Process for drying bendamustine hydrochloride monohydrate
View Patent ↗Wet bendamustine hydrochloride monohydrate may be dried by a two stage process wherein rapid drying is first carried out to provide a partially dried product, which is then further dried using an inert gas of controlled relative humidity to yield dry bendamustine hydrochloride monohydrate.
1. A method of obtaining dry bendamustine hydrochloride monohydrate, comprising the steps of:
a) drying wet bendamustine hydrochloride monohydrate under conditions effective to yield partially dried bendamustine hydrochloride monohydrate having a moisture content of about 4.4% to about 19%; and
b) contacting the partially dried bendamustine hydrochloride monohydrate with an inert gas of controlled relative humidity to yield dry bendamustine hydrochloride monohydrate.
2. The method of claim 1 , wherein step a) comprises contacting the wet bendamustine hydrochloride monohydrate with a stream of dry inert gas under vacuum.
3. The method of claim 1 , wherein the inert gas is nitrogen.
4. The method of claim 2 , wherein the dry inert gas is nitrogen.
5. The method of claim 1 , wherein the inert gas is argon.
6. The method of claim 2 , wherein the dry inert gas is argon.
7. The method of claim 1 , wherein in step b) the partially dried bendamustine hydrochloride monohydrate is contacted with a stream of inert gas of controlled relative humidity.
8. The method of claim 1 , wherein the partially dried bendamustine hydrochloride monohydrate obtained in step a) has a moisture content of from about 7% to about 10%.
9. The method of claim 1 , wherein step b) is carried out at atmospheric pressure.
10. The method of claim 1 , wherein step a) and step b) are carried out at a temperature within the range of from about 10° C. to about 35° C.
11. The method of claim 1 , wherein the inert gas in step b) has a relative humidity of from 0 to about 60%.
12. The method of claim 1 , wherein the dry bendamustine hydrochloride monohydrate contains less than 0.15%, as determined by HPLC area %, of monohydroxy-bendamustine.
13. The method of claim 1 , wherein the water content of the wet bendamustine hydrochloride monohydrate is measured about every 1 to about 4 hours during step a) until a moisture content within the range of from about 7% to about 10% by weight is achieved.
14. The method of claim 1 , wherein the wet bendamustine hydrochloride monohydrate is obtained by a recrystallization procedure involving washing a cake of wet bendamustine hydrochloride monohydrate with water followed by washing the cake with t-butyl methyl ether.
15. The method of claim 1 , wherein step a) is completed within about 48 hours.
16. The method of claim 1 , wherein step a) is completed within about 24 hours.
17. The method of claim 1 , wherein step a) is completed within about 12 hours.
18. The method of claim 1 , wherein the relative humidity of the inert gas is varied during step b).