Abstract：
Candesartan cilexetil (CC) is one of well-tolerated antihypertensive drugs, while its poor solubility and low bioavailability limit its use. Herein, two mesoporous silica (Syloid XDP 3150 and Syloid AL-1 FP) and the corresponding amino-modified products (N-XDP 3150 and N-AL-1 FP) have been selected as the carriers of Candesartan cilexetil to prepare solid dispersion through solvent immersion, and characterized through using powder X-ray diffraction analysis, infrared spectroscopy, differential scanning calorimetry, scanning electron microscopy, and solid-state nuclear magnetic resonance spectroscopy, etc. The state of CC changed from crystalline to amorphous after loading onto the silica carriers, in which no interactions between CC and silica existed. Then, the dissolution behaviors in vitro were studied through using flow-through cell dissolution method. CC-XDP 3150 sample exhibited the most extensive dissolution, and the cumulative release of CC from it was 1.88-fold larger than that of CC. Moreover, the pharmacokinetic results in rats revealed that the relative bioavailability of CC-XDP 3150 and CC-N-XDP 3150 solid dispersions were estimated to be 326 % % and 238 % % in comparison with CC, respectively. Clearly, pore size, pore volume, and surface properties of silica carrier have remarkable effect on loading, dissolution and bioavailability of CC. In brief, this work will provide valuable information in construction of mesoporous silica-based delivery system toward poorly water-soluble drugs.
摘要：
坎地沙坦西酯（CC）是一种耐受性良好的抗高血压药物，而其溶解性差和生物利用度低限制了其使用。在这里，选择两种介孔二氧化硅（SyloidXDP3150和SyloidAL-1FP）和相应的氨基修饰产物（N-XDP3150和N-AL-1FP）作为坎地沙坦酯的载体，通过溶剂浸渍制备固体分散体，并通过粉末X射线衍射分析进行了表征，红外光谱,差示扫描量热法,扫描电子显微镜，和固态核磁共振波谱，等。在负载到二氧化硅载体上之后,CC的状态从结晶变为无定形,其中CC和二氧化硅之间不存在相互作用。然后，采用流通池溶出法研究了其体外溶出行为。CC-XDP3150样品表现出最广泛的溶出度，CC的累积释放量是CC的1.88倍。此外，在大鼠体内的药代动力学结果表明，与CC相比，CC-XDP3150和CC-N-XDP3150固体分散体的相对生物利用度估计为326％和238％。分别。显然,孔径,孔隙体积,二氧化硅载体的表面性能对负载有显著影响,CC的溶出度和生物利用度。简而言之,这项工作将为构建基于介孔二氧化硅的水溶性差药物递送系统提供有价值的信息。
