塔克罗利斯的自化固体分散:物理化学和药理动力学表征
Keisuke Makino1, Ryota Tsukada1, Atsushi Kambayashi1,2,3
1Laboratory of Biopharmacy, School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan.
Biopharmaceutics & drug disposition
|August 1, 2023
概括
开发出自化固体分散剂 (SMSD) 的塔克罗利 (TAC) 显著提高了其稳定性和口服吸收. 这种新型配方与晶体TAC相比,大约提高了20倍的生物可用性.
科学领域:
- 制药科学 制药科学
- 药物输送系统 药物输送系统
- 生物制药生物制药公司
背景情况:
- 塔克罗利木斯 (TAC) 具有较差的生物制药性质,限制了其治疗疗效.
- 开发先进的药物输送系统对于提高TAC的口服吸收和稳定性至关重要.
研究的目的:
- 开发一个自化固体分散 (SMSD) 的塔克罗利斯 (TAC).
- 为了改善塔克罗利斯的物理化学稳定性和药理动力学特征.
主要方法:
- 使用Soluplus®和 propyl纤维素制备SMSD和无形固体分散 (ASD) 的TAC配方.
- 物理化学性质的表征,包括形态学,结晶性,储存稳定性,药物聚合物相互作用和菌形成.
- 在口服后对大鼠的药理动力学行为的评估.
主要成果:
- 两种SMSD/TAC和ASD/TAC配方都保持了塔克罗利斯在无形状态.
- 在SMSD/TAC中显示出优越的存储稳定性,防止在ASD/TAC中观察到的再结晶.
- 由于快速菌形成,SMSD/TAC表现出增强的溶解,导致口服生物利用率与晶体TAC相比增加20倍.
结论:
- 自化固体分散 (SMSD) 提供了一种有效的策略来稳定tacrolimus.
- SMSD配方显著增强了塔克罗利斯的口服吸收和生物制药性质.
- 这种方法有望为开发改进的塔克罗利斯剂量形式提供希望.
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