Laboratory of Pharmaceutical Technology, Ghent University, Ghent, Belgium.
Eur J Pharm Biopharm. 2012 Apr;80(3):649-56. doi: 10.1016/j.ejpb.2011.11.018. Epub 2011 Dec 7.
Dry powders containing a live-attenuated Newcastle disease vaccine (LZ58 strain) and intended for mass vaccination of poultry were prepared by spray drying using mannitol in combination with trehalose or inositol, polyvinylpyrrolidone (PVP) and/or bovine serum albumin (BSA) as stabilizers. These powders were evaluated for vaccine stabilizing capacity during production and storage (at 6 °C and 25 °C), moisture content, hygroscopicity and dry powder dispersibility. A mixture design, varying the ratio of mannitol, inositol and BSA, was used to select the stabilizer combination which resulted in the desired powder properties (i.e. good vaccine stability during production and storage, low moisture content and hygroscopicity and good dry dispersibility). Inositol-containing powders had the same vaccine stabilizing capacity as trehalose powders, but were less hygroscopic. Incorporation of BSA enhanced the vaccine stability in the powders compared to PVP-containing formulations. However, increasing the BSA concentration increased the hygroscopicity and reduced the dry dispersibility of the powder. No valid mathematical model could be calculated for vaccine stability during production or storage, but the individual experiments indicated that a formulation combining mannitol, inositol and BSA in a ratio of 73.3:13.3:13.3 (wt/wt) resulted in the lowest vaccine titre loss during production (1.6-2.0 log(10) 50% egg infectious dose (EID(50)) and storage at 6 °C (max. 0.8 log(10) EID(50) after 6 months) in combination with a low moisture content (1.1-1.4%), low hygroscopicity (1.9-2.1% water uptake at 60% relative humidity) and good dry dispersibility properties.
采用喷雾干燥法,以甘露醇、海藻糖或肌醇、聚乙烯吡咯烷酮(PVP)和/或牛血清白蛋白(BSA)为稳定剂,制备了含活减毒新城疫疫苗(LZ58 株)的干粉,用于禽类的大规模疫苗接种。这些粉末在生产和储存过程中(在 6°C 和 25°C 下)、水分含量、吸湿性和干粉分散性方面的疫苗稳定能力进行了评估。采用混合设计,改变甘露醇、肌醇和 BSA 的比例,选择稳定剂组合,得到所需的粉末特性(即生产和储存过程中疫苗稳定性好、水分含量和吸湿性低、干粉分散性好)。含肌醇的粉末具有与海藻糖粉末相同的疫苗稳定能力,但吸湿性较低。与含 PVP 的配方相比,BSA 的加入增强了粉末中的疫苗稳定性。然而,增加 BSA 浓度会增加粉末的吸湿性并降低其干粉分散性。无法计算出生产或储存过程中疫苗稳定性的有效数学模型,但单独的实验表明,一种将甘露醇、肌醇和 BSA 以 73.3:13.3:13.3(wt/wt)的比例组合的配方,在生产过程中导致疫苗效价损失最低(生产过程中损失 1.6-2.0 对数 1050%卵感染剂量(EID50),在 6°C 下储存时最大损失 0.8 对数 10EID50,6 个月后),同时具有低水分含量(1.1-1.4%)、低吸湿性(60%相对湿度下吸收 1.9-2.1%的水分)和良好的干粉分散性。