超快速的溶剂去除可以在聚合物微球中产生高负载的无形小分子药物,其体内性能可预测
Yan Lu1, Linfang Liu1, Xiaoyi Lv1
1State Key Laboratory of Natural Medicines, School of Pharmacy, China Pharmaceutical University, Nanjing 211198, China.
概括
使用流固化的连续制造克服了长效注射微球中的批量变化. 这个平台确保了一致的质量,并使得在体内准确预测药物性能.
科学领域:
- 制药制造业 制药制造业 制药制造业
- 药物输送系统 药物输送系统
- 材料科学 材料科学 材料科学
背景情况:
- 长效注射微球的传统批量加工存在制造不一致性,阻碍了临床翻译和可靠的体外-体内相关性.
- 微球生产中的波动性损害了产品质量,并为制药开发带来了重大瓶.
- 水溶性较差的药物在制成有效的长效注射剂方面存在独特的挑战.
研究的目的:
- 开发一个端到端的连续制造平台,称为流固化,以解决微球生产中的不一致性.
- 通过加快溶剂去除,在微球内制造出水溶性较差的药物的稳定无形固体分散物.
- 建立一个强大的体外-体内相关性 (IVIVC) 以预测基于制造控制的药物动力学概况.
主要方法:
- 实施了一种流固化平台,集成可控滴滴形成和超快速固化,用于微球生产.
- 利用加速溶剂去除以动态捕获药物作为无形固体分散物,增强药物聚合物相互作用并抑制结晶.
- 制造的微球具有受控的结构,高的药物负载和一致的批量质量.
主要成果:
- 流固化过程产生了具有特殊结构控制,高药载荷和一致质量的微球.
- 由于微球的优越结构完整性,建立了强大的A级体外-体内相关性 (R2 = 0.9889).
- 该IVIVC模型准确地预测了体内药理动力学概况 (Cmax和AUC) 在10%的监管基准范围内,仅使用体外释放数据.
结论:
- 流固化平台为长效注射微球建立了强大的工艺性能联系.
- 这种连续制造方法加快了对水溶性较差药物的下一代配方的开发.
- 流固化提供了一种实际的解决方案,以克服制造变异性,并实现可预测的体内药物性能.
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