PDF(Pubmed)
Abstract：
Dry-powder inhalers (DPIs) are valued for their stability but formulating them is challenging due to powder aggregation and limited flowability, which affects drug delivery and uniformity. In this study, the incorporation of L-leucine (LEU) into hot-melt extrusion (HME) was proposed to enhance dispersibility while simultaneously maintaining the high aerodynamic performance of inhalable microparticles. This study explored using LEU in HME to improve dispersibility and maintain the high aerodynamic performance of inhalable microparticles. Formulations with crystalline itraconazole (ITZ) and LEU were made via co-jet milling and HME followed by jet milling. The LEU ratio varied, comparing solubility, homogenization, and aerodynamic performance enhancements. In HME, ITZ solubility increased, and crystallinity decreased. Higher LEU ratios in HME formulations reduced the contact angle, enhancing mass median aerodynamic diameter (MMAD) size and aerodynamic performance synergistically. Achieving a maximum extra fine particle fraction of 33.68 ± 1.31% enabled stable deep lung delivery. This study shows that HME combined with LEU effectively produces inhalable particles, which is promising for improved drug dispersion and delivery.
摘要：
干粉吸入器（DPI）因其稳定性而受到重视，但由于粉末聚集和有限的流动性，配制它们具有挑战性。影响药物输送和均匀性。在这项研究中,提出将L-亮氨酸（LEU）掺入热熔挤出（HME）中以增强分散性，同时保持可吸入微粒的高空气动力学性能。这项研究探索了在HME中使用LEU来改善可吸入微粒的分散性并保持高空气动力学性能。具有结晶伊曲康唑(ITZ)和LEU的制剂通过共喷射研磨和HME然后喷射研磨制备。LEU比率变化，比较溶解度，均质化，和空气动力学性能增强。在HME,ITZ溶解度增加，结晶度下降。HME配方中较高的LEU比率降低了接触角，协同增强质量中值空气动力学直径(MMAD)大小和空气动力学性能。实现33.68±1.31%的最大额外细颗粒分数能够实现稳定的深肺递送。这项研究表明，HME与LEU结合有效地产生可吸入颗粒，这对于改善药物分散和递送是有希望的。
