无辅助剂可吸入组合外核心微粒与克洛法齐明作为外,用于在核心中延长异化的肺保留
Kolimi Prashanth Reddy1, Lakshmi Tulasi Naraharisetti2, Vani Sai Prasanna3
1Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research, Kolkata 700054 India.
International journal of pharmaceutics
|February 9, 2025
概括
这项研究开发了一种无助剂,可吸入的微粒素配方,用于联合抗结核药物,克洛法齐明和异亚,改善肺部药物输送和保留,以提高治疗效率.
科学领域:
- 制药科学 制药科学
- 药物运输 药物运输 药物运输
- 肺部医学 肺部医学
背景情况:
- 结合抗结核药物的肺输送对于预防耐药性和提高疗效至关重要.
- 反对抗结核病药物的物理化学性质对联合递送提出了挑战,特别是高剂量要求限制了辅助剂的使用.
研究的目的:
- 设计一种无助剂,可吸入的微粒素配方,用于同时提供克洛法胺 (CFZ) 和异化 (INH).
- 通过外核心微粒系统,改善INH的肺保留和受控释放,INH是一种半衰期短的药物.
主要方法:
- 开发 clofazimine shell - isoniazid 核心干粉可吸入微粒 (CFZ INH DPMs) 使用 3 流体喷嘴喷雾干燥.
- 具有特征的粒子大小,形态 (TEM,共聚焦显微镜),结晶性 (DSC,XRD) 和溶解概况.
- 研究了药物辅助剂相互作用 (DPPC,Langmuir-Blodgett异温体) 和评估了细胞吸收 (RAW巨体) 和体内肺部保留 (Wistar大鼠).
主要成果:
- CFZ INH DPM 实现了所需的空气动力学颗粒大小 (D50 ≈ 3 μm),解决了INH-酸不兼容性并提高了CFZ产量.
- DSC和XRD证实CFZ和INH在DPM中保持了晶体形式.
- 在模拟的肺液中CFZ溶解度增加了两倍,而INH溶解被延迟;观察到增强的肺脂相互作用.
- 在体内与纯INH相比,证明了细胞内化和长时间的INH肺部保留 (长达4小时).
结论:
- 开发的无助剂CFZ INH DPM显示了有效的肺向和结核病联合药物持续保留的显著潜力.
- 这种配方策略解决了用于改善结核病治疗的不同性质药物的联合输送方面的挑战.
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