title: Improvement of some physicochemical properties of arundic acid, (R)-(-)-2-propyloctanonic acid, by complexation with hydrophilic cyclodextrins.
abstract: 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 and (1)H 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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Mai
authors.initials: M
authors.lastname: Nakahara
authors.forename: Keiichi
authors.initials: K
authors.lastname: Motoyama
authors.forename: Takako
authors.initials: T
authors.lastname: Ishiguro
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Oda
authors.forename: Takashi
authors.initials: T
authors.lastname: Yamanoi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Okamoto
authors.forename: Akira
authors.initials: A
authors.lastname: Yagi
authors.forename: Hidekatsu
authors.initials: H
authors.lastname: Nishimura
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Hirayama
authors.forename: Kaneto
authors.initials: K
authors.lastname: Uekama
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Arima
mesh_terms: D002210:Caprylates / Q000737:chemistry* / Q000494:pharmacology; D055598:Chemical Phenomena / Q000187:drug effects; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D018697:Nootropic Agents / Q000737:chemistry* / Q000494:pharmacology; D011208:Powders / Q000737:chemistry; D012995:Solubility; D012996:Solutions / Q000737:chemistry; D013649:Taste / Q000187:drug effects; D055697:Taste Perception / Q000187:drug effects; D047392:beta-Cyclodextrins / Q000737:chemistry*; D047408:gamma-Cyclodextrins / Q000737:chemistry*
chemical_list: D002210:Caprylates; D005079:Excipients; D018697:Nootropic Agents; C459360:ONO2506; D011208:Powders; D012996:Solutions; D047392:beta-Cyclodextrins; D047408:gamma-Cyclodextrins