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

Modified diffusion equations with a time-dependent diffusion coefficie nt were derived to formulate the kinetics of drug release from a quick ly degradable matrix. To compare the theoretical equations with experi mental 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 ra nging from 1,900 to 9,600. ACR release profiles from the LA oligomer m icrospheres were apparently of quasi-zero order, showing no burst effe ct during the whole duration of release, unless the molecular weight o f LA oligomers was as low as a few thousand. The early stage of drug r elease from the LA oligomer microspheres was well explained in terms o f Fickian diffusion and the apparent initial diffusion coefficient cou ld be determined as a function of the molecular weight of LA oligomer. The diffusion coefficient decreased with time as a result of degradat ion of the matrix. It was concluded that the newly derived equations w ere applicable for the drug release from the biodegradable matrix such as DL-LA oligomers.