title: Development and uniform evaluation of ropinirole osmotic pump tablets with REQUIP XL both in vitro and in beagle dogs.
abstract: REQUIP XL, prolonged release formulation of ropinirole hydrochloride (RH) in market, could release ropinirole constantly and showed satisfactory therapeutic effect and good compliance. REQUIP XL was composed of more than 10 kinds of excipients and prepared by Geomatrix technology, which was complex and laborious. The purpose of this study was to obtain a dosage form of RH with similar in vitro release profile and bioequivalence in vivo compared to REQUIP XL. Osmotic pump tablet combined with fast release phase was selected as the delivery system of RH and similar release curves were obtained in different media. The tablets were also administered to beagle dogs and the pharmacokinetic parameters were calculated using a non-compartmental model. Cmax, tmax, mean residence time (MRT), and area under the curve from 0 to 24 h (AUC0-24) were 3.97 ± 0.53 ng/mL, 3.58 ± 0.49 h, 8.29 ± 0.93 h, and 35.20 ± 8.11 ng/mL ċ h for ropinirole osmotic pump tablets (ROPT) and 4.15 ± 1.07 ng/mL, 2.92 ± 0.49 h, 7.84 ± 1.09 h, and 34.34 ± 10.06 ng/mL ċ h for REQUIP XL. The log-transformed mean Cmaxand AUC0-24of ROPT were about 92.15% and 102.49% relative to that of REQUIP XL, respectively. The 90% confidence intervals of Cmaxand AUC0-24for ROPT were 75.69-115.31% and 88.89-122.30%, respectively. So it could be concluded that ROPT was uniform with REQUIP XL both in vitro and in beagles and the release profiles of Geomatrix technology may be obtained by osmotic pump combined with fast release technology.
authors.affiliation: a Pharmaceutical Research Department , Beijing Institute of Pharmacology and Toxicology , Beijing , China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Li
authors.affiliation: a Pharmaceutical Research Department , Beijing Institute of Pharmacology and Toxicology , Beijing , China.
authors.forename: Fanglin
authors.initials: F
authors.lastname: Yu
authors.affiliation: a Pharmaceutical Research Department , Beijing Institute of Pharmacology and Toxicology , Beijing , China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Di
authors.affiliation: a Pharmaceutical Research Department , Beijing Institute of Pharmacology and Toxicology , Beijing , China.
authors.forename: Xiqing
authors.initials: X
authors.lastname: Zhao
authors.affiliation: a Pharmaceutical Research Department , Beijing Institute of Pharmacology and Toxicology , Beijing , China.
authors.forename: Shiqing
authors.initials: S
authors.lastname: Zhao
authors.affiliation: a Pharmaceutical Research Department , Beijing Institute of Pharmacology and Toxicology , Beijing , China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: a Pharmaceutical Research Department , Beijing Institute of Pharmacology and Toxicology , Beijing , China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: a Pharmaceutical Research Department , Beijing Institute of Pharmacology and Toxicology , Beijing , China.
authors.forename: Zhiyuan
authors.initials: Z
authors.lastname: Wang
authors.affiliation: a Pharmaceutical Research Department , Beijing Institute of Pharmacology and Toxicology , Beijing , China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.affiliation: a Pharmaceutical Research Department , Beijing Institute of Pharmacology and Toxicology , Beijing , China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.affiliation: a Pharmaceutical Research Department , Beijing Institute of Pharmacology and Toxicology , Beijing , China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: a Pharmaceutical Research Department , Beijing Institute of Pharmacology and Toxicology , Beijing , China.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Xie
authors.affiliation: a Pharmaceutical Research Department , Beijing Institute of Pharmacology and Toxicology , Beijing , China.
authors.forename: Xingguo
authors.initials: X
authors.lastname: Mei
mesh_terms: D000818:Animals; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004285:Dogs; D018491:Dopamine Agonists / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods*; D005079:Excipients / Q000737:chemistry; D006801:Humans; D007211:Indoles / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D009995:Osmosis; D011788:Quality of Life; D012148:Restless Legs Syndrome / Q000188:drug therapy*; D013607:Tablets; D013810:Therapeutic Equivalency
chemical_list: D003692:Delayed-Action Preparations; D018491:Dopamine Agonists; D005079:Excipients; D007211:Indoles; D013607:Tablets; C046649:ropinirole
keywords: Bioequivalent; REQUIP XL; in vitro release; osmotic pump tablet; ropinirole