API Scale-up Roundtable: What we learned about the solid-state characterization of drug substances

This year, we want to shed some light on the many ways analytical tools can help process development scientists and engineers improve their process for solid-state characterization of drug substances. As part of this we have launched a webinar series API Scale-up Strategies. Through this series we’ll explore the broad range of analytical solutions that have successfully applied to predict which APIs will remain efficacious and maintain their quality when scaled-up.

To kick us off, I was joined by my colleagues Dr Anne Virden, Dr Kuo-Chih Shih, and Dr Lieven Kempenaers for a roundtable discussion. Don’t worry if you didn’t catch the live event – I’ve summarized the key takeaways for you below and you can view the full recording of the event on our website any time that suits you – you’ll find the link to the recording below.

Meet the API Scale-up panel

• Dr Anne Virden Product Manager for micromaterials, specializing in image analysis and laser diffraction
• Dr. Kuo-Chih Shih, Senior Field Applications Scientist Pharmaceutical Sciences, specializing in X-ray diffraction, small-angle X-ray scattering , laser diffraction and dynamic light scattering
• Dr. Lieven Kempenaers, Product Manager for X-ray fluorescence
• And of course myself, Dr Natalia Dadivanyan, Sector Marketing Manager (Small Molecule Pharmaceuticals) and previously Application Scientist specializing in X-ray diffraction and scattering techniques

Challenges in API scale-up

To kick off, our experts’ panel has discussed three of the main challenges in API development:

1. Particle size and shape: Dr. Anne Virden highlighted the importance of particle size and shape in the quality of APIs. She explained how these factors affect dissolution, bioavailability, and processability.
2. Crystallization and polymorphism: Dr. Kuo-Chih Shih discussed the challenges of efficient crystallization and the importance of polymorphism. He explained how these factors can impact the bioavailability of the drug.
3. Purity: Dr. Lieven Kempenaers discussed the importance of purity in API development. He highlighted the need for effective purification steps and the challenges of ensuring no catalyst residue is left during process optimization and scale-up.

Solutions to API scale-up challenges

The panel then discussed potential solutions to these challenges:

1. Assessing particle size and shape

As a recognized expert on laser diffraction, Anne provided an overview on the use of laser diffraction and automated image analysis for assessing particle size and shape. Particle size distribution of an API is a critical material attribute, affecting not only the bioavailability of the material but also its processability.  She explained how using laser diffraction will help you achieve your broader objectives, such as meeting bioavailability goals or ensuring the drug substance will pack together with excipients.

Anne also explained that elongated particles don’t flow as easily, or pack together as efficiently as spherical ones. She went on to explain that making confident decisions about material performance therefore requires a thorough analysis of particle shape data and explained how automated image analysis and the Morphologi 4 provides statistically significant particle size and shape data. 

2. Addressing crystallization and polymorphism

Drawing on his experience supporting customers in the pharmaceutical industry, Kuo-Chih talked about the use of X-ray diffraction (XRD) for addressing challenges related to crystallization and polymorphism. He explained how XRD helps process development scientists and engineers to fingerprint various polymorphs and identify and quantify polymorphic impurities as well as measure crystallinity.

Highlighting the wide adoption of Aeris, Compact XRD by pharmaceutical companies BIG and small, he explained that you don’t need a crystallographic background to become expert in measuring and analysing polymorphic composition and measure crystallinity, thanks to plug-and-play simplicity of Aeris.

We also heard from Anne how Morphologically-Directed Raman Spectroscopy (MDRS) is an increasingly popular tool in the pharmaceutical industry for determining the polymorphic form of each particle and link particle shape to polymorphic form.

3. Ensuring Purity

Lieven, a leading expert on X-ray Fluorescence technology, explained how XRF is becoming a viable alternative for ICP in the pharmaceutical sector. He explained how XRF can help identify residue catalysts, byproducts, salts, and other chemical impurities that may emerge during chemical reactions.

Like many of our customers, Lieven is particularly excited about our latest development in XRF technology: Revontium. The world’s first compact XRF system, Revontium is an energy-dispersive (ED) XRF spectrometer that allows you to: 

• Accelerate your drug development process and significantly shorten route to market  
• Perform fast, non-destructive, and robust screening for elemental purity 
• Achieve high sensitivity in a compact, safe and environmentally sustainable way  

We also heard from Anne how MDRS can help you detect and identify contaminants on a particle level.

Q&A Session

We concluded the webinar with a Q&A session, where the panel addressed questions from the audience on various topics, including the use of laser diffraction for assessing particle shape, the detection limits of XRD, the use of XRF for  analyzing byproducts, and the importance of measurements during scale-up.

Discover the API Scale-up Strategies webinar series

Want to learn more? Here’s the schedule for the full series of four webinars, all taking place at 16:30 CET and all available on-demand following the live broadcast:

Webinar	Live broadcast	Watch on-demand
Roundtable – Navigating Challenges in API Solid-State Analysis with Industry Experts	June 12, 2024	View the recording here
Perfecting Particle Size and Shape – Solid-State Analysis for Optimal Processability	June 27, 2024	View the recording here
Crystallization Command – Tools for Controlling Polymorphism & Crystallization	July 16, 2024	View the recording here
Eliminating Impurities – Eliminating Contaminants Through Solid-State Analysis	July 25, 2024	View the recording here