title: Modification of the initial release of a highly water-soluble drug from ethyl cellulose microspheres.
abstract: 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.
authors.affiliation: School of Pharmacy, College of Medicine, National Taiwan University, Taipei. wjlin@ha.cm.ntu.edu.tw
authors.forename: W J
authors.initials: WJ
authors.lastname: Lin
authors.forename: T L
authors.initials: TL
authors.lastname: Wu
mesh_terms: D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000737:chemistry*; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000737:chemistry*; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations; D005280:Fenoterol / Q000008:administration & dosage / Q000737:chemistry*; D007700:Kinetics; D008863:Microspheres; D012995:Solubility; D014867:Water / Q000737:chemistry
chemical_list: D000318:Adrenergic beta-Agonists; D001993:Bronchodilator Agents; D003692:Delayed-Action Preparations; D014867:Water; D005280:Fenoterol; C013517:ethyl cellulose; D002482:Cellulose