Aytekin Yusuf Samet, Köktürk Mustafa, Zaczek Adam, Korter Timothy M, Heilweil Edwin J, Esenturk Okan
Department of Chemistry, Middle East Technical University, Ankara 06100, Turkey.
Nobel Pharmaceuticals Research and Development Center, Düzce 81100, Turkey.
Chem Phys. 2018;512. doi: 10.1016/j.chemphys.2018.04.022.
One of the most commonly used nonsteroidal anti-inflammatory active pharmaceutical ingredient called Meloxicam has been characterized spectroscopically both by Terahertz (THz) time domain spectroscopy (THz-TDS) and by Fourier Transform Infrared (FTIR) spectroscopy in far-IR regions of electromagnetic spectrum; 0.2 THz to 20 THz. While many relatively sharp features are observed in the far-IR range between 2 THz to 20 THz as expected for being an organic substance, very distinct and relatively strong absorption bands are also observed at 1.00, 1.66, 2.07 and 2.57 THz in the THz range. These well separated, defined, and fairly strong spectral features can be used for discrimination and quantification of Meloxicam in drug analysis. Frequency dependent refractive index of the drug was determined in a range of 0.2 THz and 2.7 THz, where an almost constant index was observed with an average index of 1.75. Powder XRD, and solid-state Density Functional Theory (SS-DFT) calculations were utilized to determine the crystalline form of the Meloxicam sample in its enolic crystalline form. Single molecule DFT calculations were also performed in all four possible structures of Meloxicam. In addition, the capability of THz waves transmission through common packaging materials is demonstrated for possibility of future on-site analysis. The results suggest that drug analysis will be possible to perform not only at every stage of manufacturing without destruction but also directly at the shelf of a market after development of portable THz technologies.
一种最常用的非甾体抗炎活性药物成分美洛昔康，已通过太赫兹（THz）时域光谱（THz-TDS）和傅里叶变换红外（FTIR）光谱在电磁频谱的远红外区域（0.2太赫兹至20太赫兹）进行了光谱表征。虽然在2太赫兹至20太赫兹的远红外范围内观察到许多相对尖锐的特征，这对于一种有机物质来说是预期的，但在太赫兹范围内的1.00、1.66、2.07和2.57太赫兹处也观察到了非常明显且相对较强的吸收带。这些分离良好、明确且相当强的光谱特征可用于药物分析中美洛昔康的鉴别和定量。在0.2太赫兹至2.7太赫兹的范围内测定了该药物的频率依赖性折射率，在此范围内观察到几乎恒定的折射率，平均折射率为1.75。利用粉末X射线衍射（XRD）和固态密度泛函理论（SS-DFT）计算来确定美洛昔康样品烯醇式结晶形式的晶体结构。还对美洛昔康的所有四种可能结构进行了单分子DFT计算。此外，展示了太赫兹波透过常见包装材料的能力，以探讨未来现场分析的可能性。结果表明，不仅在制造的每个阶段都可以在不破坏的情况下进行药物分析，而且在便携式太赫兹技术发展之后，还可以直接在市场货架上进行分析。
