Uno Rio, Ohkawa Kyoko, Kojima Honami, Haraguchi Tamami, Ozeki Minoru, Kawasaki Ikuo, Yoshida Miyako, Habara Masaaki, Ikezaki Hidekazu, Uchida Takahiro
Department of Faculty of Pharmaceutical Science, Mukogawa Women's University.
Intelligent Sensor Technology Inc.
Chem Pharm Bull (Tokyo). 2023;71(2):148-153. doi: 10.1248/cpb.c22-00679.
This study aimed to evaluate the bitterness of famotidine (FAM) combined with each of three non-steroidal anti-inflammatory drugs (NSAIDs): ibuprofen (IBU), flurbiprofen (FLU), and naproxen (NAP), which have potential as fixed-dose combination (FDC) drugs. We evaluated the bitterness of FAM and each NSAID by taste sensor AN0 and C00, respectively. FAM showed high sensor output representing sensitivity to bitterness, whereas three NSAIDs did not show large sensor output, suggesting that the bitterness intensities of three NSAIDs were lower than that of FAM. The bitterness of FAM on sensor AN0 was suppressed in a concentration-dependent manner when mixed with IBU, FLU, or NAP. Among three NSAIDs, IBU most effectively inhibited bitterness on sensor output, and the gustatory sensation test confirmed that adding IBU to FAM reduced the bitterness of FAM in a concentration-dependent manner. MarvinSketch confirmed that the drugs were mostly present in an ionic solution when FAM was mixed with NSAIDs. The H-NMR spectroscopy analysis also revealed the presence of electrostatic interactions between FAM and NSAIDs, suggesting that the electrostatic interaction between FAM and NSAIDs might inhibit the adsorption of FAM on the bitter taste sensor membrane, thereby masking the bitter taste.
本研究旨在评估法莫替丁(FAM)与三种非甾体抗炎药(NSAIDs):布洛芬(IBU)、氟比洛芬(FLU)和萘普生(NAP)联合使用时的苦味,这三种药物有作为固定剂量复方(FDC)药物的潜力。我们分别通过味觉传感器AN0和C00评估了FAM和每种NSAIDs的苦味。FAM显示出较高的传感器输出,代表对苦味敏感,而三种NSAIDs未显示出较大的传感器输出,表明三种NSAIDs的苦味强度低于FAM。当与IBU、FLU或NAP混合时,FAM在传感器AN0上的苦味以浓度依赖的方式受到抑制。在三种NSAIDs中,IBU对传感器输出的苦味抑制作用最有效,味觉感受测试证实,向FAM中添加IBU可使FAM的苦味以浓度依赖的方式降低。MarvinSketch证实,当FAM与NSAIDs混合时,药物大多以离子溶液形式存在。核磁共振氢谱分析还揭示了FAM与NSAIDs之间存在静电相互作用,表明FAM与NSAIDs之间的静电相互作用可能抑制FAM在苦味传感器膜上的吸附,从而掩盖苦味。