Skip to main content
SpringerLink
Log in

Raman Mapping of Low-Content API Pharmaceutical Formulations. I. Mapping of Alprazolam in Alprazolam/Xanax Tablets

  • Research Paper
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose

Raman chemical imaging of API was carried out to provide information on whether there is any structural difference between the commercial Xanax and Alprazolam tablets (the API content less than 1% w/w in both cases) in the batches with low and good recovery.

Materials and Methods

Raman mapping spectra were collected from the flattened surfaces of six tablets. The mapping spectra were analyzed by principal component analysis because the Raman signal of the API (Alprazolam) was not reliably detected from the raw spectra. The complexity of the obtained grey-scale score images was such that no information about the domain sizes of the API could be obtained and thus binarization was applied to simplify these images.

Results

It was found that reliable detection of the Raman signal of the API was only achieved after principal component analysis was employed with the mapping being facilitated by a surprising similarity between a high principal component loading and the spectrum of the API. The binarization was successful only if the outlying pixels in the score images are eliminated.

Summary

The final chemical images represent quantitative characterization of the domains of the API in the tablets in contrast to chemical images of tablets that have been reported so far in the literature which have usually been descriptive only. The abundance of Alprazolam in all six tablets of Xanax and Alprazolam, respectively, was very similar. The domain sizes were found to be below 75 μm in diameter for all the tablets analyzed.

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
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

References

  1. S. E. J. Bell, J. R. Beattie, J. J. McGarvey, K. Peters Laota, N. M. S. Sirimuthu, and S. J. Speers. Development of sampling methods for Raman analysis of solid dosage forms of therapeutic and illicit drugs. J. Raman Spectrosc. 35:409 (2004).

    Article  CAS  Google Scholar 

  2. S. E. J. Bell, L. J. Baret, D. T. Burns, A. C. Dennis, and S. J. Speers. Tracking the distribution of ecstasy tablets by Raman composition profiling: a large scale feasibility study. Analyst 128:1331 (2003).

    Article  CAS  PubMed  Google Scholar 

  3. D. S. Hausman, R. T. Cambron, and A. Sakr. Application of Raman spectroscopy for on-line monitoring of low dose blend uniformity. Int. J. Pharm. 298:80 (2005).

    Article  CAS  PubMed  Google Scholar 

  4. D. E. Bugay. Characterization of the solid-state: spectroscopic techniques. Adv. Drug Deliv. Rev. 48:43 (2001).

    Article  CAS  PubMed  Google Scholar 

  5. G. Finni. Applications of Raman spectroscopy to pharmacy. J. Raman Spectrosc. 35:335 (2004).

    Article  CAS  Google Scholar 

  6. S. J. Strachan, D. Prativi, K. C. Gordon, and T. Rades. Quantitative analysis of polymorphic mixtures of carbamazepine by Raman spectroscopy and principal components analysis. J. Raman Spectrosc. 35:347 (2004).

    Article  CAS  Google Scholar 

  7. M. Dyrby, S. B. Engelsen, L. Nørgaard, M. Bruhn, and L. Lundsberg-Nielsen. Chemometric quantitation of the active substance (containing C≡N) in a pharmaceutical tablet using Near-Infrared (NIR) and NIR FT-Raman spectra. Appl. Spectrosc. 56:579 (2002).

    Article  CAS  Google Scholar 

  8. T. M. Niemczyk, M. M. Lopez-Delgado, and F. S. Allen. Quantitative determination of bucindolol concentration in intact gel capsules using Raman spectroscopy. Anal. Chem. 70:2762 (1998).

    Article  CAS  Google Scholar 

  9. R. L. McCreery. Raman Spectroscopy for Chemical Analysis. Wiley, New York, 2000.

    Book  Google Scholar 

  10. P. J. Treado and M. Nelson. In J. M. Chalmers and P. R. Griffiths (eds.), Handbook of Vibrational Spectroscopy, Vol. 2, Wiley, New York, 2001.

    Google Scholar 

  11. D. A. Clark and S. Šašić. Chemical images: an introduction to technical approaches and issues. Cytometry A (in press). DOI: 10.1002/cyto.a.20275.

  12. P. Geladi and H. Grahn. Multivariate Image Analysis. Wiley, New York, 1996.

    Google Scholar 

  13. E. R. Malinowski. Factor Analysis in Chemistry, 2nd ed. Wiley, New York 1991.

    Google Scholar 

  14. S. ŠašIć, D. A. Clark, J. C. Mitchell, and M. J. Snowden. Univariate versus multivariate Raman imaging—a simulation with an example from pharmaceutical practice. Analyst 129:1001 (2004).

    Article  CAS  Google Scholar 

  15. S. Šašić, D. A. Clark, J. C. Mitchell, and M. J. Snowden. Raman line mapping as a fast method for analyzing pharmaceutical bead formulations. Analyst 130:1530 (2005).

    Article  PubMed  CAS  Google Scholar 

  16. P. D. A. Pudney, T. M. Hancewicz, D. G. Cunningham, and M. C. Brown. Quantifying the microstructures of soft solid materials by confocal Raman spectroscopy. Vibr. Spectrosc. 34:123 (2004).

    Article  CAS  Google Scholar 

  17. J. -H. Wang, P. K. Hopke, T. M. Hancewicz, and S. L. Zhang. Application of modified alternating least squares regression to spectroscopic image analysis. Anal. Chim. Acta 476:93 (2003).

    Article  CAS  Google Scholar 

  18. N. B. Gallagher, J. M. Shaver, E. B. Martin, J. Morris, B. M. Wise, and W. Windig. Curve resolution for multivariate images with applications to TOF-SIMS and Raman. Chemom. Intell. Lab. Syst. 73:105 (2004).

    Article  CAS  Google Scholar 

  19. L. Zhang, M. J. Henson, and S. S. Sekulic. Multivariate data analysis for Raman imaging of a model pharmaceutical tablet. Anal. Chim. Acta 545:262 (2005).

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Ian Clegg of Pfizer Inc. is thanked for thoughtful discussions. Pfizer Inc. is acknowledged for permission to publish this study.

Author information

Authors and Affiliations

  1. Analytical R&D, Pfizer Global Research and Development, Ramsgate Road, Sandwich, CT13 9NJ, UK

    Slobodan Šašić

Authors
  1. Slobodan Šašić
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Slobodan Šašić.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Šašić, S. Raman Mapping of Low-Content API Pharmaceutical Formulations. I. Mapping of Alprazolam in Alprazolam/Xanax Tablets. Pharm Res 24, 58–65 (2007). https://doi.org/10.1007/s11095-006-9118-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-006-9118-y

Key words

Search

Navigation