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Drug Dev Ind Pharm. 2012 Mar;38(3):357-64. doi: 10.3109/03639045.2011.604330. Epub 2011 Nov 16.

Chemical interactions between an active pharmaceutical ingredient and its counterion in a tromethamine salt under forced degradation conditions.

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Pharmaceutical and Analytical Development, Novartis, East Hanover, NJ, USA.


In this study, the tromethamine salt of an active pharmaceutical ingredient containing both a carboxylic acid and ethyl ester functionality was subjected to forced degradation conditions. Based on HPLC-MS analysis, it was found that tromethamine formed both amide and ester type condensation products with the API, with amide formation predominating over ester formation. Addition of tromethamine at the carboxylic acid group of the API was favored over addition at the ethyl ester group. Tromethamine condensation products were observed only under the harshest stress conditions (80 degrees and 75% relative humidity), in which the salt physically changed from a crystalline form to a deliquesced state. Under stress conditions in which the crystalline structure of the salt remained intact, good stability was observed. Thus, the interaction between tromethamine and API occurred only in cases where the crystallinity of the salt was compromised.

[Indexed for MEDLINE]

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