截短侧耳素在醇——水复合溶剂体系溶解度的测定与关联

The determination of solubility and correlation of pleuromutilin in binary solvents of methanol-water and ethanol-water

截短侧耳素是一种三环二萜类抗生素,因其抗菌机制独特,与一般抗菌药物不发生交叉耐药,而日益受到重视。本研究测定了截短侧耳素在不同甲醇(或乙醇)-水复合溶剂(醇含量0～50%)中在273.15～333.15K溶解度,并采用多项式经验方程和Apelblat方程进行关联。结果表明,随着温度的提高,随溶剂中甲醇或乙醇含量的增加,截短侧耳素的溶解度显著同步增加。多项式经验方程和Apelblat方程都能很好拟合截短侧耳素溶解度数据,回归系数都在0.993以上。热力学分析表明,截短侧耳素在甲醇(或乙醇)-水复合溶剂中的溶解过程焓变都是正值,且随着溶剂中醇含量的增加而增加,是一吸热过程。溶解过程的熵变在纯水中是负值,随着溶剂中醇含量的增加,熵变也随之增加并且成为溶解度大幅提升的主要驱动力。本论文的研究结果可为截短侧耳素的提取工艺优化及制剂工艺开发提供重要的科学依据。

Pleuromutilin attracts more and more research interest because of its unique antibacterial mechanism and no cross-resistance to common antibiotics, especially when antibiotic resistance becomes more often nowadays. In this paper, the solubility of pleuromutilin in the binary solvents of ethanol-water and methanol-water was investigated in the temperature range of 273.15-333.15K and the alcohol content of 0-50% (V/V) by the static equilibrium method, and correlated with polynomial empirical equation and Apelblat equation. The results showed that the solubility of pleuromutilin in the binary system of ethanol-water and methanol-water increase sharply with an augment in alcohol concentration and temperature in the range investigated. In addition, solubility data were well fitted by polynomial empirical equation and Apelblat equation with a minimum R2=0.993. The analysis of thermodynamics showed that the molar enthalpy was positive, which implied that the solution process is endothermal. The molar entropy increased from negative to positive, and became the main driving force of solubility increase. The results will extend the database of experimental solubility of pleuromutilin and provide theoretical support for the optimization of pleuromutilin purification and formulation technology.