An Approach to Control Strategies for Sulfonate Ester Formation in Pharmaceutical Manufacturing Based on Recent Scientific Understanding

详细信息    查看全文

• 作者：David Elder ; Kevin L. Facchine ; Jeffrey N. Levy ; Rodney Parsons ; David Ridge ; Lesley Semo ; Andrew Teasdale
• 刊名：Organic Process Research & Development
• 出版年：2012
• 出版时间：November 16, 2012
• 年：2012
• 卷：16
• 期：11
• 页码：1707-1710
• 全文大小：152K
• 年卷期：v.16,no.11(November 16, 2012)
• ISSN：1520-586X

文摘

The issue of sulfonate ester formation is one that has been of significant concern to regulatory authorities since the start of the millennia. These concerns, focused primarily on the risk of ester formation where sulfonic acid salts are formed in alcoholic solvents, has led to the need for specific analysis for such species in the final API in any product containing a sulfonic acid counterion. This concept article examines the growing experimental data that exist showing how this risk can be negated through the application of simple process controls that effectively eliminate this risk. These data are also compared to specific product data, illustrating the practical experience of organizations. The article also reflects on the Viracept incident and how the mechanistic understanding of the reaction between sulfonic acids and alcohols readily predicts the observed outcome. It is the conclusion of the authors that the continued need for exhaustive analytical testing should be replaced instead by a scientific risk-based approach, taking into full consideration the specific process conditions.