Characterization of Polymorphs and Solvates of Terbutaline Sulfate

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• 作者：Robin K. Harris ; Paul Hodgkinson ; Tomas Larsson ; Amsaveni Muruganantham ; Ingvar Ymé ; n ; Dmitry S. Yufit ; Vadim Zorin
• 刊名：Crystal Growth & Design
• 出版年：2008
• 出版时间：January 2008
• 年：2008
• 卷：8
• 期：1
• 页码：80 - 90
• 全文大小：2174K
• 年卷期：v.8,no.1(January 2008)
• ISSN：1528-7505

文摘

Five different crystalline modifications (two anhydrates, a monohydrate, a higher hydrate, and an acetic acid solvate) of an asthma-therapy drug, terbutaline sulfate, have been identified and characterized by several solid-state techniques. X-ray powder diffraction (XRPD) and thermal analysis, that is, thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC), were used as preliminary techniques to identify the different forms. Detailed solid-state characterization was carried out by ¹³C and ¹⁵N solid state NMR (SSNMR), using the cross-polarization (CP) and magic-angle spinning (MAS) techniques. High-speed ¹H MAS spectra show signals at high frequency arising from hydrogen bonds. A ¹³C,¹H heteronuclear correlation spectrum, together with computations using the NMR-CASTEP program, yield further information on the hydrogen-bonding resonances. The structures of the monohydrate and of the higher hydrate were determined by single-crystal X-ray diffraction (XRD). The latter was found to be a 2.5 hydrate and to have some disordered atoms, including the hydroxyl group which conveys chirality on the molecule. The crystal structures of the anhydrate B, the acetic acid solvate, the monohydrate, and the higher hydrate are compared, stressing the extent of hydrogen bonding. The first three contain a common dimeric unit of terbutaline cations, linked by hydrogen bonds.