探索单步干燥法在高蛋白浓度制剂冻干中的应用

IF 2.6 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Qi Zeng, Zhaowei Jin, Jeremy Guo
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引用次数: 0

摘要

一步干燥集升华和脱附于一体。在这里,单步干燥被证明适用于高蛋白质浓度冻干产品(>50mg/mL)中含有或不含降粘剂的配方。在保持蛋白质稳定性的同时,干燥过程中的时间显著减少(68%)。首先,在不含降粘剂(蔗糖和甘露醇)的配方中,测试了货架温度(Ts)为25°C,室压(Pc)为0.3 mbar,侵蚀退火(-3°C)的单步干燥方法;其次,采用ArgHCl和NaCl两种降粘剂,进一步探索单步干燥在含降粘剂配方中的应用。值得注意的是,在所有具有可比的冻干前和冻干后质量属性以及重构时间的配方组合中,都观察到良好的蛋糕外观;最后,利用可调谐二极管激光吸收光谱(TDLAS)实时监测单步干燥过程的干燥行为。事实证明,尽管产品阻力(Rp)增加,但它有利于升华速率(比传统升华干燥过程快3倍),从而使整个干燥周期更有效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Exploring the application of single-step drying in lyophilization of high protein concentration formulations.

Objectives: Single-step drying integrates sublimation and desorption process in one step. The applicability of single-step drying in high protein concentration formulations with or without viscosity reducers remains to be explored. And drying behavior of single-step drying remains to be monitored.

Methods: Firstly, in formulations without viscosity reducers (sucrose and mannitol), the method of single-step drying at shelf temperature (Ts) of 25 °C and chamber pressure (Pc) of 0.3 mbar with aggressive annealing (-3 °C) was tested; secondly, two viscosity reducers (ArgHCl and NaCl) were applied to further explore the application of single-step drying in viscosity reducer-containing formulations; finally, drying behavior of single-step drying was monitored in real time by tunable diode laser absorption spectroscopy(TDLAS).

Results: In single-step drying process, significant cycle time reduction (68%) was achieved compared to traditional two-step drying. Good cake appearance was observed in all formulation combinations with comparable pre- and post-lyophilization quality attributes as well as reconstitution time. Three times faster sublimation rate was monitored in single-step drying process compared to traditional two-step drying.

Conclusion: Single-step drying was proved to be applicable to high protein concentration formulations with or without viscosity reducers. Significant cycle time reduction in drying process was achieved. Sublimation rate resulted in a more efficient drying cycle as a whole even though an increase of product resistance.

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来源期刊
CiteScore
5.90
自引率
2.90%
发文量
82
审稿时长
1 months
期刊介绍: Pharmaceutical Development & Technology publishes research on the design, development, manufacture, and evaluation of conventional and novel drug delivery systems, emphasizing practical solutions and applications to theoretical and research-based problems. The journal aims to publish significant, innovative and original research to advance the frontiers of pharmaceutical development and technology. Through original articles, reviews (where prior discussion with the EIC is encouraged), short reports, book reviews and technical notes, Pharmaceutical Development & Technology covers aspects such as: -Preformulation and pharmaceutical formulation studies -Pharmaceutical materials selection and characterization -Pharmaceutical process development, engineering, scale-up and industrialisation, and process validation -QbD in the form a risk assessment and DoE driven approaches -Design of dosage forms and drug delivery systems -Emerging pharmaceutical formulation and drug delivery technologies with a focus on personalised therapies -Drug delivery systems research and quality improvement -Pharmaceutical regulatory affairs This journal will not consider for publication manuscripts focusing purely on clinical evaluations, botanicals, or animal models.
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