泡腾沉淀法制备呋塞米纳米晶的工艺及药剂学特性

Preparation of furosemide nanocrystals by effervescent precipitation method and its pharmaceutical characteristic

为了改善呋塞米原料药的体外溶出度,提高其生物利用度,采用新颖的泡腾沉淀法制备了呋塞米纳米晶,通过正交实验优化工艺参数和材料属性,马尔文激光粒度仪测定纳米晶的平均粒径和多分散指数(PDI),HPLC法测定呋塞米纳米晶的载药量及溶出度。结果表明,以碳酸钠为泡腾源,稀盐酸为反溶剂,聚乙烯吡咯烷酮-30(PVPK30)为稳定剂,t=25℃,超声15 min的条件下,制备的呋塞米纳米晶平均粒径为218.7 nm,PDI为0.248;HPLC测得呋塞米纳米晶的载药量为56.33%,体外溶出度高于呋塞米原料的2倍。泡腾沉淀法制备的呋塞米纳米晶具有较小的平均粒径和PDI,其累积溶出度显著提高。

To improve the dissolution rate and increase the bioavailability of furosemide in vitro,the novel effervescent precipitation method was used to prepare furosemide nanocrystals,the process parameters and material properties were optimized by orthogonal experiment.The particle size and PDI(polydispersity index)of the nanocrystals were determined by Malvern laser particle size analyzer,the drug loading and dissolution of furosemide nanocrystals were measured by HPLC.The results show that using sodium carbonate as the effervescent source,dilute hydrochloric acid as the anti-solvent,and PVPK30 as the stabilizer,the furosemide nanocrystals were prepared at 25℃under ultrasonic stirring for 15 minutes,the average particle size,PDI and the drug loading of nanocrystals were 218.7 nm,0.248 and 56.33%,respectively.The dissolution in vitro was more than two times higher than the raw material of furosemide.The furosemide nanocrystals prepared by the effervescent precipitation method has a smaller particle size and PDI,and its cumulative dissolution rate is significantly improved.