针塞是否会改变注射药物在组织中的空间分布? 通过X射线计算机断层扫描的新见解
Fabiano Bonaventura1, Stefan Scheler1, Vladimir Novak2
1Novartis Pharmaceutical Manufacturing GmbH, Biochemiestraße 10, 6336 Langkampfen, Austria.
概括
由于药物凝固,预填注射器 (PFS) 中针塞的情况越来越令人担忧. 然而,研究表明,这些阻塞在注射过程中通常会溶解,对药物分发和吸收动力学的影响最小.
科学领域:
- 制药科学 制药科学
- 生物材料科学 生物材料科学
- 药物输送系统 药物输送系统
背景情况:
- 预填注射器 (PFS) 广泛用于亲肠道药物输送.
- 在PFS中,由于蒸发性水损失导致药物沉引起的针塞是新出现的挑战,特别是在缩药物配方中.
- 以前的研究还没有完全解决针塞的药理学影响.
研究的目的:
- 为了研究预填注射器中针塞的药理动力学意义.
- 分析针塞在注射药物的空间分布和组织命运上的影响.
- 为了将注射动态与组织分布模式相关联.
主要方法:
- 利用X射线计算机断层扫描 (XCT),包括基于管的和基于同步子的,用于可视化.
- 使用受控注射和力测量来分析流体动力学和组织分布.
- 研究单克隆抗体溶液以模拟药物行为.
主要成果:
- 针头尖上的药物堵塞通常在注射过程中溶解.
- 通过堵塞中的狭窄通道进行初始注射,可以产生高压喷气,导致轻微的深度透液体尾部 (总体积的<2.4%).
- 溶解后进入组织的块很快就会被清除.
结论:
- 在PFS中针塞,虽然可以观察到,但不太可能显著影响药物的整体吸收动力学.
- 观察到对药物分销的影响是最小的和短暂的.
- 即使有潜在的堵塞问题,PFS仍然是一个可靠的交付系统.
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