Influence of particle morphology and solvent choice on the sublimation of recrystallised ibuprofen at ambient pressure and sub-melting temperatures

Abstract

The tendency of ibuprofen to sublimate can undermine content uniformity and cause caking during storage, resulting in significant economic losses. While previous studies have predominantly investigated typical evaporation under vacuum, the solvent-mediated relationship between crystal structure, sublimation kinetics and thermodynamics under practical conditions remains unclear. This study aimed to determine how crystallisation solvent governs ibuprofen sublimation under ambient pressure and sub-melting temperatures, independent of particle size, by linking crystal structure and morphology to sublimation behaviour. Ibuprofen was recrystallised from hexane, acetonitrile, ethanol and methanol, with composition and structure verified using FTIR and PXRD. SEM and particle size analysis quantified morphology and surface area, while sublimation kinetics were measured by TGA and DVS under storage-relevant conditions and subsequently enthalpy of sublimation and change in vapour pressure by temperature were estimated. It was found that polar-solvent crystals have higher surface energy and faster sublimation, while non-polar-solvent crystals were more stable and slower sublimation. The obtained enthalpy of sublimation was lower for polar-solvent samples and estimated change in vapour pressure by temperature aligned with literature trends. Overall, crystallisation solvent is a critical determinant of ibuprofen sublimation under storage-relevant conditions, influencing plane orientation, crystallinity and morphology. Polar solvents promote faster dissolution and potentially enhanced therapeutic performance but increase sublimation risk, whereas non-polar solvents improve storage stability at the expense of dissolution rate. These findings provide practical guidance for optimising solvent selection to balance pharmaceutical performance, stability and manufacturing efficiency