Preparation and characterization of heparin-loaded polymeric microparticles.
Microparticles containing heparin were prepared by a water-in-oil-in-water emulsification and evaporation process with pure or blends of biodegradable (poly-epsilon-caprolactone and poly(D,L-lactic-co-glycolic acid)) and of positively-charged non-biodegradable (Eudragit RS and RL) polymers. The influence of polymers and some excipients (gelatin A and B, NaCl) on the particle size, the morphology, the heparin encapsulation rate as well as the in vitro drug release was investigated. The diameter of the microparticles prepared with the various polymers ranged from 80 to 130 microns and was found to increase significantly with the addition of gelatin A into the internal aqueous phase. Microparticles prepared with Eudragit RS and RL exhibited higher drug entrapment efficiency (49 and 80% respectively) but lower drug release within 24 h (17 and 3.5% respectively) than those prepared with PCL and PLAGA. The use of blends of two polymers in the organic phase was found to modify the drug entrapment as well as the heparin release kinetics compared with microparticles prepared with a single polymer. In addition, microparticles prepared with gelatin A showed higher entrapment efficiency, but a significant initial burst effect was observed during the heparin release. The in vitro biological activity of heparin released from the formulations affording a suitable drug release has been tested by measuring the anti-Xa activity by a colorimetric assay with a chromogenic substrate. The results confirmed that heparin remained unaltered after the entrapment process.
Jiao
Y Y
YY
Laboratoire de Pharmacie Galénique et Biopharmacie, Faculté de Pharmacie, 5, rue Albert Lebrun, B.P. 403, 54001 Nancy, France.
Ubrich
N
N
Hoffart
V
V
Marchand-Arvier
M
M
Vigneron
C
C
Hoffman
M
M
Maincent
P
P
D000180:Acrylic Resins / Q000737:chemistry; D001673:Biodegradation, Environmental; D003124:Colorimetry; D004337:Drug Carriers; D004339:Drug Compounding; D015951:Factor Xa / Q000737:chemistry; D065427:Factor Xa Inhibitors; D006016:Glycolates / Q000737:chemistry; D006493:Heparin / Q000737:chemistry*; D019344:Lactic Acid; D008855:Microscopy, Electron, Scanning; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry
D000180:Acrylic Resins; D004337:Drug Carriers; D065427:Factor Xa Inhibitors; D006016:Glycolates; D011091:Polyesters; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; C016240:polycaprolactone; D011100:Polyglycolic Acid; C050528:Eudragit RS; D019344:Lactic Acid; C058665:Eudragit RL; D006493:Heparin; D015951:Factor Xa