甘露醇对地塞米松PLGA植入剂体外释放行为的影响

Investigation on Effect of Mannitol on in vitro Release Behavior of Dexamethasone PLGA Implants

采用热熔挤出法制备地塞米松-聚乳酸-羟基乙酸共聚物(PLGA)植入剂,并通过体外释放度、质量损失、相对分子质量变化、差示扫描量热法(DSC)和扫描电镜等探究甘露醇对地塞米松植入剂释放的影响。DSC结果表明,处方中的甘露醇经热熔挤出后依然以晶体的形式存在于体系中,并且在释放过程中,甘露醇含量越高,其从体系中释放的速率越快。体外释放结果显示添加甘露醇可以消除地塞米松PLGA植入剂体外释放的迟滞期,并延长释放周期。对含5%、10%和15%甘露醇处方的体外释放数据用零级释放模型进行拟合,相关系数r分别为0.991、0.997、0.980。质量损失、相对分子质量变化和扫描电镜的分析结果表明,随着甘露醇含量的增加,PLGA的降解速率降低,而这主要是由于PLGA的自身催化诱导降解效应受到抑制造成的。此外,添加甘露醇能在释放和制备过程中形成孔道,从而改变药物的释放和传质机制。

The aim of this study was to evaluate the impact of the addition of mannitol to poly （lactic-co- glycolic acid） （PLGA）-based implants loaded with dexamethasone prepared by hot melt extrusion. The implants were thoroughly characterized by in vitro drug release, mass loss after exposure to the release medium, molecular weight of PLGA, differential scanning calorimetry （DSC）, gel permeation chromatography （GPC）, scanning electron microscopy （SEM）. DSC data indicated that mannitol was still in crystalline form during the extrusion and release processes. The higher amount of mannitol was, the faster release rate of mannitol from the system was. The in vitro release showed that the addition of mannitol could eliminate the lag phase of dexamethasone PLGA implants and prolong the in vitro release period. The in vitro drug release curves of the formulations containing 5 %, 10 % and 15 % mannitol were fitted well to the zero-order kinetics, and r was 0.991, 0.997 and 0.980, respectively. Mass loss, GPC and SEM results showed that the degradation rate of the polymer decreased with the increasing of mannitol amount. The SEM observations showed that the addition of mannitol could form pores during the release and preparation process. Besides, adding mannitol could alter the degradation model of implants from ＂inside to outside＂ to more uniform. These phenomena could be explained by the inhibition of autoeatalytic effect of PLGA. The resulted porosities caused by mannitol led to increase drug mobility as well as the acidic degradation products of PLGA, and hence reduced the autocatalytic degradation of PLGA in a central position of implants.