College of Pharmacy , The University of Texas at Austin , 2409 West University Avenue, PHR 4.214 , Austin , Texas 78712 , United States.
Amgen , One Amgen Center Drive , Thousand Oaks , California 91320 , United States.
Mol Pharm. 2019 Oct 7;16(10):4165-4180. doi: 10.1021/acs.molpharmaceut.9b00496. Epub 2019 Aug 26.
Pulmonary delivery of biopharmaceuticals may enable targeted local therapeutic effect and noninvasive systemic administration. Dry powder inhaler (DPI) delivery is an established patient-friendly approach for delivering large molecules to the lungs; however, the complexities of balancing protein stability with aerosol performance require that the design space of biopharmaceutical DPI formulations is rigorously explored. Utilizing four rationally selected formulations obtained using identical atomization conditions, an extensive study of the effect of the particle formation process (spray drying or spray freeze-drying) on powder properties, aerosol performance, and protein stability was performed. Multiple linear regression analysis was used to understand the relationship between powder properties, device dispersion mechanism, and aerosol performance. Spray drying and spray freeze-drying, despite the same spraying conditions, produced powders with vastly different physical characteristics, though similar aerosol performance. The resulting regression model points to the significance of particle size, density, and surface properties on the resulting aerosol performance, with these factors weighing differently according to the device dispersion mechanism utilized (shear-based or impaction-based). The physical properties of the produced spray dried and spray freeze-dried powders have differing implications for long-term stability, which will be explored extensively in a future study.
生物制药的肺部给药可以实现靶向局部治疗效果和非侵入性的全身给药。干粉吸入器（DPI）输送是一种成熟的患者友好型方法，可将大分子递送至肺部；然而，平衡蛋白质稳定性与气溶胶性能的复杂性要求对生物制药 DPI 制剂的设计空间进行严格探索。利用四种通过相同雾化条件合理选择的制剂，广泛研究了颗粒形成过程（喷雾干燥或喷雾冷冻干燥）对粉末特性、气溶胶性能和蛋白质稳定性的影响。多元线性回归分析用于理解粉末特性、装置分散机制和气溶胶性能之间的关系。尽管喷雾条件相同，但喷雾干燥和喷雾冷冻干燥产生的粉末具有截然不同的物理特性，尽管气溶胶性能相似。所得回归模型指出了粒径、密度和表面特性对气溶胶性能的重要性，这些因素根据所使用的装置分散机制（基于剪切或基于冲击）而有不同的权重。所产生的喷雾干燥和喷雾冷冻干燥粉末的物理特性对长期稳定性有不同的影响，这将在未来的研究中进行广泛探讨。
