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Keywords:

  • hot-melt extrusion;
  • amorphous;
  • solid dispersion;
  • molecular dispersion;
  • solid-state NMR;
  • physicochemical properties;
  • solubility;
  • stabilization

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