芦丁胶态二氧化硅固体分散体的制备及其生物利用度研究  

Preparation of rutin colloidal silicon dioxide solid dispersion and bioavailability in vivo

作　　者：王宁[1] 蒋燕平 牛丽娜[1] 谢茵[1] 王晓燕 梁桂贤[1] 

机构地区：[1]山西医科大学药学院,山西太原030001 [2]山西省医药与生命科学研究院,山西太原030001

出　　处：《中草药》2017年第6期1139-1145,共7页Chinese Traditional and Herbal Drugs

摘　　要：目的制备芦丁(rutin,Ru)胶态二氧化硅(colloidal silicon dioxide,CSD)固体分散体(Ru-CSD-SD),并对其促进芦丁口服吸收作用进行体内外评价。方法采用单因素试验考察Ru-CSD-SD制备处方及方法;采用平衡溶解度试验、差示扫描量热(DSC)法(热分析法)及X射线衍射(XRD)法进行表征;通过检测其体外累积溶出率和犬体内血药浓度变化评价Ru-CSD-SD体内外释药行为。结果经过单因素考察所得Ru-CSD-SD的制备条件:载体为胶态二氧化硅AEROPERL?300 pharma(CSD300),药物芦丁与载体CSD300质量比为1∶2,方法为溶剂旋蒸法。制备成Ru-CSD-SD后,芦丁平衡溶解度(198.73 mg/L)是原料药(72.69 mg/L)的2.7倍;DSC及XRD法分析表明药物以无定形状态存在于SD中。Ru-CSD-SD在5 min的累积溶出率即达到(82.01±1.04)%。犬口服芦丁普通片剂和Ru-CSD-SD后,t1/2为1.078、10.899h,tmax为1.5、0.5 h,Ru-CSD-SD的Cmax(103.45μg/m L)为普通片剂(6.69μg/m L)的15.46倍,AUC0~∞(170.406μg·h/m L)是普通片剂(13.965μg·h/m L)的12.20倍。结论以CSD300为载体材料制备Ru-CSD-SD可以增加芦丁溶解度,提高其溶出速率和口服生物利用度。Objective To prepare the solid dispersion of rutin colloidal silicon dioxide（Ru-CSD-SD） and to promote the rutin oral absorption function, in order to evaluate its in vivo and in vitro oral absorption. Methods Composition and method of Ru-CSD-SD were investigated by single factor test; Equilibrium solubility experiments, differential thermal analysis（DSC）, and X-ray diffraction（XRD） were used to determine the Ru-CSD-SD. Cumulative dissolution rates and pharmacokinetic parameters of Ru-CSD-SD were evaluated by drug releasing in vitro and in vivo. Results The preparation conditions of Ru-CSD-SD was selected on the basis of single factor test： Colloidal silicon dioxide AEROPERL？ 300 pharma（CSD300） was used as carrier, the ratio of drug（rutin） and carrier（CSD300） was 1∶2, and the method was solvent evaporation. After preparation of Ru-CSD-SD, the equilibrium solubility of rutin increased by 2.7 times from 72.69 to 198.73 mg/L; The DSC and XRD were indicated that rutin existed in the solid dispersions at amorphous form. And cumulative dissolution rates of Ru-CSD-SD reached（82.01 ± 1.04）% in 5 min. After oral administration of rutin ordinary tablets and Ru-CSD-SD, t1/2 were 1.078, and 10.899 h, tmax were 1.5, and 0.5 h, and Ru-CSD-SD of Cmax（103.45 μg/m L） was 15.46 times of ordinary tablets（6.69 μg/m L）. Ru-CSD-SD of AUC0—∞（170.406 μg·h/m L） was 12.20 times of ordinary tablets（13.965 μg·h/m L）. Conclusion The Ru-CSD-SD with CSD300 can increase the solubility, dissolution rate, and bioavailability.

关 键 词：芦丁 胶态二氧化硅 固体分散体 生物利用度 累积溶出率 药动学 体内外评价 平衡溶解度 差示扫描量热法 X射线衍射法 溶剂旋蒸法 

分 类 号：R283.6[医药卫生—中药学]