Abstract In this study, specimens of Formetrol fumerate were investigated using IR and Raman vibrational spectroscopy as well as quantum chemical calculations. The structure of formetrol fumerate was optimised using density functional theory calculations and the geometry optimization has been carried out on three different solvate crystal forms; di-hydrate, di-ethanolate, and di-isopropanolate in addition to the anhydrate form with and without intramolecular hydrogen bonding. Molecular assignments are proposed on the basis of ab initioB3LYP DFT calculations with a 6–31 G∗ basis set and vibrational wavenumbers. Crystallographic investigation has been carried out to formetrol anions and protonated anions arising from crystal structures of the studied conformers and it was evidenced that the di-hydrate form has the highest energy probably due to the greater possibility of intramolecular hydrogen bonding. Infrared and Raman spectra were calculated from the optimised structures. Many modes in the calculated spectra were matched with the experimental spectra and a description of the modes was given. By analysis of the theoretical vibrational modes, it was proved that formetrol fumerate specimens are likely to be dihydrate form with and without intramolecular hydrogen bonding. Additionally, several spectral features and band intensities in the stretching and bending regions were explained. Quantum mechanical calculations allowed improved understanding of formetrol fumerate and its vibrational spectra as an important β2 antagonistic compound in various pharmaceutical formulations. The obtained data could provide useful information about its interactions with excipients and other components.

中文翻译：

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了解富马酸福莫特罗的不同固体形式：结合计算和实验方法

摘要 在这项研究中，使用红外和拉曼振动光谱以及量子化学计算研究了富马酸福美特的样品。利用密度泛函理论计算优化了富马酸福美特的结构，并对三种不同的溶剂化物晶型进行了几何优化；除了具有和不具有分子内氢键的无水物形式之外，二水合物、二乙醇化物和二异丙醇化物。分子分配是在 ab initioB3LYP DFT 计算的基础上提出的，具有 6-31 G* 基组和振动波数。已经对由所研究构象异构体的晶体结构产生的甲三醇阴离子和质子化阴离子进行了晶体学研究，并证明二水合物形式可能具有最高的能量，这可能是由于分子内氢键的可能性更大。从优化的结构计算红外和拉曼光谱。计算光谱中的许多模式与实验光谱匹配，并给出了模式的描述。通过对理论振动模式的分析，证明富马酸福美特尔试样很可能是具有和不具有分子内氢键的二水合物形式。此外，还解释了拉伸和弯曲区域的几个光谱特征和波段强度。量子力学计算有助于更好地理解富马酸福美特及其作为各种药物制剂中重要的 β2 拮抗剂化合物的振动光谱。获得的数据可以提供有关其与赋形剂和其他成分相互作用的有用信息。