Improvement of Some Physicochemical Properties of Arundic Acid, (R)-(-)-2-Propyloctanonic Acid, by Complexation with Hydrophilic Cyclodextrins
Improvement of Some Physicochemical Properties of Arundic Acid, (R)-(-)-2-Propyloctanonic Acid, by Complexation with Hydrophilic Cyclodextrins
复制标题
通过与亲水性环糊精络合改善芦荟酸、(R)-(-)-2-丙基辛酸的一些理化性质
DOI：
10.1016/j.ijpharm.2011.04.022
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发表时间：
2011
影响因子：
5.8
通讯作者：
H.Arima
中科院分区：
文献类型：
--
作者：
Y.Miyamoto;M.Nakahara;K.Motoyama;T.Ishiguro;Y.Oda;T.Yamanoi;I.Okamoto;A.Yagi;H.Nishimura;F.Hirayama;K.Uekama;H.Arima
阿伦酸，(R)-(−)-2-丙基癸酸，是一种治疗顽固性神经退行性疾病的新型神经药物。然而，环己酸是一种油性药物，水溶性低，苦味/刺激性强。因此，需要进一步改善环己酸的这些理化性质，以开发其药物制剂。在本研究中，我们评估了母体环糊精（CyDs）和2-羟丙基化CyDs （HP-CyDs）是否能与环己酸相互作用，并具有粉化、增溶和味掩蔽性能。在各种cyd中，HP-β-CyD对环己酸的增溶作用最强。紫外和1h核磁共振光谱研究表明，环己烷酸在溶液中以1:1的摩尔比与CyDs形成包合物。与CyDs的络合作用使环酸的油状形态变为固体形态。味觉感觉研究表明，在各种cyd中，HP-β-CyD和γ-CyD分别在溶液和粉末中表现出最显著的味觉掩蔽作用。HP-β-CyD显著降低了环己酸吸附引起的电势对味觉传感器的响应。这些结果表明亲水性CyDs具有作为制备含环戊酸溶液和粉末的多功能辅料的潜力。
Arundic acid, (R)-(−)-2-propyloctanonic acid, is a novel neurological agent for intractable neurodegenerative diseases. However, arundic acid, an oily drug, has low aqueous solubility and severe bitter/irritating tastes. Consequently, these physicochemical properties of arundic acid need to be improved to develop its pharmaceutical preparations. In the present study, we evaluated whether parent cyclodextrins (CyDs) and 2-hydroxypropylated CyDs (HP-CyDs) can interact with arundic acid, and have powderization, solubilization and taste-masking properties. Of various CyDs, HP-β-CyD had the most potent solubilizing effect for arundic acid. UV and1H NMR spectroscopic studies demonstrated that arundic acid formed inclusion complexes with CyDs at a molar ratio of 1:1 in solution. The complexation with CyDs changed an oily form of arundic acid to a solid form. The gustatory sensation studies indicate that of various CyDs, HP-β-CyD and γ-CyD showed the most significant taste-masking effects in solution and powders, respectively. HP-β-CyD significantly reduced the response of the electric potential caused by the adsorption of arundic acid to the taste sensor. These results suggest that hydrophilic CyDs have potential as multifunctional excipients for preparing solutions and powders containing arundic acid.