title: Soluplus®/TPGS-based solid dispersions prepared by hot-melt extrusion equipped with twin-screw systems for enhancing oral bioavailability of valsartan.
abstract: BACKGROUND
  Soluplus(®) (SP) and D-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS)-based solid dispersion (SD) formulations were developed by hot-melt extrusion (HME) to improve oral bioavailability of valsartan (VST).
  
  
  METHODS
  HME process with twin-screw configuration for generating a high shear stress was used to prepare VST SD formulations. The thermodynamic state of the drug and its dispersion in the polymers were evaluated by solid-state studies, including Fourier-transform infrared, X-ray diffraction, and differential scanning calorimetry. Drug release from the SD formulations was assessed at pH values of 1.2, 4.0, and 6.8. Pharmacokinetic study was performed in rats to estimate the oral absorption of VST.
  
  
  RESULTS
  HME with a high shear rate produced by the twin-screw system was successfully applied to prepare VST-loaded SD formulations. Drug amorphization and its molecular dispersion in the polymer matrix were verified by several solid-state studies. Drug release from SD formulations was improved, compared to the pure drug, particularly at pH 6.8. Oral absorption of drug in rats was also enhanced in SP and TPGS-based SD groups compared to that in the pure drug group.
  
  
  CONCLUSIONS
  SP and TPGS-based SDs, prepared by the HME process, could be used to improve aqueous solubility, dissolution, and oral absorption of poorly water-soluble drugs.
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: School of Bioscience and Biotechnology, Kangwon National University, Chuncheon, Republic of Korea.
authors.forename: Wie-Soo
authors.initials: WS
authors.lastname: Kang
authors.affiliation: School of Bioscience and Biotechnology, Kangwon National University, Chuncheon, Republic of Korea.
authors.forename: Jingpei
authors.initials: J
authors.lastname: Piao
authors.affiliation: College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam, Republic of Korea.
authors.forename: In-Soo
authors.initials: IS
authors.lastname: Yoon
authors.affiliation: College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
authors.forename: Dae-Duk
authors.initials: DD
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Kangwon National University, Chuncheon, Republic of Korea.
authors.forename: Hyun-Jong
authors.initials: HJ
authors.lastname: Cho
mesh_terms: D000284:Administration, Oral; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods; D065546:Drug Liberation; D006863:Hydrogen-Ion Concentration; D008297:Male; D011092:Polyethylene Glycols / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D000068756:Valsartan / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D014810:Vitamin E / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D004337:Drug Carriers; D011145:Polyvinyls; C572167:polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer; D014810:Vitamin E; D011092:Polyethylene Glycols; D000068756:Valsartan; C014225:tocophersolan
keywords: hot-melt extrusion; oral bioavailability; solid dispersion; valsartan