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• W2912476949 endingPage "320" @default.
• W2912476949 startingPage "313" @default.
• W2912476949 abstract "Nanosuspension has been widely used to improve the bioavailability of poorly soluble drugs. ZL-004, a promising small molecular compound with the function of raising counts of white blood cells, was developed to nanosuspensions to solve the low solubility and bioavailability by the precipitation method. The effects of the important factors (THF/Water ratio, Tween-80, PEG 400) on the particle size were investigated by a central composite design. After freeze drying, with 6% sucrose as protective agent, a 399 ± 20 nm nanosuspension (NS-A) and a 208 ± 14 nm nanosuspension (NS-B) were obtained with good appearances, rapid redispersity, and stable particle sizes. The morphology and crystal forms were evaluated by scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray powder diffraction (XRPD). In vitro release test proved that the solubility and dissolution rate were improved by reducing the particle size. In vivo pharmacokinetic study and tissue distribution study in rats showed that particle size affected the pharmacokinetic behavior significantly by different accumulation in reticuloendothelial system (RES). NS-A with a larger particle size was captured and accumulated more in RES, achieving higher t1/2 and MRT; NS-B with a smaller particle size was captured and accumulated less in RES, achieving higher AUC and Cmax." @default.
• W2912476949 created "2019-02-21" @default.
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• W2912476949 date "2019-04-01" @default.
• W2912476949 modified "2023-10-17" @default.
• W2912476949 title "Preparation, optimization of intravenous ZL-004 nanosuspensions by the precipitation method, effect of particle size on in vivo pharmacokinetics and tissue distribution" @default.
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• W2912476949 doi "https://doi.org/10.1016/j.jddst.2019.01.034" @default.
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