Investigation of Electrostatic Behavior of Dry Powder-Inhaled Model Formulations.

The accumulation of electrostatic charge on drug particles and excipient powders arising from interparticulate collisions or contacts with other surfaces can lead to agglomeration and adhesion problems during the manufacturing process, filling, and delivery of dry powder inhaler (DPI) formulations. The objective of the study was to investigate the role of triboelectrification to better understand the influence of electrostatic charge on the performance of DPIs with 2 capsule-based dimensionally similar devices constructed with different materials. In addition, strategies to reduce electrostatic charge build up during the manufacturing process, and the processes involved in this phenomenon were investigated.

Investigations on the Mechanism of Magnesium Stearate to Modify Aerosol Performance in Dry Powder Inhaled Formulations.

The potential of the force control agent magnesium stearate (MgSt) to enhance the aerosol performance of lactose-based dry powder inhaled (DPI) formulations was investigated in this study. The excipient-blends were investigated with analytical techniques including time-of-flight secondary ion mass spectrometry and single particle aerosol mass spectrometry (SPAMS), and particle size, morphology, and surface properties were evaluated. Excipient-blends were manufactured either by high-shear or low-shear blending lactose carrier with different amounts of MgSt in the range from 0% to 10% (w/w).

Particle interactions of fluticasone propionate and salmeterol xinafoate detected with single particle aerosol mass spectrometry (SPAMS).

Particle co-associations between the active pharmaceutical ingredients fluticasone propionate and salmeterol xinafoate were examined in dry powder inhaled (DPI) and metered dose inhaled (MDI) combination products. Single Particle Aerosol Mass Spectrometry was used to investigate the particle interactions in Advair Diskus (500/50 mcg) and Seretide (125/25 mcg). A simple rules tree was used to identify each compound, either alone or co-associated at the level of the individual particle, using unique marker peaks in the mass spectra for the identification of each drug.

The on-line analysis of aerosol-delivered pharmaceuticals via single particle aerosol mass spectrometry.

The use of single particle aerosol mass spectrometry (SPAMS) was evaluated for the analysis of inhaled pharmaceuticals to determine the mass distribution of the individual active pharmaceutical ingredients (API) in both single ingredient and combination drug products. SPAMS is an analytical technique where the individual aerodynamic diameters and chemical compositions of many aerosol particles are determined in real-time. The analysis was performed using a Livermore Instruments SPAMS 3.

A risk-based approach to management of leachables utilizing statistical analysis of extractables.

To incorporate quality by design concepts into the management of leachables, an emphasis is often put on understanding the extractable profile for the materials of construction for manufacturing disposables, container-closure, or delivery systems. Component manufacturing processes may also impact the extractable profile. An approach was developed to (1) identify critical components that may be sources of leachables, (2) enable an understanding of manufacturing process factors that affect extractable profiles, (3) determine if quantitative models can be developed that predict the effect of those key factors, and (4) evaluate the practical impact of the key factors on the product.

Leak testing in parenteral packaging: establishment of direct correlation between helium leak rate measurements and microbial ingress for two different leak types.

A direct test method using helium leak detection was developed to determine microbial ingress in parenteral vial/rubber closure systems. The purpose of this study was to establish a direct correlation between the helium leak rate and the presence of ingress when vials were submersed under pressure in a broth of bacteria. Results were obtained for two different types of leaks: microholes that have been laser-drilled into thin metal plates, and thin copper wire that was placed between the rubber closure and the glass vial's sealing surface.

A field-based approach for deterimining ATOFMS instrument sensitities to ammonium and nitrate.

Aerosol time-of-flight mass spectrometry (ATOFMS) instruments measure the size and chemical composition of individual particles in real-time. ATOFMS chemical composition measurements are difficult to quantify, largely because the instrument sensitivities to different chemical species in mixed ambient aerosols are unknown. In this paper, we develop a field-based approach for determining ATOFMS instrument sensitivities to ammonium and nitrate in size-segregated atmospheric aerosols, using tandem ATOFMS-impactor sampling.