AAPS PharmSciTech

, Volume 15, Issue 2, pp 253–260

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

Research Article


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 words

crystallinity partial least squares sugars terahertz-pulsed spectroscopy 

Copyright information

© American Association of Pharmaceutical Scientists 2013

Authors and Affiliations

  1. 1.Leicester School of PharmacyDe Montfort UniversityLeicesterUK

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