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


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.


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.


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.


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 



differential scanning calorimetry




multiplicative scatter correction




nuclear magnetic resonance


partial least square


X-ray powder diffraction



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.


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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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