长期作用的肌肉内 vortioxetine pamoate 悬浮剂的开发:配方优化和药理动力学评估
Yanhui Li1, Ting Wang1, Menghan Liu2
1CSPC Pharmaceutical Group Co., Ltd., 896 East Zhongshan Road, Shijiazhuang 050035, PR China; State Key Laboratory of New Pharmaceutical Preparations and Excipients, Shijiazhuang 050035, PR China.
概括
这项研究开发了长期作用的肌肉内 vortioxetine pamoate (VTXP) 悬浮剂. 在动物模型中,优化的2.5微米VTXP悬浮体显示了药物释放的延长和低爆发释放,证实了其持续输送的潜力.
科学领域:
- 制药科学 制药科学
- 药物输送系统 药物输送系统
- 药理动力学 药理动力学
背景情况:
- 伏尔托克塞丁是一种抗抑郁药,需要改进的长效配方,以提高患者的遵从性.
- 肌肉内 (IM) 药物递送提供了持续释放的潜力,但挑战包括配方稳定性和注射性质.
研究的目的:
- 开发和表征长期作用的肌肉内伏尔素莫酸 (VTXP) 悬浮剂.
- 评估优化VTXP悬浮剂的药理动力学概况和体内性能.
主要方法:
- 使用行星球磨机制备VTXP悬浮剂,并用Poloxamer 338.8稳定.
- 特性包括粒子大小分析 (激光衍射),粘度,注射力,固态分析 (XRPD) 和体外释放研究.
- 在老鼠和狗身上进行了药理动力学 (PK) 研究,比较了IM和胃内 (IG) 给药.
主要成果:
- 优化15%的VTXP悬浮剂与3%的Poloxamer 338显示出合适的粘度和注射力.
- 在老鼠和狗中,2.5μm的VTXP悬浮物通过IM给药显著延长了半衰期 (t1/2) 与IG给药相比.
- 对于IM注射的悬浮剂,观察到较低的爆裂释放百分比 (大鼠10.2%,狗3.8%).
结论:
- 开发的VTXP悬浮配方适用于长期作用的肌肉内注射.
- 2.5微米颗粒大小的悬浮液显示了持续的药物释放和减少的爆发释放,提供了一个有希望的长效输送选项.
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