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

Abstract

Abstract. 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 (freezedried) 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.

Optical and THz investigations of mid-IR materials exposed to alpha particle irradiation

“…density modifications) can be conveniently located if the THz pulse propagation is studied. THz techniques were used to evaluate crystallinity of the materials4142. The optical delay of the THz transmitted signal for pristine and irradiated CaF 2 samples is given in Fig.…”

Direct measurement of molecular mobility and crystallisation of amorphous pharmaceuticals using terahertz spectroscopy

“…Wavenumber (cm -1 ) Absorbance (decadic) 100% amorphous 20% crystalline 40% crystalline 60% crystalline 80% crystalline 100% crystalline The high sensitivity of terahertz spectroscopy to detect crystallinity has also proved useful for the characterisation of amorphous drug systems prepared by different methods such as quench cooling or grinding [81], as well as spray-drying [82] and freeze-drying [83][84][85]. For example, amorphous samples prepared by grinding were found to contain nanoscopic crystalline particles which could be resolved in terahertz spectra but were not apparent in the XRD analysis [81].…”

Quantification of residual crystallinity of ball-milled, commercially available, anhydrous β-lactose by differential scanning calorimetry and terahertz spectroscopy

“…It also has potential for being used as an in-line tool for process control and has been used previously for characterizing [6] and quantification [7] of crystallinity of APIs. This technique has been used recently for measurement of crystallinity in amino acid [8] and freeze-dried sugars [9]. The benefit of this technique is that one can analyze the material in its native state, though one must be aware that physical transition into the material properties may take place during processing and measurement.…”