Journal of Inclusion Phenomena and Macrocyclic Chemistry
44 (1-4): 141-144, December 2002
Copyright © 2002 Kluwer Academic Publishers
All rights reserved
Effect of 2-Hydroxypropyl-β-cyclodextrin on Release Rate of Metoprolol from Ternary Metoprolol/2-hydroxypropyl- β-cyclodextrin/Ethylcellulose Tablets
Yoichi Ikeda, Sohko Motoune, Aya Marumoto, Yoh Sonoda, Fumitoshi Hirayama, Hidetoshi Arima, Kaneto Uekama
Author for correspondence Faculty of Pharmaceutical Sciences, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan
Abstract
The effect of 2-hydroxypropyl-β-cyclodextrin (HP-β-CyD) on the release of a water-soluble β1-selective adrenoreceptor antagonist, metoprolol (Met), from ternary Met/HP-β-CyD/ethylcellulose (EC) tablets was investigated. The release rate of Met from the ternary tablets was dependent on amounts of HP-β-CyD in the tablets, i.e., the rate decreased when small amounts of HP-β-CyD were added, while large amounts of HP-β-CyD accelerated the rate. The slowest rate was observed for the tablet consisted of a 30/10/60 weight ratio of Met/HP-β-CyD/EC. The analyses of the release rates by the Korsmeyer equation and their temperature dependence suggested that Met is released from the EC matrix containing HP-β-CyD according to the diffusion-controlled mechanism. The water penetration studies and the micro- and macroscopic observations suggested that the retarding effect of HP-β-CyD is attributable to a viscous gel formation in small pores on the surface of the tablets, where HP-β-CyD gels may work as a barrier for the water penetration into the tablets and the release of the drug from the tablets. The in-vitro release property of the ternary tablets was reflected in the in-vivo absorption profile in dogs. The results indicated that a combination of HP-β-CyD and EC is useful for the release control of water-soluble drugs such as Met.

Keywords
ethylcellulose, gel, 2-hydroxypropyl-β-cyclodextrin, release control, tablet

Keywords
cyclodextrin, ebselen, inclusion complex, solubility, solubilization, sulfobutyl ether β-cyclodextrin