Potential use of 2-hydroxypropyl-β-cyclodextrin as a release modifier of a water-soluble drug, metoprolol tartrate, from ethylcellulose tablets

Abstract

Drug release behavior was investigated for tablets of a ternary system in which metoprolol tartrate (Met)/2-hydroxypropyl-β-cyclodextrin (HP-β-CD) complexes with different molar ratios were dispersed in an ethylcellulose (EC) matrix. The release rate of Met from the tablets decreased due to the formation of the binary solid dispersion with EC and was further slowed down by dispersal of the Met/HP-β-CD complex in the EC matrix. The release rate of Met decreased with the increase in contents of HP-β-CyD in EC matrix up to (30/10)/60%w/w (Met/HP-β-CD)/EC but further increases in HP-β-CD content led to faster release rates. The analysis of the release rates by Korsmeyer's and Higuchi's equations and their temperature dependence suggested that Met is released according to a diffusion-controlled mechanism. Water penetration studies and microscopic observation suggested that the retarding effect of HP-β-CD is attributable to a gel formation in small pores of the EC matrix. Moreover, the release rate of Met from the ternary (Met/HP-β-CD)/EC ((30/10)/60%w/w) tablet was negligibly influenced by the pH of the dissolution medium, paddle rotation rate, viscosity of the solution and storage conditions of the tablet. The results suggested that HP-β-CD can work as a release rate-decelerating agent for Met when it is formulated in appropriate amounts in a hydrophobic EC matrix. Therefore, a combination of HP-β-CD and EC may be useful for the controlled release of water-soluble drugs, and the release control can be tuned by adjusting the composition of components.