Formulation and Industrial Pharmacy, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, Viikinkaari 5 E (P.O. Box 56), 00014 University of Helsinki, Finland.
Dodd-Walls Centre for Photonic and Quantum Technologies, University of Otago, Department of Chemistry, Union Place West, Dunedin 9016, New Zealand.
J Pharm Biomed Anal. 2018 Feb 5;149:343-350. doi: 10.1016/j.jpba.2017.11.013. Epub 2017 Nov 11.
This study considers the potential of low-frequency (terahertz) Raman spectroscopy in the quantitative analysis of ternary mixtures of solid-state forms. Direct comparison between low-frequency and mid-frequency spectral regions for quantitative analysis of crystal form mixtures, without confounding sampling and instrumental variations, is reported for the first time. Piroxicam was used as a model drug, and the low-frequency spectra of piroxicam forms β, α2 and monohydrate are presented for the first time. These forms show clear spectral differences in both the low- and mid-frequency regions. Both spectral regions provided quantitative models suitable for predicting the mixture compositions using partial least squares regression (PLSR), but the low-frequency data gave better models, based on lower errors of prediction (2.7, 3.1 and 3.2% root-mean-square errors of prediction [RMSEP] values for the β, α2 and monohydrate forms, respectively) than the mid-frequency data (6.3, 5.4 and 4.8%, for the β, α2 and monohydrate forms, respectively). The better performance of low-frequency Raman analysis was attributed to larger spectral differences between the solid-state forms, combined with a higher signal-to-noise ratio.
本研究探讨了低频（太赫兹）拉曼光谱在固态形式三元混合物定量分析中的潜力。首次报告了在没有干扰采样和仪器变化的情况下，直接比较低频和中频光谱区域对晶型混合物进行定量分析的结果。使用吡罗昔康作为模型药物，首次呈现了吡罗昔康β、α2 和一水合物形式的低频光谱。这些形式在低频和中频区域均表现出明显的光谱差异。两个光谱区域都提供了适合使用偏最小二乘回归（PLSR）预测混合物组成的定量模型，但基于较低的预测误差（β、α2 和一水合物形式的预测均方根误差 [RMSEP] 值分别为 2.7%、3.1%和 3.2%），低频数据给出了更好的模型，优于中频数据（β、α2 和一水合物形式的 RMSEP 值分别为 6.3%、5.4%和 4.8%）。低频拉曼分析的更好性能归因于固态形式之间更大的光谱差异，加上更高的信噪比。
