Method of purifying moxidectin through crystallization
View Patent ↗Methods for the purification of the macrolide moxidectin result in higher purity levels than can often otherwise be obtained. The crystalline moxidectin is then used in a wide variety of pharmaceutical and veterinary applications, including the prevention, treatment and control of parasites in plants, animals and humans.
1. A method for purifying moxidectin, said method comprising:
a) combining moxidectin with a first solvent to produce a moxidectin solution wherein said first solvent is methylcyclohexane;
b) concentrating said solution at a temperature at or below about 50° C., and thereafter cooling the temperature of said moxidectin solution to a temperature within the range of about 40° to 30° C.;
c) combining a second solvent with said moxidectin solution wherein said second solvent is selected from hexane, heptane, toluene, isooctane or a mixture thereof and is present in a weight ratio of 2:1 to 6:1 of second solvent to first solvent; and thereafter
d) agitating the moxidectin solution while lowering the temperature to within the range of about 30 to 10° C., so as to generate moxidectin crystals from said solution;
e) filtering said crystals from said moxidectin solution; and
f) drying said crystals.
2. The method of claim 1 wherein said dried crystals have a purity of least about 94%.
3. The method of claim 1 wherein said dried crystals have a purity of about 94-96%.
4. The method of claim 1 wherein the moxidectin solution has a total solids concentration range of about 40-50%.
5. The method of claim 4 wherein the moxidectin solution has a total solids concentration range of about 40-44%.
6. The method of claim 1 wherein said second solvent is added under agitation.
7. The method of claim 6 wherein agitation of said moxidectin solution is performed at a rate of 15-30 rpm while said second solvent is added; and thereafter the agitation rate of said moxidectin solution is increased to a rate of 50-70 rpm.
8. The method of claim 1 wherein part d) said temperature is lowered from about 25 to 10° C.
9. The method of claim 8 wherein said temperature is lowered during a time period of about 2 to 12 hours.
10. The method of claim 9 wherein said temperature is gradually lowered over said time period.
11. The method of claim 1 wherein said second solvent is n-Heptane and said first solvent is methylcyclohexane, and further wherein said n-Heptane is added to said moxidectin/methylcyclohexane solution at a ratio of about 3:1 for n-heptane to methylcyclohexane.
12. The method of claim 1 wherein the second solvent is n-hexane and said first solvent is methylcyclohexane, and further wherein said n-hexane is added to said moxidectin/methylcyclohexane solution at a ratio of about 3:1 for n-hexane to methylcyclohexane.
13. The method of claim 1 wherein part b) said solution is concentrated under vacuum.
14. The method of claim 13 wherein part b) said solution is concentrated at a temperature within a range of about 40 to 50° C.
15. The method of claim 14 wherein part b) said solution is concentrated at a temperature within a range of about 45 to 50° C.
16. The method of claim 1 wherein part a) said moxidectin is amorphous moxidectin.
17. The method of claim 16 wherein said moxidectin is obtained from a deblocking chemical reaction.
18. The method of claim 17 wherein said chemical reaction is an alkaline hydrolysis reaction.
19. The method of claim 18 wherein said amorphous moxidectin has a purity of about 90-92%.
20. The method of claim 1 wherein said moxidectin is combined with said first solvent in a weight ratio of about 1:1 to 1:2.
21. A method to purify solid moxidectin, the method comprising:
a) dissolving solid moxidectin in methylcyclohexane, (MCH), resulting in a moxidectin/MCH solution;
b) concentrating said moxidectin/MCH solution at a pot temperature of about 45° C. to 50° C. under vacuum;
c) adding n-heptane to the moxidectin/MCH solution, at a ratio of about 4:1 n-heptane to MCH, under agitation;
d) aging the resultant solution for about 4-5 hours at about 30° C.;
e) aging said solution at a temperature of about 10° C. for about 2-3 hours so as to generate moxidectin crystals; and
f) filtering and drying said crystalline moxidectin under vacuum.
22. The method of claim 21 wherein said crystalline moxidectin is at least about 94-96% pure.
23. A process for generating moxidectin crystals from amorphous moxidectin, which comprises:
a. adding amorphous moxidectin to a first solvent to produce a moxidectin solution wherein said first solvent is methylcyclohexane, and thereafter
b. causing the weight percentage of moxidectin within said solution to be within the range of about 40-44% at a temperature within the range of about 45-50° C. for said solution;
c. cooling said solution and adding a second solvent to said moxidectin solution at a temperature within the range of about 30-35° C. for said solution wherein said second solvent is selected from hexane, heptane, toluene, isooctane or a mixture thereof and is added in a weight ratio of 2:1 to 6:1 of second solvent to first solvent;
d. lowering the temperature of said solution to about 10° C. over the period of about 2-8 hours, while agitating said solution such that said agitation increases over said period so as to effect crystallization of said moxidectin; and
e. drying said moxidectin crystals.
24. The process of claim 23 wherein said moxidectin crystals are 2-5% purer than said amorphous moxidectin.