呋塞米固体分散体的制备工艺优化与大鼠体内药物动力学研究

Preparation process optimization of furosemide solid dispersion and pharmacokinetic study in rats

呋塞米作为一类强效利尿药被广泛应用,但其低溶解度限制了其药效的发挥。该试验采用溶剂蒸发法制备了呋塞米固体分散体,并进行处方筛选、制备工艺优化、表征和体内外试验,旨在提高其溶解度和溶出度,改善生物利用度。试验结果表明,呋塞米固体分散体的最优处方是呋塞米、HPMCE5和PVPK16-18的比例为1:3:2,磁力搅拌时间为4h。对呋塞米原料药与固体分散体进行体外试验和大鼠体内的药动学试验,结果显示:呋塞米固体分散体的溶解度、溶出度和生物利用度均高于塞米原料药。这表明呋塞米通过固体分散体制备工艺,可改善其在大鼠体内的药代动力学特性,提高呋塞米的临床疗效。

Furosemide as a potent diuretic is widely used,but its low solubility limits its effectiveness.Thus used solvent evaporation method to prepare furosemide solid dispersion,and optimized the prescription and preparation process,aiming to facilitate its solubility and dissolution,and improve its bioavailability.The optimal formulation for the solid dispersion of furosemide is a ratio of 1:3:2 of furosemide,HPMC E5,and PVPK16-18,with a magnetic stirring time of 4 hours.In vitro an in vivo pharmacokinetic studies of furosemide raw material and solid dispersion,and the results showed that the solubility,dissolution,and bioavailability of furosemide solid dispersion were higher than that of raw materials,indicating that the preparation of furosemide solid dispersion improved the in vivo behavior of furosemide and helped to enhance its therapeutic effect.