(Solvato-) polymorphism of formulations of rifampicin for pulmonary drug delivery prepared using a crystallization/spray drying process.

Rifampicin is an antibiotic used in tuberculosis therapy showing extensive (solvato-) polymorphism. Per oral administration of high doses is recommended, but application as dry powder for inhalation at the site of infection being the lungs, is desirable. Recrystallization from ethanol and consecutive spray drying is reported to yield a rifampicin dihydrate with suitable aerosol performance and stability. Nevertheless, the origin of water in the crystal remained unclear and demanded further investigation so to clarify its solid state throughout manufacture and storage. The present study reports the relationship of (solvato-) polymorphs occurring during manufacture and storage of samples recrystallized and spray dried from ethanol, methanol and water and it was concluded that processes involving a recrystallization from EtOH and MeOH produce particles of a common isostructural group of channel solvates. Samples recrystallized and spray dried from water were identified as members of another isostructural group, which was already characterized in literature. As a second aim, aerosol performance and storage stability of the formulations were investigated and all samples showed stable aerosol performance. Chemical stability of samples spray dried from ethanol was found suitable over a period of six months, whereas samples spray dried from methanol or water showed significant degradation.