药物-药物盐晶体的形成和左氧氟沙星和4-氨基水杨酸的共无定形肺应用†

Hiroshi Ueda, Jun Yee Tse, Tetsuya Miyano, Yuzuki Nakayama, Peiwen Mo, Yuta Hatanaka, Hiromasa Uchiyama, Yuichi Tozuka and Kazunori Kadota
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引用次数: 0

摘要

干粉吸入器是肺输送的可行配方;然而,多种药物的联合递送需要一种特殊设计的装置。本研究旨在设计左氧氟沙星(LVF)和4-氨基水杨酸(ASA)共递送的多组分晶体和非晶态结构。通过溶剂蒸发和浆液转化,形成了新的多组分晶体晶体- i和晶体- ii。热分析表明,晶体i和晶体ii分别为水合物和非水合物形态。加热后,每个晶体都转化为不同的晶体。在储存期间,所有多晶体都恢复为晶体i。通过喷雾干燥得到共非晶(CA),其玻璃化转变温度在100℃以上。通过单晶x -射线衍射和红外光谱鉴定了多组分晶体和CA为盐。分别对LVF、ASA、物理混合物(PM)、crystal-I、CA进行体外气动性能测试。纯药物LVF/ASA的细颗粒分数(FPF, %)为0.9/13.3,PM为0.4/14.1。然而,晶体i和CA的FPF(%)在LVF和ASA的共同递送下分别显著提高到25.4/29.9和20.0/20.6。我们得出的结论是,多组分晶体和共无定形的设计是一种有效的策略,同时输送吸入药物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Formation of drug–drug salt crystals and co-amorphous forms of levofloxacin and 4-aminosalicylic acid for pulmonary applications†

Formation of drug–drug salt crystals and co-amorphous forms of levofloxacin and 4-aminosalicylic acid for pulmonary applications†

A dry powder inhaler is a viable formulation for pulmonary delivery; however, the co-delivery of multiple drugs requires a specially designed device. This study aimed to design multi-component crystal and amorphous forms for the co-delivery of levofloxacin (LVF) and 4-aminosalicylic acid (ASA). New multi-component crystals of LVF and ASA, crystal-I and crystal-II, were formed by solvent evaporation and slurry conversion. Thermal analysis revealed that crystal-I and crystal-II were the hydrate and anhydrate forms, respectively. Upon heating, each crystal was converted to different crystals. All polymorphs reverted to crystal-I during storage. The co-amorphous (CA) form was obtained by spray drying, which exhibited a relatively high glass transition temperature above 100 °C. Multi-component crystals and CA were estimated as salts by single crystal X-ray diffraction and infrared spectroscopy. An in vitro aerodynamic performance test was performed for LVF, ASA, physical mixture (PM), crystal-I, and CA. The fine particle fraction (FPF, %) of LVF/ASA was 0.9/13.3 for pure drugs and 0.4/14.1 for PM. However, the FPF (%) for crystal-I and CA significantly improved to 25.4/29.9 and 20.0/20.6, respectively, with the co-delivery of LVF and ASA. We conclude that the design of multi-component crystals and co-amorphous forms is an effective strategy for the simultaneous delivery of inhalation drugs.

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