Welcome to Part 2 of our series on managing API particle size. (You can find Part 1 here.) Today we’re talking about some of the new and emerging technologies that can impact API particle sizing. We also discuss in this post how Neuland successfully manages API particle size distribution projects.
New Technologies at Work
As technology continues to develop, there are several new and emerging inventions and methods that can successfully and consistently impact and manage particle size for active pharmaceutical ingredients. Here are four methods which are not only showing promise but delivering on that promise.
1. PAT/FBRM
Process analytical technology (PAT) such as focused beam reflectance measurement (FBRM) is one of the emerging technologies used to monitor the particle size and chord length distribution online during crystallization. When technology can successfully measure and manage crystallization, companies can speed up the work of creating APIs and get consistent results. Specifically, the Blaze Matrix PAT tool is useful for identifying polymorph transitions and morphology changes during crystallization.
2. Nanotechnology or nanosizing
Nanotechnology refers to manipulating atoms and molecules at nanoscale. Currently, many pharmaceutical contract manufacturers tackle the problem of low solubility by reducing the particle size of an API using micronization techniques. However, the demand for further improvements in drug dissolution has led to a shift from micronization to nanonization, as this technology significantly improves bioavailability and therapeutic efficacy.
Some techniques used to produce nanoparticles with precise particle sizes include high-pressure homogenization, nanoprecipitation, and spray-drying. At Neuland, we currently use homogenization and spray-drying to achieve lower particle sizes.
3. In-line manufacturing and control
The in-line manufacturing process gives CDMOs the ability to conduct continuous and real-time quality assurance and control (QA/QC), which facilitates immediate adjustments during the manufacturing process. This ensures consistent particle size and improves the overall quality of the final product.
4. Artificial intelligence (AI) and machine learning (ML)
Artificial intelligence (AI) and machine learning (ML) are the newest techniques to manage API particle size. For example, a study published in Pharmaceutics included a list of ways AI and ML are currently being used in pharmaceutical product development.
One of the ways listed is using AI models for particle swarm optimization to optimize particle size distribution, dissolution profiles, and other formulation parameters. Another technique the study explores is artificial neural networks, which use AI/ML to predict the release behavior of active pharmaceutical ingredients (APIs) of various particle sizes under various conditions..
How does Neuland successfully manage API particle sizes?
Neuland’s capabilities have helped our teams successfully manage several complex particle size distribution projects. Depending on the project and the materials, we use different strategies to make sure the particle size results in an end product with the characteristics desired by our customers.
In response to the growing need for tighter control over particle size, we launched a dedicated particle engineering lab. This lab contains facilities for crystallization development to achieve desired particle size and polymorphs for NCEs and APIs. It also contains particle size reduction equipment for both dry and wet milling as well as for micronization. The Neuland team has completed several projects that required a specific particle size and distribution. These successful projects necessitated the use of all three of the above-mentioned size reduction methods. We’ve also adopted the latest particle size engineering technologies, including implementing inline and online particle size meters as well as the latest crystallization techniques.
Neuland’s scientific team has conducted particle engineering studies using micronization for products such as Indacaterol maleate (D(90) less than 5 microns) and Ticagrelor (D(90) less than 10 microns). In another project, data generated from experiments with the compound Levetiracetam were used to optimize process conditions to meet the PSD requirement prior to kg scale production.
At Neuland, one of our unique strengths is our expertise in particle size reduction. Some of the particle size reduction techniques we use most often are the hammer mill, comill, multimill, wet mill, and air jet mill. Some products will have specific characteristics such as morphology, bulk density, and flowability crystal habit. Because of these characteristics during development, the lab will thoroughly study the suitable milling techniques and ensure that they can be optimized for scale-up.
We thoroughly study the solubility profile and generate the meta stable zone width (MSZW). Based on the solubility data we often perform various crystallization techniques such as cooling, evaporative, antisolvent, and reactive crystallizations to achieve the desired particle size. If crystallization does not provide the desired properties, then we use various size reduction techniques such as pin milling, hammer mill, comill, multimill, wet mill, and micronization to achieve the desired particle size, flowability and bulk density.
Have specific questions about how Neuland Labs can help you ensure the correct API particle size? Contact us to learn more.
