Evaluation of the Microcrystallinity of a Drug Substance, Indomethacin, in a Pharmaceutical Model Tablet by Chemometric FT-Raman Spectroscopy
- 272 Downloads
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 Wordschemometrics 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.
- 1.FDA Paper. Guideline for submitting supporting documentation in drug applications for the manufacture of drug substances. February 1987.Google Scholar
- 2.Otsuka, M., Matsuda, Y. 1995Polymorphism: pharmaceutical aspectsSwarbrick, J.Boylan, J. C. eds. Encyclopedia of Pharmaceutical Technology. Vol. 12Marcel DekkerNew York305326Google Scholar
- 6.Yoshino, H., Hagiwara, Y., Kobayashi, S., Samejima, M. 1984Estimation of polymorphic transformation degree of pharmaceutical raw materialsChem. Pharm. Bull.3215231536Google Scholar
- 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/).
- 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.Hendra, P. J. 1996Fourier transform-Raman spectroscopy in pharmaceutical analysis and researchAm. Lab.281724Google Scholar
- 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
- 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
- 19.Martens, H., Næs, T. 1989Multivariate CalibrationJohn Wiley & SonsNew YorkGoogle Scholar
- 20.Boldyreva, E. V. 2004Molecules in strained environmentNATO Science Series, II: Mathematics, Physics and Chemistry Chem.140495512(High-Pressure Crystallography)Google Scholar
- 21.Arora, A. K. 2002Pressure-induced amorphizationProc. Int. Sch. Phys. “Enrico Ferm”147545565(High Pressure Phenomena)Google Scholar
- 22.Yamanaka, T., Nagai, T., Tsuchiya, T. 1997Mechanism of pressure-induced amorphizationZeitschr. Kristall.212401410Google Scholar
- 24.Train, D. 1957Transmission of forces through a powder mass during the process of pelletingTrans. Inst. Chem. Eng.35258266Google Scholar