Improved physicochemical characteristics of felodipine solid dispersion particles by supercritical anti-solvent precipitation process

Int J Pharm. 2005 Sep 14;301(1-2):199-208. doi: 10.1016/j.ijpharm.2005.05.017.

Abstract

Solid dispersions of felodipine were formulated with HPMC and surfactants by the conventional solvent evaporation (CSE) and supercritical anti-solvent precipitation (SAS) methods. The solid dispersion particles were characterized by particle size, zeta potential, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), powder X-ray diffraction (XRD), solubility and dissolution studies. The effects of the drug/polymer ratio and surfactants on the solubility of felodipine were also studied. The mean particle size of the solid dispersions was 200-250 nm; these had a relatively regular spherical shape with a narrow size distribution. The particle size of the solid dispersions from the CSE method increased at 1 h after dispersed in distilled water. However, the particle sizes of solid dispersions from the SAS process were maintained for 6 h due to the increased solubility of felodipine. The physical state of felodipine changed from crystalline to amorphous during the CSE and SAS processes, confirmed by DSC/XRD data. The equilibrium solubility of the felodipine solid dispersion prepared by the SAS process was 1.5-20 microg/ml, while the maximum solubility was 35-110 microg/ml. Moreover, the solubility of felodipine increased with decreasing drug/polymer ratio or increasing HCO-60 content. The solid dispersions from the SAS process showed a high dissolution rate of over 90% within 2 h. The SAS process system may be used to enhance solubility or to produce oral dosage forms with high dissolution rate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calorimetry, Differential Scanning
  • Chemical Phenomena
  • Chemistry, Physical
  • Chromatography, High Pressure Liquid
  • Drug Compounding
  • Electrochemistry
  • Felodipine / chemistry*
  • Kinetics
  • Microscopy, Electron, Scanning
  • Particle Size
  • Solubility
  • Solvents
  • Tablets
  • Water
  • X-Ray Diffraction

Substances

  • Solvents
  • Tablets
  • Water
  • Felodipine