Heat-stable measles vaccine produced by spray drying
Heat-stable measles vaccine produced by spray drying
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DOI：
10.1016/j.vaccine.2009.11.024
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发表时间：
2010-02-03
期刊：
影响因子：
5.5
通讯作者：
Truong-Le, Vu
中科院分区：
文献类型：
--
作者：
Ohtake, Satoshi;Martin, Russell A.;Truong-Le, Vu
采用独特的稳定剂和温和的喷雾干燥工艺条件相结合，生产热稳定的麻疹疫苗粉末。来自Serum Institute of India的减毒活麻疹疫苗用药学上批准的稳定剂配制，包括糖、蛋白质、氨基酸、聚合物、表面活性剂和增塑剂以及带电离子。此外，还考察了缓冲盐和pH值对麻疹病毒保存稳定性的影响。通过在Vero细胞上进行TCID 50测定，定量了在几种温度下储存的干燥疫苗的效价。作为与其他工艺方法的比较，铅制剂还经受冷冻干燥和泡沫干燥。在37 ° C下测试的优化的麻疹疫苗制剂稳定约8周（即llogTCID（50）损失的时间）。麻疹滴度呈双相下降，最初在第一周内迅速下降，但此后相对稳定。处方筛选过程中确定的关键稳定剂为L-精氨酸、人血清白蛋白和二价阳离子组合。喷雾干燥被确定为制备干燥疫苗的最佳加工方法，因为其通常导致可忽略的工艺损失，并且与其他工艺相比具有相当的储存稳定性（如果不是更好的话）。开发了加工方法和制剂组分，生产出在37摄氏度下稳定长达8周的麻疹疫苗，超过了世卫组织在该温度下1周热稳定性的要求。(C)2009爱思唯尔有限公司保留所有权利。
A combination of unique stabilizers and mild spray drying process conditions was employed to produce heat-stable measles vaccine powder. Live attenuated measles vaccine from Serum Institute of India was formulated with pharmaceutically approved stabilizers, including sugars, proteins, amino acids, polymers, surfactants, and plasticizers, as well as charged ions. In addition, the effects of buffer salt and pH on the storage stability of measles virus were examined. The potency of the dried vaccine stored at several temperatures was quantified by TCID50 assay on Vero cells. As a comparison to other process methods, lead formulations were also subjected to freeze drying and foam drying. The optimized measles vaccine formulation tested at 37 degrees C was stable for approximately 8 weeks (i.e. time for 1logTCID(50) loss). The measles titer decreased in a bi-phasic manner, with initial rapid loss within the first week but relative stability thereafter. Key stabilizers identified during the formulation screening processes were L-arginine, human serum albumin, and a combination of divalent cations. Spray drying was identified as the optimal processing method for the preparation of dried vaccine, as it generally resulted in negligible process loss and comparable, if not better storage stability, with respect to the other processes. Processing methods and formulation components were developed that produced a measles vaccine stable for up to 8 weeks at 37 degrees C, which surpassed the WHO requirement for heat stability of I week at that temperature. (C) 2009 Elsevier Ltd. All rights reserved.