Why was anhydrous form I of dabigatran etexilate mesylate chosen for development despite anhydrous form II being thermodynamically more stable?
Label:chem
Topic
One study states that anhydrous form II is thermodynamically more stable than anhydrous form I, yet form I was selected for development.
Answer
The selection of anhydrous form I of dabigatran etexilate mesylate for development, despite anhydrous form II being thermodynamically more stable, was primarily based on form I's superior bulk processing properties during drug substance synthesis and further drug product processing, as well as its slightly better chemical stability in pivotal long-term stability studies. Although metastable, anhydrous form I demonstrated sufficient stability, with limited conversion to the more stable form II observed during synthesis and manufacturing, and no transformation during long-term storage or under stress conditions (up to 4 weeks at 70°C).
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