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


IMAGE COURTESY OF THE AUTHOR
Across the pharmaceutical industry, laser-diffraction technology is well established for particle-size measurement. Laser diffraction is an efficient method of particle sizing and lends itself to automation as evidenced by the ready availability of highly automated laboratory instruments and real-time sizing technology for pilot and commercial scale applications. Ongoing advancement of the technique offers considerable benefits to the pharmaceutical industry with recent extensions of the application of dry-powder measurement an especially useful innovation.

Although dry particle-size measurement is particularly beneficial for moisture-sensitive materials, it also offers wider efficiency and environmental advantages. Maximizing the use of dry measurement enhances instrument productivity through rapid measurement and cleaning while at the same time minimizing the waste-disposal issues associated with the use of dispersants in wet measurement. Dry measurement, however, relies on being able to efficiently disperse the sample, without causing particle damage, in order to access accurate primary particle-size data. This dry dispersion can be particularly challenging for some of the fine and fragile materials routinely handled by pharmaceutical manufacturers.

In this article, the author contrasts the benefits and limitations of wet- and dry-sample preparation by focusing on the benefits of dry dispersion. The mechanisms that give rise to agglomerate break-up are discussed with reference to different designs of the dispersion unit, and experimental data are presented to show the suitability of different dispersion environments for different types of material.

Preparing samples for particle-size measurement

One of the attractions of laser-diffraction particle-size measurement is that sample-preparation requirements are minimal. That said, it is vital that the particle-size data measured are fully relevant to the application. In some instances, it is the size of particles present in the raw sample that is of interest perhaps because of the need to investigate process performance or to evaluate the agglomeration of a fine material during storage. More usually, however, it is the need for primary particle-size data that drives analysis because particle size defines important attributes such as solubility and bioavailability. This requirement makes it essential to disperse the sample prior to measurement, to break up any agglomerates or aggregates present and ensure that discrete particles are reliably introduced into the measurement zone of the instrument. There are two possible approaches: wet or dry dispersion.

Wet measurement involves the production of a stable suspension using a suitable dispersant. The choice of dispersant will depend upon the solubility of the material to be analyzed; therefore, water-soluble materials often require a suitable organic dispersant. Ultrasound is often applied, in combination with defined levels of agitation, to achieve a homogeneous suspension, and in some instances, additives also will be required for stabilization and wetting. The most advanced laser-diffraction instruments allow wet measurements to be made on very fine powders with particle-size distributions extending down to 0.01 micron in size.

The dispersion mechanisms applied in wet measurement, although effective, are relatively gentle, which means wet measurement can be successfully used for even the finest and most fragile of particles. Wet dispersion is useful for establishing a baseline against which the success of dry dispersion can be judged. The less appealing aspects of wet measurement are that it takes longer than the dry alternative and produces waste in the form of used dispersants and additives. The time required and the production of waste are particular drawbacks for polydispersed samples, where the volume of sample must be large to ensure representative data for every size fraction.

With the latest laser-diffraction instrumentation, dry-powder dispersion can be applied to materials in the particle-size range 0.1 to 3500 microns. The widest possible use of dry dispersion maximizes the productivity of a laser-diffraction analyzer, simultaneously minimizing environmental impact. The challenge, however, is to apply sufficient energy to deagglomerate the sample without causing primary particle damage. Using dry measurement, the sample is dispersed into a compressed air flow. Increasing the pressure of this air makes the dispersion process more energetic, but the design of the disperser is crucial in defining the aggressiveness of the dispersive action. The breadth of samples for which dry measurement is feasible with a given particle-size analyzer, therefore, directly depends on the design of the dry disperser.


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