静态法与动态法测定药物水中溶解度的探讨

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（RSD11.94%～22.18%）和0.063～0.078 mg/mL（RSD3.2%～7.8%）;盐酸小檗碱为7.072～8.230 mg/mL（RSD3.4%～14.5%）和7.654～9.771 mg/mL（RSD2.2%～5.0%）,葛根素为7.305～9.479 mg/mL（RSD7.5%～14.5%）和6.057～8.046 mg/mL（RSD2.5%～6.8%）;对乙酰氨基酚为8.708～9.771 mg/mL（RSD3.2%～13.6%）和8.965～10.932 mg/mL（RSD1.5%～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。

Study on the determination of the drugs'solubility in water by stationary method compared with dynamic method

Objective To 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.