Skip to main content
SpringerLink
Log in

Elucidation of spheroid formation with and without the extrusion step

  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

Spheroid formation mechanisms were investigated using extrusion-spheronization (ES) and rotary processing (RP). Using ES (cross-hatch), ES (teardrop), and RP (teardrop), spheroids with similar mass median diameter (MMD) and span were produced using equivalent formulation and spheronization conditions. During spheronization, the teardrop-studded rotating frictional surface, with increased peripheral tip speed and duration, produced spheroids of equivalent MMD and span to those produced by the cross-hatch rotating frictional plate surface. The roundness of these spheroids was also similar. RP required less water to produce spheroids of MMD similar to that of spheroids produced by ES. However, these RP spheroids were less spherical. Image analysis of 625 spheroids per batch indicated that the size distribution of RP spheroids had significantly greater SD, positive skewness, and kurtosis. Morphological examination of time-sampled spheroids produced by ES indicated that spheroid formation occurred predominatly by attrition and layering, while RP spheroids were formed by nucleation, agglomeration, layering, and coalescence. RP produced spheroids with higher crushing strength than that of ES-produced spheroids. The amount of moisture lost during spheronization for spheroids produced by ES had minimal influence on their eventual size. Differences in process and formulation parameters, in addition to size distribution and observed morphological changes, enabled a greater understanding of spheroid formation and methods to optimize spheroid production.

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

Similar content being viewed by others

References

  1. Sellassie IG. Pellets: a general overview. In: Sellassie IG, ed.Pharmaceutical Pelletization Technology. New York, NY: Marcel Dekker; 1989:1–13.

    Google Scholar 

  2. Vervaet C, Baert L, Remon JP. Extrusion-spheronization, a literature review.Int J Pharm. 1995;116:131–146.

    Article  CAS  Google Scholar 

  3. O'Conner RE, Schwartz JB. Extrusion and spheronization technology. In: Sellassie IG, ed.Pharmaceutical Pelletization Technology. New York, NY: Marcel Dekker; 1989;187–216.

    Google Scholar 

  4. Baert L, Remon JP. Influence of amount of granulation liquid on the drug release rate from pellets made by extrusion spheronization.Int J Pharm. 1993;95:135–146.

    Article  CAS  Google Scholar 

  5. 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;81:205–224.

    Article  CAS  Google Scholar 

  6. Liew CV, Wan LSC, Heng PWS. Influence of polytetrafluoroethylene on spheroid production by rotary processing.STP Pharma Sci. 1998; 8:297–302.

    CAS  Google Scholar 

  7. Pisek R, Sirca J, Svanjak G, Sricic S. Comparison of rotor direct pelletization (fluid bed) and extrusion/spheronization method for pellet production.Pharm Ind. 2001;63:1202–1209.

    CAS  Google Scholar 

  8. Robinson RL, Hollenbeck RG. Manufacture of spherical acetaminophen pellets: comparison of rotary processing with multiple-step extrusion and spheronization.Pharm Technol. 1991;15:48–56.

    CAS  Google Scholar 

  9. Newton JM, Chapman SR, Rowe RC. The influence of process variables on the preparation and properties of spherical granules by process of extrusion and spheronization.Int J Pharm. 1995;120:101–109.

    Article  CAS  Google Scholar 

  10. Heng PWS, Liew CV, Gu L. Influence of teardrop studs on the rotating frictional base plate on spheroid quality in rotary spheronization.Int J Pharm. 2002;241:173–184.

    Article  CAS  Google Scholar 

  11. Wan LSC, Heng PWS, Liew CV. Spheronization conditions on spheroid shape and size.Int J Pharm. 1993;96:59–65.

    Article  CAS  Google Scholar 

  12. Podezeck F, Rahman SR, Newton JM. Evaluation of a standardized procedure to assess the shape of pellets using image analysis.Int J Pharm. 1999;192:123–138.

    Article  Google Scholar 

  13. Heng PWS, Wan LSC, Tan YTF. Optimization of spheroid production by centrifugal rotary processing.Int J Pharm. 1996;143:107–112.

    Article  Google Scholar 

  14. Morris NJ, Warburton B. Particle size analysis of microcapsules.J Pharm Pharmacol. 1984;36:73–76.

    CAS  Google Scholar 

  15. Wanibe Y, Itoh T. Distribution of particle sizes. In: Wanibe Y, Itoh T, eds.New Quantitative Approach to Powder Technology. New York, NY: John Wiley & Sons; 1998:29–47.

    Google Scholar 

  16. Iveson SM, Litster JD, Hapgood K, Ennis BJ. Nucleation, growth and breakdown phenomena in agitated wet granulation processes: a review.Powder Technol 2001;117:3–39.

    Article  CAS  Google Scholar 

  17. Heng PWS, Koo OMY. A study of the effects of the physical characteristics of microcrystalline cellulose on performance in extrusion spheronization.Pharm Res. 2001;18:480–487.

    Article  CAS  Google Scholar 

  18. Hoornaert F, Wauters PAL, Meesters GMH, Pratsinis SE Scarlett B. Agglomeration behaviour of powders in a Lödige mixer granulator.Powder Technol. 1998;96:116–128.

    Article  CAS  Google Scholar 

  19. Vertommen J, Rombaut P, Michoel A, Kinget R. Estimation of the amount of water removed by gap and atomization air streams during pelletization in a rotary processor.Pharm Dev Technol. 1998;3:63–72.

    Article  CAS  Google Scholar 

  20. Newton JM, Chapman SR, Rowe RC. The assessment of the scale-up performance of the extrusion/spheronisation process.Int J Pharm. 1995;120:95–99.

    Article  CAS  Google Scholar 

  21. Harris MR, Sellassie IG. Formation variables. In: Sellassie IG, ed.Pharmaceutical Pelletization Technology. New York, NY: Marcel Dekker; 1989:217–239.

    Google Scholar 

  22. Kleinebudde P, Schroder M, Schultz P, Muller BW, Waaler T, Nymo L. Importance of the fraction of microcrystalline cellulose and spheronization speed on the properties of extruded pellets made from binary mixtures.Pharm Dev Technol. 1999;4: 397–404.

    Article  CAS  Google Scholar 

  23. Vertommen J, Rombaut P, Kinget R. Internal and external structure of pellets made in a rotary processor.Int J Pharm. 1998;161: 225–236.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacy, National University of Singapore, 18 Science Drive 4, 117543, Singapore, Singapore

    Celine V. Liew, Siang Meng Chua & Paul W. S. Heng

Authors
  1. Celine V. Liew
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Siang Meng Chua
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paul W. S. Heng
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Paul W. S. Heng.

Additional information

Published: February 9, 2007

Rights and permissions

Reprints and permissions

About this article

Cite this article

Liew, C.V., Chua, S.M. & Heng, P.W.S. Elucidation of spheroid formation with and without the extrusion step. AAPS PharmSciTech 8, 10 (2007). https://doi.org/10.1208/pt0801010

Download citation

  • Received:

  • Accepted:

  • DOI: https://doi.org/10.1208/pt0801010

Keywords

Search

Navigation