Next generation pharmaceutical impactor: a new impactor for pharmaceutical inhaler testing. Part III. extension of archival calibration to 15 L/min.

An extension of the archival calibration of the recently developed 30-100-L/min seven-stage impactor, the Next Generation Pharmaceutical Impactor (NGI), has been undertaken at 15 L/min. The NGI stage cut sizes are 0.98-14.1 microm aerodynamic diameter at this flow rate. This 15-L/min calibration was motivated by the desire to sample the entire aerosol produced by a nebulizer when tested in accordance with a new international standard developed by the Comite Européen de Normalisation (CEN), as well as the need to test various types of inhalers at flow rates lower than 30 L/min for pediatric applications. Measurements were undertaken with monodisperse oleic acid droplets in the range of 0.7-22 microm aerodynamic diameter following a procedure established in the original 30-100-L/min calibration study. The NGI was found to be effective for particle size separation at 15 L/min. Users should decide the most applicable configuration that meets their needs, based on the following recommendations: (1) the pre-separator should not normally be used, as its performance is significantly degraded by the influence of gravity, resulting in interference with stage 1; and (2) a filter should be inserted below the micro-orifice collector (MOC), as the size corresponding to 80% collection efficiency of the MOC becomes excessively large with decreasing flow rate, so that this component becomes ineffective as a means of collecting fine particles that penetrate beyond stage 7.

Next generation pharmaceutical impactor (a new impactor for pharmaceutical inhaler testing). Part I: Design.

A new cascade impactor has been designed specifically for pharmaceutical inhaler testing. This impactor, called the Next Generation Pharmaceutical Impactor (NGI), has seven stages and is intended to operate at any inlet flow rate between 30 and 100 L/min. It spans a cut size (D50) range from 0.54-microm to 11.7-microm aerodynamic diameter at 30 L/min and 0.24 microm to 6.12 microm at 100 L/min. The aerodynamics of the impactor follow established scientific principles, giving confident particle size fractionation behavior over the design flow range. The NGI has several features to enhance its utility for inhaler testing. One such feature is that particles are deposited on collection cups that are held in a tray. This tray is removed from the impactor as a single unit, facilitating quick sample turn-around times if multiple trays are used. For accomplishing drug recovery, the user can add up to approximately 40 mL of an appropriate solvent directly to the cups. Another unique feature is a micro-orifice collector (MOC) that captures in a collection cup extremely small particles normally collected on the final filter in other impactors. The particles captured in the MOC cup can be analyzed in the same manner as the particles collected in the other impactor stage cups. The user-friendly features and the aerodynamic design principles together provide an impactor well suited to the needs of the inhaler testing community.

Next generation pharmaceutical impactor (a new impactor for pharmaceutical inhaler testing). Part II: Archival calibration.

A new seven-stage cascade impactor, the Next Generation Pharmaceutical Impactor (NGI), has been developed for the pharmaceutical industry. A calibration following "good laboratory practice (GLP)" procedures has been performed on a specific archival NGI, deemed to be representative of all NGIs. Thus, this impactor had nozzle dimensions for each stage manufactured close to the middle of the tolerance band for the design specification, and therefore the average nozzle diameter was equal to the nominal value for that stage. An essential feature of the NGI is that it is designed to operate at any flow rate between 30 and 100 L/min. Thus, the calibration was made at inlet flow rates of 30, 60 and 100 L/min representing the lower bound, mid-region and upper bound of the specified range of operation for the impactor. The calibration data were then used to develop equations that predict the particle cut size for all components of the impactor at any flow rate from 30 to 100 L/min.

Aerodynamic diameter measurement of cellulose acetate fibers from cigarette filters: what is the potential for human exposure?

Aerodynamic diameter is a major determinant of particle and fiber deposition and toxicity in the respiratory tract. To characterize cellulose acetate fibers released from the filter end of cigarettes puffed under conditions approximating smoking, we designed multistage impactors to determine the aerodynamic diameters of large fibers with circumscribed diameters between 20 and 35 microm and aspect ratios ranging from subfiber ratios up to 40. This range of diameters encompasses all of the cellulose acetate fiber sizes that are commercially manufactured. When commercially available cigarettes with filters made from acetate fibers in this circumscribed diameter range were puffed directly into the impactor, on average 10 fibers/cigarette were released and their aerodynamic diameters were determined. In our studies, we found that the aerodynamic diameters of the cellulose acetate fibers were always greater than 23 microm. Using standard lung deposition models, we concluded that the fibers are nonrespirable with a very low probability of penetration to the distal lung. Our findings, which demonstrate release of only a small number of these large fibers with an extremely low likelihood of reaching the distal lung, indicate that these fibers are not a risk for human lung disease.