Salt Stability -The Effect of pHmax on Salt to Free Base Conversion

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• 作者：Yi-Ling Hsieh ; Jeremy M. Merritt ; Weili Yu ; Lynne S. Taylor
• 关键词：buffering capacity ; mathematical modelling ; pHmax ; salt disproportionation
• 刊名：Pharmaceutical Research
• 出版年：2015
• 出版时间：September 2015
• 年：2015
• 卷：32
• 期：9
• 页码：3110-3118
• 全文大小：558 KB
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• 作者单位：Yi-Ling Hsieh (1) (2)
  Jeremy M. Merritt (3)
  Weili Yu (4)
  Lynne S. Taylor (1)
  
  1. Department of Industrial and Physical Pharmacy, Purdue University, 575 Stadium Mall Dr., West Lafayette, Indiana, 47907, USA
  2. Novartis Pharmaceutical Corporation, 201 Industrial Rd., San Carlos, California, 94070, USA
  3. Eli Lilly & Co, 1400 W. Raymond St., Indianapolis, Indiana, 46221, USA
  4. Pfizer Global Research and Development, Eastern Point Road, MS 8156-007, Groton, Connecticut, 06340, USA
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Pharmacology and Toxicology
  Pharmacy
  Biochemistry
  Medical Law
  Biomedical Engineering
  
• 出版者：Springer Netherlands
• ISSN：1573-904X

文摘

Purpose The aim of this study was to investigate how the disproportionation process can be impacted by the properties of the?salt, specifically pHmax. Methods 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. Results 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. Conclusion 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.