The release of 5-fluorouracil from microspheres of poly(epsilon-caprolactone-co-ethylene oxide).
The purpose of this study was to evaluate the in vitro release of 5-fluorouracil from microspheres prepared using a novel triblock copolymer of epsilon-caprolactone and ethylene oxide as the encapsulating material. Microspheres of poly(epsilon-caprolactone-co-ethylene oxide) were prepared by employing the "hot-melt" method of microencapsulation. Microspheres were sized using sieve analysis and scanning electron microscopy (SEM). Release studies were performed using a custom-made rotating paddle dissolution apparatus. Copolymer microspheres, fabricated by the hot melt method were shown by electron microscopy to have smooth, nonporous surfaces. Drug-loaded microspheres were found to have a broad distribution of sizes, which was thought to be a consequence of the wide range of crystal sizes of the encapsulated unmilled drug. Nonlinear release kinetics were observed from microspheres in the size fraction 75-250 microns, with a pronounced "burst release" associated with the presence of drug at the surface of the microspheres. A specific delineation of the drug release mechanism was not possible due to rapid gelation, swelling, and subsequent dissolution of the microspheres that occurred on hydration. This work describes the preparation of microspheres that swell rapidly and coalesce together on hydration, accompanied by rapid drug release and copolymer dissolution over a 2-hr period.
Martini
L G
LG
SmithKline Beecham, Pharmaceutical Technologies Department, Harlow, Essex, UK.
Collett
J H
JH
Attwood
D
D
D000465:Algorithms; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage* / Q000737:chemistry; D005079:Excipients / Q000737:chemistry*; D005472:Fluorouracil / Q000008:administration & dosage* / Q000737:chemistry; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D008863:Microspheres; D010316:Particle Size; D011091:Polyesters / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D012995:Solubility
D000964:Antimetabolites, Antineoplastic; D005079:Excipients; D011091:Polyesters; C405621:poly(epsilon-caprolactone-co-ethylene oxide); D011092:Polyethylene Glycols; D005472:Fluorouracil