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使用超临界流体技术稳定干粉制剂中的蛋白质。

Stabilization of proteins in dry powder formulations using supercritical fluid technology.

作者信息

Jovanović Natasa, Bouchard Andréanne, Hofland Gerard W, Witkamp Geert-Jan, Crommelin Daan J A, Jiskoot Wim

机构信息

Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, 3508 TB Utrecht, The Netherlands.

出版信息

Pharm Res. 2004 Nov;21(11):1955-69. doi: 10.1023/b:pham.0000048185.09483.e7.

Abstract

Therapeutic proteins have become essential in the treatment of many diseases. Their formulation in dry form is often required to improve their stability. Traditional freeze-drying or spray-drying processes are often harmful to labile proteins and could be replaced by supercritical fluid (SCF) drying to produce particles with defined physicochemical characteristics in a mild single step. A survey of the current SCF drying processes for proteins is presented to give insight into the effect of SCF drying on protein stability and to identify issues that need further investigation. Methods used for drying aqueous and organic protein solutions are described. In particular, effects of process and formulation parameters on particle formation and protein stability are discussed. Although SCF methodology for drying proteins is still in its infancy, it can provide a serious alternative to existing drying methods for stabilizing proteins.

摘要

治疗性蛋白质在多种疾病的治疗中已变得至关重要。通常需要将它们制成干燥形式以提高其稳定性。传统的冷冻干燥或喷雾干燥工艺往往对不稳定的蛋白质有害,可用超临界流体(SCF)干燥取而代之,以便在温和的单一步骤中生产出具有特定物理化学特性的颗粒。本文对当前用于蛋白质的SCF干燥工艺进行了综述,以深入了解SCF干燥对蛋白质稳定性的影响,并确定需要进一步研究的问题。描述了用于干燥水性和有机蛋白质溶液的方法。特别讨论了工艺和配方参数对颗粒形成和蛋白质稳定性的影响。尽管用于蛋白质干燥的SCF方法仍处于起步阶段,但它可为现有蛋白质稳定化干燥方法提供一种重要的替代方法。

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