The release of 5-fluorouracil from a swellable matrix of a triblock copolymer of epsilon-caprolactone and ethylene oxide.
OBJECTIVE
The purpose of this study was to investigate the influence of hydration characteristics on the in vitro release of 5-fluorouracil from a swellable matrix prepared using a novel triblock copolymer of poly(epsilon-caprolactone) and poly(oxyethylene).


METHODS
Matrices were prepared by dry compression of mixtures of the drug and copolymer using low compressional forces. Release studies were performed using a custom made rotating basket dissolution apparatus. The positions of the eroding and swelling fronts within the matrices during hydration were monitored using freeze fracture scanning electron microscopy.


RESULTS
Analysis of the release data revealed a predominantly diffusion controlled mechanism. Observations of the swelling characteristics of the copolymer matrices on immersion in Sørensen's buffer at pH 7.4 revealed gel formation and preferential swelling in the radial direction with visible erosion of the matrix after 4h. During hydration, a gradual increase in gel layer thickness was noted prior to the erosion and eventual dissolution of the matrix.


CONCLUSIONS
This study demonstrates a means of differentiating the relative importance of the swelling characteristics in determining the release mechanism and subsequent release rate from swellable matrices.
Martini
L G
LG
Department of Pharmacy, University of Manchester, United Kingdom.
Collett
J H
JH
Attwood
D
D
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry*; D002021:Buffers; D004058:Diffusion; D004339:Drug Compounding; D005027:Ethylene Oxide; D005079:Excipients; D005472:Fluorouracil / Q000008:administration & dosage / Q000737:chemistry*; D005614:Freeze Fracturing; D008855:Microscopy, Electron, Scanning; D012685:Sepharose / Q000031:analogs & derivatives*
D000964:Antimetabolites, Antineoplastic; D002021:Buffers; D005079:Excipients; C024903:aminohexyl-sepharose; D012685:Sepharose; D005027:Ethylene Oxide; D005472:Fluorouracil