从喷雾干燥的PLGA微球中初始突破释放leuprolide的机械评估
Richard Schutzman1, Nian-Qiu Shi2, Karl F Olsen1
1Department of Pharmaceutical Sciences, The Biointerfaces Institute, University of Michigan, 2800 Plymouth Rd., Ann Arbor, MI 48109, USA.
概括
从喷雾干燥的微球中控制初始药物释放至关重要. 持续监测和探针扩散研究显示,通过聚合物矩阵扩散是关键机制,有助于配方开发和预测体内性能.
科学领域:
- 生物材料科学 生物材料科学
- 制药技术 制药技术 制药技术
- 药物输送系统 药物输送系统
背景情况:
- 喷雾干燥的多乳糖酸 (PLGA) 微球提供与溶剂蒸发方法相似的长期药物释放,但与初始爆发释放作斗争.
- 不受控制的初始爆发释放阻碍了对载微球的产品开发和生物等价性建立.
- 对这些微球的初始爆发释放机制的有限理解阻碍了优化.
研究的目的:
- 为了研究喷雾干燥的烯酸微球的初始爆裂释放的机制和程度.
- 为了比较在体外释放动力学与在体内的药理动力学在老鼠在前24小时.
- 评估持续监测和探针扩散方法在表征微球配方中的实用性.
主要方法:
- 使用了16种喷雾干燥的PLGA微球配方,加载了烯酸,模仿商业产品.
- 使用连续监测系统和传统的样本和分离方法测量爆发释放动力学.
- 通过SEM成像和bodipy-dextran探针吸收来评估微球结构和透性.
主要成果:
- 持续监测区分了高爆破的微球,与采样和分离方法不同.
- 观察到类似毛孔的遮和广泛的内部毛孔,表明颗粒的胀有助于扩散.
- 在24小时内确定了快速初级释放阶段 (∼80%),随后是常速二级阶段 (∼20%).
- 对于大多数喷雾干燥配方,在体内吸收和体内释放之间发现了强烈的相关性,但对于商业产品而言并非如此.
- 证明了体外无维时间与喷雾干燥微球的药理学参数相关.
结论:
- 通过聚合物矩阵的扩散是初始释放的重要机制,无论是体外还是体外.
- 一个固定的下限释放建议一个额外的,替代的释放机制.
- 持续的监测和探针扩散显示出利普罗利德配方的差异化和将体外释放与体外吸收联系在一起的前景.
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