The Release of 5-Fluorouracil from Polycaprolactone Matrices

The release of 5-fluorouracil (5-FU) from monolithic dispersions in poly(caproiactone), [FUPC], was studied and compared with the release of 5-FU from the copolymers of 1-(N-2-ethylmethacryIcarbamoyl)-5-fluorouracil, [EMCF], with methyl methacrylate, [MMA]. Whereas the EMCF:MMA copolymers always exhibited zero-order release of the 5-FU (i.e., constant level of drug released with time), the [FUPC] systems did not. Up to about 25% 5-FU, the [FUPC] systems exhibited a profile in which the 5-FU release was dependent on the square root of time. On the other hand, the EMCF:MMA copolymers showed a constant release of the 5-FU regardless of whether the sample was in a powdered or a pellet form. The release rates were also slower for the copolymer systems than for the monolithic FUPC systems, and much higher concentrations of the drug could be incorporated into the copolymer systems. These differences in the release profiles are caused by differences in the basic nature of the two kinds of systems and the mechanisms of the release of the 5-FU from each. These differences and the mechanisms of the release are discussed in detail.