作者：袁飞，何琳，丁沐淦，龙晓英，李志棠，梁静敏，林小玲
【摘要】 目的比较采用静态法与动态法对药物水中平衡溶解度测定结果的影响。 方法 静态法：超声1 h、25 ℃水浴恒温24 h，25 ℃气浴振荡24 h，25 ℃水浴恒温放置7 d及16 d;动态法：超声1 h、25 ℃气浴振荡24 h，25 ℃气浴振荡24 h，25 ℃水浴搅拌24 h，分别测定布洛芬、盐酸小檗碱、葛根素、对乙酰氨基酚在水中的溶解度。 结果 25 ℃条件下采用静态法及动态法测得药物在水中的平衡溶解度如下：布洛芬为0.067~0.078 mg/mL(RSD 11.94%~22.18%)和0.063~0.078 mg/mL(RSD 3.2%~7.8%);盐酸小檗碱为7.072~8.230 mg/mL(RSD 3.4%~14.5%)和7.654~9.771 mg/mL(RSD 2.2%~5.0%)，葛根素为7.305~9.479 mg/mL(RSD 7.5%~14.5%)和6.057~8.046 mg/mL(RSD 2.5%~6.8%);对乙酰氨基酚为8.708~9.771 mg/mL(RSD 3.2%~13.6%)和8.965~10.932 mg/mL(RSD 1.5%~6.6%)。结论 4种药物在水中的平衡溶解度以动态法重现性较好，其中采用水浴搅拌24 h测得的结果重现性最好，最低RSD值为1.5%;而采用超声与恒温气浴振荡结合法，除溶解度特别小的药物造成误差较大外，基本能满足大部分药物溶解度测定的要求(RSD<2.5%)，而且，相对于水浴搅拌，该法处理样品量大，可广泛应用。
【关键词】 静态法;动态法;平衡溶解度
Abstract:ObjectiveTo compare the effect of stationary method and dynamic method on the results of drugs′ equilibrium solubility in water.Methods The solubility of ibuprofen,berberine,puerarin and paracetamol in water were determined by stationary method,i.e.,ultrasound 1 h,then stay in water bath 24 h at 25 ℃ or oscillated in air bath 24 h at 25 ℃,then stay 7 d and 16 d at the same temperature; and by dynamic method,i.e.,oscillated in air bath 24 h at 25 ℃,ultrasound 1 h and then oscillated in air bath 24 h at 25 ℃,or agitated in water bar 24 h at 25 ℃,respectively.Results The solubility of ibuprofen,berberine,puerarin and paracetamol by stationary and dynamic method were 0.067~0.078 mg/mL(RSD=11.94%~22.18%)and 0.063~0.078 mg/mL(RSD=3.2%~7.8%),7.072~8.230 mg/mL(RSD=3?4%~14.50%)and 7.654~9.771 mg/mL(RSD=2.2%~5.0%),7.305~9.479 mg/mL(RSD=7?5%~14.50%)and 6.057~8.046 mg/mL(RSD=2.5%~6.8%),8.708~9.771 mg/mL(RSD=3?2%~13.6%)and 8.965~10.932 mg/mL(RSD=1.5%~6.6%),respectively.Conclusion The solubility data of four drugs in water exhibits good reproducibility by dynamic method,especially with agitating in water bar 24 h and the lowest RSD is 1.5%.The RSD of combination of ultrasound and oscillation of air bath is less than 2.5%,which satisfies the requirement of determining most drugs′ solubility,except the drug′s solubility is very low.Moreover,compared with agitation in water,it can deal with mass samples with combination of ultrasound and oscillation of air bath,which can be widely used.
Key words:stationary method; dynamic method; equilibrium solubility
溶解度是指在一定温度下，在一定量溶剂中达饱和时溶解的最大药量，是反映药物溶解性的重要指标[1]，与制剂、剂型的选择以及处方、工艺、质量控制等具有密切的相关性。实际工作中多以药物在实际环境条件下的平衡溶解度来表示。测定平衡溶解度的常用方法是配制药物饱和溶液，置恒温条件下振荡至平衡，经滤膜过滤，取滤液分析，测定药物在溶液中的实际浓度。笔者在多次实验中发现，平衡溶解度测定的结果重现性较差。本实验选择布洛芬、盐酸小檗碱、葛根素、对乙酰氨基酚4种难溶性药物为对象，比较不同的测定方法及条件对平衡溶解度测量结果的影响，为准确测定药物溶解度提供借鉴。