缬沙坦纳米混悬剂的制备及其体外溶出度考察

Preparation of valsartan nanosuspensions and its in vitro dissolution

为提高缬沙坦体外溶出的速度和程度,制备了缬沙坦纳米混悬剂。采用辅以超声处理的反沉淀技术制备缬沙坦纳米混悬剂,通过预实验发现有机相中药物、助稳定剂的浓度及水相中稳定剂的浓度对制剂的稳定性影响较大,因此采用星点设计效应面法,以上述3种因素为考察因素、制剂粒径为考察指标进行处方优化,进行了二次多项式模型拟合,采用Origin 8.0软件绘制三维效应面图和二维等高线图,得出最优处方区域,并对其进行粒径、zeta电位和体外释放考察,且通过冻干将制剂固化,进而提高其稳定性。缬沙坦纳米混悬剂的最优处方的平均粒径约为216.6 nm,zeta电位为57.7 mV。与自制微米混悬剂和市售制剂相比,其溶出速率明显提高。结果表明,自制的缬沙坦纳米混悬剂溶出速度快,生物利用度可能提高。

To increase the dissolution rate and extent of valsartan, valsartan nanosuspensions have been prepared. Controlled precipitation assisted with sonication is utilized to prepare valsartan nanosuspensions, the concentration of the drug, stabilizer and costablizer had a great effect on the stability of the preparation according to the pre-experiment. So the method of central composite design-response surface is used to optimize the prescription based on the above three factors and the particle size as the response value. The software Origin 8.0 is used to draw the view of the three-dimensional effects and 2D contour map, to get the optimal prescription area. Valsartan nanosuspensions were prepared. The mean diameter and zeta potential are about 216.6 nm and -57.7 mV, respectively. Compared with the microsuspensions and commercial preparation, the dissolution of valsartan nanosuspensions was faster and the bioavailability can be enhanced to some extent.