Preparation and Evaluation of Inhalable Microparticles with Improved Aerodynamic Performance and Dispersibility Using L-Leucine and Hot-Melt Extrusion

Autor: Jin-Hyuk Jeong, Ji-Su Kim, Yu-Rim Choi, Dae Hwan Shin, Ji-Hyun Kang, Dong-Wook Kim, Yun-Sang Park, Chun-Woong Park
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: Pharmaceutics, Vol 16, Iss 6, p 784 (2024)
Druh dokumentu: article
ISSN: 16060784
1999-4923
DOI: 10.3390/pharmaceutics16060784
Popis: 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.
Databáze: Directory of Open Access Journals
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