Inhalable ciprofloxacin/polymyxin B dry powders in respiratory infection therapy

Abstract

The current study focused on the formulation, physicochemical characterization, and antibacterial susceptibility testing of inhalable spray dried powders containing ciprofloxacin (CIP) and polymyxin B sulfate (PMB). CIP nanosuspensions with an average particle diameter of 435.9 ± 9.3 nm were initially obtained using the wet-milling protocol and subsequently co-spray dried with PMB solutions to yield inhalable dry powders. The Powder X-Ray Diffraction (P-XRD) results showed that the wet-milled CIP nanoparticles were in a 4.8 hydrate state, which were transformed to 3.7 hydrates and amorphous materials after co-spray drying. The PMB remained in an amorphous state in the dry powders. Differential Scanning Calorimetry (DSC) analyses revealed that the glass transition temperatures (Tgs) of the co–spray dried formulations were higher than the Tg of CIP, but lower than the Tg of PMB. Fourier Transform Infrared Spectrometer (FTIR) studies suggested the existence of π - π interactions between CIP and PMB in the co-spray dried powders. These powders also retained antimicrobial effects against Pseudomonas aeruginosa strain PAO1. In addition, the spray-dried powder formulations exhibited satisfactory solid-state stability and aerodynamic characteristics when stored under 3% relative humidity and 20 ± 5 °C for 4 months. Overall, the newly developed inhalable CIP/PMB dry powders are a promising therapeutic strategy for respiratory tract infections.

Keywords

• inhalable dry powders
• nanosuspensions
• co-spray drying
• solid state characteristics
• aerodynamic properties
• antibiotic susceptibility