Modification of the release rate of aclarubicin from polylactic acid microspheres by using additives.

Polylactic acid (PLA) microspheres containing aclarubicin were prepared by a solventevaporation process and their release patterns were examined in vitro. When microspheres were prepared with the drug and PLA, the release rates of the drug were extremely small. When microspheres were prepared with fatty acid esters as additives, the release rates of the drug were significantly increased depending on the amount of the additive incorporated. Two additives, isopropyl myristate and medium-chain triglyceride, exhibited similar effects on the steady-state release rates of the drug from the microspheres. In addition, the effect of alkyl chain length of the additives on the release rate of the drug was examined by using a series of ethyl and butyl esters of fatty acids. A parabolic relationship was obtained between the steady-state release rate of the drug and the alkyl chain length of the additives. Therefore the release rate of the drug could be controlled by proper selection of the additive and by adjusting the amount of the additive used in the preparation of the microspheres.