拉莫三嗪与邻苯二甲酰亚胺共晶的太赫兹光谱研究

Terahertz Spectroscopy of Lamotrigine and Phthalimide co-Crystals

利用太赫兹时域光谱技术(THz-TDS)研究了拉莫三嗪与邻苯二甲酰亚胺共晶的太赫兹光谱.测试了拉莫三嗪、邻苯二甲酰亚胺、二者物理混合物及其共晶在0.5~5.0 THz的实验谱.结果显示,拉莫三嗪与邻苯二甲酰亚胺共晶在2.18和2.49 THz处出现了新的吸收峰,表明THz-TDS可有效鉴别拉莫三嗪、邻苯二甲酰亚胺及其共晶体.基于密度泛函理论对构建的共晶体理论晶型和晶胞结构进行结构优化与频谱模拟,模拟结果能较好地对实验谱进行重构.通过共晶THz吸收峰来源的讨论与分析,发现拉莫三嗪共晶体的分子间作用力主要源于π-π堆积力,且氢键有少量贡献.

Lamotrigine is a prescribed pharmaceutical for the treatment of epilepsy,convulsions,and other symptoms,but it has low solubility in water.Pharmaceutical cocrystals,as a new solid form of drugs,are formed through the non-covalent bonding of active pharmaceutical ingredients(API)and cocrystal formers(CCF).This non-covalent bonding can alter the internal structure of drug molecules and the weak intermolecular interactions,effectively improving the physicochemical properties of APIs,such as solubility,stability and bioavailability.In this article,lamotrigine-phthalimide co-crystals were investigated using terahertz time-domain spectroscopy(THz-TDS).Initially,the experimental THz spectra of lamotrigine,phthalimide,their physical mixture and the cocrystals were measured in the 0.5—5.0 THz range.Experimental data reveal new absorption peaks at 2.18 and 2.49 THz in the co-crystal,indicating that THz-TDS can effectively distinguish lamotrigine,phthalimide,and their co-crystals.Structural optimization and spectral simulation were carried out on the constructed theoretical form and periodic structure using density functional theory,and the calculated results can effectively reconstruct the experimental spectrum.Through the discussion and analysis of the origins of THz absorption peaks in co-crystals,it is found that the intermolecular forces of lamotrigine-phthalimide co-crystals mainly originate fromπ-πstacking force,and hydrogen bonding contributes slightly.