Hsieh Yi-Ling, Merritt Jeremy M, Yu Weili, Taylor Lynne S
Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Dr., West Lafayette, Indiana, 47907, USA.
Pharm Res. 2015 Sep;32(9):3110-8. doi: 10.1007/s11095-015-1691-5. Epub 2015 Apr 15.
The aim of this study was to investigate how the disproportionation process can be impacted by the properties of the salt, specifically pHmax.
Five miconazole salts and four sertraline salts were selected for this study. The extent of conversion was quantified using Raman spectroscopy. A mathematical model was utilized to estimate the theoretical amount of conversion.
A trend was observed that for a given series of salts of a particular basic compound (both sertraline and miconazole are bases), the extent of disproportionation increases as pHmax decreases. Miconazole phosphate monohydrate and sertraline mesylate, although exhibiting significantly different pHmax values (more than 2 units apart), underwent a similar extent of disproportionation, which may be attributed to the lower buffering capacity of sertraline salts.
This work shows that the disproportionation tendency can be influenced by pHmax and buffering capacity and thus highlights the importance of selecting the appropriate salt form during the screening process in order to avoid salt-to-free form conversion.
本研究旨在探究盐的性质，特别是最大pH值（pHmax）如何影响歧化过程。
本研究选用了五种咪康唑盐和四种舍曲林盐。使用拉曼光谱法定量转化程度。利用数学模型估算理论转化量。
观察到一种趋势，即对于特定碱性化合物的给定系列盐（舍曲林和咪康唑均为碱），随着最大pH值降低，歧化程度增加。磷酸咪康唑一水合物和甲磺酸舍曲林，尽管表现出显著不同的最大pH值（相差超过2个单位），但歧化程度相似，这可能归因于舍曲林盐较低的缓冲能力。
这项工作表明歧化趋势可受最大pH值和缓冲能力影响，因此突出了在筛选过程中选择合适盐形式以避免盐向游离形式转化的重要性。
