Development of inhalable formulations of anti-inflammatory drugs to potentially treat smoke inhalation injury in burn victims

Abstract

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 (≤5 μm) 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.