Enhancing Particle-Size Measurement Using Dry Laser-Diffraction Particle-Size Analysis - Pharmaceutical Technology

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Enhancing Particle-Size Measurement Using Dry Laser-Diffraction Particle-Size Analysis
The author examines dry dispersion and outlines the related analytical method development.

Pharmaceutical Technology
Volume 37, Issue 5, pp. 60-63

Understanding the mechanisms of dry dispersion

The interparticle forces that bind particles together include van der Waals forces, electrostatics, and liquid bonds. As particle size decreases these forces become stronger, thereby making dispersion tougher for finer materials. In dry dispersion, the mechanisms that can be applied are, in order of aggressiveness:

  • velocity gradients caused by shear stress
  • particle to particle collisions
  • particle to wall collisions.

The design of the disperser used dictates which mechanism is applied during measurement. The disperser geometry shown in Figure 1 (a), for example, has no impaction surfaces. As sample drops down from the sample tray into the funnel, it is entrained into the compressed air, which enters at right angles to the powder. Dispersion is achieved by accelerating the particles through the venturi into the measurement zone through the application of shear and as a result of particle–particle collisions. This design is, therefore, suitable for relatively fragile particles.

Figure 1: The design of a disperser in a laser-diffraction system defines its flexibility for dry-powder measurement. Figure 1 (a) shows the design suitable for more fragile samples. Figure 1 (b) shows the impaction dispersion mechanism required to handle robust, cohesive powders. (ALL FIGURES ARE COURTESY OF THE AUTHOR.)
In the alternative, high-energy venturi shown in Figure 1(b) the inclusion of a 90-degree bend creates an effective impaction zone that brings the third dispersion mechanism into play. For highly cohesive materials, this impaction is a useful strategy, but only if the particles are sufficiently robust to withstand the applied forces.

The latest laser-diffraction systems (e.g., Mastersizer 3000, Malvern Instruments) offer multiple dispersion-configuration options that streamline the use of different geometries to allow users to apply alternative set-ups for different materials. By simultaneously enabling precise control of the powder-feed rate and the pressure of the compressed air, such systems enable the manipulation of dispersion to achieve robust dry measurement for a wide range of sample types as illustrated in the following case study.

Case study: Identifying an optimal dry dispersion method for a lactose-based formulation

In an experiment to identify the optimal method for the dry measurement of a lactose-based formulation, various tests were carried out using a dry-dispersion engine (Aero S, Malvern Instruments) of a laser-diffraction system (Mastersizer 3000, Malvern Instruments), which can be configured with either a standard (see Figure 1[a]) or a high-energy (see Figure 1[b]) venturi geometry. With both dispersers, a standard pressure titration was carried out; that is particle size was measured as a function of the pressure of the compressed air used for dispersion. In addition, a wet dispersion of the formulation was measured to set a baseline for the evaluation of dry methods.

Figure 2: Pressure-titration data for a lactose formulation shows close agreement between the wet (blue) and dry measurement obtained with a compressed air pressure of 3 bar with (a) the standard venturi (upper plot) and at 1 bar with (b) the more aggressive venturi (lower plot). US refers to after ultrasound; HE refers to high energy.
Figure 2 shows the pressure-titration results for both venturis with data sets overlaid for dry and wet measurement. These results indicate that with the standard design, agglomerates are still present at air pressures in the region of 0.5 to 1 bar. A pressure of 3 bar is required for complete dispersion and to achieve close agreement between the wet and dry data.


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