both quantitative and qualitative surface studies showed that surface roughness of pellets depended on the particle size of XPVP and lactose used in the formulation. Increase in XPVP or lactose particle size resulted in rougher pellets. Formulations containing MCC produced pellets with smoother surfaces than those containing XPVP. Furthermore, surface roughness of the resultant pellets did not appear to depend on MCC particle size. Starting material particle size was found to be a critical factor for determining the surface roughness of pellets produced by extrusion–spheronization. Smaller particles can pack well with lower peaks and valleys, resulting in pellets with smoother surfaces. Similar surface roughness of pellets containing different MCC grades could be due to the deaggregation of MCC particles into smaller subunits with more or less similar sizes during wet processing. Hence, for starting materials that deaggregate during the wet processing, pellet surface roughness is influenced by the particle size of the material upon deaggregation.

KEY WORDS

extrusion–spheronization filler particle size pelletization aid surface roughness 

Notes

ACKNOWLEDGMENTS

The authors wish to acknowledge research funding support from GEA-NUS Pharmaceutical Processing Research Laboratory fund (N-148-000-008-001) and A*STAR SERC grant number 102 161 0049 (R-148-000-157-305).

REFERENCES

  1. 1.
    Rodriguez EC, Torrado JJ, Nikolakakis I, Torrado S, Lastres JL, Malamataris S. Micromeritic and packing properties of diclofenac pellets and effects of some formulation variables. Drug Dev Ind Pharm. 2001;27(8):847–55.PubMedCrossRefGoogle Scholar
  2. 2.
    Chopra R, Podczeck F, Newton JM, Alderborn G. The influence of film coating on the surface roughness and specific surface area of pellets. Part Part Syst Charact. 2002;19(4):277–83.CrossRefGoogle Scholar
  3. 3.
    Podczeck F, Brown S, Newton JM. Monitoring film coating with surface profilometry. Pharm Technol. 1999;23(5):48–56.Google Scholar
  4. 4.
    Andersson M, Holmquist B, Lindquist J, Nilsson O, Wahlund KG. Analysis of film coating thickness and surface area of pharmaceutical pellets using fluorescence microscopy and image analysis. J Pharm Biomed Anal. 2000;22(2):325–39.PubMedCrossRefGoogle Scholar
  5. 5.
    Chopra R, Newton JM, Alderborn G, Podczeck F. Preparation of pellets of different shape and their characterization. Pharm Dev Technol. 2001;6(4):495–503.PubMedCrossRefGoogle Scholar
  6. 6.
    Hellen L, Yliruusi J, Kristoffersson E. Process variables of instant granulator and spheroniser: II. Size and size distributions of pellets. Int J Pharm. 1993;96(1–3):205–16.CrossRefGoogle Scholar
  7. 7.
    Hellen L, Yliruusi J. Process variables of instant granulator and spheroniser: III. Shape and shape distributions of pellets. Int J Pharm. 1993;96(1–3):217–23.CrossRefGoogle Scholar
  8. 8.
    Hellen L, Yliruusi J, Merkku P, Kristoffersson E. Process variables of instant granulator and spheroniser: I. Physical properties of granules, extrudate and pellets. Int J Pharm. 1993;96(1–3):197–204.CrossRefGoogle Scholar
  9. 9.
    Soh JLP, Yang L, Liew CV, Cui FD, Heng PWS. Importance of small pores in microcrystalline cellulose for controlling water distribution during extrusion–spheronization. AAPS PharmSciTech. 2008;9(3):972–81.PubMedCentralPubMedCrossRefGoogle Scholar
  10. 10.
    Sinha VR, Agrawal MK, Kumria R. Influence of formulation and excipient variables on the pellet properties prepared by extrusion spheronization. Curr Drug Deliv. 2005;2(1):1–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Heng PWS, Koo OMY. A study of the effects of the physical characteristics of microcrystalline cellulose on performance in extrusion spheronization. Pharm Res. 2001;18(4):480–7.PubMedCrossRefGoogle Scholar
  12. 12.
    Liew CV, Gu L, Soh JLP, Heng PWS. Functionality of cross-linked polyvinylpyrrolidone as a spheronization aid: a promising alternative to microcrystalline cellulose. Pharm Res. 2005;22(8):1387–98.Google Scholar
  13. 13.
    Verheyen P, Steffens KJ, Kleinebudde P. Use of crospovidone as pelletization aid as alternative to microcrystalline cellulose: effects on pellet properties. Drug Dev Ind Pharm. 2009;35(11):1325–32.PubMedCrossRefGoogle Scholar
  14. 14.
    Sarkar S, Heng PWS, Liew CV. Insights into the functionality of pelletization aid in pelletization by extrusion–spheronization. Pharm Dev Technol. 2013;18(1):61–72.PubMedCrossRefGoogle Scholar
  15. 15.
    Bornhöft M, Thommes M, Kleinebudde P. Preliminary assessment of carrageenan as excipient for extrusion/spheronisation. Eur J Pharm Biopharm. 2005;59(1):127–31.PubMedCrossRefGoogle Scholar
  16. 16.
    Thommes M, Kleinebudde P. The behavior of different carrageenans in pelletization by extrusion/spheronization. Pharm Dev Technol. 2008;13(1):27–35.PubMedCrossRefGoogle Scholar
  17. 17.
    Agrawal AM, Howard MA, Neau SH. Extruded and spheronized beads containing no microcrystalline cellulose: influence of formulation and process variables. Pharm Dev Technol. 2004;9(2):197–217.PubMedCrossRefGoogle Scholar
  18. 18.
    Charoenthai N, Kleinebudde P, Puttipipatkhachorn S. Use of chitosan-alginate as alternative pelletization aid to macrocrystalline cellulose in extrusion/spheronization. J Pharm Sci. 2007;96(9):2469–84.PubMedCrossRefGoogle Scholar
  19. 19.
    Chatlapalli R, Rohera BD. Rheological characterization of diltiazem HCl/cellulose wet masses using a mixer torque rheometer. Int J Pharm. 1998;175(1):47–59.CrossRefGoogle Scholar
  20. 20.
    Chatlapalli R, Rohera BD. Physical characterization of HPMC and HEC and investigation of their use as pelletization aids. Int J Pharm. 1998;161(2):179–93.CrossRefGoogle Scholar
  21. 21.
    Alvarez L, Concheiro A, Gómez-Amoza JL, Souto C, Martínez-Pacheco R. Powdered cellulose as excipient for extrusion–spheronization pellets of a cohesive hydrophobic drug. Eur J Pharm Biopharm. 2003;55(3):291–5.PubMedCrossRefGoogle Scholar
  22. 22.
    Fechner PM, Wartewig S, Füting M, Heilmann A, Neubert RHH, Kleinebudde P. Properties of microcrystalline cellulose and powder cellulose after extrusion/spheronization as studied by Fourier transform Raman spectroscopy and environmental scanning electron microscopy. AAPS J. 2003;5(4):XXI–II.Google Scholar
  23. 23.
    Dukić-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.PubMedCrossRefGoogle Scholar
  24. 24.
    Fielden KE, Newton JM, Rowe RC. The effect of lactose particle size on the extrusion properties of microcrystalline cellulose–lactose mixtures. J Pharm Pharmacol. 1989;41(4):217–21.PubMedCrossRefGoogle Scholar
  25. 25.
    Fielden KE, Newton JM, Rowe RC. The influence of lactose particle size on spheronization of extrudate processed by a ram extruder. Int J Pharm. 1992;81(2–3):205–24.CrossRefGoogle Scholar
  26. 26.
    Wan LSC, Heng PWS, Liew CV. Spheronization conditions on spheroid shape and size. Int J Pharm. 1993;96(1–3):59–65.CrossRefGoogle Scholar
  27. 27.
    Fielden KE, Newton JM, Rowe RC. The influence of moisture content on spheronization of extrudate processed by a ram extruder. Int J Pharm. 1993;97(1–3):79–92.CrossRefGoogle Scholar
  28. 28.
    Goyanes A, Souto C, Martínez-Pacheco R. Control of drug release by incorporation of sorbitol or mannitol in microcrystalline-cellulose-based pellets prepared by extrusion–spheronization. Pharm Dev Technol. 2010;15(6):626–35.PubMedCrossRefGoogle Scholar
  29. 29.
    Ghanam D, Kleinebudde P. Suitability of a flat die press for the manufacture of pharmaceutical pellets by extrusion/spheronization. Drug Dev Ind Pharm. 2011;37(4):456–64.PubMedCrossRefGoogle Scholar
  30. 30.
    Newton M, Petersson J, Podczeck F, Clarke A, Booth S. The influence of formulation variables on the properties of pellets containing a self-emulsifying mixture. J Pharm Sci. 2001;90(8):987–95.PubMedCrossRefGoogle Scholar
  31. 31.
    Sarkar S, Wong TW, Liew CV. Importance of wet packability of component particles in pellet formation. AAPS PharmSciTech. 2013;14:1267–77.Google Scholar
  32. 32.
    Kleinebudde P. The crystallite-gel-model for microcrystalline cellulose in wet-granulation, extrusion, and spheronization. Pharm Res. 1997;14(6):804–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Suzuki T, Kikuchi H, Yamamura S, Terada K, Yamamoto K. The change in characteristics of microcrystalline cellulose during wet granulation using a high-shear mixer. J Pharm Pharmacol. 2001;53(5):609–16.PubMedCrossRefGoogle Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2013

Authors and Affiliations

  • Srimanta Sarkar
    • 1
  • Bee Hwee Ang
    • 1
  • Celine Valeria Liew
    • 1
  1. 1.GEA-NUS Pharmaceutical Processing Research Laboratory, Department of PharmacyNational University of SingaporeSingaporeSingapore

Personalised recommendations