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Application of Principal Component Analysis (PCA) to Evaluating the Deformation Behaviors of Pharmaceutical Powders

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Abstract

Introduction

This study uses principal component analysis (PCA) to investigate deformation during powder compaction, in order to classify common pharmaceutical materials according to their relative plasticity.

Methods

A variety of mechanical measurements were used during PCA modeling, including both applied force-dependent measurements and deformation parameters derived from various consolidation models. The applied force-dependent measurements included solid fraction, density change during elastic recovery, work of compression (w c ), work of decompression (w d ), normalized radial tensile strength (σT/σT, ε = 0), elasticity, and the work of compression and decompression (w c/d ). The models of consolidation included those proposed by Heckel, Walker, Alderborn, Gurnham, and Denny’s proposed modification to the Heckel model. The initial PCA model was calibrated based on 12, well-characterized pharmaceutical materials with a wide span of plastic, brittle, and elastic deformation properties.

Results and Conclusions

It was found that the first principal component seemed to be consistent with the relative plasticity of each material predicted by traditional methods. The variables contributing most to the variance explained by the first PC were found to be the c value from Gurnham model, w c , and w c/d . Further analysis of five additional materials indicated that the c value, alone, provided adequate differentiation of the materials’ relative plasticities. The advantages of multivariate analysis in analyzing the mechanical data and future application of PCA modeling are also discussed.

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References

  1. Augsburger LL, Hoag SW. Pharmaceutical dosage forms: tablets, volume: 1. 3rd ed. New York: Informa Healthcare USA Inc; 2008.

    Book  Google Scholar 

  2. Duberg M, Nystrom C. Studies on direct compression of tablets XVII. Porosity–pressure curves for the characterization of volume reduction mechanisms in powder compression. Powder Technol. 1986;46(1):67–75.

    Article  CAS  Google Scholar 

  3. Heckel RW. Density–pressure relationships in powder compaction. Trans Met Soc AIME. 1961;221:671–5.

    CAS  Google Scholar 

  4. Heckel RW. An analysis of powder compaction phenomena. Trans Met Soc AIME. 1961;221:1001–8.

    Google Scholar 

  5. Gurnham CF, Masson HJ. Expression of liquids from fibrous materials. Ind Eng Chem. 1946;38(12):1309–15.

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  7. Higuchi T, Nelson E, Busse LW. The physics of tablet compression. Determination of energy expenditure in the tablet compression process. J Am Pharm Assoc Sci Ed. 1955;44(4):223–5.

    Google Scholar 

  8. Celik M, Marshall K. Use of compaction simulator system in tableting research. Drug Dev Ind Pharm. 1989;15(5):759–800.

    Article  CAS  Google Scholar 

  9. Aburub A, Buckner I, Mishra D. Use of compaction energetics for understanding particle deformation mechanism. Pharm Dev Technol. 2007;12(4):405–14.

    Article  PubMed  CAS  Google Scholar 

  10. Sonnergaard JM. A critical evaluation of the Heckel equation. Int J Pharm. 1999;193(1):63–71.

    Article  PubMed  CAS  Google Scholar 

  11. Rue PJ, Rees JE. Limitations of the Heckel relation for predicting powder compaction mechanism. J Pharm Pharmacol. 1978;30(10):642–3.

    Article  PubMed  CAS  Google Scholar 

  12. Jover I, Podczeck F, Newton M. Evaluation by a stastically designed experiment, of an experimental grade of microcrystalline cellulose, Avicel 955, as a technology to aid the production of pellets with high drug loading. J Pharm Sci. 1996;85(7):700–5.

    Article  PubMed  CAS  Google Scholar 

  13. Pinto JF, Podczeck F, Newton JM. Investigation of tablets prepared from pellets produced by extrusion and spheronisation. Part I: The application of canonical analysis to correlate the properties of the tablets to the factors studied in combination with principal component analysis to select the most relevant factors. Int J Pharm. 1997;147(1):79–93.

    Article  CAS  Google Scholar 

  14. Pinto JF, Podczeck F, Newton JM. Investigation of tablets prepared from pellets produced by extrusion and spheronisation. II. Modelling the properties of the tablets produced using regression analysis. Int J Pharm. 1997;152(1):7–16.

    Article  CAS  Google Scholar 

  15. Haware RV, Tho I, Bauer-Brandl A. Application of multivariate methods to compression behavior evaluation of directly compressible materials. Eur J Pharm Biopharm. 2009;72(1):148–55.

    Article  PubMed  CAS  Google Scholar 

  16. Haware RV, Tho I, Bauer-Brandl A. Multivariate analysis of relationships between material properties, process parameters and tablet tensile strength for α-lactose monohydrate. Eur J Pharm Biopharm. 2009;73(3):424–31.

    Article  PubMed  CAS  Google Scholar 

  17. Klevan I, Nordstrom J, Tho I, Alderborn G. A statistical approach to evaluate the potential use of compression parameters for classification of pharmaceutical powder materials. Eur J Pharm Biopharm. 2010;75(3):425–35.

    Article  PubMed  CAS  Google Scholar 

  18. Roopwani R, Buckner IS. Understanding deformation mechanisms during powder compaction using principal component analysis of compression data. Int J Pharm. 2011;418(2):227–34.

    Article  PubMed  CAS  Google Scholar 

  19. Bolhuis GK, Chowhan ZT. Materials for direct compression. In: Alderborn G, Nystrom C, editors. Pharmaceutical powder compaction technology. 1st ed. New York: Marcel Dekker Inc; 1996. pp. 429, 443, 458, 460, 470, 491.

    Google Scholar 

  20. Busignies V, Tchoreloff P, Leclerc B, Besnard M, Couarraze G. Compaction of crystallographic forms of pharmaceutical granular lactoses. I. Compressibility. Eur J Pharm Biopharm. 2004;58(3):569–76.

    Article  PubMed  CAS  Google Scholar 

  21. Hersey JA, Rees JE, Cole ET. Density changes in lactose tablets. J Pharm Sci. 1973;62(12):2060.

    Article  PubMed  CAS  Google Scholar 

  22. Sonnergard JM. Investigation of a new mathematical model for compression of pharmaceutical powders. Eur J Pharm Sci. 2001;14(2):149–57.

    Article  Google Scholar 

  23. Schmidt PC, Herzog R. Calcium phosphates in pharmaceutical tableting. 2. Comparison of tableting properties. Pharm World Sci. 1993;15(3):116–22.

    Article  PubMed  CAS  Google Scholar 

  24. Podczeck F. Investigations into the fracture mechanics of acetylsalicylic acid and lactose monohydrate. J Mat Sci. 2001;36(19):4687–93.

    Article  CAS  Google Scholar 

  25. Buckner IS, Wurster DE, Aburub A. Interpreting deformation behavior in pharmaceutical materials using multiple consolidation models and compaction energetics. Pharm Dev Technol. 2010;15(5):492–9.

    Article  PubMed  CAS  Google Scholar 

  26. Buckner IS. Compression calorimetry, powder compaction thermodynamics and deformation mechanisms, Ph.D. Thesis. University of Iowa, Iowa, 2008.

  27. Denny PJ. Compaction equations: a comparison of the Heckel and Kawakita equations. Powder Technol. 2002;127(2):162–72.

    Article  CAS  Google Scholar 

  28. Alderborn G. A novel approach to derive a compression parameter indicating effective particle deformability. Pharm Dev Technol. 2003;8(4):367–77.

    Article  PubMed  CAS  Google Scholar 

  29. Sun C, Grant DJW. Influence of elastic deformation of particles on Heckel analysis. Pharm Dev Technol. 2001;6(2):193–200.

    Article  PubMed  CAS  Google Scholar 

  30. Wise BM, et al. PLS_Toolbox 3.0 Manual, Eigenvector Research Inc.; 2003.

  31. Rowe RC, Roberts RJ. Mechanical properties. In: Alderborn G, Nystrom C, editors. Pharmaceutical powder compaction technology. 1st ed. New York: Dekker; 1996. p. 283–322.

    Google Scholar 

  32. Rowlings CE, Wurster DE, Ramsey PJ. Calorimetric analysis of powder compression: II The relationship between energy terms measured with a compression calorimeter and tableting behavior. Int J Pharm. 1995;116(2):191–200.

    Article  CAS  Google Scholar 

  33. Vachon MG, Chulia D. The use of energy indices in estimating powder compaction functionality of mixtures in pharmaceutical tableting. Int J Pharm. 1999;177(2):183–200.

    Article  PubMed  CAS  Google Scholar 

  34. Hiestand EN. Rationale for and the measurement of tableting indices. In: Alderborn G, Nystrom C, editors. Pharmaceutical powder compaction technology. 1st ed. New York: Dekker; 1996. p. 219–25.

    Google Scholar 

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Authors and Affiliations

  1. Graduate School of Pharmaceutical Sciences, Duquesne University, 600 Forbes Ave, Pittsburgh, PA, 15282, USA

    Rahul Roopwani

  2. Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, 46285, USA

    Zhenqi Shi

  3. Graduate School of Pharmaceutical Sciences, Duquesne University, 600 Forbes Ave, Pittsburgh, PA, 15282, USA

    Ira S. Buckner

Authors
  1. Rahul Roopwani
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  2. Zhenqi Shi
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  3. Ira S. Buckner
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Corresponding author

Correspondence to Ira S. Buckner.

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Roopwani, R., Shi, Z. & Buckner, I.S. Application of Principal Component Analysis (PCA) to Evaluating the Deformation Behaviors of Pharmaceutical Powders. J Pharm Innov 8, 121–130 (2013). https://doi.org/10.1007/s12247-013-9153-2

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  • DOI: https://doi.org/10.1007/s12247-013-9153-2

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