KINETICS OF DIFFUSION-MEDIATED DRUG-RELEASE ENHANCED BY MATRIX DEGRADATION

Modified diffusion equations with a time-dependent diffusion coefficient were derived to formulate the kinetics of drug release from a quickly degradable matrix. To compare the theoretical equations with experimental observation, microspheres containing aclarubicin hydrochloride (ACR) were prepared by the solvent evaporation method using DL-lactic acid (LA) oligomers with different weight-average molecular weights ranging from 1,900 to 9,600. ACR release profiles from the LA oligomer microspheres were apparently of quasi-zero order, showing no burst effect during the whole duration of release, unless the molecular weight of LA oligomers was as low as a few thousand. The early stage of drug release from the LA oligomer microspheres was well explained in terms of Fickian diffusion and the apparent initial diffusion coefficient could be determined as a function of the molecular weight of LA oligomer. The diffusion coefficient decreased with time as a result of degradation of the matrix. It was concluded that the newly derived equations were applicable for the drug release from the biodegradable matrix such as DL-LA oligomers.