title: Extruded Soluplus/SIM as an oral delivery system: characterization, interactions, in vitro and in vivo evaluations.
abstract: The aim of this study was to obtain a stable, amorphous solid dispersion (SD) with Soluplus, prepared by hot-melt extrusion (HME) as an effective and stable oral delivery system to improve the physical stability and bioavailability of the poorly water-soluble simvastatin (SIM), a drug with relatively low Tg. The drug was proved to be miscible with Soluplus by calculation and measurements. The solubility, dissolution, thermal characteristics, interactions and physical stability of the SIM/Soluplus SDs were investigated. The crystal state of simvastatin in the SD was found to change from crystalline to amorphous form during the HME process and also hydrogen bonds were observed between SIM and the extruded Soluplus. The phase solubility showed the solubilization effect of Soluplus was strong and spontaneous. The equilibrium solubility illustrated that Soluplus/SIM SDs gained much higher solubility than its corresponding physical mixtures (PMs). Both of the dissolution profiles and in-vivo performance showed that the SIM/Soluplus SD obtained a marked enhancement, compared with the PM. There was a little change in the SIM/Soluplus SD during a 3-month storage period (40 °C, 75%), indicating the good physicochemical stability. The extruded Soluplus system prepared by HME is a good alternative for the water-insoluble SIM to improve the stability and bioavailability.
authors.affiliation: a Department of Pharmaceutics , Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: a Department of Pharmaceutics , Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Liu
authors.affiliation: a Department of Pharmaceutics , Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Yanfei
authors.initials: Y
authors.lastname: Luo
authors.affiliation: a Department of Pharmaceutics , Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yao
authors.affiliation: a Department of Pharmaceutics , Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: a Department of Pharmaceutics , Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Bin
authors.initials: B
authors.lastname: Tian
authors.affiliation: a Department of Pharmaceutics , Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Xing
authors.initials: X
authors.lastname: Tang
mesh_terms: D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D004337:Drug Carriers / Q000737:chemistry*; D004355:Drug Stability; D011108:Polymers / Q000737:chemistry*; D019821:Simvastatin / Q000008:administration & dosage* / Q000737:chemistry*; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D014867:Water / Q000737:chemistry*
chemical_list: D004337:Drug Carriers; D011108:Polymers; D014867:Water; D019821:Simvastatin
keywords: Bioavailability; Soluplus; simvastatin; solid dispersion; stability