title: Application of hot-melt extrusion technology for designing an elementary osmotic pump system combined with solid dispersion for a novel poorly water-soluble antidepressant.
abstract: TP1 is a novel antidepressant with poor solubility. To reduce fluctuations in blood concentration and increase oral bioavailability, a controlled-release system was developed by combining a solid dispersion (SD) and an elementary osmotic pump (EOP). The study compared different methods of preparing SDs. Hot-melt extrusion (HME) exhibited clear advantages over the traditional melting technique. An in vitro release study demonstrated that HME-EOP tablets released TP1 in a zero-order manner over 12 h and the drug release was in dependent of the release medium and agitation speed, whereas release from molten-EOP tablets lasted only 8 h. In contrast to immediate-release tablets, the HME-EOP tablets exhibited less fluctuation in blood concentration and higher bioavailability in vivo. In summary, the osmotic pump system combined with an HME-based SD of TP1 presented controlled release in vitro, high bioavailability in vivo and a good in vivo-in vitro correlation.
authors.affiliation: a Department of Pharmaceutics , School of Pharmacy, Yantai University , Yantai , People's Republic of China and.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Zhang
authors.affiliation: a Department of Pharmaceutics , School of Pharmacy, Yantai University , Yantai , People's Republic of China and.
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.affiliation: a Department of Pharmaceutics , School of Pharmacy, Yantai University , Yantai , People's Republic of China and.
authors.forename: Pei
authors.initials: P
authors.lastname: Li
authors.affiliation: a Department of Pharmaceutics , School of Pharmacy, Yantai University , Yantai , People's Republic of China and.
authors.forename: Aiping
authors.initials: A
authors.lastname: Wang
authors.affiliation: a Department of Pharmaceutics , School of Pharmacy, Yantai University , Yantai , People's Republic of China and.
authors.forename: Rongcai
authors.initials: R
authors.lastname: Liang
authors.affiliation: b State Key Laboratory of Long-Acting and Targeting Drug Delivery System, Shandong Luye Pharmaceutical Co., Ltd. , Yantai , People's Republic of China.
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Gai
authors.affiliation: a Department of Pharmaceutics , School of Pharmacy, Yantai University , Yantai , People's Republic of China and.
authors.forename: Wanhui
authors.initials: W
authors.lastname: Liu
authors.affiliation: a Department of Pharmaceutics , School of Pharmacy, Yantai University , Yantai , People's Republic of China and.|b State Key Laboratory of Long-Acting and Targeting Drug Delivery System, Shandong Luye Pharmaceutical Co., Ltd. , Yantai , People's Republic of China.
authors.forename: Youxin
authors.initials: Y
authors.lastname: Li
authors.affiliation: a Department of Pharmaceutics , School of Pharmacy, Yantai University , Yantai , People's Republic of China and.
authors.forename: Kaoxiang
authors.initials: K
authors.lastname: Sun
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D004285:Dogs; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation; D006863:Hydrogen-Ion Concentration; D008297:Male; D009995:Osmosis / Q000187:drug effects*; D012995:Solubility; D013607:Tablets / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D013678:Technology, Pharmaceutical / Q000379:methods; D014867:Water / Q000737:chemistry*
chemical_list: D000928:Antidepressive Agents; D003692:Delayed-Action Preparations; D013607:Tablets; D014867:Water
keywords: Bioavailability; TP1; controlled release; pharmacokinetics; solubility