水/乙醇溶剂中阿奇霉素的热力学及多晶型研究

在278.2~308.2 K温度范围内,测定阿奇霉素在水/乙醇混合溶剂中的溶解度,根据固液平衡理论建立了该体系的溶解度修正模型。采用X线粉末衍射法和差示扫描量热法,对阿奇霉素在不同温度、不同体积比的水/乙醇混合溶剂中得到的晶体进行鉴别。同时利用溶解度数据估算了阿奇霉素在水/乙醇体系中的溶解热(-25.26~-16.11 k J/mol)、混合热(-9.94~-3.25 k J/mol)。通过溶液化学理论推导了阿奇霉素溶剂化平衡常数K与活度系数γ2的方程:γ2=1/(1+K),建立了溶剂化焓与温度、水/乙醇两者体积比(φ)之间的关系式,为ΔH=RTln(17.86exp(3.4φ)-1)。采用溶析结晶方法得到的6种阿奇霉素晶体,均属单斜晶系,但具有不同的晶胞参数且其密度和熔点也不同。同时发现温度越高,水/乙醇体积比越大,得到的晶体稳定性越差(晶体的熔点和密度降低)。在水/乙醇混合溶剂的溶析结晶体系中,产生阿齐霉素多晶型的现象与溶剂化作用的强弱有关。

Polymorphism and thermodynamic of azihromycin in mixed water-ethanol solvent

The solubility of azithromycin in water.ethanol solvent was measured by the static method between 278.2 and 308.2 K.A modified general solubility model was established based on the solid.liquid equilibrium theory.The polymorphs of azithromycin prepared in the mixed solvent with different ratio of water to ethanol under different temperatures were identified by X.ray diffraction （ XRD ） and differential scanning calorimetry（ DSC）.The dissolution heat （-25.26.-16.11 kJ/mol） and the mixing heat （-9.94.-3.25 kJ/mol ） of azithromycin were estimated from the solubility experimental data.The relationship between the activity coefficientγ2 and the solvation constant K of azithromycin was deduced as follows：γ2 =1/（1 ＋K） . An expression correlating the solvation enthalpy with the temperature and the volume ratio of water and ethanol （φ） in the mixed solvent was established according to theory of the solution chemistry （ ΔH =RTln（17.86exp（3.4φ） - 1） ）.Six crystals of azithromycin obtained by the anti.solvent crystallization belong to clinorhombic system,but with different cell parameters,density and melting point.It was also observed that stability of the azithromycin crystal become weaker （ the melting point and the density of crystals decreased） as the temperature and the ratio of water to ethanol in mixed solvent increased.As conclusion,in the water.ethanol anti.solvent crystallization system,the formation of＆amp;nbsp;azihromycin polymorphism could be related with the solvation interactions.