灯盏花素的理化性质及其稳定性影响因素研究

Study on physicochemical properties and influence factors on stability of breviscapine

目的:考察灯盏花素的平衡溶解度、油水分配系数等理化常数,研究温度、pH及抗氧剂等对其水溶液稳定性的影响。方法:建立灯盏花乙素的HPLC测定方法,测定灯盏花素在不同介质中的平衡溶解度与不同pH条件下的表观油/水分配系数(Papp),以10 h的药物含量变化率为指标考察介质、温度、pH及抗氧剂对其稳定性的影响。结果:方法学考察表明,精密度、稳定性、重现性、回收率等均符合要求;灯盏花素在生理盐水,蒸馏水,pH7.0磷酸盐缓冲液(PBS),pH7.5 PBS,Ringer'S液,甲醇及乙醇中的平衡溶解度分别为(20.68±1.12),(79.35±0.68),(7 954.62±34.90),(18 708.17±253.05),(3 670.40±27.64),(210.71±0.74),(184.34±1.47)mg.L-1;灯盏花素在pH 3.0,4.0,5.0,6.5,7.0下的Papp分别为5.362,0.542,0.371,0.328,0.143;灯盏花素在Ringer'S液中的稳定性差;温度、pH升高,其稳定性均显著降低;EDTA-2Na能显著提高灯盏花素溶液的稳定性。结论:本研究建立的灯盏乙素HPLC测定方法专属性较好、简便,灯盏花素的Papp随着pH增大而减小,在水性介质中的平衡溶解度随着pH增大而增大,但是pH增大,灯盏花素水溶液的稳定性显著降低,EDTA-2Na可以作为灯盏花素溶液剂的抗氧剂。

Objective： To investigate the physicochemical constants such as equilibrium solubility and apparent partition coefficients （ Papp ）, and study the effects of temperature, pH value and antioxidants on the stability of breviscapine solution. Method： The equihbrium solubility of breviscapine in various medium and the Papp of breviscapine under different pH conditions were determinated by RP-HPLC, and the effects of temperature, pH value and antioxidants on the stability of solution were investigated by taking change rates of drug content in 10 h as detection index. Result： The equilibrium solubility of breviscapine in saline, distilled water, pH 7. 0 PBS, pH 7. 5 PBS, Ringer ＇S fluid, methanol and ethanol were （ 20. 68 ± 1.12 ）, （ 79. 35 ± 0. 68 ）, （ 7 954. 62 ± 34. 90 ）, （ 18 708. 17 ± 253. 05 ）, （3 670. 40 ± 27. 64 ）, （210. 71 ± 0. 74 ）, （ 184. 34 ± 1.47 ） mg · L^- 1 respectively; while in pH value 3.0, 4. O, 5. 0, 6. 5,7.0 solution, the Papp were 5. 362, 0. 542,0. 371, 0. 328 and 0. 143 respectively. The stability of breviscapine in the Ringer＇s fluid was the worst and the stability was significantly decreased with the increase of temperature and pH value and it could be improved by EDTA-2Na. Conclusion： The established HPLC assay was accurate and convenient. The Papp of breviscapine is decreased by increased the pH value, while in the aqueous solution the equilibrium solubility of breviscapine increase with the pH in crese. EDTA-2Na can be used as an antioxidant of breviscapine solution.