Development of a sustained-release microcapsule for delivery of metoprolol succinate.

Abstract

Sustained-release (SR) formulations of metoprolol succinate (MS) may minimize fluctuations in plasma concentration and decrease the resulting adverse events. The aim of the present study was to optimize the loading capacity of microcapsules and the SR of MS. A uniform design method was applied to optimize the formulation of SR microcapsules, composed of ethyl cellulose and polyethylene glycol 6,000, in one step via emulsion-solvent diffusion. In vitro release was studied, and the in vivo bioavailability of MS following dosing with novel microcapsules was compared with a commercially available MS formulation in beagle dogs. The present methodology achieved an entrapment efficiency of 83.2%, with 96.1% of drug released in vitro in 18 h, and the release was close to linear over a 12-h period. Pharmacokinetic studies of MS microcapsules in beagle dogs demonstrated a superior SR profile compared with conventional SR tablets. MS microcapsules were developed with high encapsulation efficiency, which had desirable SR properties in vitro and in vivo.