缬沙坦在乙酸乙酯中的溶解度及介稳区

Solubility and metastable zone of valsartan in ethyl acetate

采用静态平衡法测定缬沙坦在乙酸乙酯中278.15-323.15K的溶解度数据,利用Modified Apelblat、NRTL和λh方程分别对溶解度数据进行了关联,并通过van’t Hoff分析计算了缬沙坦在溶解过程中的热力学参数（焓变、熵变和吉布斯自由能）。结果表明,缬沙坦在乙酸乙酯中的溶解度随着温度升高而显著增大,3个模型均具有较好的关联性,平均相对偏差分别为1.03%、3.87%、1.72%,Modified Apelblat方程对溶解度数据关联的效果最好;缬沙坦在乙酸乙酯中的溶解过程为自发吸热熵驱动过程,焓变在溶解过程中对吉布斯自由能贡献较大。利用激光法测定了缬沙坦在乙酸乙酯中的超溶解度,研究了不同搅拌速率、降温速率对结晶介稳区的影响。结果表明,随饱和温度的升高,介稳区显著变宽;搅拌速率越小、降温速率越快,介稳区越宽,降温速率的影响相对较小。

The solubility of valsartan in ethyl acetate was measured by a static equilibrium method at temperatures from 278.15K to 323.15K. The solubility data were correlated by the modified Apelblat equation,the NRTL equation,and theλhequation. In addition,the thermodynamic parameters （including the enthalpy,entropy and Gibbs energy） were calculated by the van’t Hoff analysis. The results showed that the solubility of valsartan obviously increased with an increase of temperature. The experimental data were well correlated with the above models because the mean deviation values of these three models were 1.03%,3.87%,and 1.7%,respectively. Therefore,the modified Apelblat equation was the best choice in the correlation of the solubility data of valsartan. The values of thermodynamic parameters proved that the dissolution process of valsartan in ethyl acetate was endothermic,spontaneous and entropy-driven. The main contributor to the standard molar Gibbs energy of solution was the enthalpy change during the dissolution process. Furthermore,the supersolubility of valsartan in ethyl acetate was measured at different stirring rates and cooling rates by the laser method. The results indicated that the metastable zone was wider under the condition of low stirring rate,high temperature and large cooling rate. Meanwhile,the temperature effect was remarkable but the cooling rate had little effect on the metastable zone.