The low solubility and bioavailability of aqueous insoluble drugs are critical challenges in the field of pharmaceuticals that need to be overcome. Nanocrystal technology, a novel pharmacological route to address the poor aqueous solubility problem of many poorly soluble drugs, has recently demonstrated great potential for industrial applications and developments. This review focuses on today's preparation technologies, containing top-down, bottom-up, and combinative technology. Among them, the highlighted combinative technology can improve the efficiency of particle size reduction and overcome the shortcomings of a single technology. Then, the characterization methods of nanocrystal production are presented in terms of particle size, morphology, structural state, and surface property. After that, we introduced performance evaluations on the stability, safety, and the in vitro/in vivo dissolution of drug nanocrystals. Finally, the applications and prospects of nanocrystals in drug development are presented. This review may provide some references for the further development and optimization of poorly soluble drug nanocrystals.

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In this work, three novel drug−drug multicomponent crystals containing two drugs to treat diabetes, epalrestat (EP) and edaravone (ED) or pregabalin (PR), namely, EP-ED cocrystal, EP − -PR-H + salt-cocrystal monohydrate, and the dehydrate EP-PR, were successfully synthesized. The purpose is to improve the low solubility and photostability of EP and simultaneously achieve the synergistic effect of the drugs, which may enhance the therapeutic effect of diabetic peripheral neuropathy. As expected, the drug− drug multicomponent crystals exhibit better physicochemical properties. The enhanced photostability can be attributable to the alleviated Z,Z-isomerization of EP and the abundant interactions (mainly hydrogen bonds) inside the EP-PR multicomponent crystals. Moreover, the solubility and dissolution rate become better since ED or PR with better solubility participates in the crystal structure arrangement of multicomponent crystals. We believe that the drug−drug multicomponent crystals of EP and ED or PR have potential applications in the treatment of diabetic peripheral neuropathy owing to the improved physicochemical properties and the drug synergistic effect.