title: Synchronous delivery of felodipine and metoprolol tartrate using monolithic osmotic pump technology.
abstract: The synchronous sustained-release of two drugs was desired urgently for patients needing combination therapy in long term. However, sophisticated technologies were used generally to realize the simultaneous delivery of two drugs especially those with different physico-chemical properties. The purpose of this study was to obtain the concurrent release of felodipine and metoprolol tartrate, two drugs with completely different solubilities, in a simple monolithic osmotic pump system (FMOP). Two types of blocking agents were used in monolithic osmotic pump tablets and the synchronous sustained-release of FMOP was acquired in vitro. The tablets were also administered to beagle dogs and the plasma levels of FMOP were determined by HPLC-MS/MS. The pharmacokinetic parameters were calculated using a non-compartmental model. Cmax of both felodipine and metoprolol from the osmotic pump tablets were lower, tmax and mean residence time of both felodipine and metoprolol from the osmotic pump tablets were longer significantly than those from immediate release tablets. These results verified prolonged release of felodipine and metoprolol tartrate from osmotic pump formulations. The similar absorption rate between felodipine and metoprolol in beagles was also obtained by this osmotic pump formulation. Therefore, it could be supposed that the accordant release of two drugs with completely different solubilities may be realized just by using monolithic osmotic pump technology.
authors.affiliation: a Beijing Institute of Pharmacology and Toxicology , Beijing , People's Republic of China.
authors.forename: Shiqing
authors.initials: S
authors.lastname: Zhao
authors.affiliation: a Beijing Institute of Pharmacology and Toxicology , Beijing , People's Republic of China.
authors.forename: Fanglin
authors.initials: F
authors.lastname: Yu
authors.affiliation: a Beijing Institute of Pharmacology and Toxicology , Beijing , People's Republic of China.
authors.forename: Nan
authors.initials: N
authors.lastname: Liu
authors.affiliation: a Beijing Institute of Pharmacology and Toxicology , Beijing , People's Republic of China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Di
authors.affiliation: a Beijing Institute of Pharmacology and Toxicology , Beijing , People's Republic of China.
authors.forename: Kun
authors.initials: K
authors.lastname: Yan
authors.affiliation: a Beijing Institute of Pharmacology and Toxicology , Beijing , People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: a Beijing Institute of Pharmacology and Toxicology , Beijing , People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: a Beijing Institute of Pharmacology and Toxicology , Beijing , People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: a Beijing Institute of Pharmacology and Toxicology , Beijing , People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: a Beijing Institute of Pharmacology and Toxicology , Beijing , People's Republic of China.
authors.forename: Zhenbo
authors.initials: Z
authors.lastname: Yang
authors.affiliation: a Beijing Institute of Pharmacology and Toxicology , Beijing , People's Republic of China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Li
authors.affiliation: a Beijing Institute of Pharmacology and Toxicology , Beijing , People's Republic of China.
authors.forename: Xingguo
authors.initials: X
authors.lastname: Mei
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations; D004285:Dogs; D016503:Drug Delivery Systems; D015736:Felodipine / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D008790:Metoprolol / Q000008:administration & dosage* / Q000493:pharmacokinetics; D009995:Osmosis; D012995:Solubility; D013607:Tablets / Q000008:administration & dosage*
chemical_list: D000959:Antihypertensive Agents; D003692:Delayed-Action Preparations; D013607:Tablets; D008790:Metoprolol; D015736:Felodipine
keywords: Felodipine; metoprolol tartrate; monolithic osmotic pump technology; simultaneous delivery