药学学报
藥學學報
약학학보
ACTA PHARMACEUTICA SINICA
2007年
8期
886-891
,共6页
葛根素%自乳化%表面活性剂
葛根素%自乳化%錶麵活性劑
갈근소%자유화%표면활성제
puerarin%self-emulsifying%surfactant
本文将水不溶性药物葛根素制备成自乳化制剂.测定了葛根素在不同油相及表面活性剂的溶解度,结果表明葛根素在油酸、Tween 80中的溶解度较好,1,2-丙二醇不但能增加药物的溶解度,而且能够提高自乳化能力.以油酸为油相,Tween 80为表面活性剂,1,2-丙二醇为助表面活性剂,配制一系列混合物,通过绘制三元相图得到自乳化区,考察不同自乳化处方的自乳化性质,采用激光粒度散射仪测定乳化后粒子大小,在体外评价基础上选择较好的3个处方进行比格犬体内药动学研究,比较不同处方自乳化制剂在比格犬体内的生物利用度包括药代动力学参数Cmax, Tmax, AUC0-t.结果表明处方2和处方3的AUC0-t值[(5.201±0.511) ng·mL-1·h, (5.174±0.498) ng·mL-1·h]和Cmax值[(1.524±0.125) ng·mL-1, (1.513±0.157) ng·mL-1]显著高于处方4[(3.013±0.623) ng·mL-1·h, (0.939±0.089) ng·mL-1],通过体内研究结果获得较优处方为油酸(17.5%)、Tween 80(34.5%)、1,2-丙二醇(34.5%).自乳化释药系统提供了水不溶性药物口服给药的新途径.
本文將水不溶性藥物葛根素製備成自乳化製劑.測定瞭葛根素在不同油相及錶麵活性劑的溶解度,結果錶明葛根素在油痠、Tween 80中的溶解度較好,1,2-丙二醇不但能增加藥物的溶解度,而且能夠提高自乳化能力.以油痠為油相,Tween 80為錶麵活性劑,1,2-丙二醇為助錶麵活性劑,配製一繫列混閤物,通過繪製三元相圖得到自乳化區,攷察不同自乳化處方的自乳化性質,採用激光粒度散射儀測定乳化後粒子大小,在體外評價基礎上選擇較好的3箇處方進行比格犬體內藥動學研究,比較不同處方自乳化製劑在比格犬體內的生物利用度包括藥代動力學參數Cmax, Tmax, AUC0-t.結果錶明處方2和處方3的AUC0-t值[(5.201±0.511) ng·mL-1·h, (5.174±0.498) ng·mL-1·h]和Cmax值[(1.524±0.125) ng·mL-1, (1.513±0.157) ng·mL-1]顯著高于處方4[(3.013±0.623) ng·mL-1·h, (0.939±0.089) ng·mL-1],通過體內研究結果穫得較優處方為油痠(17.5%)、Tween 80(34.5%)、1,2-丙二醇(34.5%).自乳化釋藥繫統提供瞭水不溶性藥物口服給藥的新途徑.
본문장수불용성약물갈근소제비성자유화제제.측정료갈근소재불동유상급표면활성제적용해도,결과표명갈근소재유산、Tween 80중적용해도교호,1,2-병이순불단능증가약물적용해도,이차능구제고자유화능력.이유산위유상,Tween 80위표면활성제,1,2-병이순위조표면활성제,배제일계렬혼합물,통과회제삼원상도득도자유화구,고찰불동자유화처방적자유화성질,채용격광립도산사의측정유화후입자대소,재체외평개기출상선택교호적3개처방진행비격견체내약동학연구,비교불동처방자유화제제재비격견체내적생물이용도포괄약대동역학삼수Cmax, Tmax, AUC0-t.결과표명처방2화처방3적AUC0-t치[(5.201±0.511) ng·mL-1·h, (5.174±0.498) ng·mL-1·h]화Cmax치[(1.524±0.125) ng·mL-1, (1.513±0.157) ng·mL-1]현저고우처방4[(3.013±0.623) ng·mL-1·h, (0.939±0.089) ng·mL-1],통과체내연구결과획득교우처방위유산(17.5%)、Tween 80(34.5%)、1,2-병이순(34.5%).자유화석약계통제공료수불용성약물구복급약적신도경.
The main purpose of this work is to prepare self-emulsifying drug delivery system (SEDDS) of a poorly water soluble drug, puerarin. Solubility of puerarin was determined in various oils and surfactants. Oleic acid and Tween 80 provided higher solubility. Addition of propylene glycol as cosurfactant improved solubility of puerarin and the spontaneity of self-emulsification. A series of mixtures comprising oleic acid, propylene glycol and Tween 80 were prepared and their self-emulsifying properties were studied. Pseudo-ternary phase diagrams were constructed to identify the efficient self-emulsification region and particle sizes of the resultant emulsions were determined using a laser diffraction sizer. The harmacokinetic behaviors of three different SEDDS formulations (F2, F3, F4) were investigated in Beagle dogs. The bioavailability was compared using the pharmacokinetic parameters, peak plasma concentration (Cmax), time to reach peak plasma concentration (Tmax) and total area under the plasma concentration-time curve (AUC0-t). AUC0-t was significantly higher in formulation F2 group (5.201±0.511) ng·mL-1·h and formulation F3 group (5.174±0.498) ng·mL-1·h than that in formulation F4 group (3.013±0.623) ng·mL-1·h. Also, Cmax was significantly higher in formulation F2 group (1.524±0.125) ng·mL-1 and formulation F3 group (1.513±0.157) ng·mL-1 than that in formulation F4 group (0.939±0.089) ng·mL-1. Further analysis of the data showed a statistically significant difference between F2 and F4 (P<0.01) as well as F3 and F4 (P<0.01) with regard to the values of AUC0-∞ and Cmax for three SEDDS formulations, but not between those of F2 and F3 (P>0.05). From these studies, the SEDDS formulation containing oleic acid (17.5%), Tween 80 (34.5%) and propylene glycol (34.5%) (w/w) was selected as an optimized SEDDS formulation of puerarin. The data suggest the potential use of SEDDS to improve oral absorption of puerarin.
