Aerodynamic and electrostatic properties of model dry powder aerosols: a comprehensive study of formulation factors.

The impact of formulation variables on aerodynamic and electrostatic properties of dry powder aerosol particles is of great importance to the development of efficient and reproducible inhaler products. Systematic evaluation requires a well-designed series of experiments using appropriate methods. A factorial experimental design was employed.

Dry powder PA-824 aerosols for treatment of tuberculosis in guinea pigs.

Novel treatments for multidrug-resistant tuberculosis (MDR-TB), extensively drug-resistant tuberculosis (XDR-TB), or latent TB are needed urgently. Recently, we reported the formulation and characterization of the nitroimidazo-oxazine PA-824 for efficient aerosol delivery as dry powder porous particles and the subsequent disposition in guinea pigs after pulmonary administration. The objective of the present study was to evaluate the effects of these PA-824 therapeutic aerosols on the extent of TB infection in the low-inoculum aerosol infection guinea pig model.

Prediction of dry powder inhaler formulation performance from surface energetics and blending dynamics.

The purpose of these studies was to investigate the ability of surface energy measurements and rates of mixing in dry powder inhaler (DPI) formulations to predict aerosol dispersion performance. Two lactose carrier systems comprising either spray-dried or milled particles were developed such that they had identical physical characteristics except for surface morphology and surface energies avoiding confounding variables common in other studies. Surface energy measurements confirmed significant differences between the powder systems.

Critical assessment of inverse gas chromatography as means of assessing surface free energy and acid-base interaction of pharmaceutical powders.

Inverse gas chromatography (IGC) has been employed as a research tool for decades. Despite this record of use and proven utility in a variety of applications, the technique is not routinely used in pharmaceutical research. In other fields the technique has flourished.

Inhaled large porous particles of capreomycin for treatment of tuberculosis in a guinea pig model.

Capreomycin is used for the treatment of multidrug-resistant tuberculosis (MDR-TB), but it is limited therapeutically by its severe side effects. The objectives of the present studies were (i) to design low-density porous capreomycin sulfate particles for efficient pulmonary delivery to improve local and systemic drug bioavailability and capacity to reduce the bacillary load in the lungs in a manner similar to that achieved with intramuscular injections; (ii) to determine pharmacokinetic parameters after pulmonary administration of these capreomycin particles; and (iii) to evaluate the efficacy of these particles in treating animals in a small-aerosol-inoculum guinea pig model of TB. Capreomycin particles were manufactured by spray drying and characterized in terms of size and drug content.