Drug Design, Development and Therapy (2015-05-01)

Soluplus®/TPGS-based solid dispersions prepared by hot-melt extrusion equipped with twin-screw systems for enhancing oral bioavailability of valsartan

  • Lee JY,
  • Kang WS,
  • Piao J,
  • Yoon IS,
  • Kim DD,
  • Cho HJ

Journal volume & issue
Vol. 2015, no. default
pp. 2745 – 2756


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Jae-Young Lee,1,* Wie-Soo Kang,2,* Jingpei Piao,2 In-Soo Yoon,3 Dae-Duk Kim,1 Hyun-Jong Cho4 1College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, 2School of Bioscience and Biotechnology, Kangwon National University, Chuncheon, 3College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Jeonnam, 4College of Pharmacy, Kangwon National University, Chuncheon, Republic of Korea *These authors contributed equally to this work Background: Soluplus® (SP) and ᴅ-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. Conclusion: 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. Keywords: hot-melt extrusion, oral bioavailability, solid dispersion, valsartan