Amorphous solid dispersions have been widely used as an effective formulation strategy in the oral delivery of poorly soluble drugs. However, one of the main challenges in the development of amorphous drugs is to maintain their physical stability. The underlying mechanism of amorphous drugs crystallized in polymeric matrices is still poorly understood. Herein, we report the phenomenon of polymer enrichment at the crystal–liquid interface during the crystallization of griseofulvin (GSF) containing poly­(ethylene oxide) (PEO). Confocal Raman microscopy, scanning electron microscope (SEM), and energy-dispersive X-ray spectroscopy (EDS) are employed to reveal the heterogeneous distribution of GSF and PEO at the crystal growth front. The concentration of PEO in the polymer-rich phase at the crystal–liquid interface is determined by Raman spectroscopic analysis. At a given temperature, the crystal growth rates of GSF initially increase with increasing the PEO loading in the bulk and then reach a plateau at high polymer loadings. We propose that the crystal growth rates of GSF are predominantly controlled by the local concentration of PEO at the growth front rather than the overall bulk concentration. This study provides the direct evidence of physical mechanisms that contributes to the local phase separation occurred at the crystal–liquid interface, which governs the kinetics of crystal growth in amorphous solid dispersions. These results are important for understanding the crystallization behavior of amorphous solid dispersions and beneficial for the rational design of robust amorphous formulations.

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Phloretin (PHL) is an abundant dietary flavonoid possessing several pharmacological activities but with poor aqueous solubility and low bioavailability. Herein, two new cocrystals of phloretin-nicotinamide (PHL-NIC) and phloretin-isonicotinamide (PHL-INM) have been synthesized and characterized by various analytical methods. Two cocrystals exhibited different crystal packing and intermolecular interactions. Strong photoluminescence was observed in the PHL-NIC cocrystal while not in the PHL-INM cocrystal and pure PHL. Density functional theory (DFT) calculations were conducted to interpret the distinct photoluminescent behavior between the cocrystals. Both cocrystals exhibited enhanced dissolution performance in comparison with the pure PHL. This study demonstrates that cocrystallization is a powerful strategy to tune the physical properties of functional organic solids.

Metallofullerenes have attracted considerable attention as potential novel noninvasive high-relaxivity magnetic resonance contrast agents. However, the applications of metallofullerenes as stimuli-responsive biosensors to monitor biological processes are still scarce. Herein, manganese-fullerenes core–shell nanocomposites are prepared via a facile one-pot approach to achieve GSH-activatable magnetic resonance/fluorescence bimodal imaging functions. The nanocomposites initially have a FRET-induced quenched fluorescence, and water-resisting stimulated low T 1-MRI contrast. Upon exposure to GSH, collapse of the outer MnO2 shell led to reconstruction of the nanoprobes and subsequently resulted in multicolor fluorescence recovery and longitudinal (T 1) relaxivity enhancement (r 1 value up to 29.8 mM–1 s–1 at 0.5 T based on Mn ion). Our work demonstrates feasibility of using fullerenes to fabricate activatable probes for molecular imaging of GSH, which may promote the development of new fullerene-based stimuli-responsive multimodal probes for the detection and regulation of particular biological processes in vivo.

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