Revealing hidden molecular nanostructure details in the pellet formulation of ibuprofen by combining Synchrotron and laboratory sources

A. Hodzic*, G. Birarda, K. Juraic, P. Sket, S. Eder, M. Kriechbaum, F. D'Amico, O. DeGiacomo, E. Roblegg

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Previous studies could report about different behavior of dried pellets at the 50°C due to the lack of constant rate period of drying. Now, one step further, the synchrotron (i.e. FT-IR, SWAXS) supported with laboratory sources (SWAXS, NMR) allowed deeper analytics reporting hidden partly molecular degradation invents from the frequently used drug ibuprofen in 4-isobutylacetophenone, and that molecule is no longer a drug but a toxic one. In the medication matrix CaSt was no degradation detected but the structural undulation seen with SAXS was also confirmed by FT-IR. However, we also show that a medical molecular degradation in their solid formulation could be detected and predicted not only by chemical analytics but also correlated and identified by a physical method based on X-Ray inner surface calculation. Such molecular degradation from active pharmaceutical ingredients (API) that occurs in the process of drug preparation in solid formulation can automatically be correlated with drug-dissolution. Thus, the Nano-analytical parameters based on the Small Angle X-Ray scattering (SAXS) signals of different electron densities in the material, identify the specific surface area, which could be seen even in closed pores and can be correlated with drug molecular degradation. As an example, is taken a very well-defined pellet solid ibuprofen calcium-stearate formulation. Using a synchrotron and a laboratory multi-technical package, we could reveal hidden nanostructures and molecular information, which have not been detected in previous studies. The Small and Wide X-Ray Scattering (SWAXS) spectra of pellets show that process variables do not affect the crystalline state of components but slight changes in the crystal lattice undulations (i.e., SAXS). Additionally, using the high-resolution NMR, Raman and Synchrotron-beam line FT-IR method, we can identify the molecular partial degradation of the Active Pharmaceutics Ingredient (API) in 4-isobutylacetophenone only at 50 °C in terms of the drying and preparation-condition. Such molecular degradation could not be detected in previous study due to the lack of high-resolution analytical laboratories and synchrotron tools that we were able to apply in this paper. For this sample also SAXS specific surface area display higher values and can be correlated as an indication and prediction for the molecular degradation but also dissolution due to increase of electron density contrasts. In general, such analyzes are helpful for the detection in time before the product comes on the market. Thus, we propose the idea of additional high-resolution multi-techniques i.e. Synchrotrons and new methods to become more common for revealing hidden medical molecular degradations, which can induce non-therapeutically but side effects.

Original languageEnglish
Article number103114
JournalJournal of Drug Delivery Science and Technology
Publication statusPublished - Feb 2022


  • Crystallinity
  • Nuclear magnetic resonance
  • Powder
  • Purity
  • Small-angle X-ray scattering
  • Solid-state drugs

ASJC Scopus subject areas

  • Pharmaceutical Science


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