Rupture and drug release characteristics of multi-reservoir type microspheres with poly( dl-lactide- co-glycolide) and poly( dl-lactide)

Abstract

For the multi-reservoir type microspheres composed of polylactide (PLA) and poly( dl-lactide- co-glycolide) (PLGA), the influence of inner drug-holding layer/outer layer ratio on drug release profiles was studied. The microspheres were prepared by the O/W type emulsion-solvent evaporation technique, and cisplatin was used as a model drug. The water-uptake and the erosion of each polymer were evaluated to clarify the mechanism of drug release for multi-reservoir type microspheres. The formulations were classified by the influence of the blending ratio on drug-release profiles: the formulations with the drug-release profiles independent of the blending ratio (Typel group) and the formulations with drug-release profiles depending on the blending ratio (type 2 group). The formulations of type 1 group showed the uniform swelling during drug-release test, and provided the drug-release governed by the erosion of the inner drug-holding layer. On the other hand, the formulations of Type2 group showed the rupture of outer layer which was induced by the swelling of inner drug-holding layer, and the microspheres with the low ratio of the PLGA provided the drug-release rate which exceeded the estimate from the erosion profiles. The results of present study revealed that two types of drug-release mechanism exist for multi-reservoir type microspheres.