THE EFFECT OF GAMMA-IRRADIATION ON DRUG-RELEASE FROM POLY(LACTIDE) MICROSPHERES

The physicochemical properties of gamma-irradiated poly(lactide) microspheres was studied to elucidate the effect of gamma-irradiation (5-100 kGy) on their release characteristics. gamma-Irradiation of microspheres reduced the average molecular weight of the polymer and increased the carboxylic acid content as a function of the dose. This suggests that gamma-irradiation caused polymer decomposition including hydrolysis. The polymer degradation caused by irradiation at a dose up to 25 kGy brought about no significant changes in the glass transition temperature (T-g) and initial drug release rate. Irradiation at 100 kGy, however, significantly increased the initial release rate and also brought about an abrupt increase in release rate in the course of drug release. The abrupt increase in release rate occured when the T-g was lowered below the 37 degrees C point at which release studies were carried out. This indicates that the polymer decomposition caused by irradiation may accelerate polymer decomposition in the release media and shorten the time required for the T-g to become lower than 37 degrees C. The results suggest that the release rate will not be significantly affected by irradiation at a dose up to 25 kGy if the microspheres are designed to complete drug release before the T-g reaches 37 degrees C.