Aerodynamic assessment and in vitro evaluation of capreomycin oleate fine powder for tuberculosis therapy

Purpose. To assess the aerodynamic properties of capreomycin oleate powder and their lactose blends and to evaluate the in vitro performances in infected THP-1 human acute monocytic leukemia cells. Methods. Capreomycin oleate powder was produced using a nano spray dryer B90 (Büchi, Italy). Powders were characterized in terms of particle dimensions, morphology, free drug content and percentage of complexed capreomycin. Aerodynamic properties of capreomycin oleate alone and blended with different percentage of inhalation lactose (Lactohale LH200, Domo, Germany) were studied using a twin stage impinger according to the European Pharmacopoeia. The device used to load HPMC capsules was the HandiHaler (Boehringer-Ingelheim). Capreomycin sulfate and oleate were also tested in vitro in infected THP-1 human acute monocytic leukemia cells to evaluate their efficacy in inhibiting Mycobacterium growth. Results. Capreomycin oleate powder was characterized by both a nanometric and a narrow micrometric population and showed a wrinkled surface. Capreomycin drug content was around 30%. The emitted dose was in the range of 75-85%, both with and without lactose. The percentage of fine powder with respect to the emitted dose was ~20% with capreomycin oleate and increased to ~35% when blended with lactose. The best ratio between capreomycin oleate and Lactohale LH200 was 1:50 (w:w). An influence of capreomycin/lactose mixing time was observed as well. From the preliminary in vitro results, capreomycin oleate showed to be efficacious in inhibiting Mycobacterium growth. Conclusion. Capreomycin oleate powder was successfully obtained using nano spray drying. The powder characteristics seem to be promising for the treatment of pulmonary tuberculosis by inhalation.