There has been increasing interest in research and development of nanocrystals for the delivery of poorly water-soluble drugs that can be directly produced from solution.Compared with traditional carrier-based or encapsulation designs,drug nanocrystals circumvent possible side-effects due to carrier polymers and poor stability issues associated with encapsulation.The production of carrier-free nanocrystals requires careful control of nucleation and thus a thorough unde~tanding of the relevant solution’s metastable zone.A solution may stay supersaturated without forming any nuclei and become metastable.The maximal degree of supersaturation is known as the metastable zone width.When nucleation is triggered directly from the metastable zone,it helps to produce homogeneous nuclei leading to uniform nanocrystals.Herein,we report a study in which the solubility and metastable limit of paclitaxel (PTX) in ethanol aqueous solution were measured at 40 ℃.A wide range of metastable compositions were studied to prepare carrier-free PTX nanocrystals with particle size smaller than 250 nm and PDI less than 0.25.Compared with the raw material,dissolution rate of PTX nanocrystals was significantly increased.The study enables production of high-quality drug nanocrystals for treating patients.