Perlovich German L, Volkova Tatyana V, Manin Alex N, Bauer-Brandl Annette
University of Tromsø, Institute of Pharmacy, Breivika, N-9037 Tromsø, Norway.
J Pharm Sci. 2008 Sep;97(9):3883-96. doi: 10.1002/jps.21260.
Temperature dependency of saturated vapour pressure and thermochemical characteristics of fusion processes for 2-, 3- and 4-methoxybenzoic acids (anisic acids) were measured and thermodynamic functions of sublimation, fusion, and evaporation calculated. A new approach to split specific and nonspecific energetic terms in the crystal lattice was developed. For methoxybenzoic acid isomers as well as for a number of analogous molecules, a parameter describing molecular packing density by the ratio of free volume of the molecules in the crystal lattice and van der Waals molecular volume is defined. Its relationship to Gibbs energy of sublimation and to the respective melting points was analysed. Temperature dependencies of solubility in buffers with pH 2.0 and 7.4, n-octanol and n-hexane were measured. The thermodynamic functions of solubility, solvation and transfer processes were deduced. Concentration dependence of partition coefficients for the outlined isomers was measured. Specific and nonspecific solvation terms were distinguished using the transfer from the 'inert' n-hexane to the other solvents. Comparison analysis of specific and nonspecific interactions in the solid state and in solution was carried out. A diagram enabling analysis of the mechanism of the partitioning process was applied. It was found that position of substituents essentially affects the mechanism of partitioning in buffer pH 2.0, however, at pH 7.4, the mechanism is independent of the position of the substituent.
测量了2-、3-和4-甲氧基苯甲酸（茴香酸）的饱和蒸气压的温度依赖性以及熔融过程的热化学特性，并计算了升华、熔融和蒸发的热力学函数。开发了一种新方法来区分晶格中的特定和非特定能量项。对于甲氧基苯甲酸异构体以及许多类似分子，定义了一个通过晶格中分子的自由体积与范德华分子体积之比来描述分子堆积密度的参数。分析了其与升华吉布斯能量以及各自熔点的关系。测量了在pH值为2.0和7.4的缓冲液、正辛醇和正己烷中的溶解度的温度依赖性。推导了溶解度、溶剂化和转移过程的热力学函数。测量了上述异构体的分配系数的浓度依赖性。通过从“惰性”正己烷转移到其他溶剂来区分特定和非特定溶剂化项。对固态和溶液中的特定和非特定相互作用进行了比较分析。应用了一个能够分析分配过程机制的图表。结果发现，取代基的位置在很大程度上影响了在pH值为2.0的缓冲液中的分配机制，然而，在pH值为7.4时，该机制与取代基的位置无关。
