Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
J Pharm Sci. 2011 May;100(5):1935-43. doi: 10.1002/jps.22417. Epub 2010 Dec 28.
Reduction of bitterness of antihistaminic drugs by cyclodextrin (CyD) complexation was examined. The stability constant (Kc) of the 1:1 CyD inclusion complexes with antihistaminic drugs increased in the order of 2-hydroxypropyl-β-CyD (HP-β-CyD) ≈ β-CyD > γ-CyD > α-CyD for diphenhydramine and epinastine, and HP-β-CyD ≈ β-CyD > α-CyD > γ-CyD for hydroxyzine, cetirizine, and dl-chlorpheniramine. The inclusion complexes inhibited the adsorption of antihistaminic drugs to lipid membrane using liposomes, as the magnitude of Kc increased. From human gustatory sensation tests, β-CyD and HP-β-CyD potently suppressed the bitterness of antihistaminic drugs in a dose-dependent manner. Further, an artificial taste sensor analysis revealed that β-CyD and HP-β-CyD inhibited the bitterness of antihistaminic drugs in solution. The results suggest that CyDs suppress the bitterness of antihistaminic drugs in solutions through the formation of inclusion complexes. These results may provide useful information for masking or elimination of bitterness of drugs using CyDs.
通过环糊精（CyD）包合作用来降低抗组胺药物的苦味。抗组胺药物与环糊精形成 1:1 包合物的稳定常数（Kc）按羟丙基-β-CyD（HP-β-CyD）≈β-CyD＞γ-CyD＞α-CyD的顺序增加，对于苯海拉明和依匹斯汀，而对于羟嗪、西替利嗪和 dl-氯苯那敏则为 HP-β-CyD≈β-CyD＞α-CyD＞γ-CyD。包合物通过脂质体抑制抗组胺药物对脂质膜的吸附，因为 Kc 值增加。从人体味觉测试来看，β-CyD 和 HP-β-CyD 以剂量依赖的方式强烈抑制抗组胺药物的苦味。此外，人工味觉传感器分析表明β-CyD 和 HP-β-CyD 抑制了抗组胺药物在溶液中的苦味。结果表明，CyD 通过形成包合物来抑制抗组胺药物在溶液中的苦味。这些结果可能为使用 CyD 掩蔽或消除药物的苦味提供有用的信息。
