Quality by Design for Particulate Systems

  • Anthony J. Hickey
  • Stefano Giovagnoli
Part of the AAPS Introductions in the Pharmaceutical Sciences book series (AAPSINSTR)


The foregoing sections described the methods of manufacturing and characterization of pharmaceutical particulate systems. Scrutiny of these systems defines key physicochemical properties establishing their quality as a preliminary to inclusion in a dosage form. This is fundamental to monitoring and control of critical properties of these systems with a view to optimization and establishing quality by design. The use of statistical experimental design during optimization and statistical process control during manufacturing allows the production of the dosage form to meet the target product profile within narrow limits that assure its uniformity. Ultimately, assuring the quality translates into a safe and efficacious drug product.


  1. 1.
    Mullin J. Crystallization. 3rd ed. Oxford, UK: Butterworth-Heinemann; 1993.Google Scholar
  2. 2.
    Parrott E. Milling of pharmaceutical solids. J Pharm Sci. 1974;63:813–29.CrossRefPubMedGoogle Scholar
  3. 3.
    Masters K. Spray drying handbook. 5th ed. New York: Wiley; 1991.Google Scholar
  4. 4.
    Vehring R. Pharmaceutical particle engineering via spray drying. Pharm Res. 2008;25:999–1022.CrossRefPubMedGoogle Scholar
  5. 5.
    Guckenberger D, deGroot T, Wan A, Beebe D, Young E. Micromilling: a method for ultra-rapid prototyping of plastic microfluidic devices. Lab Chip. 2015;15:2364–78.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Hickey A, Ganderton D. Pharmaceutical process engineering. New York: Informa Healthcare; 2010.Google Scholar
  7. 7.
    Kottke M, Rudnic E. Tablet dosage forms. In: Banker G, Rhodes C, editors. Modern pharmaceutics. 4th ed. New York: Marcel Dekker; 2002. p. 437–511.Google Scholar
  8. 8.
    Yu L. Pharmaceutical quality by design. Product and process development, understanding and control. Pharm Res. 2008;25:781–91.CrossRefPubMedGoogle Scholar
  9. 9.
    Anderson T. An Introduction to multivariate statistical analysis. New York: Wiley; 1958.Google Scholar
  10. 10.
    Cochran W, Cox G. Experimental designs. New York: Wiley; 1957.Google Scholar
  11. 11.
    Taylor J. Statistical techniques for data analysis. Boca Raton: CRC Press; 1990.Google Scholar
  12. 12.
    Yu L, Amidon G, Khan M, Hong S, Polli J, Raju G, et al. Understanding pharmaceutical quality by design. AAPS J. 2014;16:771–83.CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Box G, Hunter W, Hunter J. Statistics for experimenters. An introduction to design, data analysis and model building. New York: Wiley; 1978.Google Scholar
  14. 14.
    Oakland J, Followell R. Statistical process control. 2nd ed. Oxford, UK: Heinnemann Newnes; 1990.Google Scholar
  15. 15.
    Kourti T. The process analytical technology initiative and multivariate process analysis, monitoring and control. Anal Bioanal Chem. 2006;384:1043–8.CrossRefPubMedGoogle Scholar
  16. 16.
    Mohammed A, Sunkari P, PSrinivas RA. Quality by design in action 1. Controlling critical quality attributes of an active pharmaceutical ingredient. Org Process Res Dev. 2015;19:1634–44.CrossRefGoogle Scholar
  17. 17.
    Ilie G, Ciocoiu C. Application of fishbone diagram to determine the risk of an event with multiple causes. Manag Res Pract. 2010;2:1–20.Google Scholar
  18. 18.
    Liliana L. A new model of Ishikawa diagram for quality assessment. IOP Conf Ser: Mater Sci Eng. 2016;161:012099.CrossRefGoogle Scholar
  19. 19.
    Lionberger R, Lee S, Lee L, Raw A, Yu L. Quality by design concepts for ANDAs. AAPS J. 2008;10:268–76.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Cairoli R, Dalang R. Sequential stochastic optimization. New York: Wiley; 1996.CrossRefGoogle Scholar
  21. 21.
    Lee C. Fuzzy logic in control systems: fuzzy logic controller, Part II. IEEE Trans Syst Man Cybern. 1990;20:419–35.CrossRefGoogle Scholar
  22. 22.
    Yen J, Langari R. Fuzzy Logic: intelligence, control and information. Upper Saddle River: Prentice-Hall; 1998.Google Scholar

Copyright information

© American Association of Pharmaceutical Scientists 2018

Authors and Affiliations

  • Anthony J. Hickey
    • 1
  • Stefano Giovagnoli
    • 2
  1. 1.Discovery Science and TechnologyRTI InternationalResearch Triangle ParkUSA
  2. 2.Department of Pharmaceutical SciencesUniversity of PerugiaPerugiaItaly

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