EVALUATION OF AERODYNAMIC PARTICLE SIZE DISTRIBUTION OF DRUGS USED IN INHALATION THERAPY: A CONCISE REVIEW

Most of the inhalation products in the market use metered dose inhaler (MDI) technology or dry powder inhaler (DPI) technology. MDIs use propellant to deliver desired dose of liquid formulation in aerosol form. DPI contains active in fine particulate form embedded onto an inert carrier. In both cases, amount of drug dispensed from the device reaching the lungs is dependent upon drug product characteristics as well as formulation-device relationship. Hence, in addition to particle size, aerodynamic distribution of the drug upon delivery by the device plays an important role in determining amount of drug reaching the lungs. Therefore particle size characterization is an important tool in determining the extent of drug delivery from the metered dose inhaler. Aerodynamic particle size distribution is frequently determined by use of cascade impactors and data so generated is accepted by regulatory agencies as a tool for predicting efficacy of MDIs and DPIs. This review discusses principle and working of cascade impactors. Additionally, the review also examines the role of laser diffraction technique in estimating size of dispersed particles.

Intercomparison of four different cascade impactors for fine and ultrafine particle sampling in two European locations

Due to the need to better characterise the ultrafine particles fraction and related personal exposure, several impactors have been developed to enable the collection of ultrafine particles (<100 nm). However, to the authors’ kno wledge there have been no field campaigns to-date intercomparing impactor collection of ultrafine particles. The purpose of this study was two-fold: 1) to assess the performance of a number of conventional and nano-range cascade impactors with regard to the particle mass size distribution under different environmental conditions and aerosol loads and types, and 2) to characterise aerosol size distributions including ultrafine particles using impactors in 2 European locations. The impactors used were: (i) Berner low-pressure impactor (BLPI; 26 nm - 13.5 μm), (ii) nano-Berner low-pressure impactor (nano-BLPI; 11 nm - 1.95 μm) and (iii) Nano-microorifice uniform deposit impactor (nano-Moudi; 10 nm-18 μm), and (iv) Personal cascade impactor Sioutas (PCIS; <250 nm - 10 μm). Taking the BLPI as an internal reference, the best agreement regarding mass size distributions was obtained with the nano-BLPI, independently of the aerosol load and aerosol chemical composition. The nano-Moudi showed a good agreement for part icle sizes >320 nm, whereas for particle diameters <320 nm this instrument recorded larger mass concentrations in outdoor air than the internal reference. This difference could be due to particle bounce, to the dissociation of semi volatiles in the coarser stages and/or to particle shrinkage during transport through the impactor due to higher temperature inside this impactor. Further research is needed to understand this behaviour. With regard to the PCIS, their size-resolved mass concentrations were compar able with other impactors for PM1, PM2 and PM10, but the cut-off at 250 nm did not seem to be consistent with that of the internal reference.

Particle size distribution of workplace aerosols in manganese alloy smelters applying a personal sampling strategy

Air samples were collected by personal sampling with five stage Sioutas cascade impactors and respirable cyclones in parallel among tappers and crane operators in two manganese (Mn) alloy smelters in Norway to investigate PM fractions.

A Simplified Model for the Flow Inside Cascade Impactor

In this paper we developed a new mathematical model for the flow inside cascade impactors and via this simplified model, we determined the particle size distribution by a fast and low cost computational method. Using cascade impactors for determining the particle size distribution, one can use comprehensive CFD methods to fully simulate the particle traces. Although the results from those CFD analyses can be very accurate, usually that is not a time and cost efficient routine. In contrast, we showed that by using our proposed calculation we can estimate the particle size distribution very fast and yet with the slight error — comparing to the results from CFD method. Cascade impactors are being used to measure the range of substances moving through an opening and determine the particle size of distributed substances. Air flow containing aerosol entering in each stage, after colliding vertically with a plate will deviate 90 degrees from its original direction. Larger (massive) particles cannot follow the flow because of their larger linear momentum. Hence, they will deviate from the flow and deposit on the plate instead. The mass difference before and after the experiment represents the deposited mass in each stage. By integrating multiple uniquely designed stages into one impactor, we can determine size of particles in the flow. Typical cascade impactors consist of up to ten stages in which different size of aerosols are being separated. This paper presents a simple model for the flow in one single stage of a cascade impactor. Flow inside cascade impactor is approximated by stagnation point potential flow with the stream function of Psi = Axy, and particles are tracked by velocity verlet algorithm. Absorbed particles are associated with unit value; otherwise they are associated with zero. It is assumed that particles in entrance have random size distribution and location. Drag, Saffman and Brownian forces are taken into account in this model for different particle sizes. The results are discussed in detail and compared with data driven from different approaches in the literature.