Ramezani Vahid, Vatanara Alireza, Seyedabadi Mohammad, Nabi Meibodi Mohsen, Fanaei Hamed
a Department of Pharmaceutics, Faculty of Pharmacy , Shahid Sadoughi University of Medical Sciences , Yazd , Iran.
b Department of Pharmaceutics, Faculty of Pharmacy , Tehran University of Medical Sciences , Tehran , Iran.
Drug Dev Ind Pharm. 2017 Jul;43(7):1103-1111. doi: 10.1080/03639045.2017.1293679. Epub 2017 Mar 1.
Dry powder formulations are extensively used to improve the stability of antibodies. Spray drying is one of important methods for protein drying. This study investigated the effects of trehalose, hydroxypropyl beta cyclodextrin (HPBCD) and beta cyclodextrin (BCD) on the stability and particle properties of spray-dried IgG.
D-optimal design was employed for both experimental design and analysis and optimization of the variables. The size and aerodynamic behavior of particles were determined using laser light scattering and glass twin impinger, respectively. In addition, stability, ratio of beta sheets and morphology of antibody were analyzed using size exclusion chromatography, IR spectroscopy and electron microscopy, respectively.
Particle properties and antibody stability were significantly improved in the presence of HPBCD. In addition, particle aerodynamic behavior, in terms of fine-particle fraction (FPF), enhanced up to 52.23%. Furthermore, antibody was better preserved not only during spray drying, but also during long-term storage. In contrast, application of BCD resulted in the formation of larger particles. Although trehalose caused inappropriate aerodynamic property, it efficiently decreased antibody aggregation.
HPBCD is an efficient excipient for the development of inhalable protein formulations. In this regard, optimal particle property and antibody stability was obtained with proper combination of cyclodextrins and simple sugars, such as trehalose.
干粉制剂被广泛用于提高抗体的稳定性。喷雾干燥是蛋白质干燥的重要方法之一。本研究考察了海藻糖、羟丙基-β-环糊精（HPBCD）和β-环糊精（BCD）对喷雾干燥IgG稳定性和颗粒性质的影响。
采用D-最优设计进行实验设计以及变量的分析和优化。分别使用激光散射和玻璃双撞击器测定颗粒的大小和空气动力学行为。此外，分别使用尺寸排阻色谱法、红外光谱法和电子显微镜分析抗体的稳定性、β-折叠比例和形态。
在HPBCD存在的情况下，颗粒性质和抗体稳定性显著提高。此外，就细颗粒分数（FPF）而言，颗粒的空气动力学行为增强了52.23%。此外，抗体不仅在喷雾干燥过程中，而且在长期储存过程中都得到了更好的保存。相比之下，BCD的应用导致形成更大的颗粒。虽然海藻糖导致了不合适的空气动力学性质，但它有效地减少了抗体聚集。
HPBCD是开发可吸入蛋白质制剂的有效辅料。在这方面，通过环糊精和单糖（如海藻糖）的适当组合可获得最佳的颗粒性质和抗体稳定性。
