Description
Low aqueous drug solubility in pharmaceuticals is a pervasive issue. It is estimated that around 70% of pipeline drugs in development today are poorly soluble molecules. Amorphization and formation of solid dispersions using crystalline structures of active pharmaceutical ingredients is one of the most effective methods to enhance their solubility and bioavailability as well as to reduce side effects. However, different methods of the production (vitrification, milling, compression, solvation) of amorphous-like drugs and applied conditions (temperature, pressure, frequency) may affect their atomic-scale structure and yield different properties such as physical stability and solubility. Therefore, the characterization of the correlations between the preparation method, structure and properties is a prerequisite to the wider commercialization of amorphous-like drugs.
In this contribution, we would like to present our recent studies of the atomic and supramolecular structure of amorphous-like pharmaceuticals (such as ritonavir, probucol, itraconazole) using laboratory and synchrotron X-ray scattering methods, including high-pressure in-situ X-ray diffraction and pair-distribution function. The analysis of very subtle differences in the amorphous-like structures is supported by molecular dynamics simulations and modeling, vibrational and dielectric spectroscopy, and other complementary techniques. We will demonstrate that the amorphous like-phases, which give very similar, on the first sight, diffraction patterns, may significantly differ in the intermolecular architecture, degree of the local order and the size of coherent domains, H-boding pattern, and molecular conformations.
Authors acknowledge financial support from the National Science Centre (Poland), grant number: Opus 21 No. 2021/41/B/NZ7/01654, and the European Synchrotron Radiation Facility (ESRF), Grenoble, France, ID15B and ID22 beamlines (proposals: SC-5158, HC5404). The access to ESRF was financed by the Polish Ministry of Education and Science – decision number: 2021/WK/11.
