Characterisation of Crystalline-Amorphous Blends of Sucrose with Terahertz-Pulsed Spectroscopy: the Development of a Prediction Technique for Estimating the Degree of Crystallinity with Partial Least Squares Regression
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The control of the amorphous and crystalline states of drugs and excipients is important in many instances of product formulation, manufacture, and packaging, such as the formulation of certain (freeze-dried) fast melt tablets. This study examines the use of terahertz-pulsed spectroscopy (TPS) coupled with two different data analytical methods as an off-line tool (in the first instance) for assessing the degree of crystallinity in a binary mixture of amorphous and polycrystalline sucrose. The terahertz spectrum of sucrose was recorded in the wave number range between 3 and 100 cm−1 for both the pure crystalline form and for a mixture of the crystalline and amorphous (freeze-dried) form. The THz spectra of crystalline sucrose showed distinct absorption bands at ∼48, ∼55, and ∼60 cm−1 while all these features were absent in the amorphous sucrose. Calibration models were constructed based on (1) peak area analysis and (2) partial least square regression analysis, with the latter giving the best LOD and LOQ of 0.76% and 2.3%, respectively. The potential for using THz spectroscopy, as a quantitative in-line tool for percent crystallinity in a range of complex systems such as conventional tablets and freeze-dried formulations, is suggested in this study.
Key wordscrystallinity partial least squares sugars terahertz-pulsed spectroscopy
- 3.Jenkins R, Snyder R. Introduction to X-ray powder diffractometry. New Jersey: Wiley; 2012.Google Scholar
- 4.The United States Pharmacopoeial Convention. X-Ray Diffraction, General test-941. In: United States Pharmacopoeia 25, editor. 25. Rockville, MD, 2001. pp. 2088–9.Google Scholar
- 8.Chantry GW. Submillimetre spectroscopy: A guide to the theoretical and experimental physics of the far infrared. London: Academic Press; 1971.Google Scholar
- 9.Mantsch HH, Naumann D. Terahertz spectroscopy: The renaissance of far infrared spectroscopy. J Mol Struct 964(1–3):1–4.Google Scholar
- 16.Shen Y-C, Taday PF, Pepper M. Elimination of scattering effects in spectral measurement of granulated materials using terahertz pulsed spectroscopy. App Phys Lett. 2008;92.Google Scholar
- 18.Oetjen GW. Freeze-drying. New York: Wiley; 2008.Google Scholar
- 19.Oetjen GW, Haseley P. Foundations and process engineering. In: Oetjen GW, Haseley P, editors. Freeze-drying. Weinheim: Wiley; 2008. p. 1–154.Google Scholar
- 23.Darkwah J, Smith G, Ermolina I, Mueller-Holtz M. A THz spectroscopy method for quantifying the degree of crystallinity in freeze-dried gelatin/amino acid mixtures: An application for the development of rapidly disintegrating tablets. Int J Pharm. 2013; (in press).Google Scholar
- 24.R Core Team R: A Language and Environment for Statistical Computing Vienna, Austria. 2008. Available from: http://www.r-project.org/.
- 26.Yenia O, Goktas A. A comparison of partial least squares regression with other prediction methods. Hacettepe Journal of Mathematics and Statistics. 2002;31:99–111.Google Scholar
- 27.ICH. Validation of analytical procedures: test and methodology. 1996.Google Scholar
- 28.Sarsfield BA, Davidovich M, Desikan S, Fakes M, Futernik S, Hilden JL, et al., editors. Powder x-ray diffraction detection of crystalline phases in amorphous pharmaceuticals. Denver X-ray Conferences; 2006; Denver.Google Scholar