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) providing a solution of moxidectin, wherein the moxidectin is dissolved or prepared in a first organic solvent;
b) concentrating said provided moxidectin solution such that the percentage of total solids in the concentrated moxidectin solution is about 40-50% by weight;
c) adding a second organic solvent to said concentrated moxidectin solution, wherein said second organic solvent is present in a weight ratio of 2:1 to 6:1 with respect to said first organic solvent; and said second organic solvent is a non-polar organic solvent;
d) lowering the temperature of the moxidectin solution formed in c), so as to form moxidectin crystals; and
e) recovering said moxidectin crystals.
2. The method of claim 1 , further comprising drying the recovered crystals.
3. The method of claim 1 , wherein the moxidectin dissolved or prepared in the first organic solvent is amorphous moxidectin.
4. The method of claim 1 , wherein in b) said solution is concentrated at a temperature within a range of about 40 to 50° C.
5. The method of claim 4 , wherein the temperature of the concentrated solution is cooled to a temperature within the range of about 40 to 30° C. before adding the second organic solvent.
6. The method of claim 1 , wherein in b) said solution is concentrated under vacuum.
7. The method of claim 1 , wherein in c) said second organic solvent is added under agitation.
8. The method of claim 1 , wherein in d) said temperature is lowered from about 30 to 10° C. so as to effect crystallization of said moxidectin.
9. The method of claim 8 , wherein in d) said temperature is lowered during a time period of about 2 to 12 hours.
10. The method of claim 1 , wherein said moxidectin is combined with said first organic solvent in a weight ratio of about 1:1 to 1:2.
11. The method of claim 1 , wherein said first organic solvent is selected from the group consisting of methanol, ethanol, methylcyclohexane, hexane, benzyl alcohol, toluene, heptane, or a mixture thereof.
12. The method of claim 1 , wherein said second organic solvent is selected from the group consisting of hexane, heptane, toluene, isooctane and mixtures thereof.
13. The method of claim 1 , wherein said second organic solvent is n-heptane and said first organic solvent is methylcyclohexane.
14. The method of claim 13 , wherein said n-heptane is added to said moxidectin/methylcyclohexane solution at a ratio of about 3:1-5:1 for n-heptane to methylcyclohexane.
15. The method of claim 1 , wherein the second organic solvent is n-hexane and said first organic solvent is methylcyclohexane.
16. The method of claim 15 , wherein said n-hexane is added to said moxidectin/methylcyclohexane solution at a ratio of about 3:1 for n-hexane to methylcyclohexane.
17. The method of claim 3 , wherein said amorphous moxidectin has a purity of about 90-92%.
18. The method of claim 1 , wherein said crystalline moxidectin is at least about 94-96% pure.
19. The method of claim 3 , wherein said recovered moxidectin crystals are 2-5% purer than said amorphous moxidectin.