Skip to main content
SpringerLink
Log in

Multivariate Data Analysis as a Semi-quantitative Tool for Interpretive Evaluation of Comparability or Equivalence of Aerodynamic Particle Size Distribution Profiles

  • Research Article
  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

The purpose of this article is to investigate the performance of multivariate data analysis, especially orthogonal partial least square (OPLS) analysis, as a semi-quantitative tool to evaluate the comparability or equivalence of aerodynamic particle size distribution (APSD) profiles of orally inhaled and nasal drug products (OINDP). Monte Carlo simulation was employed to reconstitute APSD profiles based on 55 realistic scenarios proposed by the Product Quality Research Institute (PQRI) working group. OPLS analyses with different data pretreatment methods were performed on each of the reconstituted profiles. Compared to unit-variance scaling, equivalence determined based on OPLS analysis with Pareto scaling was shown to be more consistent with the working group assessment. Chi-square statistics was employed to compare the performance of OPLS analysis (Pareto scaling) with that of the combination test (i.e., chi-square ratio statistics and population bioequivalence test for impactor-sized mass) in terms of achieving greater consistency with the working group evaluation. A p value of 0.036 suggested that OPLS analysis with Pareto scaling may be more predictive than the combination test with respect to consistency. Furthermore, OPLS analysis may also be employed to analyze part of the APSD profiles that contribute to the calculation of the mass median aerodynamic diameter. Our results show that OPLS analysis performed on partial deposition sites do not interfere with the performance on all deposition sites.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Adams WP, Christopher D, Lee DS, Morgan B, Pan Z, Singh GJ, et al. Product Quality Research Institute evaluation of cascade impactor profiles of pharmaceutical aerosols, part 1: background for a statistical method. AAPS PharmSciTech. 2007;8:4.

    Article  PubMed  Google Scholar 

  2. Hickey AJ. Pulmonary drug delivery-pharmaceutical chemistry and aerosol technology. In: Wang B, Siahaan T, Soltero R, editors. Drug delivery: principles and applications. New York: Wiley; 2005. p. 341–61.

    Google Scholar 

  3. Hickey AJ, Kazantseva M, Garcia-Contreras L. Debugging the lungs: the use of therapeutic aerosols in the treatment of pulmonary infectious diseases. In: Smith SR, Paul-Aviles F, Liu J, editors. Pharmaceutical approaches to infectious disease therapy. Godalming: Horwood; 2002. p. 67–93.

    Google Scholar 

  4. Hickey AJ. Summary of common approaches to pharmaceutical aerosol administration. In: Hickey AJ, editor. Pharmaceutical inhalation aerosol technology. 2nd ed. New York: Marcel Dekker; 2004. p. 385–421. 385–421.

    Google Scholar 

  5. Tsong Y. Statistical comparison of particle size distribution profiles. 2004; Available at: http://pqri.org/commworking/minutes/pdfs/dptc/psdpcwg/Addl/DC01-475116-v2-Yi_Tsong_Statistical_Archive_PQRI_Profile_Comparisons.DOC. Accessed June 22, 2007.

  6. FDA/CDER. Draft guidance for industry: bioavailability and bioequivalence studies for nasal aerosols and nasal sprays for local action. Food and Drug Administration Web site. 1999; Available at: http://www.fda.gov/cder/guidance/2070DFT.pdf. Accessed March 28, 2007.

  7. FDA. CDER. Statistical information from the June 1999 Draft Guidance and Statistical Information for In Vitro Bioequivalence Data Posted on August 18, 1999. Available at: http://www.fda.gov/cder/guidance/5383stats.pdf. Accessed January 14, 2007.

  8. United States Pharmacopeial Convention. Chapter 601. Aerosols, metered-dose inhalers, and dry powder inhalers. In: USP30-NF25. Rockville, MD: USP;2007. 220–240.

  9. P.P. DeLuca, Lyapustina, S. Product Quality Research Institute reports. AAPS PharmSciTech [serial online]. 2007;8:article 6.

  10. PQRI APSD Profile Comparisons Working Group. SAS code implementing the chi-square ratio method. 2006; Available at: http://www.pqri.org/structure/psdp.asp. Accessed May 29, 2007. Accessed May 29, 2007.

  11. Christopher D, Adams WP, Lee DS, Morgan B, Pan Z, Singh GJ, et al. Product Quality Research Institute evaluation of cascade impactor profiles of pharmaceutical aerosols, part 2: evaluation of a method for determining equivalence. AAPS PharmSciTech. 2007;8:5.

    Article  PubMed  Google Scholar 

  12. PQRI Profile Comparisons Working Group. Systematic study of 38 scenarios. 2005; Available at: http://pqri.org/commworking/minutes/pdfs/dptc/psdpcwg/Addl/38%20Systematic%20Scenarios.pdf. Accessed November 1, 2006.

  13. PQRI APSD Profile ComparisonsWorking Group. Description of the PBE approach. 2007; Available at: http://www.pqri.org/commworking/minutes/pdfs/dptc/psdpcwg/Addl/DC01-526048-v1-PBE_Description_for_PQRI_Prof_Comp.pdf. Accessed May 29, 2007. Accessed May 29, 2007.

  14. Christopher D, Adams W, Amann A, Bertha C, Byron PR, Doub W, et al. Product Quality Research Institute evaluation of cascade impactor profiles of pharmaceutical aerosols, part 3: final report on a statistical procedure for determining equivalence. AAPS PharmSciTech. 2007;8:E90.

    Article  PubMed  Google Scholar 

  15. Eriksson L, Johansson E, Kettaneh-Wold N, Trygg J, Wikstrom C, Wold S. Multi- and megavariate data analysis. Part 1. Basic principles and applications. Second Revised and Enlarged Edition. Umetrics Academy. 2006.

  16. PQRI Profile Comparisons Working Group. Realistic scenarios 1-33 of 55. 2005; Available at: http://pqri.org/commworking/minutes/pdfs/dptc/psdpcwg/Addl/Realistic%20Scenarios%201-33%20of%2055.pdf. Accessed October 19, 2006.

  17. PQRI Profile Comparisons Working Group. Realistic scenarios 34-55 of 55. 2005; Available at: http://pqri.org/commworking/minutes/pdfs/dptc/psdpcwg/Addl/Realistic%20Scenarios%2034-55%20of%2055.pdf. Accessed October 19, 2006.

  18. Rochfort S. Metabolomics reviewed: a new “omics” platform technology for systems biology and implications for natural products research. J Nat Prod. 2005;68:1813–20.

    Article  CAS  PubMed  Google Scholar 

  19. van den Berg RA, Hoefsloot HC, Westerhuis JA, Smilde AK, van der Werf MJ. Centering, scaling, and transformations: improving the biological information content of metabolomics data. BMC Genomics. 2006;7:142.

    Article  PubMed  Google Scholar 

  20. Noda I. Scaling techniques to enhance two-dimensional correlation spectra. J Mol Struct. 2008;883:216–27.

    Article  Google Scholar 

  21. Shi S, Ashley ES, Alexander BD, Hickey AJ. Initial characterization of micafungin pulmonary delivery via two different nebulizers and multivariate data analysis of aerosol mass distribution profiles. AAPS PharmSciTech. 2009;10:129–37.

    Article  PubMed  Google Scholar 

Download references

Acknowledgment

The authors gratefully acknowledge the comments and suggestions of Dr. Thomas O’Connell, Dr. Walter Hauck, and Mr. David Christopher on drafts of this manuscript.

Author information

Authors and Affiliations

  1. School of Pharmacy, University of North Carolina at Chapel Hill, CB# 7360 Kerr Hall Room 1310, Chapel Hill, North Carolina, 27599, USA

    Shuai Shi & Anthony J. Hickey

Authors
  1. Shuai Shi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anthony J. Hickey
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Anthony J. Hickey.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Shi, S., Hickey, A.J. Multivariate Data Analysis as a Semi-quantitative Tool for Interpretive Evaluation of Comparability or Equivalence of Aerodynamic Particle Size Distribution Profiles. AAPS PharmSciTech 10, 1113–1120 (2009). https://doi.org/10.1208/s12249-009-9303-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1208/s12249-009-9303-5

Key words

Search

Navigation