How Do You Analyze Particle Size? Understanding Particle Size Distribution and Analysis Requirements

The performance, quality, and traits of particulate materials can be determined by particle size. Powders, aerosols, emulsions, and suspensions are an example of this. For instance, the shape and dimension of powders can indicate their compaction and flow strengths. Larger, rounded particles tend to have better flow than smaller ones. However, smaller particles mix quickly and increase suspension viscosities. Droplets of powder measuring 2-5µm can disperse rapidly and enter the lungs better than larger particles. That's why studying particle-size distribution (PSD) is essential. It also helps identify the suitable size of a particle for a specific purpose and put it through different processes accordingly, such as emulsification, crushing, microfluidization, homogenization, etc, while monitoring changes. Particle size also comes in handy with separation techniques, such as cyclones, filtering, and screening.

·         Particle size analysis

Particle analysis is a critical step in ascertaining the particle sizes. After analyzing the sizes, users can report the outcomes in many ways. Some researchers only want to know the average size; however, expert scientists look for central distribution points and other values to report distribution width. Almost all biotherapeutics feature 2 to 100 µm of subvisible particles in several shapes and quantities. Still, particle size is emphasized more in particulate samples because it influences a product's success. Through distribution analysis of the particle sizes, one can learn about particle size variation and volume in a drug represented as a frequency distribution graph. A more significant number of particle diameter calculations create a bell curve, where the x-axis stands for the particle size and the y-axis signals the frequency of the specific particle size.

The process covers some statistical parameters, such as mode, mean, and median. Mean is the population size; median or middle size shows two varying population sizes—one above and the other below; and mode is the commonly occurring particle size. The shape of the bell curves can vary, and each shape can help with particle characterization in a product. Mode, mean, and median give insight into that shape.

·         Particle size analysis techniques

Multiple options are available. However, dynamic light scattering (DLS), Laser diffraction, and Sieving are most popular.

1.      DLS

It is a unique method representing the mean value of the Z average or intensity distribution and PDI or the polydispersity index to reveal distribution width. If you know your sample’s refractive index, you can distribute volume from intensity. During the analysis, millions of particles are randomly passed through a camera for a quick examination for size and shape specifications.

2.      Laser diffraction

This analysis procedure is also known as static laser light scattering (SLS). The process checks the particles’ scattered laser light intensity distributions. However, the size is analyzed indirectly. Through this process, one can discover that larger particles spread the light in small angles while smaller ones do this in larger angles. The main downside of this method is the lack of shape evaluation, as it considers all particles spherical-shaped. Sensitivity and low resolution can also hinder the sample's efficiency. Still, you may use this method in specific scenarios if you find it helpful.

3.      Sieving

This traditional particle size evaluation method uses woven-wire mesh sieves with desired pore sizes. Various sieves form the stack, each having an increasing aperture size. Due to this, the sample is placed in the uppermost large sieve. A mechanical process starts to shake the sample in the sieve shaker to help the particles reach the smallest aperture. The application of this method depends on the aperture sizes. While it's an old method, several labs resort to Sieving. Some common challenges faced with this particle size analysis technique include data transfer errors, overloading risks, and time-consuming steps of weighing, sieving, cleaning, etc.

·         Particle size analysis equipment or devices

These tools can be complex, from simple mesh designs to electron microscopes. For example, laser diffraction size analyzers can offer detailed accounts of particle sizes. Different instruments and techniques will affect measurement accuracy. More accurate results demand the use of sophisticated processes and methods. When dealing with samples containing bigger homogeneous particles, you can easily rely on sieve analysis.

Conversely, complex biotherapeutic formulations involving various particle size distributions will be ideal to tackle with more advanced systems. In this context, it helps to know that DLS can track particle sizes down to 0.3 nm and laser diffraction to 10 nm. Remembering this point is crucial because every method faces particle size limitations, reducing their ability to evaluate all types of visible and subvisible particles.

Determining the precise particle size division through proper analysis in medicine and life sciences is crucial to ensure product quality and consistency. Otherwise, the active ingredient in the drug will face difficulty with entering the targeted body part in an adequate concentration. Too large particles can be challenging to inhale and get trapped in the throat. Simultaneously, particles that are too small can quickly disperse before entering the lungs. However, the right-sized particles are less likely to interfere with the gastrointestinal tract and can do their intended job effortlessly. Additionally, distributing particle size is necessary to manufacture a good drug because it can affect a tablet's efficiency in remaining intact and its shelf life.

·         Distribution analysis issues and solutions

There are two main obstacles – regulatory requirements and the complexity of biotherapeutic formulations. At the same time, one must be able to manufacture premium drugs with the lowest rejection rates or losses. To comply with the FDA and USP standards, you can remove the sample's subvisible particles for higher resolution. Why should you do this? It allows you to use systems and processes that can detect particle sizes to a minimum of 5 µm. So, choose your technique accordingly. Plus, particle shape is also a critical factor. If you assume all particles are round-shaped, your chances of making an error will be high, and achieving accuracy will be dismal. Typically, light-diffusion processes provide particle shape characterization. Hence, it can be worth considering them.

Cells, genes, proteins, vaccines, and other complex biotherapeutics are becoming the mainstay in medicine due to their efficacy and target orientation for several diseases that were earlier challenging to treat. However, these advanced solutions depend on accurate particle size results for their safety and quality. That’s why manufacturers and regulators seek trustworthy particle size analysis systems.