Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Department of Chemistry, Faculty of Sciences, University of Copenhagen, Universitetsparken 5, DK-2100, Copenhagen, Denmark.
Int J Pharm. 2017 Dec 20;534(1-2):263-271. doi: 10.1016/j.ijpharm.2017.10.021. Epub 2017 Oct 12.
Formulation composition and processing conditions can be adjusted to enhance the structural integrity as well as the bioactivity of proteins in the spray drying process. In this study, lysozyme was chosen as a model pharmaceutical protein to study these aspects when spray drying from water-ethanol mixtures. The effect of formulation additives (trehalose, Tween 20 and phosphate-buffered saline) and processing conditions (inlet temperature and storage time of lysozyme in the feed solution before the spray drying process) on the protein bioactivity was investigated. The results showed that the bioactivities of spray dried lysozyme with these additives were about 5-10% higher than that without additives. The bioactivity of the spray dried lysozyme was found to increase with a decrease in the inlet temperature from 130°C to 80°C, with similar findings when shortening the storage time of the feed solutions prior to spray drying. Fourier Transform Infrared (FTIR) and Circular Dichroism (CD) results showed that the native structures of lysozyme were largely restored upon reconstitution of the spray dried powder in water after the spray drying process. This suggests that the bioactivity of lysozyme could be preserved adequately by optimization of both the formulation composition and process conditions even when spray drying from a water-ethanol mixture.
制剂组成和加工条件可以进行调整，以增强蛋白质在喷雾干燥过程中的结构完整性和生物活性。在这项研究中，溶菌酶被选为模型药物蛋白，用于研究从水-乙醇混合物中喷雾干燥时的这些方面。研究了制剂添加剂（海藻糖、吐温 20 和磷酸盐缓冲盐水）和加工条件（入口温度和喷雾干燥前在进料溶液中溶菌酶的储存时间）对蛋白质生物活性的影响。结果表明，添加这些添加剂的喷雾干燥溶菌酶的生物活性比没有添加剂的高约 5-10%。发现喷雾干燥溶菌酶的生物活性随入口温度从 130°C 降低到 80°C 而增加，在喷雾干燥前缩短进料溶液的储存时间时也有类似的发现。傅里叶变换红外（FTIR）和圆二色性（CD）结果表明，喷雾干燥粉末在喷雾干燥后用水重构时，溶菌酶的天然结构得到了很大程度的恢复。这表明，即使从水-乙醇混合物中喷雾干燥，通过优化制剂组成和加工条件，也可以充分保持溶菌酶的生物活性。
