氨酸保护吸入干粉免受不可逆转的潮湿诱导的聚合
Evalyne M Jansen1, Luke van der Koog2,3, Henderik W Frijlink1
1Department of Pharmaceutical Technology and Biopharmacy, Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, University of Groningen, 9713 AV Groningen, The Netherlands.
Pharmaceutics
|November 27, 2025
概括
在储存过程中,添加白氨酸到胰岛素粉末可以防止潮湿引起的聚合,从而保持物理稳定性. 然而,它并不能保护依赖于玻璃化处理的蛋白质,这表明生物药物输送的特定应用.
科学领域:
- 制药科学 制药科学
- 材料科学 材料科学 材料科学
- 生物技术是生物技术.
背景情况:
- 肺部药物输送是使用生物药物治疗呼吸系统疾病的关键途径.
- 喷雾干燥常用于制造可吸入的粉末,通常使用无形糖作为稳定剂.
- 添加了氨酸等疏水性氨基酸,以提高粉末的分散性.
研究的目的:
- 为了评估白对水分诱导的干粉聚合和储存期间蛋白质稳定性的影响.
- 评估在不同湿度下含有或不含有白素的以胰岛素为基础的粉末的长期物理和化学稳定性.
主要方法:
- 喷雾干燥含有或不含4重量%白素的胰岛素粉末.
- 在各种相对湿度 (RH) 级别 (43%,58%,69%,75%) 的20 ± 2°C下保存粉末,长达20天.
- 评估颗粒聚合,玻璃过渡温度 (Tg) 和蛋白质稳定性 (乳酸脱酶和β-银酶).
主要成果:
- 只有胰岛素的粉末在RH≥58%时不可逆地聚合,而含有白的粉末在所有条件下保持完整.
- 蛋白质稳定性有所不同:两种模型蛋白在43%的RH时都保持了活性. 在75%的RH,β-galactosidase保持稳定,但乳酸脱酶失去了活性.
- 添加白氨酸可以防止粉末聚合,但不能保护依赖玻璃化稳定性的蛋白质.
结论:
- 氨酸显著提高了胰岛素粉末的物理稳定性,防止潮湿诱导的聚合.
- 氨酸的保护作用是特定的,并未扩展到所有蛋白质类型,特别是那些依赖玻璃化.
- 胰岛素和白素配方显示出降低某些生物制品严格储存条件要求的潜力.
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