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

Takayuki Furuishi; Shoma Takahashi; Noriko Ogawa; Mihoko Gunji; Hiromasa Nagase; Toyofumi Suzuki; Tomohiro Endo; Haruhisa Ueda; Etsuo Yonemochi; Kazuo Tomono

doi:10.1016/j.ejps.2017.05.047

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

Eur J Pharm Sci. 2017 Aug 30:106:79-86. doi: 10.1016/j.ejps.2017.05.047. Epub 2017 May 22.

Authors

Affiliations

¹ Department of Physical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan. Electronic address: t-furuishi@hoshi.ac.jp.
² Laboratory of Pharmaceutics, School of Pharmacy, Nihon University, 7-7-1 Narashinodai, Funabashi-shi, Chiba 274-8555, Japan.
³ Department of Pharmaceutical Engineering, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto-cho, Chikusa-ku, Nagoya, Aichi 464-8650, Japan.
⁴ Department of Physical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
⁵ Central Research Laboratories, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
⁶ School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan.
⁷ Department of Physical Chemistry, School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan; Department of Pharmaceutical Sciences, Nihon Pharmaceutical University, 10280 Komuro, Ina-machi, Kitaadachigun, Saitama, 362-0806, Japan.

PMID: 28546106
DOI: 10.1016/j.ejps.2017.05.047

Abstract

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.

Keywords: Cogrinding; Cyclodextrin; Enhancer; Epalrestat; Skin permeation; Solubility.

MeSH terms

Administration, Cutaneous
Aldehyde Reductase / antagonists & inhibitors*
Animals
Calorimetry, Differential Scanning / methods
Chromatography, High Pressure Liquid / methods
Drug Carriers / chemistry*
Drug Liberation
Male
Mice
Permeability
Rhodanine / analogs & derivatives*
Rhodanine / chemistry
Rhodanine / pharmacology
Skin Absorption
Solubility
Surface Properties
Thiazolidines / chemistry*
Thiazolidines / pharmacology*
X-Ray Diffraction / methods
beta-Cyclodextrins / chemistry*

Substances

Drug Carriers
Thiazolidines
beta-Cyclodextrins
methyl-beta-cyclodextrin
epalrestat
Rhodanine
Aldehyde Reductase