塞莱科克西布载有自化固体分散抑制其延迟吸收在老鼠中,胃肠机动性受损
Mizuki Ogino1, Keisuke Yakushiji1, Hiroki Suzuki1
1Laboratory of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka.
Chemical & pharmaceutical bulletin
|October 1, 2023
概括
这项研究开发了一种自化固体分散式赛莱可西布 (SMSD/CEL),可改善药物吸收. 在患有胃肠功能受损的老鼠中,SMSD/CEL有效抵消了延迟吸收,表明增强了疼痛缓解.
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:
- 严重的疼痛会损害胃肠道 (GI) 的分泌和运动,延迟药物吸收.
- 这些肠道功能障碍可能会对切莱科克西布 (CEL) 的吸收产生负面影响.
- 开发先进的药物输送系统对于在受损的生理条件下确保治疗疗效至关重要.
研究的目的:
- 开发一种具有增强溶解的自化固体分散剂 (SMSD/CEL).
- 调查SMSD/CEL克服因肠道功能受损引起的延迟吸收的能力.
- 评估SMSD/CEL的潜力,以改善严重疼痛和相关的胃肠道问题患者的疼痛管理.
主要方法:
- 使用冷化制备基于Soluplus®的SMSD/CEL.
- 对SMSD/CEL的物理化学表征,包括化,溶解和固态稳定性.
- 在大鼠中进行的药理动力学评估,这些大鼠的胃肠道分泌和运动受 propantheline 诱导而受损.
主要成果:
- 在酸性条件下,SMSD/CEL形成了微粒 (153 nm),与结晶式赛莱科西布相比,溶解赛莱科西布在酸性条件下增加了2.1倍.
- 无形形式的SMSD/CEL表现出良好的存储稳定性,没有显著的结晶.
- 在用普朗林治疗的老鼠中,SMSD/CEL抑制了延迟的平均吸收时间,并降低了与晶体赛莱可西布观察到的AUC0-4下降.
结论:
- 即使在肠道分泌和运动受损的条件下,SMSD/CEL也有效地增强了赛莱科西布的溶解和吸收.
- 这种配方通过确保药物的持续生物可用性,显示出改善疼痛缓解的潜力.
- SMSD/CEL代表了一种有前途的策略,用于管理患有严重疼痛和肠道功能受损的患者的赛莱科克西布治疗.
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