When it comes to pharmaceutical development, you are always seeking ways to know what is actually going on with your formulations. The slightest of impurities, disproportional coating, or alterations in how active pharmaceutical ingredient (API) is distributed can influence the performance of a drug. Time-of-Flight Secondary Ion Mass Spectrometry provides an opportunity to view these details explicitly and on a very small scale.

Below, we discuss how ToF-SIMS can assist you in identifying impurities, analyzing API distribution, and learning about drug product chemistry.

Detecting contaminants at minimal doses

The smallest contaminant can make a huge difference in the field of pharmaceuticals. It could be a factory pollutant, packaging pollutant, or processing pollutant. ToF-SIMS enables you to identify these components at incredibly low concentrations. In most cases, you cannot see them with other methods.

ToF-SIMS only analyzes the layers closest to the surface. Hence, it proves particularly helpful when you need to:

• Check unwanted residues on tablet coatings.
• Confirm that cleaning procedures actually removed what they are supposed to.
• Test the surfaces of devices, such as inhalers or patches. This helps to identify trace contaminants.
• Find chemical species that occur in storage or aging.

The process helps you to observe the chemical fingerprints behind a problem rather than speculating.

Learning about API distribution in formulations

When working on solid oral dosage forms, patches, implants, or other products, the API should be well distributed. ToF-SIMS analysis provides you with a detailed image of the location of the molecules.

It can be used to visualize API location in surfaces such as:

• Tablet coatings
• Film layers
• Polymer matrices
• Transdermal systems
• Microspheres or drug-delivery particles.

In some cases, you will have an API that appears to build up in a particular area, or that reacts with an excipient in a manner that you did not anticipate. Since ToF-SIMS offers chemical maps, you can visualize patterns of distribution.

Such information may assist you in knowing:

• Performance concerns
• Stability issues
• Unpredictable release problems.

Studying the interaction of drugs and excipients

The role of excipients is greater than usually perceived. They are capable of stabilizing APIs. But they may also give undesirable interactions. ToF-SIMS can assist you in studying these interactions on a surface scale, where many of the initial reactions occur.

You might use it to look for:

• Migration of plasticizers.
• Surface enrichment of additives.
• Long-term degradation patterns.
• Unexpected ion formation.
• Mixing or separation within layered systems.

This will assist you in making improved decisions in formulation and in solving problems before they become costly failures.

A closer look at stability and aging

When pharmaceutical products are stored on shelves or subjected to stress tests, their surfaces may vary. You can use ToF-SIMS to monitor chemical shifts that can influence performance, including:

• Oxidation.
• Moisture-related changes.
• API crystallization.
• Excipient breakdown.

These minute changes are usually manifested first at the surface. Hence, surface-sensitive methods prove to be of great value.

The bottom line

In the end, ToF-SIMS gives you:

• A high sensitivity to impurities.
• Accurate API distribution maps.
• Surface insights that complement other analytical methods.
• Data that facilitates quality, safety, and performance.

In case you require a closer examination of the action on the surface of your formulation, ToF-SIMS will provide the much-needed clarity.