Improvement of some physicochemical properties of arundic acid, (R)-(-)-2-propyloctanonic acid, by complexation with hydrophilic cyclodextrins

被引：9

作者：

Miyamoto, Yuji ^{[1
,2
]}

Nakahara, Mai ^{[1
]}

Motoyama, Keiichi ^{[1
]}

Ishiguro, Takako ^{[1
,3
]}

Oda, Yoshiki ^{[4
]}

Yamanoi, Takashi ^{[4
]}

Okamoto, Ichiro ^{[5
]}

Yagi, Akira ^{[2
]}

Nishimura, Hidekatsu ^{[5
]}

Hirayama, Fumitoshi ^{[3
]}

Uekama, Kaneto ^{[3
]}

Arima, Hidetoshi ^{[1
]}

机构：

[1] Kumamoto Univ, Grad Sch Pharmaceut Sci, Kumamoto 8620973, Japan

[2] Ono Pharmaceut Co Ltd, Pharmaceut Dev Labs, Shimamoto, Osaka 6188585, Japan

[3] Soja Univ, Fac Pharmaceut Sci, Kumamoto 8600082, Japan

[4] Noguchi Inst, Itabashi Ku, Tokyo 1730003, Japan

[5] Ono Pharmaceut Co Ltd, Pharmaceut Engn Labs, Higashinari Ku, Osaka 5370003, Japan

来源：

INTERNATIONAL JOURNAL OF PHARMACEUTICS | 2011年 / 413卷 / 1-2期

关键词：

Arundic acid; Cyclodextrins; Complexation; Powderization; Solubilization; Taste masking; ASTROCYTE-MODULATING AGENT; TASTE SENSOR; PHARMACEUTICAL APPLICATIONS; DRUG FORMULATION; LIPID RAFTS; BITTERNESS; SWEET; MICE; NEUROTOXICITY; SUPPRESSION;

D O I：

10.1016/j.ijpharm.2011.04.022

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Arundic acid, (R)-(-)-2-propyloctanonic acid, is a novel neurological agent for intractable neurodegenerative diseases. However, anindic 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-beta-CyD had the most potent solubilizing effect for arundic acid. UV and H-1 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-beta-CyD and gamma-CyD showed the most significant taste-masking effects in solution and powders, respectively. HP-beta-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. (C) 2011 Elsevier B.V. All rights reserved.

引用

页码：63 / 72

页数：10

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