以甘肃省食用油为油相的呋塞米微乳制备·优化和体外释放

Preparation,Optimization and Release in vitro of Furosemide Microemulsion with Edible Oil from Gansu Province as Oil Phase

[目的]以甘肃生产的食用植物油作为油相制备呋塞米微乳,进行处方优化,了解体外释放行为。[方法]选取对呋塞米溶解度最大的食用油、表面活性剂和助表面活性剂,利用单因素试验进行空白微乳处方筛选,以电导率、浊度、载药量作为响应值,利用Box-Behnken Design响应面法建立多元回归模型,绘制响应面图,考察油相用量、混合表面活性剂(S_(mix))与水质量比、乳化时间的影响,利用透析法测定微乳和片剂的体外累积释放度,确定释放特性。[结果]微乳处方确定为杏仁油240μL,表面活性剂为OP-10,助表面活性剂为PEG400,二者质量比为1∶1,S_(mix)与水的质量比为2.78,乳化时间为2 min。S_(mix)与水的质量比是影响微乳质量的显著因素,优化处方实际值与预测值相对误差较小,得到的微乳澄清透明,为水包油型,粒径小、稳定性好、载药量较高,体外释放缓慢且完全,能够持续释放72 h。[结论]成功将食用油作为油相制备了呋塞米微乳,方法简单,获得的微乳均一透明、载药量高,具有明显的缓释性能。

[Objective]To prepare furosemide microemulsion with edible vegetable oil produced in Gansu Province as oil phase,optimize the prescription and to know the release behavior in vitro.[Method]Edible oil,surfactant,co-surfactant which dissolved the most furosemide were selected.Single factor test was used to screen blank microemulsion formulations.Taking conductivity,turbidity,and drug loading as the response values,the Box-Behnken Design response surface method was used to establish a multiple regression model,and the response surface map was drawn to investigate the effect of dosage of oil phase,the mass ratio of mixed surfactant(S_(mix))and water,and the emulsifying time.The cumulative release of microemulsion and tablets in vitro were determined by dialysis method in order to determine release characteristics.[Result]The microemulsion was composed of almond oil 240μL,the mass ratio of emulsifier OP-10(surfactant)to PEG400(co-surfactant)was 1∶1,the mass ratio of mixed surfactant to water was 2.78,and the emulsifying time was 2 min.The mass ratio of mixed surfactant to water was a significant factor affecting the quality of the microemulsion.The relative error between the actual and predicted values of the optimized formula was relatively small.The microemulsion was clear and transparent,oil in water,small particle size,good stability and high drug loading.The release in vitro could last 72 h slowly and completely.[Conclusion]Furosemide microemulsion was successfully prepared by using edible oil as oil phase.The preparation method is simple.The microemulsion obtained is uniform,transparent,and the drug loading is high,the performance of slow release is obvious.