Effect of 2-hydroxypropyl-β-cyclodextrin on release rate of metoprolol from ternary metoprolol/2-hydroxypropyl-β-cyclodextrin/ethylcellulose tablets

The effect of 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) on the release of a water-soluble beta(1)-selective adrenoreceptor antagonist, metoprolol ( Met), from ternary Met/HP-beta-CyD/ethylcellulose (EC) tablets was investigated. The release rate of Met from the ternary tablets was dependent on amounts of HP-beta-CyD in the tablets, i.e., the rate decreased when small amounts of HP-beta-CyD were added, while large amounts of HP-beta-CyD accelerated the rate. The slowest rate was observed for the tablet consisted of a 30/10/60 weight ratio of Met/HP-beta-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-beta-CyD according to the diffusion-controlled mechanism. The water penetration studies and the micro- and macroscopic observations suggested that the retarding effect of HP-beta-CyD is attributable to a viscous gel formation in small pores on the surface of the tablets, where HP-beta-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-beta-CyD and EC is useful for the release control of water-soluble drugs such as Met.