School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang, 110016, China.
AAPS J. 2021 Apr 15;23(3):55. doi: 10.1208/s12248-021-00582-0.
Dry powder inhaler (DPI) is recognized as the first choice for lung diseases' treatment. However, it lacks a universal way for DPI formulation development. Fine lactose is commonly added in DPIs to improve delivery performance; however, the fine ratio-dependent mechanism is unclear. Therefore, the objective of this study is to explore the influence of fine lactose ratio on DPI powder properties and aerodynamic behavior, and the fine lactose ratio-dependent mechanism involved during powder fluidization and lung deposition. Here salbutamol sulfate was used as a model drug, Lactohale® 206 as coarse carrier, and Lactohale® 300 as fine component; the mixtures were prepared at 1% drug content, with fine content up to 20%. It was shown that with the fine addition, flowability of the mixtures was improved, interaction among particles was increased, and the presence of fines could help to improve DPI's aerosolization performance. When the fines added were less than 3%, the "active site" hypothesis played a leading role. When the added fines were over 3% but less than 10%, fluidization enhancement mechanism was more important. After the added fines reaching 10%, aggregate mechanism started to dominate. However, FPF cannot be further increased once the fines reached 20%. Moreover, the correlations between FPF and dynamic powder parameters were verified in ternary mixtures, and cohesion had a greater impact on FPF than that of flowability. In conclusion, adding lactose fines is an effective way to improve lung deposition of DPI, with the concrete mechanism lactose fine ratio dependent.
干粉吸入器（DPI）被认为是肺部疾病治疗的首选。然而，它缺乏一种通用的 DPI 制剂开发方法。细乳糖通常添加到 DPIs 中以改善输送性能；然而，精细比例依赖性机制尚不清楚。因此，本研究的目的是探索细乳糖比例对 DPI 粉末性质和空气动力学行为的影响，以及细乳糖比例依赖性机制在粉末流化和肺部沉积过程中的作用。本文以硫酸沙丁胺醇为模型药物，Lactohale®206 为粗载体，Lactohale®300 为细颗粒；混合物以 1%的药物含量和高达 20%的细颗粒含量制备。结果表明，随着细颗粒的加入，混合物的流动性得到改善，颗粒间的相互作用增加，细颗粒的存在有助于提高 DPI 的雾化性能。当添加的细颗粒小于 3%时，“活性点”假说起主导作用。当添加的细颗粒超过 3%但小于 10%时，流化增强机制更为重要。当添加的细颗粒达到 10%后，团聚机制开始起主导作用。然而，一旦细颗粒达到 20%，FPF 就无法进一步提高。此外，在三元混合物中验证了 FPF 与动态粉末参数之间的相关性，并且与流动性相比，内聚性对 FPF 的影响更大。总之，添加乳糖细颗粒是提高 DPI 肺部沉积的有效方法，具体机制取决于乳糖细颗粒的比例。
