清开灵注射液中水难溶性成分在不同条件下的表观溶解度测定

Apparent Solubility Determination of Insoluble Ingredients in Qingkailing Injection under Different Conditions

目的:测定清开灵注射液中3种水难溶性成分黄芩苷(BCL)、胆酸(CA)、猪去氧胆酸(HA)在不同条件下的表观溶解度,为增溶研究提供基础。方法:将BCL、CA、HA制成水及不同p H值缓冲液的饱和溶液,采用HPLC法,借鉴《中华人民共和国药典》2010版一部中清开灵注射液中难溶性成分含量测定方法进行测定。结果:(25.0±0.5)℃、p H 5.78的去离子水中,BCL的表观溶解度为0.048 7 mg·m L^(-1),为"几乎不溶或不溶"范畴;CA的表观溶解度为0.147 9 mg·m L^(-1),为"极微溶解"范畴;HA的表观溶解度非常小,在该高效液相色谱-二级阵列管检测器(HPLC-DAD)条件下未能检出;但在一定p H范围的缓冲溶液中,BCL、CA、HA的溶解度随p H增大而激增,在p H 7.6的缓冲液中,BCL、CA的溶解度分别相当于p H 5.78的去离子水中的1555倍、131倍。结论:在不同p H条件下,3种水难溶性成分的表观溶解度差异较大,应调节适宜的p H以满足制剂质量标准中对各成分含量的要求。

Objective： Qingkailing Injection which contains three insoluble ingredients： baicalin （BCL）, cholic acid （CA） and hyodeoxycholic acid （HA）, the above three ingredients were used as research carriers and determine the Apparent Solubility under different conditions. Methods： The saturated solution of BCL, CA, HA into water and buffer solution of different pH value, HPLC was used to determine the contents of insoluble ingredients of Qingkailing Injection and reference to ＂Chinese Pharmacopoeia＂ 2010 Edition of method. Results： In the deionized water （25.0 ± 0. 5） ℃, pH 5.78, the Apparent Solubility of BCL and CA were 0. 048 7, 0. 147 9 mg·mL^-1, respectively; BCL belong to the category of ＂very slightly soluble＂, CA belong to the category of ＂slightly soluble＂ . The Apparent Solubility of HA were under the LOD by HPLC-DAD ; The solubility of BCL, CA and HA all increased remarkably with buffer of a certain pH value, In buffer solution （pH 7.6）, the solubility of BCL, CA were equivalent to 1555 times, 131 times of the deionized water （pH 5.78）, respectively. Conclusion： Under the conditions of different pH value, the difference of apparent solubility of three insoluble ingredients is relatively large, and the appropriate value should be adjusted to meet the requirements of the content of each component in the quality standard of the preparation.