Enhanced dissolution and skin permeation profiles of epalrestat with β-cyclodextrin derivatives using a cogrinding method

Publication date: 30 August 2017
Source:European Journal of Pharmaceutical Sciences, Volume 106
Author(s): Takayuki Furuishi, Shoma Takahashi, Noriko Ogawa, Mihoko Gunji, Hiromasa Nagase, Toyofumi Suzuki, Tomohiro Endo, Haruhisa Ueda, Etsuo Yonemochi, Kazuo Tomono
Epalrestat (EPL) is a water-insoluble drug (14μM) that inhibits aldose reductase. This study investigated the interactions between β-cyclodextrin (CD) derivatives and EPL to determine the solubilizing effect on EPL from phase solubility diagrams. We improved the solubility of EPL in water by adding β-CD derivatives. Moreover, the solubility of EPL mixed with β-CD derivatives by cogrinding in a ball mill method was about 2–3 times higher than those of EPL with the same CD concentration (5mM) calculated from phase solubility diagrams. In addition, we investigated the effect of β-CD derivatives on in vitro percutaneous absorption of EPL through hairless mouse skin. Among the coground mixtures of EPL and β-CD derivatives, the mixture containing methyl (ME)-β-CD showed the strongest enhancement of EPL skin permeation. Furthermore, adding 10wt% urea as a skin permeation enhancer after cogrinding with ME-β-CD improved the flux of EPL 300 times compared to the flux of EPL alone. This result indicates the ME-β-CD ground mixture system with urea has potential as a new transdermal drug delivery system of EPL for diabetic neuropathy.

Graphical abstract

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