Abstract：
Pressurized metered dose inhalers (pMDIs) require optimized formulations to provide stable, consistent lung delivery. This study investigates the feasibility of novel rugose lipid particles (RLPs) as potential drug carriers in pMDI formulations. The physical stability of RLPs was assessed in three different propellants: the established HFA-134a and HFA-227ea and the new low global-warming-potential (GWP) propellant HFO-1234ze. A feedstock containing DSPC and calcium chloride was prepared without pore forming agent to spray dry two RLP batches at inlet temperatures of 55 °C (RLP55) and 75 °C (RLP75). RLPs performance in pMDI formulations was compared to two reference samples that exhibit significantly different performance when suspended in propellants: well-established engineered porous particles and particles containing 80% trehalose and 20% leucine (80T20L). An accelerated stability study at 40 °C and relative humidity of 7% ± 5% was conducted over 3 months. At different time points, a shadowgraphic imaging technique was used to evaluate the colloidal stability of particles in pMDIs. Field emission electron microscopy with energy dispersive X-ray spectroscopy was used to evaluate the morphology and elemental composition of particles extracted from the pMDIs. After 2 weeks, all 80T20L formulations rapidly aggregated upon agitation and exhibited significantly inferior colloidal stability compared to the other samples. In comparison, both the RLP55 and RLP75 formulations, regardless of the propellant used, retained their rugose structure and demonstrated excellent suspension stability comparable with the engineered porous particles. The studied RLPs demonstrate great potential for use in pMDI formulations with HFA propellants and the next-generation low-GWP propellant HFO-1234ze.
摘要：
加压计量吸入器(pMDI)需要优化的配方，以提供稳定的、一致的肺部分娩。这项研究调查了新型皱纹脂质颗粒（RLPs）作为pMDI制剂中潜在药物载体的可行性。在三种不同的推进剂中评估了RLPs的物理稳定性：已建立的HFA-134a和HFA-227ea以及新型低全球变暖潜势（GWP）推进剂HFO-1234ze。在55°C(RLP55)和75°C(RLP75)的入口温度下,制备含有DSPC和氯化钙的原料,以喷雾干燥两个RLP批次。将pMDI制剂中的RLPs性能与两种参比样品进行比较,所述参比样品在悬浮于推进剂中时表现出显著不同的性能:良好确立的工程多孔颗粒和含有80%海藻糖和20%亮氨酸(80T20L)的颗粒。在40°C和7%±5%的相对湿度下进行3个月的加速稳定性研究。在不同的时间点,阴影成像技术用于评估pMDI中颗粒的胶体稳定性。使用具有能量色散X射线光谱的场发射电子显微镜来评估从pMDI中提取的颗粒的形态和元素组成。2周后,与其他样品相比,所有80T20L制剂在搅拌时快速聚集,并且表现出显著较差的胶体稳定性。相比之下,RLP55和RLP75配方，无论使用何种推进剂,保留了它们的皱纹结构，并证明了与工程多孔颗粒相当的优异的悬浮稳定性。所研究的RLP显示出在具有HFA推进剂和下一代低GWP推进剂HFO-1234ze的pMDI配方中使用的巨大潜力。
