Application of hot-melt extrusion technology for designing an elementary osmotic pump system combined with solid dispersion for a novel poorly water-soluble antidepressant. (16th November 2016)

• Record Type: Journal Article
• Authors: Zhang, Xuemei; Wang, Meng; Li, Pei; Wang, Aiping; Liang, Rongcai; Gai, Yunyun; Liu, Wanhui; Li, Youxin; Sun, Kaoxiang
• Is Part Of: Pharmaceutical development and technology. Volume 21:Number 8(2016)
• Page Start: 1006
• Page End: 1014
• Publication Date: 2016-11-16
• Subjects: Bioavailability -- controlled release -- pharmacokinetics -- solubility -- TP1; Drug delivery systems -- Periodicals; Pharmaceutical technology -- Periodicals; Drugs -- Administration -- Research -- Periodicals; Drug Delivery Systems -- Periodicals; Pharmaceutical Preparations -- Periodicals; Technology, Pharmaceutical -- Periodicals; 615
• DOI: 10.3109/10837450.2015.1089896
• Languages: English
• ISSNs: 1083-7450

Abstract

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.