稳定剂对固体纳米晶体配方中的生物相关介质中的颗粒大小和分散行为的影响
Nils Christian Böck1, Julius Sundermann1, Mirko Koziolek1
1Small Molecule CMC Development Development Sciences AbbVie Deutschland GmbH & Co. KG Germany.
概括
阳离子表面活性剂的选择显著影响固体纳米晶体的再分散性. 阴离子稳定剂对于小颗粒大小至关重要,但可以导致API聚合,特别是在胃条件下.
科学领域:
- 制药科学 制药科学
- 材料科学 材料科学 材料科学
- 药物运输 药物运输 药物运输
背景情况:
- 纳米晶体配方需要稳定剂来防止粒子生长和聚合.
- 在转化为固体剂型期间保持纳米悬浮的完整性对于体内性能至关重要.
- 固体纳米晶体在生理条件下的再分散性对于药物的生物可用性至关重要.
研究的目的:
- 研究非离子和离子表面活性剂在固体纳米晶体配方中的行为.
- 评估不同表面活性剂在生物相关条件下对纳米晶体再分散性的影响.
- 了解API物理化学特性对表面活性剂性能和配方稳定性的影响.
主要方法:
- 制造纳米晶体配方使用纳米磨与各种API (伊特拉科纳,利托纳维尔,纳普罗,纤维酸盐).
- 非离子聚合物的组合与离子 (二甲基硫酸盐,脱氧化酸盐,酸盐) 或非离子表面活性剂 (聚酸盐80,维生素E-TPGS) 的组合.
- 热化以制造固体药物产品,随后在生物相关介质 (不同pH值) 中进行再分散性测试,粒子大小分布 (PSD) 和表面电荷分析.
主要成果:
- 无离子表面活性剂是必要的,以达到小于500纳米的粒子大小.
- 阴离子稳定配方显示在胃介质 (低pH) 中存在凝聚的风险.
- 对于基本的APIs,在pH值增加时可逆聚合与脱氧化;对于二甲基硫酸盐和二甲酸盐,不可逆.
结论:
- 阴离子稳定剂的选择对于固体纳米晶体配方的开发至关重要.
- 阳离子稳定剂类型与API的物理化学性质 (基本性,酸性,中性) 之间的相互作用决定了重新分散性和稳定性.
- 需要仔细考虑这些因素,以确保药物产品在重新分散后的有效性能.
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