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.

Physical characterization of component particles included in dry powder inhalers. II. Dynamic characteristics.

Characteristics of particles included in dry powder inhalers is extended from our previous report (in this journal) to include properties related to their dynamic performance. The performance of dry powder aerosols for pulmonary delivery is known to depend on fluidization and dispersion which reflects particle interactions in static powder beds. Since the solid state, surface/interfacial chemistry and static bulk properties were assessed previously, it remains to describe dynamic performance with a view to interpreting the integrated database.

Physical characterization of component particles included in dry powder inhalers. I. Strategy review and static characteristics.

The performance of dry powder aerosols for the delivery of drugs to the lungs has been studied extensively in the last decade. The focus for different research groups has been on aspects of the powder formulation, which relate to solid state, surface and interfacial chemistry, bulk properties (static and dynamic) and measures of performance. The nature of studies in this field, tend to be complex and correlations between specific properties and performance seem to be rare.

Investigation of triboelectric charging in dry powder inhalers using electrical low pressure impactor (ELPI).

Electrostatics and triboelectrification phenomena in dry powder inhalers (DPI) are not well understood, but as shown in this study they may play an important role. Using model formulations of albuterol in lactose, the extent of triboelectrification in the operation of DPI was investigated using an electrical low pressure impactor (ELPI). An experimental apparatus was developed, the performance of the ELPI was evaluated for consistency and reproducibility, and compared to a conventional inertial impactor.

Dry powder inhaler formulation.

A drug product combines pharmacologic activity with pharmaceutical properties. Desirable performance characteristics are physical and chemical stability, ease of processing, accurate and reproducible delivery to the target organ, and availability at the site of action. For the dry powder inhaler (DPI), these goals can be met with a suitable powder formulation, an efficient metering system, and a carefully selected device.