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Pharmaceutical Research

, Volume 22, Issue 8, pp 1350–1357 | Cite as

Evaluation of the Microcrystallinity of a Drug Substance, Indomethacin, in a Pharmaceutical Model Tablet by Chemometric FT-Raman Spectroscopy

  • Takehiro Okumura
  • Makoto Otsuka
Research Paper

Purpose

To establish a chemometric method for the precise evaluation of the microcrystallinity of indomethacin (IMC) in a pharmaceutical model tablet, based on FT-Raman spectroscopy.

Methods

Standard sample powders of homogeneous mixtures of amorphous and crystalline IMC were prepared in various proportions. A calibration model for the crystallinity of IMC was constructed by partial least-square (PLS) analysis based on the multiplicative scatter correction (MSC) + second-derivative transformed Raman spectra. A calibration model for the crystallinity of IMC in a model pharmaceutical product (IMC/mannitol = 1:9 wt/wt) was also constructed using homogeneous standard sample powders of various degrees of crystallinity of IMC.

Results

This technique was validated to detect to 2% an amorphous or crystalline material in IMC contained in the model product (0.2% of the total mass of the tablet). Using this technique, not only pressure-induced amorphization but also the difference in microcrystallinity of IMC at the surface and interior of a model product tablet was elucidated after compaction of the tablet.

Conclusions

The established technique is ideally suited for precise quantification of microanalysis of drug substances and drug products, particularly at the surface and interior of the tablet.

Key Words

chemometrics compaction crystallinity indomethacin Raman spectroscopy 

Abbreviations

DSC

differential scanning calorimetry

IMC

indomethacin

MSC

multiplicative scatter correction

NIR

near-infrared

NMR

nuclear magnetic resonance

PLS

partial least square

XRD

X-ray powder diffraction

Notes

Acknowledgments

The authors wish to thank Miss Harui, Thermo Electron K. K. for technical assistance in FT-Raman spectroscopy, and also Mr. Nakazono, Sumitomo Pharmaceuticals Co., Ltd. for preparing compaction samples.

References

  1. 1.
    FDA Paper. Guideline for submitting supporting documentation in drug applications for the manufacture of drug substances. February 1987.Google Scholar
  2. 2.
    Otsuka, M., Matsuda, Y. 1995Polymorphism: pharmaceutical aspectsSwarbrick, J.Boylan, J. C. eds. Encyclopedia of Pharmaceutical Technology. Vol. 12Marcel DekkerNew York305326Google Scholar
  3. 3.
    Taylor, L. S., Zografi, G. 1998The quantitative analysis of crystallinity using FT-raman spectroscopyPharm. Res.15755761CrossRefPubMedGoogle Scholar
  4. 4.
    Black, D. B., Lovering, E. G. 1977Estimation of the degree of crystallinity in digoxin by X-ray and infrared methodsJ. Pharm. Pharmacol.29684687PubMedGoogle Scholar
  5. 5.
    Fuchs, S., Schmidt, T., Jerosch, J. 1998Change in crystalliniry by sterilization and processing of ultrahigh molecular polyethylene used in endoprostheticsUnfallchirung101382387CrossRefGoogle Scholar
  6. 6.
    Yoshino, H., Hagiwara, Y., Kobayashi, S., Samejima, M. 1984Estimation of polymorphic transformation degree of pharmaceutical raw materialsChem. Pharm. Bull.3215231536Google Scholar
  7. 7.
    Otsuka, M., Kaneniwa, N. 1988A kinetic study of the crystallization process of noncrystalline indomethacin under isothermal conditionsChem. Pharm. Bull.3640264032PubMedGoogle Scholar
  8. 8.
    Ahmed, H., Buckton, G., Rawlins, D. A. 1996The use of isothermal microcalorimetry in the study of small degrees of amorphous content of a hydrophobic powderInt. J. Pharm.130195 201CrossRefGoogle Scholar
  9. 9.
    M. Otsuka, F. Kato and Y. Matsuda. Comparative evaluation of the degree of indomethacin crystallinity by chemoinfometrical fourie-transformed near-infrared Spectroscopy and conventional powder X-ray diffractometry. AAPS Pharmsci. 2(1) article 9 (2000) (http://www.pharmsci.org/).
  10. 10.
    Gidley, M. J., Bociek, S. M. 1985Molecular organization in starches: a 13C CP/MAS NMR studyJ. Am. Chem. Soc.10770407044CrossRefGoogle Scholar
  11. 11.
    Davies, M. C., Binns, J. S., Melia, C. D., Hendra, P. J., Bourgeois, D., Church, S. P., Stephenson, P. J. 1990FT Raman spectroscopy of drugs in polymersInt. J. Pharm.66223232Google Scholar
  12. 12.
    Hendra, P. J. 1996Fourier transform-Raman spectroscopy in pharmaceutical analysis and researchAm. Lab.281724Google Scholar
  13. 13.
    Jedvert, I., Josefson, M., Langkilde, F. 1998Quantification of an active substance in a tablet by NIR and Raman spectroscopyJ. Near Infrared Spectrosc.6279289Google Scholar
  14. 14.
    Taylor, L. S., Langkilde, F. W. 2000Evaluation of solid-state forms present in tablets by Raman spectroscopyJ. Pharm. Sci.8913421353CrossRefPubMedGoogle Scholar
  15. 15.
    Pelletier, M. J. 2003Quantitative analysis using Raman spectrometryAppl. Spectrosc.5720A42ACrossRefPubMedGoogle Scholar
  16. 16.
    T. Okumura and M. Otsuka. A novel standard sample powder preparation method for quantitative analysis of polymorphs. J. Pharm. Sci. 94:1013–1023 (2005)Google Scholar
  17. 17.
    Otsuka, M., Kato, F., Matsuda, Y. 2001Determination of indomethacin polymorphic contents by chemometric near-infrared spectroscopy and conventional powder X-ray diffractometryAnalyst12615781582CrossRefPubMedGoogle Scholar
  18. 18.
    Helland, I. S., Nacs, T., Isaksson, T. 1995Related versions of the multiplicative scatter correction method for preprocessing spectroscopic dataChemom. Intell. Lab. Syst.29233CrossRefGoogle Scholar
  19. 19.
    Martens, H., Næs, T. 1989Multivariate CalibrationJohn Wiley & SonsNew YorkGoogle Scholar
  20. 20.
    Boldyreva, E. V. 2004Molecules in strained environmentNATO Science Series, II: Mathematics, Physics and Chemistry Chem.140495512(High-Pressure Crystallography)Google Scholar
  21. 21.
    Arora, A. K. 2002Pressure-induced amorphizationProc. Int. Sch. Phys. “Enrico Ferm”147545565(High Pressure Phenomena)Google Scholar
  22. 22.
    Yamanaka, T., Nagai, T., Tsuchiya, T. 1997Mechanism of pressure-induced amorphizationZeitschr. Kristall.212401410Google Scholar
  23. 23.
    Sharma, S. M., Sikka, S. K. 1996Pressure induced amorphization of materialsProg. Mater. Sci.40177CrossRefGoogle Scholar
  24. 24.
    Train, D. 1957Transmission of forces through a powder mass during the process of pelletingTrans. Inst. Chem. Eng.35258266Google Scholar

Copyright information

© Springer Science + Business Media, Inc. 2005

Authors and Affiliations

  1. 1.Organic Synthesis Research LaboratorySumitomo Chemical Co., Ltd.OsakaJapan
  2. 2.Department of Pharmaceutical TechnologyKobe Pharmaceutical UniversityKobeJapan

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