Molecular dynamics and physical stability of ibuprofen in binary mixtures with an acetylated derivative of maltose

Abstract

In this paper, we explore the strategy increasingly used toimprove the bioavailability of poorly water-soluble crystalline drugs byformulating their amorphous solid dispersions. We focus on the potentialapplication of a low molecular weight excipient octaacetyl-maltose (acMAL) toprepare physically stable amorphous solid dispersions with ibuprofen (IBU)aimed at enhancing water solubility of the drug compared to that of itscrystalline counterpart. We thoroughly investigate global and local moleculardynamics, thermal properties, and physical stability of the IBU+acMAL binarysystems by using broadband dielectric spectroscopy and differential scanningcalorimetry as well as test their water solubility and dissolution rate. Theobtained results are extensively discussed by analyzing several factorsconsidered to affect the physical stability of amorphous systems, includingthose related to the global mobility, such as plasticization/antiplasticization effects, the activation energy, fragility parameter, and thenumber of dynamically correlated molecules as well as specific intermolecular interactions like hydrogen bonds, supporting the latterby density functional theory calculations. The observations made for the IBU+acMAL binary systems and drawn recommendationsgive a better insight into our understanding of molecular mechanisms governing the physical stability of amorphous solid dispersions.