磺胺二甲嘧啶-对羟基苯甲酸共晶在乙腈溶剂中的三元相图测定

Determination of ternary phase diagram of sulfamethazine-phydroxybenzoic acid cocrystal in acetonitrile solvent

建立一种HPLC同时分析测定溶液中磺胺二甲嘧啶和对羟基苯甲酸含量的方法,结果表明,以乙腈-磷酸水溶液(p H=3.15)为流动相,两者体积比为18∶82时,能使磺胺二甲嘧啶和对羟基苯甲酸在9min内迅速分离,该法精密度和稳定性的相对标准偏差(RSD)均小于2%,磺胺二甲嘧啶和对羟基苯甲酸的平均回收率分别为98.73%、98.90%。在该基础上,采用溶液法制备磺胺二甲嘧啶-对羟基苯甲酸共晶,分别在298.15、303.15 K时,建立共晶体在乙腈中的三元相图。采用XRD、DSC、SEM对磺胺二甲嘧啶、对羟基苯甲酸和在298.15K时部分干燥固相进行表征分析。结果表明,磺胺二甲嘧啶-对羟基苯甲酸-乙腈体系相图是对称相图,随着温度的升高,磺胺二甲嘧啶-对羟基苯甲酸共晶区域增大,有利于共晶的形成,可根据相图的规律性制备磺胺二甲嘧啶-对羟基苯甲酸共晶,提高磺胺二甲嘧啶的溶解度。

A HPLC method for the simultaneous determination of sulfamethazine and p-hydroxybenzoic acid in solution was established. The results showed that when the mobile phase consisted of acetonitrile and phosphoric acid aqueous solution(pH=3.15) with a volume ratio of acetonitrile to phosphoric acid aqueous solution of 18∶82, sulfamethazine and p-hydroxybenzoic acid could be quickly separated in 9 minutes. The relative standard deviation(RSD) of precision and stability of this method was less than 2%. The average recoveries of sulfamethazine and p-hydroxybenzoic acid were 98.73% and 98.90%, respectively. On this basis, the sulfamethazine-p-hydroxybenzoic acid cocrystal was prepared by solution method. At 298.15 and 303.15 K, the ternary phase diagram of the cocrystal in acetonitrile was established. XRD, DSC and SEM were used to characterize sulfamethazine, p-hydroxybenzoic acid and partially dried solid phase at 298.15 K. The results revealed that the phase diagram of sulfamethazine-p-hydroxybenzoic acid-acetonitrile system was symmetrical. With the increase of temperature, the sulfamethazine-p-hydroxybenzoic acid cocrystal region increased, which is beneficial to the formation of cocrystals. Sulfamethazine-p-hydroxybenzoic acid cocrystals could be prepared by regulating the phase diagram to improve the solubility of sulfamethazine.