Integrating Molecular Modeling and Nanoemulsion Characterization for Ibuprofen

Ibuprofen (IBU), a widely used nonsteroidal anti-inflammatory drug, exhibits low aqueous solubility and polymorphic behavior, which can compromise its bioavailability and pharmaceutical performance. This study investigated the structural, electronic, and supramolecular properties of two polymorphic forms of IBU and assessed their influence on the development and performance of emulsion-based delivery systems. The solid-state description included Hirshfeld surface analysis and the quantum theory of atoms in molecules complemented by density functional theory and electronic reactivity descriptors. Two formulations, an emulsion (EM-IBU) and a nanoemulsion (NE-IBU), were prepared and characterized by droplet size, polydispersity index, zeta potential, density, and drug content via mass spectrometry. Compared to EM-IBU, NE-IBU exhibited a considerably smaller particle size (31.3 ± 0.3 nm vs 235.4 ± 4.3 nm), a lower polydispersity index (0.23 vs 0.16), a more negative zeta potential (-25.8 vs -22.1 mV), and a higher density (0.989 vs 0.967 g cm^-3). These quantitative results demonstrate superior colloidal stability and a wider pH stability range for NE-IBU, confirming its physicochemical robustness and pharmaceutical potential for hydrophobic drug delivery.