论文部分内容阅读
目的测定蒿甲醚在正辛醇-水/缓冲体系中的表观油水分配系数(lgP)及其在常用的注射用油、乳化剂及助乳化剂等不同介质中的平衡溶解度。方法使用摇瓶法测定蒿甲醚在正辛醇-水中的lgP;采用高效液相色谱法(HPLC)测定蒿甲醚在各种介质中的浓度。结果在37℃下,蒿甲醚在水及pH 5.0、6.8、7.4、8.0的磷酸盐缓冲液中的lgP分别为2.2、1.6、1.5、2.6、2.2。在37℃时,蒿甲醚在注射用油中链甘油三酯(MCT)、橄榄油、大豆油、蓖麻油及肉豆蔻酸异丙酯(IPM)中的平衡溶解度分别为306.9、246.6、222.8、265.0、273.3mg/mL。在乳化剂(6mg/mL胶束溶液)泊洛沙姆188(F68)、壬基酚聚氧乙烯醚(OP乳化剂)、聚山梨酯80、大豆卵磷脂、聚氧乙烯氢化蓖麻油(RH40)中的平衡溶解度分别为0.1、1.4、0.5、0.6、0.6mg/mL。在无水乙醇、1,2-丙二醇、丙三醇、异丙醇、正丁醇中的平衡溶解度分别为177.3、37.0、3.4、204.1、303.1mg/mL。结论蒿甲醚表观油水分配系数随水相pH不同而不同;蒿甲醚在注射用油MCT、OP乳化剂、助乳化剂正丁醇中的溶解度较大。
OBJECTIVE To determine the apparent oil-water partition coefficient (lgP) of artemether in n-octanol-water / buffer system and its equilibrium solubility in different media such as commonly used oil for injection, emulsifier and co-emulsifier. Methods The shake flask method was used to determine the lgP of artemether in n-octanol-water. The concentration of artemether in various media was determined by high performance liquid chromatography (HPLC). Results The lgP of artemether in water and pH 5.0, 6.8, 7.4, 8.0 phosphate buffer was 2.2, 1.6, 1.5, 2.6, 2.2 at 37 ° C, respectively. The equilibrium solubilities of artemether in injection oils medium chain triglycerides (MCT), olive oil, soybean oil, castor oil, and isopropyl myristate (IPM) at 37 ° C were 306.9, 246.6, 222.8 , 265.0, 273.3 mg / mL. Poloxamer 188 (F68), nonylphenol polyoxyethylene ether (OP emulsifier), polysorbate 80, soybean lecithin, polyoxyethylene hydrogenated castor oil (RH40 ) In the equilibrium solubility were 0.1,1.4,0.5,0.6,0.6 mg / mL. The equilibrium solubility in absolute ethanol, 1,2-propanediol, glycerol, isopropanol and n-butanol was 177.3, 37.0, 3.4, 204.1 and 303.1 mg / mL, respectively. Conclusions The apparent oil-water partition coefficients of artemether varied with the pH of the aqueous phase. Artemether was more soluble in the oil MCT, OP emulsifier and co-emulsifier n-butanol.