Insights into atomic-level interaction between mefenamic acid and eudragit EPO in a supersaturated solution by high-resolution magic-angle spinning NMR spectroscopy.
Insights into atomic-level interaction between mefenamic acid and eudragit EPO in a supersaturated solution by high-resolution magic-angle spinning NMR spectroscopy.
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通过高分辨率的魔术旋转NMR光谱法，在过饱和溶液中，在过饱和溶液中，洞察级相互作用的见解。
DOI：
10.1021/mp4005723
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发表时间：
2014-01-06
影响因子：
4.9
通讯作者：
Ramamoorthy A
中科院分区：
文献类型：
--
作者：
Higashi K;Yamamoto K;Pandey MK;Mroue KH;Moribe K;Yamamoto K;Ramamoorthy A
使用高分辨率魔角旋转（HRMAS）核磁共振（NMR）光谱法研究了甲芬那酸（MFA）（一种水溶性差的非甾体抗炎药）和Eudragit® EPO（EPO）（一种水溶性聚合物）在其过饱和溶液中的分子间相互作用。通过将无定形固体分散体分散到pH 5.5和37 °C的d-乙酸盐缓冲液中，制备具有3.0 mg/mL的高MFA浓度的稳定过饱和溶液。借助2.7 kHz的MAS，可以很好地分辨过饱和溶液一维1H NMR谱中MFA的极宽且未分辨的1H共振，从而能够完全归属水溶液中的MFA 1H共振。二维（2D）1H/1H核Overhauser效应谱（NOESY）和MAS条件下的射频驱动再耦合（RFDR）揭示了MFA与EPO在原子水平上的相互作用。在2D 1H/1H NMR谱中观察到的强交叉相关表明MFA的芳族基团与EPO的主链之间存在疏水相互作用。此外，EPO侧链中的氨基烷基与MFA的羧基形成亲水性相互作用，其可以是静电键或氢键。我们相信MFA和EPO分子之间的这些疏水和亲水相互作用在这种极其稳定的过饱和溶液的形成中起着关键作用。此外，2D 1H/1H RFDR表明分子MFA-EPO相互作用是相当灵活和动态的。
The intermolecular interaction between mefenamic acid (MFA), a poorly water-soluble non-steroidal anti-inflammatory drug, and Eudragit® EPO (EPO), a water-soluble polymer, is investigated in their supersaturated solution using high-resolution magic-angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy. The stable supersaturated solution with a high MFA concentration of 3.0 mg/mL is prepared by dispersing the amorphous solid dispersion into a d-acetate buffer at pH 5.5 and 37 °C. By virtue of MAS at 2.7 kHz, the extremely broad and unresolved 1H resonances of MFA in one-dimensional 1H NMR spectrum of the supersaturated solution are well resolved, thus enabling the complete assignment of MFA 1H resonances in the aqueous solution. Two-dimensional (2D) 1H/1H nuclear Overhauser effect spectroscopy (NOESY) and radio frequency-driven recoupling (RFDR) under MAS conditions reveal the interaction of MFA with EPO in the supersaturated solution at an atomic level. The strong cross-correlations observed in the 2D 1H/1H NMR spectra indicate a hydrophobic interaction between the aromatic group of MFA and the backbone of EPO. Furthermore, the aminoalkyl group in the side chain of EPO forms a hydrophilic interaction, which can be either electrostatic or hydrogen bonding, with the carboxyl group of MFA. We believe these hydrophobic and hydrophilic interactions between MFA and EPO molecules play a key role in the formation of this extremely stable supersaturated solution. In addition, 2D 1H/1H RFDR demonstrates that the molecular MFA-EPO interaction is quite flexible and dynamic.
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