Enhancement of felodipine dissolution rate through its incorporation into Eudragit® E-PHB polymeric microparticles: in vitro characterization and investigation of absorption in rats.
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.
Department of Pharmacy, Universidade da Região de Joinville (UNIVILLE), Joinville, Santa Catarina, Brazil. gbazzo@uol.com.br
Giovana C
GC
Bazzo
Daniela B
DB
Caetano
Maura L T
ML
Boch
Mileine
M
Mosca
Luiza C
LC
Branco
Melissa
M
Zétola
Eduardo M
EM
Pereira
Bianca R
BR
Pezzini
D000042:Absorption; D000179:Acrylates / Q000008:administration & dosage*; D000818:Animals; D002121:Calcium Channel Blockers / Q000008:administration & dosage*; D002851:Chromatography, High Pressure Liquid; D015736:Felodipine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D006885:Hydroxybutyrates / Q000008:administration & dosage*; D008297:Male; D011091:Polyesters / Q000008:administration & dosage*; D011108:Polymers / Q000008:administration & dosage*; D000091402:Prohibitins; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D014961:X-Ray Diffraction; D000094122:Polyhydroxybutyrates
D000179:Acrylates; D002121:Calcium Channel Blockers; D015736:Felodipine; D006885:Hydroxybutyrates; D011091:Polyesters; D011108:Polymers; D000091402:Prohibitins; C477020:Eudragit E100; C000717332:Phb protein, rat; C003182:poly-beta-hydroxybutyrate; D000094122:Polyhydroxybutyrates