Physicochemical characterization of felodipine-kollidon VA64 amorphous solid dispersions prepared by hot-melt extrusion

Authors

  • Yuejun Song,

    1. College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China
    2. Laboratory of Magnetic Resonance Spectroscopy and Imaging, Suzhou Institute of Nano-tech and Nano-bionics, Chinese Academy of sciences, Suzhou 215123, China
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  • Lianyan Wang,

    1. Laboratory of Magnetic Resonance Spectroscopy and Imaging, Suzhou Institute of Nano-tech and Nano-bionics, Chinese Academy of sciences, Suzhou 215123, China
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  • Ping Yang,

    Corresponding author
    1. College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China
    • College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou 215123, China. Tel: +86-512-65880361; Fax: +86-512-65880089
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  • Robert M. Wenslow Jr.,

    1. Crystal Pharmatech, Suzhou Industrial Park, Suzhou 215123, China
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  • Bo Tan,

    1. Laboratory of Magnetic Resonance Spectroscopy and Imaging, Suzhou Institute of Nano-tech and Nano-bionics, Chinese Academy of sciences, Suzhou 215123, China
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  • Hailu Zhang,

    Corresponding author
    1. Laboratory of Magnetic Resonance Spectroscopy and Imaging, Suzhou Institute of Nano-tech and Nano-bionics, Chinese Academy of sciences, Suzhou 215123, China
    • Laboratory of Magnetic Resonance Spectroscopy and Imaging, Suzhou Institute of Nano-tech and Nano-bionics, Chinese Academy of sciences, Suzhou 215123, China. Tel: +86-512-62872713; Fax: +86-512-62603079.
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  • Zongwu Deng

    1. Laboratory of Magnetic Resonance Spectroscopy and Imaging, Suzhou Institute of Nano-tech and Nano-bionics, Chinese Academy of sciences, Suzhou 215123, China
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Abstract

To improve the dissolution and hence the oral bioavailability, amorphous felodipine (FEL) solid dispersions (SDs) with Kollidon® VA 64 (PVP/VA) were prepared. Hot-melt extrusion was employed with an extruding temperature below the melting point (Tm) of FEL. X-ray powder diffraction (XRPD) and 13C CP/MAS nuclear magnetic resonance (NMR) measurements show that the extrudates are amorphous. The intermolecular interaction between FEL and PVP/VA in SDs was investigated by Fourier transform infrared spectroscopy, 15N CP/MAS NMR, and 1H high-resolution MAS NMR. Furthermore, a single glass transition temperature (Tg) was detected by differential scanning calorimetry in addition to a single 1H T1 or T1rho relaxation time detected by 13C NMR signals. These results confirm that the extrudates contain FEL dispersed into the polymer matrix at a molecular level with no detectable phase separation. This molecular-scale mixing results in a significantly faster dissolution rate compared with the pure crystalline FEL. Additionally, the molecular-scale mixing prevents the amorphous drug from recrystallizing even after being stored at 40°C/75% Relative Humidity for 2 months. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:1915–1923, 2013

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