Production of capreomycin fine powder and loaded PLGA microparticles for tuberculosis inhalation therapy.

Purpose. To produce capreomycin dry powder and capreomycin loaded PLGA microparticles intended for tuberculosis inhalation therapy, using simple and scalable methods. Methods. Capreomycin physico-chemical characteristics have been modified by hydrophobic ion pairing with sodium oleate. The powder water suspension was processed by high pressure homogenization (1000 Bar, 5 cycles) and spray-dried using a mini spray dryer B290 (Büchi, Italy). Spray-drying was also used to prepare capreomycin oleate loaded PLGA microparticles. Capreomycin oleate powder was suspended in the organic phase containing Resomer RG502H (2% w/v) by high shear mixing (8000 rpm, 30 seconds) and the suspension was spray-dried at an inlet temperature of 70°C and a pump flow rate of 2 ml/min. Particle dimensions were determined using both a Nicomp 380 autocorrelator (PSS Inc., Santa Barbara, USA) and an Accusizer C770 (PSS Inc., Santa Barbara, CA). Morphology was investigated by scanning electron microscopy (SEM) and capreomycin content by UV spectrophotometry. Results. Capreomycin physico-chemical properties have been modified to increase polymeric microparticle content and to obtain respirable capreomycin oleate powder. High pressure homogenization allowed to reduce capreomycin oleate particle dimensions (~ 317 nm) even though a micrometric population (volume mean diameter of 6.18 μm) was evidenced by the SPOS analysis. SEM pictures showed not perfectly spherical particles with a wrinkled surface, generally suitable for inhalation. Loaded PLGA particles were characterized by a high encapsulation efficiency (about 90%) and dimensions (volume mean diameter of 6.69 μm) suitable for inhalation. Conclusion. Two different formulations were successfully developed for capreomycin pulmonary delivery. The hydrophobic ion pair strategy led to a noticeable increase of the drug content.