Long-acting injectable moxidectin formulations and novel moxidectin crystal forms
This invention provides for novel antiparasitic and pesticidal forms of moxidectin, including a long-acting polymeric implant. The resulting compounds may be used in veterinary compositions which are used in treating, controlling and preventing of endo- and ectoparasite infections in animals.
1. Polymorphic A form of moxidectin having a melting point of 210° C.
2. Moxidectin.2EtOH solvate characterized by the following parameters:
a) monoclinic P2 1 space group with the
b) a=11.2731(15) Å;
c) b=8.9286(12) Å;
d) c=21.955(3) Å;
e) β=93.623(2)°;
f) V=2205.4(5) Å 3 ;
g) Z=2.
3. Moxidectin.1.5BuOH solvate.
4. Moxidectin.2IPA solvate.
5. A process for making a moxidectin crystal form having a melting point of 210° C., comprising either the step of heating amorphous moxidectin under specific conditions of temperature and time, or the step of rapidly desolvating the moxidectin solvate of claim 2 , thereby making the crystal form.
6. A long-acting polymeric implant for non-human animals comprising PLGA and the crystalline form or solvate of moxidectin as set forth in any one of claims 1 to 4 .
7. The implant of claim 6 wherein the PLGA has an L:G ratio of about 50-75% to about 25-50% L:G.
8. The implant of claim wherein the L:G ratio is 75:25.
9. The implant of claim 8 which is active against endoparasites for a period of greater than 3 months.
10. The implant of claim 9 which is active against endoparasites for a period of greater than 4 months.
11. The implant of claim 10 which is active against endoparasites for a period of greater than 6 months.
12. The implant of claim 6 wherein the endoparasites are heartworms.
13. The implant of claim 6 wherein the animals are cats or dogs or cattle.
14. A composition for the treatment or prevention of a parasitic infection in an animal comprising the moxidectin crystal form of any one of claims 1 to 4 , or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable carrier, and an antioxidant.
15. The process of claim 5 , wherein the heating of the amorphous moxidectin is carried out from about 180 to about 210° C., to yield the Polymorphic A form of moxidectin.
16. The process of claim 15 , wherein the heating is carried out at about 190° C.