Abstract
Purpose. 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(ε-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.
Similar content being viewed by others
REFERENCES
P. Colombo, P. L. Catellani, N. A. Peppas, L. Maggi, and U. Conte. Swelling characteristics of hydrophilic matrices for controlled release: new dimensionless number to describe the swelling and release behaviour, Int. J. Pharm. 88:99–109 (1992).
P. L. Ritger, and N. A. Peppas. A simple equation for description of solute release. II. Fickian and anomalous release from swellable devices, J. Contr. Release 5:37–42 (1987).
N. A. Peppas, and J. J. Sahlin. A simple equation for description of solute release. III. Coupling of diffusion and relaxation, Int. J. Pharm. 57:169–172 (1989).
M. Summerhayes. New ways of using 5-fluorouracil, Pharm. J. 757 (1992).
L. Martini, D. Attwood, J. H. Collett, C. V. Nicholas, S. Tanodekaew, N. J. Deng, F. Heatley, and C. Booth. Micellisation and gelation of a triblock copolymer of ethylene oxide and ε-caprolactone, CLn Em CLn, in aqueous solution, J. Chem. Soc. Faraday Trans. 90:1961–1966 (1994).
E. Papadimitriou, G. Buckton, and M. Efentakis. Probing the mechanisms of swelling of hydroxypropylmethyl cellulose matrices, Int. J. Pharm. 98:57–62 (1993).
N. A. Peppas, P. Colombo, U. Conte, and L. Maggi. Dimensionality in swelling of polymer carriers and its importance in drug release, SAFYBI 32:22–27 (1992).
U. Conte, P. Colombo, N. A. Peppas, L. Maggi, and T. Vitali. Swelling dimensionality and drug release, Proc. 10th Pharm. Tech. Conf. 3:316–332 (1991).
J. S. Binns, M. C. Davies, and C. D. Melia. A study of polymer hydration and drug distribution within hydrophilic matrices by cryogenic SEM and EDX, Proc. Int. Symp. Controlled Release Bioactive Materials, 17:339–340 (1990).
C. D. Melia. Hydrophilic matrix sustained release systems based on polysaccharide carriers, Crit. Revs. Ther. Drug Carrier Systems. 8:395–421 (1991).
U. Conte, P. Colombo, A. Gazzaniga, M. E. Sangalli, and A. LaManna. Swelling-activated drug delivery systems, Biomaterials 9:489–493 (1988).
P. I. Lee and W. R. Good. Overview of controlled-release drug delivery. In P. I. Lee and W. R. Good (eds), Controlled Release Technology, Pharmaceutical Applications, ACS Symposium Series 348, American Chemical Society, Washington, DC, USA, 1987, Chap. 1. pp. 1–13.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Martini, L.G.A., Collett, J.H. & Attwood, D. The Release of 5-Fluorouracil from a Swellable Matrix of a Triblock Copolymer of ε-Caprolactone and Ethylene Oxide. Pharm Res 12, 1786–1790 (1995). https://doi.org/10.1023/A:1016290411383
Issue Date:
DOI: https://doi.org/10.1023/A:1016290411383