No abstract

Aerosolized RPLGA reduced most measures of tuberculosis (TB) infection. These studies are further evidence for the potential of inhaled aerosol therapy for the treatment of TB. However, additional studies are required to elucidate underlying mechanisms of action and optimize this route of drug delivery.

The purpose of this study was to determine if aerosol delivery of drug loaded microparticles to lungs infected with Mycobacterium tuberculosis may be achieved by predicting dispersion of dry powders through knowledge of particle surface properties. Particle sizes of rifampicin-loaded poly(lactide-co-glycolide) microparticles (R-PLGA), rifampicin alone, and lactose and maltodextrin carrier particles (bulk and 75-125-µm sieved fractions) were determined by electron microscopy for the projected area diameter (D p ) and laser diffraction for the volume diameter (D v ). Surface energies (γ) of R-PLGA, rifampicin alone, lactose, and maltodextrin were obtained by inverse phase gas chromatography, surface areas (S a ) by N 2 adsorption, and cohesive energy densities by calculation. Particle dispersion was evaluated (Andersen nonviable impactor) for 10% blends of R-PLGA and rifampicin alone with bulk and sieved fractions of the carriers. D p for R-PLGA and rifampicin alone was 3.02 and 2.83 µm, respectively. D v was 13 ± 1 and 2 ± 1 µm for R-PLGA and rifampicin alone, respectively, indicating that R-PLGA was more aggregated. This was evident in γ of 35 ± 1 and 19 ± 6 mJ/m 2 for R-PLGA and rifampicin alone. D p for lactose and maltodextrin (sieved and bulk) was approximately 40 mm. Bulk maltodextrin (D v = 119 ± 6 mm) was more aggregated than bulk lactose (D v = 54 ± 2 mm). This was a result of the higher S a for maltodextrin (0.54 m 2 /g) than for lactose (0.21 m 2 /g). The γ of bulk lactose and maltodextrin was 40 ± 4 and 60 ± 6 mJ/m 2 and of sieved lactose and maltodextrin was 39 ± 1 and 50 ± 1 mJ/m 2 . Impaction studies yielded higher fine particle fractions of R-PLGA from sieved lactose, 13% ± 3%, than from sieved maltodextrin, 7% ± 1%, at 90 L/min. An expression, based on these data, is proposed as a predictor of drug dispersion from carrier particles.Delivery of dry powder formulations can be achieved by characterizing particle surfaces and predicting impact on dispersion.

Experiments were designed to study the kinetics of adsorption of two industrial dyes-methylene blue (cationic) and sulfur blue (anionic)-by kaolinite and montmorillonite clays. The cationic dye was removed from aqueous solution at a continuously decreasing rate from 10 mg/g min to 0.07 mg/g min by montmorillonite whereas kaolinite adsorbed the dye at a faster and uniform rate of 16 mg/g min. The anionic dye was removed at a uniform rate of 2.3 mg/g min by kaolinite and 2.6 mg/g min by montmorillonite. The apparent control of ion-exchange capacities and nature of exchange sites of the clays on the rates of color removal is pointed out.

The preseparator of an Andersen impactor with different coating treatments for a range of particle-size distributions was evaluated. Limited theoretical simulations constrained by simplifying assumptions of the airflow fields in the preseparator and upper stages of an 8-stage Andersen impactor were used to reveal low-velocity and high-pressure regions for potential deposition. These regions were then sampled in subsequent particle deposition experiments. Disodium fluorescein aerosols were sampled with different coating treatments of the preseparator floor. Particles collected at impactor stages determined particle size distributions. Stage deposition was compared between different preseparator treatments (buffer and silicon oil). Collection efficiency in the preseparator followed the pattern buffer > silicon oil > untreated. Statistical differences (P < 0.05) were noted in collection efficiency of large particles (45 µm-75 µm) in the preseparator. The mass median aerodynamic diameters and geometric standard deviations showed some statistical differences when different preseparator treatments for large particles were used; therefore, preseparator coating was shown to influence performance and thereby estimates of particle size by inertial impaction.