Preparations of meta-iodobenzylguanidine and precursors thereof
The present disclosure provides purified forms of iobenguane and preparations of a precursor to iobenguane, such as a polymer, the polymer comprising a monomer of formula (I) or a pharmaceutically acceptable salt thereof, the preparation comprising leachable tin at a level of 0 ppm to 850 ppm.
1. A method for preparing a purified composition of a polymer comprising a monomer of formula (I):
or a pharmaceutically acceptable salt thereof,
the method comprising the steps of:
counter ion exchange of a hydrochloric acid form of the monomer of formula (I) with sodium acetate to thereby provide a preparation comprising the monomer of formula (I) in the form of a HOAc salt;
a first solvent treating step, comprising contacting the preparation with aqueous alcohol, and then removing substantially all of the aqueous alcohol;
a second solvent treating step, comprising contacting preparation with anhydrous alcohol, and then removing substantially all of the anhydrous alcohol so that a solvent-depleted material comprising the polymer is generated; and
subjecting the solvent-depleted material to vacuum, and to a temperature within a range of about 30° C. to about 50° C., the subjecting being performed under conditions and for a time sufficient to thereby provide the purified composition of the polymer, or pharmaceutically acceptable salt thereof;
wherein no more than 150 ppm of leachable tin is present in the purified composition of the polymer.
2. The method of claim 1 , wherein the aqueous alcohol comprises ethanol.
3. The method of claim 1 , wherein the anhydrous alcohol is or comprises ethanol.
4. The method of claim 1 , wherein the aqueous alcohol is or comprises ethanol and the anhydrous alcohol is or comprises ethanol.
5. The method of claim 1 , the purified composition comprising less than 1.5 wt % water relative to the wt % of the composition.
6. The method of claim 1 , the purified composition comprising less than 1.0 wt % water relative to the wt % of the composition.
7. The method of claim 1 , further comprising a step of: storing the purified composition under an inert gas.
8. The method of claim 1 , wherein the purified composition comprises less than 2.0 wt % water relative to the wt % of the purified composition.
9. The method of claim 3 , wherein the first solvent treating step comprises treating the preparation with aqueous ethanol.
10. The method of claim 9 , wherein the second solvent treating step comprises treating the preparation with absolute ethanol.
11. The method of claim 1 , wherein the removal of substantially all of the aqueous alcohol or the anhydrous alcohol comprises a first removal step of drying the preparation at ambient temperature and pressure with a flow of nitrogen.
12. The method of claim 11 , wherein the removal of substantially all of the aqueous alcohol or the anhydrous alcohol comprises a first removal step of drying the preparation at ambient temperature and pressure with a flow of nitrogen and then further comprises a second removal step of drying the preparation at ambient temperature under vacuum with a flow of nitrogen.
13. The method of claim 1 , wherein the purified composition comprises not more than about 120 ppm of leachable tin.
14. The method of claim 1 , wherein the purified composition comprises not more than about 90 ppm of leachable tin.
15. The method of claim 1 , wherein the purified composition comprises not more than about 50 ppm of leachable tin.
16. The method of claim 1 , wherein the subjecting being performed under conditions and for a time sufficient so that not more than about 0.5 wt % organic solvent relative to the wt % of the composition is present.
17. The method of claim 1 , wherein the subjecting being performed under conditions and for a time sufficient so that not more than about 0.3 wt % organic solvent relative to the wt % of the composition is present.