Suraweera Ruwani K, Spann Kirsten M, Izake Emad L, Wells Timothy J, Wang Xiaodong, Islam Nazrul
Pharmacy Discipline, School of Clinical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD 4000, Australia.
Centre for Immunology and Infection Control (CIIC), Faculty of Health, Queensland University of Technology, Brisbane, QLD 4000, Australia.
Pharmaceutics. 2024 Nov 22;16(12):1506. doi: 10.3390/pharmaceutics16121506.
This study explores the development and characterization of spray-dried composite microparticles consisting of levofloxacin (LVX, a broad-spectrum antibiotic), and ambroxol (AMB, a mucolytic agent that has antibacterial and antibiofilm properties), for the intended application of the drug against lower respiratory tract infections (LRTIs). A range of LVX to AMB mass ratios (1:1, 1:0.5, and 1:0.25) were prepared, with and without the use of the dispersibility enhancer leucine (LEU), and spray-dried following pre-optimized parameters to achieve the required particle size (1-5 µm) and flow properties. The formulations were characterized by attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy, scanning electron microscopy (SEM), powder X-ray diffraction (PXRD), and a thermogravimetric analysis (TGA). The in vitro aerosolization performance of the new formulation was evaluated with a twin-stage impinger (TSI) at a flow rate of 60 ± 5 L/min. Using a validated RP-HPLC method, LVX and AMB were quantitatively determined. The combined spray-dried LVX, AMB, and LEU particles were spherically shaped with sizes ranging from 1.9 to 2.9 µm, thus complying with the size requirements for effective deep lung deposition. The dispersibility enhancer leucine produced a high yield and enhanced the flow properties and aerosolization characteristics of the spray-dried formulations. The LVX to AMB mass ratios showed a remarkable impact on the aerosolization properties, with the LVX to AMB 1:1 mass ratio demonstrating the best flow and FPFs for both drugs. There must be a balanced ratio of these components for spray drying the composite particles to obtain composite particles of the required size and with the appropriate flow property. The addition of 5% of LEU significantly ( < 0.005) improved the FPF of all the formulations, probably by enhancing the surface hydrophobicity of the composite particles. : The spray-dried combined antibiotics formulation has a strong potential for efficient lung delivery intended for the management of LRTIs.
本研究探索了喷雾干燥复合微粒的研制与特性，该微粒由左氧氟沙星（LVX，一种广谱抗生素）和氨溴索（AMB，一种具有抗菌和抗生物膜特性的黏液溶解剂）组成，旨在用于治疗下呼吸道感染（LRTIs）。制备了一系列LVX与AMB的质量比（1:1、1:0.5和1:0.25），有使用和未使用分散性增强剂亮氨酸（LEU）两种情况，并按照预先优化的参数进行喷雾干燥，以达到所需的粒径（1 - 5 µm）和流动性。通过衰减全反射 - 傅里叶变换红外（ATR - FTIR）光谱、扫描电子显微镜（SEM）、粉末X射线衍射（PXRD）和热重分析（TGA）对制剂进行表征。使用双级撞击器（TSI）以60 ± 5 L/min的流速评估新制剂的体外雾化性能。采用经过验证的反相高效液相色谱（RP - HPLC）方法对LVX和AMB进行定量测定。喷雾干燥的LVX、AMB和LEU组合颗粒呈球形，尺寸范围为1.9至2.9 µm，因此符合有效深部肺沉积的尺寸要求。分散性增强剂亮氨酸产生了高产率，并增强了喷雾干燥制剂的流动性和气雾化特性。LVX与AMB的质量比对雾化特性有显著影响，LVX与AMB质量比为1:1时两种药物的流动性和细颗粒分数（FPFs）最佳。对于喷雾干燥复合颗粒而言，这些成分必须有一个平衡的比例，以获得所需尺寸且具有适当流动性的复合颗粒。添加5%的LEU显著（< 0.005）提高了所有制剂的FPF，可能是通过增强复合颗粒的表面疏水性实现的。：喷雾干燥的联合抗生素制剂在用于治疗LRTIs的高效肺部给药方面具有很大潜力。
