Modification of the initial release of a highly water-soluble drug from ethyl cellulose microspheres

The aim of this study was to develop a microspherical dosage form for a highly water-soluble drug, fenoterol HBr, by using the water insoluble, non-biodegradable polymer, ethyl cellulose. Fenoterol HBr was used as a model drug, based on its pharmacokinetic properties, i.e. the short half-life, incomplete absorption from the gastrointestinal tract due to the first pass effect. Three factors, the initial amount of drug, the volume of non-solvent (petroleum benzin) and the stirring speed of homogenizer, were varied during microsphere preparation. The release of fenoterol HBr from these microparticulate delivery systems was compared, and a possible release mechanism was proposed. The encapsulation efficiency of the drug, the morphology and the particle size of the microspheres were also investigated. The oil-in-oil solvent evaporation method efficiently encapsulated fenoterol HBr in these ethyl cellulose microspheres. A significant increase in the encapsulation efficiency of fenoterol was observed when the drug/polymer ratio was decreased from 15% to 5% (p < 0.05). The particle size of microparticles was in the range of 10-250 microm, and most microspheres had a particle size smaller than 100 microm. Only the volume of petroleum benzin showed a significant effect on the particle size of prepared microspheres (p < 0.05). Both the initial drug loading and the addition of nonsolvent significantly affected the initial release of fenoterol from the ethyl cellulose microspheres. The diffusion-controlled release followed by a constant release was exhibited in these microspheres.