Long-acting injectable formulations comprising an isoxazoline active agent, methods and uses thereof

1. A long-acting injectable formulation for the treatment of parasite infestations or infections in an animal comprising:

a) an antiparasitic effective amount of at least one isoxazoline active agent of formula (Ib):

or a pharmaceutically acceptable salt thereof

wherein:

R 2 independently is halogen, C 1 -C 6 alkyl or C 1 -C 6 haloalkyl;

R 4 is H or C 1 -C 6 alkyl;

R 5 is C 1 -C 4 alkyl optionally substituted with one or more R 7 ;

R 7 is independently halogen, C 2 -C 7 alkylcarbonyl, C 2 -C 7 alkoxycarbonyl, C 2 -C 7 alkylaminocarbonyl, C 3 -C 9 dialkylaminocarbonyl, C 2 -C 7 haloalkylcarbonyl, C 2 -C 7 haloalkoxycarbonyl, C 2 -C 7 haloalkylaminocarbonyl, C 3 -C 9 dihaloalkylaminocarbonyl; and

n is 0, 1 or 2;

b) poloxamer 124 or poloxamer 181;

c) a co-solvent selected from the group consisting of liquid polyethylene glycol, ethanol, isopropanol, and a mixture thereof;

d) optionally, an antioxidant; and

e) optionally at least one pharmaceutically acceptable additive, excipient or mixtures thereof;

wherein the only pharmaceutically acceptable polymers present in said long-acting injectable formulation is said poloxamer, wherein the formulation treats parasitic infestations or infections for about 3 to 6 months.

2. The long-acting injectable formulation according to claim 1 , wherein the at least one isoxazoline active agent is a compound of formula (Ia):

or a pharmaceutically acceptable salt thereof.

3. The long-acting injectable formulation according to claim 1 , wherein the at least one isoxazoline active agent is enriched in an enantiomer.

4. The long-acting injectable formulation according to claim 3 , wherein the at least one isoxazoline active agent is enriched in a compound of formula (S)-(Ia):

or a pharmaceutically acceptable salt thereof.

5. The long-acting injectable formulation according to claim 1 wherein the formulation treats parasite infestations or infections for about 5 to 6 months.

6. The long-acting injectable formulation according to claim 1 wherein the formulation treats parasite infestations or infections for about 6 months.

7. The long-acting injectable formulation according to any one of claims 5 or 6 , wherein the parasites are fleas or ticks.

8. The long-acting injectable formulation according to claim 1 comprising:

a) about 5 to 30% (w/v) of the at least one isoxazoline active compound of formula (Ib) or a pharmaceutically acceptable salt thereof,

b) poloxamer 124 or poloxamer 181;

c) about 5% to 40% (w/v) of co-solvent selected from the group consisting of liquid polyethylene glycol, ethanol, isopropanol, and a mixture thereof;

d) optionally, about 0.01% to about 2.0% (w/v) of an antioxidant; and

e) optionally, about 0.01% to about 5.0% (w/v) of a pharmaceutically acceptable additive,

excipient or mixtures thereof;

wherein the only pharmaceutically acceptable polymer present in said long-acting injectable composition is said poloxamer and wherein the poloxamer is present in the overall composition in a proportion representing the complement to 100% of the composition.

9. The long-acting injectable formulation according to claim 8 , wherein the at least one isoxazoline active agent is:

or a pharmaceutically acceptable salt thereof.

10. The long-acting formulation according to claim 1 , which further comprises an effective amount at least one additional pharmaceutically active agent.

11. The long-acting formulation according to claim 10 , wherein the at least one additional pharmaceutically active agent is a macrocyclic lactone.

12. The long-acting formulation according to claim 11 , wherein the macrocyclic lactone is abamectin, dimadectin, doramectin, emamectin, eprinomectin, ivermectin, latidectin, lepimectin, selamectin, ML-1,694,554, milbemectin, milbemycin D, moxidectin or nemadectin.

13. A method for treating a parasitic infection or infestation in an animal in need thereof for a period of 3 to 6 months which comprises administering the long acting injectable formulation according to any one of claim 1 , 2 - 4 , or 8 - 12 to said animal.

14. The method according to claim 13 wherein the animal is a dog, cat, sheep or cattle.

15. The method according to claim 13 wherein the parasites are treated for about 5 to 6 months.

16. The method according to claim 13 wherein the parasites are treated for about 6 months.

17. The method according to claim 13 wherein the parasites are fleas and/or ticks.