Advanced Drug Delivery Group, Faculty of Pharmacy (A15), University of Sydney, Sydney, NSW, 2006, Australia.
Int J Pharm. 2010 Apr 15;389(1-2):41-52. doi: 10.1016/j.ijpharm.2010.01.014. Epub 2010 Jan 18.
Injury arising from smoke inhalation is a significant mortality risk in severe burned patients. Inflammatory processes are major contributors to the development of respiratory insufficiency owing to pulmonary oedema, formation of airway fibrin clots and hypoxaemia. Anti-inflammatory and anti-coagulant drugs such as heparin and pentoxifylline are currently systemically administered for the treatment of smoke inhalation. Delivery of these drugs in the form of inhalable particles could be an effective manner to achieve rapid targeted action for acceleration of the treatment. The study developed and characterised a series of spray-dried heparin and pentoxifylline dry powder formulations suitable for inhalation administration. Drug particles were co-spray-dried with leucine in varying ratios. Particle size analysis confirmed all powders (except 2%, w/w, pentoxifylline with 1%, w/w, leucine in spray-drying feed solution) had particle size in the optimal range (< or =5 microm) for deep lung drug deposition. Leucine supplementation dramatically altered heparin surface topography while pentoxifylline formulations were a mixture of elongated needles interspersed with wrinkly particles. Addition of leucine improved fine particle fraction of heparin and pentoxifylline. The study indicated manufacture of inhalable heparin and pentoxifylline was feasible and can potentially be an attractive delivery alternative to the more conventional systemic delivery route.
吸入烟雾导致的损伤是严重烧伤患者的一个重要死亡风险。炎症过程是导致呼吸功能不全的主要原因，其表现为肺水肿、气道纤维蛋白血栓形成和低氧血症。肝素和己酮可可碱等抗炎和抗凝药物目前被系统地用于治疗烟雾吸入。以可吸入颗粒的形式给予这些药物可能是一种有效的方法，可以实现快速靶向作用，从而加速治疗。该研究开发并表征了一系列适合吸入给药的喷雾干燥肝素和己酮可可碱干粉制剂。药物颗粒与亮氨酸以不同的比例共喷雾干燥。粒径分析证实，所有粉末（除了喷雾干燥进料溶液中 2%（w/w）的己酮可可碱和 1%（w/w）的亮氨酸）的粒径都在适合深肺部药物沉积的最佳范围内（<或=5 微米）。亮氨酸的添加极大地改变了肝素的表面形貌，而己酮可可碱制剂则是长针和皱缩颗粒的混合物。亮氨酸的添加改善了肝素和己酮可可碱的微细颗粒分数。该研究表明，可吸入肝素和己酮可可碱的制造是可行的，并且可能是一种有吸引力的替代传统全身给药途径的给药方式。
