Production and in vitro evaluation of hydrophobic ion pair fine powders for tuberculosis inhalation therapy.

Purpose. To produce capreomycin hydrophobic ion pairs for inhalation therapy and to evaluate their in vitro performances in Mycobacterium tuberculosis cultures. Methods. Potentially respirable capreomycin powders were produced by modifying the physico-chemical characteristics of the peptide by hydrophobic ion pairing with sodium oleate, sodium linoleate, and sodium linolenate. The hydrophobic ion pair was prepared at different molar ratios in order to enhance the final capreomycin content. Hydrophobic ion pairs were prepared in ethanol-water or acetone-water mixtures and the obtained suspensions were spray-dried using a mini spray dryer B290 (Büchi, Italy). Powders were characterized in terms of particle dimensions, morphology, free drug content and percentage of complexed capreomycin. Powders were also tested in vitro on Mycobacterium tuberculosis H37Ra cultures to evaluate their efficacy in inhibiting Mycobacterium growth. Results. All three powders were characterized by both a nanometric and a narrow micrometric population assessing their potential suitability for inhalation in pulmonary tuberculosis treatment. Moreover, since capreomycin physico-chemical properties have been modified, particles could be phagocytised by alveolar macrophages, site of infection of tuberculosis, minimizing its solubilisation in the pulmonary fluids and its systemic side effects. Capreomycin drug content was around 30% in all cases. From the preliminary in vitro results, the three powders showed the same efficacy in inhibiting Mycobacterium growth with respect to capreomycin sulfate. Conclusion. Three different formulations were successfully developed for capreomycin pulmonary delivery. Ion pairing strategy may be successful in treating Mycobacterium tuberculosis infection