Effect of 2-Hydroxypropyl-beta-cyclodextrin on release Rate of Metoprolol from Ternary Metoprolol/2-hydroxypropyl-beta-cyclodextrin/Ethylcellulose Tablets

摘要

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