[b19901111]

Hi all,

The active ingredient Sunitinib is patented as Sutent (Sunitinib Malate).
However, I also found Sunitinib Mesylate.
My question is: what are the difference of physicochemical properites between these two form?
Is it advantageous of Malate form that companies produce it?

Thank you.

[Yggdrasil]

Although different salt forms of drugs are often considered to be equivalent, there are cases where the different counterion can sometimes affect the compound's therapeutic effectiveness.  See http://bjcardio.co.uk/2009/11/pharmaceutical-salts-a-formulation-trick-or-a-clinical-conundrum/

[b19901111]

Although different salt forms of drugs are often considered to be equivalent, there are cases where the different counterion can sometimes affect the compound's therapeutic effectiveness.  See http://bjcardio.co.uk/2009/11/pharmaceutical-salts-a-formulation-trick-or-a-clinical-conundrum/

Thank you so much.

According to the article you linked, their are basically two main categories: covalent attachment and ionic association of the counter-ion. I would like to know if mesylate belongs to ionic association and malate belongs to covalent attachment?

[kriggy]

Wow since when is ester of molecule called covalent salt (figure 1)? Is it some kind of pharma thingy? 

Thank you so much.

According to the article you linked, their are basically two main categories: covalent attachment and ionic association of the counter-ion. I would like to know if mesylate belongs to ionic association and malate belongs to covalent attachment?

I would guess its ionic association for both since there is not many parts of molecule where youc an make covalent bond.
And as I  just read on wiki, there is difference between mesylate (ester of methansulfonic acid) and mesilate (salt of mentioned acid)

[discodermolide]

Salts often help solubilise drug substances. There is a big list of pharmaceutically available salts.
Where I was the mesylate salts were tended not to be widely used because of the reactivity of methane sulfonic acid. QA though it could be an alkylating agent and we had to ensure that the  residual levels of the acid were very low.
Fumarates are also not so loved due to their propensity to undergo Michael additions with the drug substance, especially if this contained animo or other nucleophillic groups.

[b19901111]

Salts often help solubilise drug substances. There is a big list of pharmaceutically available salts.
Where I was the mesylate salts were tended not to be widely used because of the reactivity of methane sulfonic acid. QA though it could be an alkylating agent and we had to ensure that the  residual levels of the acid were very low.
Fumarates are also not so loved due to their propensity to undergo Michael additions with the drug substance, especially if this contained animo or other nucleophillic groups.

Thank you!

Would you further describe the reactivity of methanesulfonic acid for me please.

Like imatinib mesylate (Gleevec), marketed by Norvartis, is there any clue that we can figure out how they choose the salt form?

I know sometimes it's because companies want to develope generic drugs, they make different salt form to be patented.

[discodermolide]

Different salts themselves are not patentable, but the different polymorphs can be patented (if they show advantage over existing ones).
As for Gleevec, stones have a better solubility. Part of the process is done in methane sulfonic acid as it is the only thing that gets it into solution, therefore it comes out as a mesylate salt.