Liu Zhewei, Ma Ying, Shao Yuanyuan, Wei Xiaoyang, Hu Binjie, Zhu Jesse
Department of Chemical and Environmental Engineering, University of Nottingham Ningbo China, 199 Taikang East Road, Ningbo, 315100, China.
Department of Chemical and Biochemical Engineering, University of Western Ontario, 1151 Richmond Street, London, N6A 3K7, Canada.
Pharm Res. 2025 Jul 1. doi: 10.1007/s11095-025-03883-7.
This study explores the co-spray-drying of chitosan and L-leucine to optimize inhalable microparticles for heparin sodium. Chitosan provides sustained release and pulmonary retention, while L-leucine improves powder dispersibility and aerosolization performance. By tuning the chitosan-to-leucine ratio, the formulation achieves an optimal balance between deep lung deposition and prolonged therapeutic effect, offering a promising strategy for polysaccharide-based pulmonary delivery.
Inhalable microparticles were prepared via co-spray-drying of heparin sodium with chitosan and L-leucine. In-vitro aerosolization performance was evaluated using the Next Generation Impactor. Particle morphology was examined via scanning electron microscopy (SEM). Solid-state properties were analyzed using X-ray powder diffraction (XRPD) to assess changes in crystallinity. Stability was assessed at 25 °C and 55% RH over 4 weeks. Drug release was studied using the in-vitro dialysis method and modeled with five kinetic models: Zero-order, First-order, Higuchi, Hixson-Crowell, and Korsmeyer-Peppas.
Heparin sodium microparticles containing chitosan and L-leucine exhibited favorable aerosolization performance, especially in the HSCL1 formulation. SEM showed that L-leucine-induced wrinkling improved dispersibility, while excess chitosan caused surface cracking. XRPD analysis indicated that chitosan suppressed crystallinity while L-leucine retained partial crystalline features, supporting matrix stability and powder dispersion. In-vitro release study demonstrated biphasic kinetics in chitosan-containing formulations. HSCL1 showed sustained, non-Fickian release and enhanced storage stability.
Co-spray-dried heparin sodium microparticles with chitosan and L-leucine achieved balanced aerosolization performance, sustained release, and storage stability. Their combination overcomes the limitations of single-excipient systems. The optimized formulation demonstrates strong potential for effective pulmonary drug delivery with improved therapeutic consistency.
本研究探索壳聚糖与L-亮氨酸的共喷雾干燥工艺，以优化肝素钠的可吸入微粒。壳聚糖可实现缓释并促进肺部滞留，而L-亮氨酸则可改善粉末的分散性和气雾化性能。通过调整壳聚糖与亮氨酸的比例，该制剂在肺部深层沉积和延长治疗效果之间实现了最佳平衡，为基于多糖的肺部给药提供了一种有前景的策略。
通过肝素钠与壳聚糖和L-亮氨酸的共喷雾干燥制备可吸入微粒。使用下一代撞击器评估体外雾化性能。通过扫描电子显微镜（SEM）检查颗粒形态。使用X射线粉末衍射（XRPD）分析固态性质，以评估结晶度的变化。在25°C和55%相对湿度下评估4周的稳定性。使用体外透析法研究药物释放，并采用零级、一级、Higuchi、Hixson-Crowell和Korsmeyer-Peppas五种动力学模型进行建模。
含有壳聚糖和L-亮氨酸的肝素钠微粒表现出良好的雾化性能，尤其是在HSCL1制剂中。SEM显示，L-亮氨酸引起的皱纹改善了分散性，而过量的壳聚糖导致表面开裂。XRPD分析表明，壳聚糖抑制了结晶度，而L-亮氨酸保留了部分结晶特征，支持了基质稳定性和粉末分散性。体外释放研究表明含壳聚糖制剂具有双相动力学。HSCL1表现出持续的非Fickian释放并提高了储存稳定性。
壳聚糖和L-亮氨酸共喷雾干燥的肝素钠微粒实现了雾化性能、缓释和储存稳定性的平衡。它们的组合克服了单一辅料系统的局限性。优化后的制剂在有效肺部给药和改善治疗一致性方面显示出强大的潜力。
