Formulation of rifampicin softpellets for high dose delivery to the lungs with a novel high dose dry powder inhaler

Lung tuberculosis (TB) is the most deadly infectious disease worldwide although it is treatable. High doses of antibiotics are used for therapy over a period of at least 6 months. Since in many treated patients only sub-therapeutic concentrations are reached in the infected tissue of the lung, about half a million cases of multi drug resistant tuberculosis (MDR TB) occur every year. In order to increase the concentration of the active pharma-ceutical ingredient (API) at the site of the primary infection, inhalation of antibiotics seems to be promising. In this study, we show the capability of softpellets, engineered dry powder agglomerates, to deliver high doses to the lungs. For this, the antibiotic rifampicin was milled and processed into softpellets which were then dispersed utilising a novel high dose dry powder inhaler, the 8Shot from Hovione Technology. Aerodynamic assessment resulted in a fine particle dose of 21.35 mg with a device retention of < 15% after loading all eight chambers of the inhaler with 10 mg softpellet formulation. At the same time, we present a new process design to produce softpellets, namely vibro-pelletisation.