Boc Susan, Momin Mohammad A M, Farkas Dale R, Longest Worth, Hindle Michael
School of Pharmacy, Department of Pharmaceutics, Virginia Commonwealth University, 410 North 12th Street, P.O. Box 980533, Richmond, Virginia, 23298-0533, USA.
Department of Mechanical & Nuclear Engineering, Virginia Commonwealth University, Richmond, Virginia, USA.
AAPS PharmSciTech. 2021 Apr 15;22(4):136. doi: 10.1208/s12249-021-02001-1.
This study aimed to develop and characterize a spray-dried powder aerosol formulation of a commercially available surfactant formulation, Survanta® intratracheal suspension, using the excipient enhanced growth (EEG) approach. Survanta EEG powders were prepared by spray drying of the feed dispersions containing Survanta® (beractant) intratracheal suspension, hygroscopic excipients (mannitol and sodium chloride), and a dispersion enhancer (l-leucine or trileucine) in 5 or 20% v/v ethanol in water using the Buchi Nano Spray Dryer B-90 HP. Powders were characterized for primary particle size, morphology, phospholipid content, moisture content, thermal properties, moisture sorption, and surface activity. The aerosol performance of the powders was assessed using a novel low-volume dry powder inhaler (LV-DPI) device operated with 3-mL volume of dispersion air. At both ethanol concentrations, in comparison to trileucine, l-leucine significantly reduced the primary particle size and span and increased the fraction of submicrometer particles of the Survanta EEG powders. The l-leucine-containing Survanta EEG powders exhibited good aerosolization performance with ≥ 88% of the mass emitted (% nominal) after 3 actuations from the modified LV-DPI device. In addition, l-leucine-containing powders had a low moisture content (< 3% w/w) with transition temperatures close to the commercial surfactant formulation and retained their surface tension reducing activity after formulation processing. A Survanta EEG powder containing l-leucine was developed which showed efficient aerosol delivery from the modified LV-DPI device using a low dispersion air volume.
本研究旨在采用辅料增强生长（EEG）方法，开发并表征一种市售表面活性剂制剂Survanta®气管内混悬液的喷雾干燥粉末气雾剂制剂。通过使用Buchi Nano喷雾干燥器B-90 HP，对含有Survanta®（贝拉克坦）气管内混悬液、吸湿辅料（甘露醇和氯化钠）以及分散增强剂（L-亮氨酸或三亮氨酸）的进料分散液在5%或20% v/v乙醇水溶液中进行喷雾干燥，制备Survanta EEG粉末。对粉末的一次粒径、形态、磷脂含量、水分含量、热性质、水分吸附和表面活性进行了表征。使用一种新型小容量干粉吸入器（LV-DPI）装置，以3 mL分散空气体积运行，评估粉末的气雾剂性能。在两种乙醇浓度下，与三亮氨酸相比，L-亮氨酸显著降低了Survanta EEG粉末的一次粒径和跨度，并增加了亚微米级颗粒的比例。含L-亮氨酸的Survanta EEG粉末表现出良好的雾化性能，从改良的LV-DPI装置进行3次启动后，质量排放量≥88%（标称%）。此外，含L-亮氨酸的粉末水分含量低（<3% w/w），转变温度接近市售表面活性剂制剂，并且在制剂加工后保留了其降低表面张力的活性。开发了一种含L-亮氨酸的Survanta EEG粉末，该粉末在使用低分散空气体积的情况下，从改良的LV-DPI装置显示出高效的气雾剂递送。
