Abstract
Tuberculosis is still one of the leading causes of death from a single infectious agent (i.e. Mycobacterium tuberculosis). First line therapy includes per oral administration of high doses of rifampicin over several months and is often times accompanied by the occurrence of unwanted side effects that might limit the patient’s adherence to the therapy. Thus, local antibiotic treatment at the site of infection i.e. the lungs is desirable. Amongst other approaches, spray drying of solutions of rifampicin has been shown as suitable method to produce respirable dry powders. In this work, we present inhalable formulations manufactured via spray drying of aqueous solutions of rifampicin. Powders manufactured were characterized for their aerodynamic and solid state properties, as well as their physical and chemical stability. The main focus of this study was to investigate the mechanism of particle formation using an acoustic levitator. Fine particle fractions of the test formulations ranged from 80 to 89% whereas a reference formulation (a spray dried isopropyl alcoholic solution of rifampicin) showed a lower fine particle fraction of 37%. Acoustic levitator and surface tension experiments showed that interfacial properties of rifampicin lead to early crust formation upon drying of the droplets, which eventually decoupled from the liquid core and formed highly collapsed, low apparent density powders with excellent aerosol properties.
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