کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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2480836 | 1556206 | 2013 | 8 صفحه PDF | دانلود رایگان |
The present study aimed to develop an amorphous solid dispersion (SD) of nobiletin (NOB), a citrus polymethoxylated flavone, with the aim of improving its biopharmaceutical and hepatoprotective properties. SD formulation of NOB (NOB/SD) was prepared by wet-milling and subsequent freeze drying, and its stability and dissolution properties were characterized. The hepatoprotective effects and pharmacokinetic behavior of orally dosed NOB/SD were evaluated in rats. During the storage of NOB/SD for 4 weeks under accelerated conditions, there were no significant transitions in the appearance, particle size, and amorphousity of wet-milled NOB. In comparison with crystalline NOB, the NOB/SD exhibited significant improvement in the dissolution with a 10-fold higher dissolution rate. In a rat model of acute liver injury, repeated treatment with NOB/SD (2 mg NOB/kg) every 4 h led to marked attenuation of hepatic damage as evidenced by decreased ALT and AST, surrogate biomarkers for hepatic injury; however, crystalline NOB was found to be less effective. After oral administration of NOB/SD (2 mg NOB/kg) in rats, compared with crystalline NOB, improved pharmacokinetic behavior was observed with increases of bioavailability and hepatic delivery by ca. 7- and 6-fold, respectively, possibly leading to better hepatoprotection. Given the improved physicochemical and biopharmaceutical properties, the SD formulation strategy might be efficacious for enhancing the therapeutic potential of NOB.
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Journal: European Journal of Pharmaceutical Sciences - Volume 49, Issue 4, 16 July 2013, Pages 453–460