Conor Evans, PhD, an Associate Investigator at the Wellman Center for Photomedicine at Massachusetts General Hospital and Associate Professor at Harvard Medical School, is senior author of a new study in the journal Analyst, Quantitative Analysis of Drug Tablet Aging by Fast Hyperspectral Raman Scattering Microscopy.


It can be challenging to measure how drugs and inactive ingredients, also known as excipients, are packed into drug tablets. This information is crucial in both creating tablets with reliable drug release profiles as well as in assuring batch-to-batch quality. This technology can help companies build better drug products for patients.

What Question Were You Investigating with this Study?

Inspired by challenges in the manufacturing and storage of solid oral tablets, our multidisciplinary team developed a new, rapid method of imaging and quantifying the drugs and inactive ingredients within tablets.

This work will be published in the Royal Society of Chemistry’s journal Analyst and is featured as its cover article.

What Was Your Approach?

The method we developed provides direct “chemical” imaging of tablets at sub-micrometer resolution via a novel Stimulated Raman Scattering method.

Existing Process Analytical Technology tools are either too low in resolution to make out each grain or too slow to be used for routine imaging.

This new approach, coined “S4RS” can make use of a special laser by Refined Laser Systems to “jump” across the vibrational spectrum to create precise chemical maps of drugs and excipients in a fraction of the time of other methods. This advance can be translated for formulating tablets as well as for rapid quality control.

In most chemical imaging methods, mapping and quantification of drugs and inactive ingredients is accomplished by acquiring high-resolution optical spectra at each and every location in a tablet.

The industry-standard method known as near-infrared spectroscopy does this well, but has inherently low imaging resolution that can make it blind to the tiny particles that pack within tablets, meaning that it can miss key details and interactions crucial in building oral dosages for patients.

The other major technique, spontaneous Raman scattering, is an extremely weak process, such that imaging a single tablet can take hours or days – far too long for routine quality inspection.

S4RS solves these challenges in two ways: First, it has considerably better imaging resolution, down to hundreds of nanometers, to see even the smallest grains of drugs and excipients.

Second, instead of painstakingly acquiring a full optical spectrum at each location, it “jumps” to only the most important points in the spectrum to acquire only the information needed to map each grain.

This allows for imaging at tens to hundreds of times faster than current methods without losing chemical information.

What Were the Results?

Of major importance, the team was able to demonstrate mapping degradation in tablet content and structure under aging and stress conditions, a step that could be used to assess crucial gaps in the industry’s understanding of drug storage and drug expiration. This work is part of the Evans team’s long-term program in mapping drugs and their effects (pharmacokinetics and pharmacodynamics) using chemical imaging.

What are the Implications?

Immediate applications for this S4RS method include its use for formulating tablets, where drug manufacturers determine the granulation, blending, and mixing parameters to build high quality, consistent drugs with well-defined drug release profiles. The same approach can also be used for quality control to check the consistency of tablet manufacturing between batches.

What are the Next Steps?

Beyond the lab, the team’s aim is to partner with industry to translate this technology out of the lab and into practice. This approach can become a process analytical technology tool in the formulation and quality control of solid oral tablets.

Paper Cited:

Wei, Y., Pence, I. J., Wiatrowski, A., Slade, J. B., & Evans, C. L. (2023). Quantitative analysis of drug tablet aging by fast hyper-spectral stimulated Raman scattering microscopy. The Analyst, 10.1039/d3an01527k. Advance online publication.

About the Massachusetts General Hospital

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The Mass General Research Institute conducts the largest hospital-based research program in the nation, with annual research operations of more than $1 billion and comprises more than 9,500 researchers working across more than 30 institutes, centers and departments.MGH is a founding member of the Mass General Brigham healthcare system.