Extended release injectable formulations comprising an isoxazoline active agent, methods and uses thereof
This invention relates to extended release injectable formulations for combating parasites in animals, comprising at least one isoxazoline active agent, a pharmaceutically acceptable polymer, and a solvent. This invention also provides for improved methods for eradicating, controlling, and preventing parasite infections and infestations in an animal comprising administering the extended release injectable formulations of the invention to the animal in need thereof.
1 . An extended release injectable composition for the treatment or prevention of a parasitic infestation or infection in an animal comprising:
a) 5 to 20% (w/w) of an isoxazoline compound of Formula (IIc):
or a pharmaceutically acceptable salt thereof;
b) about 8% (w/w) to about 20% (w/w) of a pharmaceutically acceptable polymer which is a copolymer of polylactides and polyglycolides that has a lactide to glycolide ratio of 70:30 to 80:20 (weight:weight);
c) about 40 to about 85% (w/w) of a solvent which is a mixture comprising propylene carbonate and triacetin wherein the ratio of propylene carbonate to triacetin is about 2:1 to about 6:1 (w/w);
d) optionally, about 0.01% to 2.0% (w/w) of an antioxidant;
e) optionally, about 0.1% to 10% (w/w) of a surfactant; and
f) optionally, about 0.01 to 5.0% (w/w) of a pharmaceutically acceptable additive, excipient or mixtures thereof.
2 . The extended release injectable composition according to claim 1 , wherein the isoxazoline compound is enriched in an enantiomer.
3 . The extended release injectable composition according to claim 2 , wherein in the isoxazoline compound is:
or a pharmaceutically acceptable salt thereof.
4 . The extended release injectable composition according to claim 1 wherein the solvent mixture further comprises a poloxamer.
5 . The extended release injectable composition according to claim 4 , which comprises about 0.5 to about 20% (w/w) of the poloxamer.
6 . The extended release injectable composition according to claim 1 wherein the ratio of the copolymer of polylactides and polyglycolides to the isoxazoline compound is about 1.5:1 to about 1:1.5 (weight:weight).
7 . The extended release injectable composition according to claim 6 , wherein the weight average molecular weight of the copolymer of polylactides and polyglycolides is from about 5 to about 20 kDa.
8 . The extended release injectable composition according to claim 1 , which further comprises an effective amount at least one additional pharmaceutically active agent.
9 . The extended release injectable composition according to claim 3 wherein the additional pharmaceutically active agent is a macrocyclic lactone.
10 . The extended release injectable composition according to claim 9 , wherein the macrocyclic lactone is abamectin, dimadectin, doramectin, emamectin, eprinomectin, ivermectin, latidectin, lepimectin, selamectin, milbemectin, milbemycin D, milbemycin oxime, moxidectin or nemadectin.
11 . A method for treating an ectoparasitic infestation in an animal in need thereof comprising administering a long acting injectable composition to said animal, wherein the long acting injectable composition comprises:
a) 5 to 20% (w/w) of an isoxazoline compound of Formula (IIc):
or a pharmaceutically acceptable salt thereof;
b) about 8% (w/w) to about 20% (w/w) of a pharmaceutically acceptable polymer which is a copolymer of polylactides and polyglycolides that has a lactide to glycolide ratio of 460 70:30 to 80:20 (weight:weight);
c) about 40 to about 85% (w/w) of a solvent which is a mixture comprising propylene carbonate and triacetin wherein the ratio of propylene carbonate to triacetin is about 2:1 to about 6:1 (w/w);
d) optionally, about 0.01% to 2.0% (w/w) of an antioxidant;
e) optionally, about 0.1% to 10% (w/w) of a surfactant; and
f) optionally, about 0.01 to 5.0% (w/w) of a pharmaceutically acceptable additive, excipient or mixtures thereof,
wherein the ectoparasitic infestation is treated for about 5 to 6 months.
12 . The method according to claim 11 wherein the animal is a dog, cat, sheep or cattle.
13 . The method according to claim 11 wherein the ectoparasitic infestation is a flea and/or tick infestation.
14 . The method according to claim 11 , wherein the isoxazoline compound is:
or a pharmaceutically acceptable salt thereof.
15 . The method according to claim 14 wherein the animal is a dog, cat, sheep or cattle.
16 . The method according to claim 14 wherein the ectoparasitic infestation is a flea and/or tick infestation.
17 . The method according to claim 11 wherein the solvent mixture further comprises a poloxamer.
18 . The method according to claim 17 which comprises about 0.5 to about 20% (w/w) of the poloxamer.
19 . The method according claim 11 , wherein the ratio of the copolymer of polylactides and polyglycolides to the isoxazoline compound or a pharmaceutically acceptable salt thereof is about 1.5:1 to about 1:1.5 (weight:weight).
20 . The method according to claim 11 , wherein the weight average molecular weight of the copolymer of polylactides and polyglycolides is from about 5 to about 20 kDa.
21 . The method according to claim 11 , further comprising an effective amount of at least one additional pharmaceutically active agent.
22 . The method according to claim 21 , wherein the additional pharmaceutically active agent is a macrocyclic lactone.
23 . The method according to claim 22 , wherein the macrocyclic lactone is selected from the group consisting of abamectin, dimadectin, doramectin, emamectin, eprinomectin, ivermectin, latidectin, lepimectin, selamectin, milbemectin, milbemycin D, milbemycin oxime, moxidectin or nemadectin.
24 . The method according to claim 11 , comprising 10 to 20% (w/w) of the isoxazoline compound of Formula (IIc).
25 . The method according to claim 11 , comprising about 60 to about 85% (w/w) of the solvent.
26 . The method according to claim 11 , wherein the ratio of propylene carbonate to triacetin is about 2:1 to about 3:1 (w/w).
27 . The method according to claim 11 , comprising 10 to 20% (w/w) of the isoxazoline compound of Formula (IIc), and about 60 to about 85% (w/w) of the solvent, wherein the ratio of propylene carbonate to triacetin is about 2:1 to about 3:1 (w/w).