title: Preparation, release and pharmacokinetics of a risperidone elementary osmotic pump system.
abstract: Preparation and in vitro/in vivo evaluation of risperidone elementary osmotic pump (RIS-EOP) formulations were investigated. A method for the preparation of RIS-EOP tablets was developed by modulating RIS solubility with citric acid. The influence of osmotic agents and the compositions of semipermeable membrane on drug release profiles was evaluated. The formulation of RIS-EOP was optimized by orthogonal design. The in vitro release profile of the optimum formulation achieved to deliver RIS at an approximate zero-order up to 12 h. The pharmacokinetic profiles of RIS-EOP were evaluated compared with immediate release tablets in beagle dogs. The mean tmax and mean residence time of RIS-EOP for RIS and its active metabolite, 9-hydroxyrisperidone, were remarkably longer, compared with immediate release tablets. These results corroborated prolonged release of RIS from EOP formulations. Moreover, drug plasma levels with lower fluctuations could be achieved with RIS-EOP tablets. These results suggested that increasing drug solubility by adding or reacting with alkali/acid might be used for the preparation of EOP tablets of certain poorly water-soluble drugs.
authors.affiliation: Pharmaceutical Department, Beijing Institute of Pharmacology and Toxicology , Beijing , China and.
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Dan-Yu
authors.initials: DY
authors.lastname: Mei
authors.forename: Meiyan
authors.initials: M
authors.lastname: Yang
authors.forename: Xing-Guo
authors.initials: XG
authors.lastname: Mei
mesh_terms: D000818:Animals; D003692:Delayed-Action Preparations; D004285:Dogs; D015918:Infusion Pumps, Implantable; D008297:Male; D009995:Osmosis / Q000187:drug effects; D018967:Risperidone / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000493:pharmacokinetics*
chemical_list: D003692:Delayed-Action Preparations; D018967:Risperidone
keywords: Controlled release; elementary osmotic pump; risperidone; solubility-modulated