Preparation, characterisation and pharmacokinetics evaluation of dry power inhalation formulations of polymyxin B.

Abstract

This study aims to develop an alternative and effective drug delivery system through inhalation therapy to address the limitations of polymyxin B (PMB) intravenous treatment for pneumonia. PMB dry powder inhalers (DPIs) were prepared and characterized. The in vitro lung deposition and antibacterial efficacy were also assessed. To compare the systemic exposure following changes in administration routes, blood concentration measurements were conducted for different routes of administration spherical PMB particles, measuring 3 microns in diameter, achieved the highest fine particle fraction (FPF) of 53%. When particles transition from regular shapes to irregular blocks, a decrease of 1 micron in particle size resulted in an approximate 20% increase in FPF. Moreover, the FPF of PMB particles combined with smooth-surfaced lactose was approximately 10% less than that of PMB particles combined with rough-surfaced mannitol. The bioavailability of PMB DPI reached a peak of 77.46% within 10 min. In a murine model of acute lung infection, treatment with PMB DPI significantly reduced the bacterial load in lung tissues compared to the control group with intravenous PMB administration. In summary, particles with reduced size and increased sphericity displayed a greater FPF led to enhanced therapeutic efficacy and safety.