A new respirable form of rifampicin

The aim of this research was to investigate a novel dry powder formulation of rifampicin (RF) that presents an improved lung deposition profile by means of a polymorphic transformation into a flake-like crystal hydrate. Rifampicin dihydrate (RFDH) was prepared by recrystallization of RF in anhydrous ethanol. A control formulation, amorphous RF (RFAM) was prepared by spray drying. The physicochemical properties of the RFDH and the RFAM were characterized. Aerosol performances of RFDH and RFAM were studied with two dry powder inhalers (DPIs), an Aerolizer® and a Handihaler®, using a Next Generation Impactor (NGI). The RFDH powder was successfully prepared using simple recrystallization process and had a MMAD of 2.2 μm. The RFDH powders were characterized as having a very thin flaky structure; this unique morphology provided improved aerosolization properties with a decreased device dependency upon aerosolization. The flaky morphology of RFDH resulted in a reduced agglomeration tendency than that of spherical RFAM particles. The maximum fine particle fraction (FPFTD) of 68% for the RFDH was achieved with the Aerolizer® device. Significant chemical degradation was not observed from the RFDH, while the RFAM showed significant chemical degradation at 9 months. The excipient-free formulation of the RFDH offers the benefit of delivering a maximum potency formulation, of the antibiotic, directly to the site of infection, the lung.

A novel respirable form of rifampicin (RF) has been manufactured by polymorphic transformation. SEM images of (A) rifampicin dihydrate (RFDH) and (B) spray-dried rifampicin (RFAM). The flaky RFDH showed significantly improved aerodynamic performances compared to the spherical RFAM since the unique morphology of RFDH crystals prevents the formation of strong particle aggregates.Figure optionsDownload as PowerPoint slide