Investigation of sulfamethoxazole polymorphism with terahertz time-domain spectroscopical technique
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摘要: 磺胺甲噁唑(SMX)作为典型的一类光谱抗生素，经常被用于敏感菌引起的各类感染。由于其晶体内部结构的不同，SMX 将以两种不同的多晶型形式存在。不同晶型常常具有不同的物理化学性质，这些差异可能会对药物的流动性、稳定性以及药效等有较大影响。新兴发展起来的太赫兹光谱技术对于分子间弱的相互作用及大分子的骨架振动、偶极子的旋转和振动跃迁以及晶体中晶格的低频振动吸收都非常敏感，在药物以及生物等领域获得了重要的应用。利用太赫兹时域光谱(THz-TDS)技术在室温下对两种不同多晶型SMX 类药物在0.2~1.5 THz 范围内进行了光谱测量，得到对应的吸收谱，发现其在太赫兹波段都有明显的特征吸收峰，可作为其指纹谱用于该类药物多晶型的识别。不同温度下(95~296 K)获得太赫兹时域波形以及对应的频域吸收谱图，结果发现时域波形以及频域吸收谱均与温度呈现规律变化。该研究结果表明THz-TDS 技术药物与生物领域研究、区分药物分子多晶型现象等方面具有重要的应用。Abstract: Sulfamethoxazole (SMX), one of the well-known effective and tolerable antibacterial agents, is widely used to treat urinary tract infections. Due to the variations in crystallinity structure, SMX exist in two different polymorphic forms I and II. These polymorphs have the same chemical composition but unique physio-chemical properties which will influence the corresponding different stability, solubility, dissolution rate and also other performance characteristics. Terahertz time-domain spectroscopy(THz-TDS) becomes a promising analytical technique relevant to the pharmaceutical and biological fields. THz-TDS measurement is able to characterize and distinguish the different polymorphs according to the rich information yielded, due to the sensitivity of THz absorption in this low-frequency region to the structures over length scales greater than intramolecular bond distances. In this study, absorption spectra in the terahertz region between 6 and 50 cm-1 (0.2-1.5 THz) were measured for SMX pharmaceutical molecule with different polymorphic forms (forms Ⅰ and Ⅱ, and also raw material) using THz -TDS technique at room temperature. The temperature-dependent THz-TDS of the raw SMX material was also investigated between 95 K and 296 K. Different absorption features were observed for these two model polymorphs. The observed THz absorption bands are strikingly sensitive to the change of subtle conformational structures existed within such crystal molecules with different polymorphism. The results show that the THz -TDS technique is a promising method in solid-state analytical tools to distinguish or differentiate such compounds with different polymorphs in pharmaceutical and biological fields.
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