Embil K, Torosian G
J Pharm Sci. 1982 Feb;71(2):191-3. doi: 10.1002/jps.2600710213.
The theromdynamic pKa values for doxepin and its metabolite desmethyldoxepin were determined by the solubility method to be 8.96 and 9.75, respectively at 25 degrees. The intrinsic solubilities for doxepin and desmethyldoxepin were linearly dependent upon ionic strength. The intrinsic solubilities at zero ionic strength and 25 degrees were determined to be 1,13 x 10(-4) M for doxepin and 3.95 x 10(-4) M for desmethyldoxepin. The solubility experiment was repeated at different temperatures and a constant ionic strength of 0.167 M. The change in enthalpy (6.71 kcal/mole) and entropy (-4.16 cal/mole degrees K) of solution for doxepin was determined from a van't Hoff plot for this nonideal system. The apparent partition coefficient between hexane and water for the doxepin free base was determined to be 13,615 at an ionic strength of 0.067 M.
通过溶解度法测定，多塞平及其代谢产物去甲基多塞平在25℃时的热力学pKa值分别为8.96和9.75。多塞平和去甲基多塞平的固有溶解度与离子强度呈线性相关。在零离子强度和25℃时，多塞平的固有溶解度测定为1.13×10⁻⁴ M，去甲基多塞平的固有溶解度测定为3.95×10⁻⁴ M。在不同温度和0.167 M的恒定离子强度下重复进行溶解度实验。根据该非理想体系的范特霍夫图，确定了多塞平溶解的焓变（6.71千卡/摩尔）和熵变（-4.16卡/摩尔·开尔文）。在离子强度为0.067 M时，多塞平游离碱在己烷和水之间的表观分配系数测定为13615。
