The structure of pharmaceuticals subjected to cryo-milling and compression

The dosage of pharmaceuticals produced in non-crystalline phases, such as nanoparticles or glasses, has a great advantage due to their better bioavailability and solubility than crystalline counterparts. The modification of pharmaceutical by mechanical perturbation, e.g., milling or compaction, may lead to the desired amorphization of the structure that resembles the structure of glass produced by the standard vitrification. However, mechanically-stressed pharmaceuticals often exhibit distinct functional properties from ordinary glasses. The origin of these differences can be traced to the structure at the atomic and supramolecular levels. In this project, we are going to reveal the nature of the structural disorder introduced by milling and pressurization for selected active pharmaceutical ingredients (APIs). The pair distribution function (PDF) is nowadays one of the most powerful tools to study the local structure and will be applied in this context for the amorphized APIs.