Enhancement of felodipine dissolution rate through its incorporation into Eudragit® E-PHB polymeric microparticles: in vitro characterization and investigation of absorption in rats

J Pharm Sci. 2012 Apr;101(4):1518-23. doi: 10.1002/jps.23044. Epub 2012 Jan 6.

Abstract

In this study, felodipine was incorporated into microparticles prepared with Eudragit® E and it blended with poly(3-hydroxybutyrate) (PHB) using the emulsion-solvent evaporation technique, with the aim of improving the dissolution rate of the drug. The formulation prepared with Eudragit® E showed irregular and fragmented microparticles, with a loading efficiency (LE) of 82.6%. When the microparticles were prepared with a blend of Eudragit® E and PHB, they had a spherical form with a LE of 103.9%. X-ray diffraction and differential thermal analysis indicated a reduction in the crystallinity of felodipine after its incorporation into the microparticles, which caused a significant increase in the felodipine dissolution rate. An investigation into the absorption in rats was carried out using high-performance liquid chromatography analysis of the blood collected 20 and 60 min after the animals were administered felodipine [30 mg/Kg, orally (p.o.)] or felodipine microparticles (30 mg/Kg, p.o.). Animals that were given felodipine showed mean plasmatic levels of 0.0125 (±0.00156) and 0.0240 (±0.0069) μg mL(-1) after 20 and 60 min, respectively, whereas animals that received microparticles containing felodipine showed respective mean plasmatic levels of 0.0651 (±0.0120) and 0.0369 (±0.0145) μg mL(-1) . Our data suggest that the incorporation into microparticles significantly enhanced the release of felodipine, improving its absorption in rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Absorption
  • Acrylates / administration & dosage*
  • Animals
  • Calcium Channel Blockers / administration & dosage*
  • Chromatography, High Pressure Liquid
  • Felodipine / administration & dosage*
  • Felodipine / chemistry
  • Felodipine / pharmacokinetics
  • Hydroxybutyrates / administration & dosage*
  • Male
  • Polyesters / administration & dosage*
  • Polymers / administration & dosage*
  • Prohibitins
  • Rats
  • Rats, Wistar
  • Solubility
  • X-Ray Diffraction

Substances

  • Acrylates
  • Calcium Channel Blockers
  • Eudragit E100
  • Hydroxybutyrates
  • Phb protein, rat
  • Polyesters
  • Polymers
  • Prohibitins
  • poly-beta-hydroxybutyrate
  • Felodipine