摘要
目的采用反相高效液相色谱(RP-HPLC)法测定水杨酸25℃平衡溶解度及表观油水分配系数(Papp),为其制剂的设计与制备提供理论依据。方法采用摇瓶法及HPLC法,Waters C18色谱柱(4.6 mm×250 mm,5μm);流动相:甲醇-0.1%磷酸溶液=(47∶53);柱温:室温;流速:1.0 m L·min-1,检测波长:270 nm;进样量20μL。考察25℃水杨酸在水中,p H值1.0盐酸溶液,p H值2.0,3.0,4.0,5.0,6.0,7.0,7.8磷酸盐缓冲溶液体系中平衡溶解度及Papp。结果25℃下水杨酸在水中平衡溶解度为(2.205±0.020)mg·m L^(-1),Papp为(6.18±0.08);在p H值1.0盐酸溶液,p H值2.0,3.0,4.0,5.0,6.0,7.0,7.8磷酸盐缓冲液中平衡溶解度分别为(1.169×10-3±7.40×10-6),(2.250±0.010),(2.410±0.010),(2.694±0.003),(5.208±0.010),(5.826±0.006),(6.255±0.030),(3.353±0.070)mg·m L^(-1),相应的Papp分别为(16.39±0.19),(4.23±0.07),(6.03±0.11),(5.56±0.10),(1.25±0.01),(0.27±0.001),(0.08±0.001),(0.07±0.002)。结论水杨酸的平衡溶解度随溶液p H值增大而增大;Papp随着p H值的增大而减小。其溶解度小,脂溶性小,属于生物药剂学分类系统(BCS)的Ⅳ类药物。
ObjectiveTo determine equilibrium solubility and apparent partition coefficient of salicylic acid at 25 ℃,and to provide a theoretical basis for design and preparation of its formulation. MethodsEquilibrium solubility and apparent partition coefficient (Papp) of salicylic acid were respectively investigated in water, hydrochloric acid solution (pH 1.0) and phosphate buffer solution system (pH 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 7.8) at 25 ℃. The shake flask method and HPLC were used. The column was Waters C18 (4.6 mm×250 mm, 5 μm) with the mobile phase as methanol-0.1% phosphoric acid water (47∶53). The column temperature was room temperature. The flow rate was 1.0 mL·min^-1. The detection wavelength was 270 nm and injection volume was 20 μL. ResultsEquilibrium solubility of salicylic acid was (2.205±0.020) mg·mL-1 at 25 ℃ in Water and its Papp was (6.18±0.08). The solubility were (1.169×10^-3±7.40×10^-6),(2.250±0.010),(2.410±0.010),(2.694±0.003),(5.208±0.010),(5.826±0.006),(6.255±0.030),(3.353±0.070) mg·mL-1, respectively, at hydrochloric acid solution (pH 1.0) and phosphate buffer solution system (pH 2.0, 3.0, 4.0, 5.0, 6.0, 7.0, 7.8), and the corresponding Papp were (16.39±0.19),(4.23±0.07),(6.03±0.11),(5.56±0.10),(1.25±0.01),(0.27±0.001),(0.08±0.001) and (0.07±0.002), respectively. ConclusionThe solubility of salicylic acid increases and its oil-water partition coefficient declines with pH value increasing. Salicylic acid is slightly soluble in water and oil. It belongs to Class Ⅳ drug in Biopharmaceutics Classification System (BCS).
出处
《医药导报》
CAS
2017年第2期186-189,共4页
Herald of Medicine
基金
国家自然科学基金青年基金资助项目(81202884)
关键词
水杨酸
平衡溶解度
表观油水分配系数
色谱法
高效液相
Salicylic acid
Equilibrium solubility
Apparent partition coefficient
Chromatography, high performance liquid