title: Evaluation of polymer carriers with regard to the bioavailability enhancement of bifendate solid dispersions prepared by hot-melt extrusion.
abstract: OBJECTIVE
  The aim of this study was to evaluate several polymer carriers with regard to the bioavailability enhancement of bifendate solid dispersions (SD) prepared by hot-melt extrusion (HME) and select the most appropriate polymer carrier.
  
  
  METHODS
  Solid dispersions containing bifendate in different polymers, including Plasdone(®) S-630, Eudragit(®) EPO and Kollidon(®) VA 64 were prepared by hot-melt extrusion. Differential scanning calorimetry (DSC), Powder X-ray diffraction (XRD) and dissolution testing were used to characterize the systems. Then, the thermal degradation during the HME process and the storage stability of tablets consisting of bifendate-Kollidon(®) VA 64 SD were investigated. Finally, the oral bioavailability of bifendate dosage forms with bifendate-Plasdone(®) S-630 (1/9), bifendate-Eudragit(®) EPO (1/4) and bifendate-Kollidon(®) VA 64 (1/9) SD in beagle dogs was compared with that of commercially available benfidate pills.
  
  
  RESULTS
  DSC and XDR analysis showed the dispersion of the drug in the polymer on a molecular basis or in the amorphous state. The drug release from both bifendate-Plasdone(®) S-630 SD and bifendate-Eudragit(®) EPO SD was up to more than 90% with the pH 1.2 simulated gastric fluid as the dissolution medium, while the relative bioavailability was just 87.8 ± 51.8% and 110 ± 62% compared with commercial pills, respectively. The directly compressed tablets with bifendate-Kollidon(®) VA 64 SD were found to dissolve rapidly over 95% within 30 min and the relative bioavailability was 145.0 ± 35.2%.
  
  
  CONCLUSIONS
  The bioavailability of water-insoluble bifendate was markedly enhanced by dispersing the drug in the polymer carrier Kollidon(®) VA 64 employing HME technology.
authors: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, China.
authors: Jia
authors: J
authors: Feng
authors: Lishuang
authors: L
authors: Xu
authors: Renchao
authors: R
authors: Gao
authors: Yanfei
authors: Y
authors: Luo
authors: Xing
authors: X
authors: Tang
mesh_terms: D000818:Animals; D001682:Biological Availability; D001713:Biphenyl Compounds / Q000737:chemistry*; D004285:Dogs; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods; D006358:Hot Temperature; D011108:Polymers / Q000737:chemistry*; D012995:Solubility
chemical_list: D001713:Biphenyl Compounds; D004337:Drug Carriers; D011108:Polymers; C465548:bifendate