Multiple techniques help scientists understand drug’s reaction to humidity

Posted by Nancy Lamontagne

You are likely familiar with the solid dosage form of pharmaceuticals, but you might know it better as a tablet. When developing tablets pharmaceutical companies analyze them carefully for performance. In fact, they study each polymorph of the active ingredient because each form may behave differently.

Craig A.J. Kemp and Michael J. Skibic of Eli Lilly and Company in Indianapolis, Indiana, turned to several microanalytical techniques to get to the bottom of a problem that was occurring in one form of a drug.

The Form C polymorph was chosen as the form of a drug to manufacture because it performed favorably in tests, but when it was exposed to high or low humidity it would transform into another polymorph. This might not seem like a problem, but when Form C transformed to Form B it then began to exhibit poor dissolution performance. However, Form B tablets exposed to high humidity did not have the suppressed dissolution performance.

The scientists used SEM/energy-dispersive spectroscopy (EDS), Tof-Sims, and X-ray micro-CT to study the tablets. The X-ray micro-CT images showed that intact tablets exposed to different humidity levels had a subtle difference in granularity. SEM and ToF-SIMS analysis showed that Form C tablets exposed to humidity formed “long needles,” but the Form B tablets did not show the same needles. EDS mapping revealed that the needles were made of the active ingredient. The ToF-SIMS data suggests that polysorbate 80 (a wetting agent) pools after exposure to moisture and this could impact dissolution.

Although the scientists have more analysis to perform, the various microanalytical techniques they used let them visualize changes in tablet structure, which helped them learn more about some of the changes brought on by humidity.