Why Is It Important to Measure API Size Distribution?

 

 

Pharmaceutical development is a long and often arduous process, ranging from the steps necessary to identify a new active ingredient to the clinical trials that can take years to complete. Taking an active pharmaceutical ingredient (API) and turning it into something suitable for human use isn’t easy, especially considering that these ingredients are often measured in particle size.

 

By Emily Newton

 

Why is it essential to measure API size distribution? What impact can these particle sizes have on API safety and efficacy? Here’s what’s vital to know.

 

Defining Particle Size Distribution

 

Particle size distribution (PSD) measures the particle in a drug according to size. Researchers use laser diffraction, sieve analysis, image analysis or dynamic light scattering to count the number of particles and collect data about them.

 

The precise measurement will depend on the shape — spherical particles are measured by their diameter, while square ones might be measured by length and width. Unfortunately, these measurements can be difficult and time-consuming, so in many cases, all particles are assumed to be spherical and measured by their approximate diameter.

 

The Particle Size Bell Curve

 

API measurements usually fall on a bell curve, marking the particle size on the x-axis and the frequency it occurs on the y-axis. Researchers can use three D-values along this curve to calculate particle size and density within a given sample — D50, D10 and D90.

 

The D50 value indicates the average particle size within the sample, with approximately 50% of particles being more significant than this value and 50% smaller. D10 measures that 10% of a sample’s particles are smaller than this criteria, while a D90 indicates that more than 90% are more diminutive.

 

The tighter the data grouping between these three values, the more uniform they are in a particular sample. Uniformity doesn’t always guarantee optimal distribution because that variable depends on other factors and the drug’s production details. Still, uniform particles are easier to manage regarding quality control and production.

 

What Can Particle Size Distribution Impact?

 

The size, quality and distribution of API particles can impact various factors, including:

 

●     Ease of manufacture

●     Drug efficacy

●     Quality

●     Bioavailability

●     Shelf life

●     Yield

●     Production

●     Profits

 

Incorrectly sized particles can interfere with effective absorption. For example, inhaled mediation needs a very carefully chosen particle size. If it’s too small, it gets carried out on the exhale before the lungs can absorb it, and if it's too large, the particles get lodged in the throat and don’t offer the same therapeutic effect. It can also impact the bioavailability of the drug or the body’s ability to absorb and use the substance.

 

Not all APIs require a specific particle size for bioavailability, but obtaining or maintaining a particular size can be vital for ease of manufacture and quality control. Once established, these processes aim to create a product with the same quality and efficacy every time.

 

Particle Size Distribution Methods in Pharmaceuticals

 

Traditionally, physicians could use simple tools like a mortar and pestle to grind APIs to the proper size. While effective, they don’t deliver the uniform results necessary to comply with quality control requirements. Instead, pharmaceutical companies rely on various milling and grinding techniques to provide the same results every time.

 

These distribution techniques include:

 

●     Cryogenic grinding, which reduces the temperature of the grinding process to protect temperature-sensitive components.

 

●     Micronization, which uses fluid jets to break down particles into micron-sized parts. It’s effective, but only functional for a small class of drugs.

 

●     Pulverizing, which uses an automated hammer to break components down. In addition to measuring API size, it's helpful when crushing broken or poorly formed tablets.

 

●     Conventional milling, which uses a cone-shaped millstone to grind materials down to the target size.

 

Evolving Technologies

 

Measuring API size and the concept of size distribution measurement aren’t new, but the technologies haven’t changed much in the last decade or two. Adopting new and evolving methods can help make the process more efficient and effective. Artificial intelligence and machine learning are swiftly becoming invaluable tools in the pharmaceutical industry.

 

These systems are unparalleled when it comes to data collection and processing. They can sort through and catalog large amounts of information in a fraction of the time it would take a human analyst or researcher. Studying data collected by previous experiments allows an AI or machine learning system to find patterns and even identify new APIs for further experimentation in the future.

 

Measure API Size to Create a Healthier Future

 

Measuring API size distribution is vital for more than just determining particle sizes. Size and distribution can impact everything from manufacturing to the final product’s efficacy and effectiveness in the patient’s body. Even minor errors can be dangerous, so implementing a comprehensive measurement system and adopting new technologies like AI and machine learning to assist with the process can go a long way toward creating a healthier future.

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