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).
Return to Home Chemical List
Knowledge you may be interested in
What is Gonadorelin and its mechanism of action? What is Ritonavir and its use in treating HIV, and its potential for COVID-19? What is Indinavir and its use in treating HIV? What is Lopinavir and its use in treating HIV and its repurposing for COVID-19? What is Camostat and its potential as a protease inhibitor? What is Afamelanotide and its properties? What is Ombitasvir and its use in treating hepatitis C? What is Dasabuvir and its use in treating hepatitis C? What is Grazoprevir and its use in treating hepatitis C? What is K-11777 and its potential as an antiviral agent? How do the crystalline forms of dabigatran etexilate mesylate differ structurally and how were these differences characterized? What are the solubility characteristics of dabigatran etexilate mesylate and what phenomenon occurs in aqueous media at higher pH values? Why is Phenobarbital considered a highly cost-effective treatment for early and established Status Epilepticus (SE)? What are the key pharmacological characteristics of phenobarbital? How does phenobarbital penetrate the brain during status epilepticus compared to a healthy brain? What are the historical origins of barbituric acid, barbital, and phenobarbital? How do barbiturates, including phenobarbital and pentobarbital, primarily enhance inhibition? Why is polystyrene recycling important, and what are the challenges associated with its current recycling methods? What is the significance of monomer-grade styrene purity in the chemical recycling process of polystyrene, and how is it achieved? What is the role of α-methyl styrene in the polystyrene pyrolysis process and its potential applications?