Abstract
Purpose. To establish if FT-Raman Spectroscopy can be used to quantitate the degree of crystallinity in a model compound.
Methods. Mixtures containing different proportions of amorphous and crystalline indomethacin were prepared. Using the peak intensity ratio 1698 cm−1 (crystalline) to 1680 cm−1 (amorphous), a correlation curve was prepared. This correlation curve was validated by testing further samples of known composition. Partially crystalline indomethacin was prepared by milling crystalline indomethacin.
Results. A linear correlation curve was obtained across the entire range of 0−100% crystallinity. Using this method, it was possible to detect down to either 1% amorphous or crystalline content. The largest errors were found to result from inhomogeneities in the mixing of the calibration and validation samples. The spectra of the mechanically processed samples were similar to the spectra of the calibration samples, and the degree of crystallinity could be estimated in these samples.
Conclusions. FT-Raman Spectroscopy is a potentially useful method to complement existing techniques for the quantitative determination of crystallinity.
Similar content being viewed by others
REFERENCES
B. C. Hancock and G. Zografi. Characteristics and significance of the amorphous state. J. Pharm. Sci. 86:1–12 (1997).
A. Saleki-Gerhardt, C. Ahlneck, and G. Zografi. Assessment of disorder in crystalline solids. Int. J. Pharm. 101:237–247 (1994).
H. P. Klug and L. E. Alexander. X-Ray diffraction procedures for polycrystalline and amorphous materials. Wiley, New York, 1974.
D. B. Black and E. G. Lovering. Estimation of the degree of crystallinity in digoxin by X-ray and infrared methods. J. Pharm. Pharmacol. 29:684–687 (1977).
T. Sebhatu, M. Angberg, and C. Alhneck. Assessment of the degree of disorder in crystalline solids by isothermal microcalorimetry. Int. J. Pharm. 104:135–144 (1994).
F. W. Langkilde, J. Sjöblom, L. Tekenbergs-Hjelte, and J. Mrak. Quantitative FT-Raman analysis of two crystal forms of a pharmaceutical compound. J. Pharm. Biomed. Anal. 15:687–696 (1997).
C. M. Deeley, R. A. Spragg, and T. L. Threlfall. A comparison of Fourier transform infrared and near-infrared Fourier transform Raman spectroscopy for quantitative measurements: an application in polymorphism. Spectrochimica Acta 47A:1217–1223 (1991).
A. M. Tudor, S. J. Church, P. J. Hendra, M. C. Davies, and C. D. Melia. The qualitative and quantitative analysis of chlorpropamide mixtures by near-infrared Fourier transform Raman spectroscopy. Pharm. Res. 10:1772–1776 (1993).
L. S. Taylor and G. Zografi. Spectroscopic characterization of interactions between PVP and indomethacin in amorphous molecular dispersions. Pharm. Res. 14:1691–1698 (1997).
D. E. Bugay, A. W. Newman, and P. Findlay. Quantitation of cefepime 2 HCl in cefepime 2HCl monohydrate by diffuse reflectance IR and powder X-ray diffraction techniques. J. Pharm. Biomed. Anal. 15:49–61 (1996).
M. Otsuka, T. Matsumoto, and N. Kaneniwa. Effect of environmental temperature on polymorphic solid-state transformation of indomethacin during grinding. Chem. Pharm. Bull. 34:1784–1793 (1986).
M. Yoshioka, B. C. Hancock, and G. Zografi. Crystallization of indomethacin from the amorphous state below and above its glass transition temperature. J. Pharm. Sci. 83:1700–1705 (1994).
C. G. Kontoyannis, N. C. Bouropoulos, and P. G. Koutsoukos. Use of Raman spectroscopy for the quantitative analysis of calcium oxalate hydrates: application for the analysis of urinary stones. Appl. Spectrosc. 51:64–67 (1997).
R. Hüttenrauch, S. Fricke, and P. Zielke. Mechanical activation of pharmaceutical systems. Pharm. Res. 2:302–306 (1985).
J. C. Miller and J. N. Miller. Statistics for Analytical Chemistry. Ellis Horwood, New York 1993, pp. 101–139.
L. E. Briggner, G. Buckton, K. Bystrom, and P. Darcy. The use of isothermal microcalorimetry in the study of changes in crystallinity induced during the processing of powders. Int. J. Pharm. 105:125–135 (1994).
M. V. Pellow-Jarman, P. J. Hendra, and R. J. Lehnert. The dependence of Raman signal intensity on particle size for crystal powders. Vibrational Spectroscopy 12:257–261 (1996).
P. A. Hailey, P. Doherty, P. Tapsell., T. Oliver, and P. K. Aldridge. Automated system for the on-line monitoring of powder blending processes using near-infrared spectroscopy Part I. System development and control. J. Pharm. Biomed. Anal. 14:551–559 (1996).
D. J. Wargo and J. K. Drennen. Near-infrared spectroscopic characterization of pharmaceutical powder blends. J. Pharm. Biomed. Anal. 14:1415–1423 (1996).
M. C. Davies, J. S. Binns, C. D. Melia, P. J. Hendra, D. Bourgeois, S. P. Church, and P. J. Stephenson. FT Raman spectroscopy of drugs in polymers. Int. J. Pharm. 66:223–232 (1990).
P. J. Hendra. Fourier transform-Raman spectroscopy in pharmaceutical analysis and research. American Laboratory 28:17–24 (1996).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Taylor, L.S., Zografi, G. The Quantitative Analysis of Crystallinity Using FT-Raman Spectroscopy. Pharm Res 15, 755–761 (1998). https://doi.org/10.1023/A:1011979221685
Issue Date:
DOI: https://doi.org/10.1023/A:1011979221685