Powder properties and their influence on dry powder inhaler delivery of an antitubercular drug

Abstract

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- microm 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 (gamma) of R-PLGA, rifampicin alone, lactose, and maltodextrin were obtained by inverse phase gas chromatography, surface areas (S(a)) by N2 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 microm, respectively. D(v) was 13 +/- 1 and 2 +/- 1 microm for R-PLGA and rifampicin alone, respectively, indicating that R-PLGA was more aggregated. This was evident in gamma of 35 +/- 1 and 19 +/- 6 mJ/m2 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 microm) was more aggregated than bulk lactose (D(v) = 54 +/- 2 microm). This was a result of the higher S(a) for maltodextrin (0.54 m2/g) than for lactose (0.21 m2/g). The gamma of bulk lactose and maltodextrin was 40 +/- 4 and 60 +/- 6 mJ/m2 and of sieved lactose and maltodextrin was 39 +/- 1 and 50 +/- 1 mJ/m2. 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