SOLID ORAL PHARMACEUTICAL COMPOSITIONS FOR ISOXAZOLINE COMPOUNDS
A solid oral pharmaceutical composition for delivery of a pharmaceutically acceptable active ingredient to an animal where the composition comprises an isoxazoline compound, a solvent and an excipient, a process for the manufacture of such solid oral pharmaceutical composition and a method of controlling a parasite infection administering such solid oral pharmaceutical composition.
1 - 29 . (canceled)
30 . A soft chewable veterinary pharmaceutical composition comprising an isoxazoline compound of Formula (I)
wherein
R 1 =halogen, CF 3 , OCF 3 , CN,
n=integer from 0 to 3,
R 2 =C 1 -C 3 -haloalkyl,
T=5- or 6-membered ring, which is optionally substituted by one or more radicals Y,
Y=methyl, halomethyl, halogen, CN, NO 2 , NH 2 —C═S, or two adjacent radicals Y form together a chain, especially a three or four membered chain;
Q=X—NR 3 R 4 or a 5-membered N-heteroaryl ring, which is optionally substituted by one or more radicals;
X=CH 2 , CH(CH 3 ), CH(CN), CO, CS,
R 3 =hydrogen, methyl, haloethyl, halopropyl, halobutyl, methoxymethyl, methoxyethyl, halomethoxymethyl, ethoxymethyl, haloethoxymethyl, propoxymethyl, ethylaminocarbonylmethyl, ethylaminocarbonylethyl, dimethoxyethyl, propynylaminocarbonylmethyl, N-phenyl-N-methyl-amino, haloethylaminocarbonylmethyl, haloethylaminocarbonylethyl, tetrahydrofuryl, methylaminocarbonylmethyl, (N,N-dimethylamino)-carbonylmethyl, propylaminocarbonylmethyl, cyclopropylaminocarbonylmethyl, propenylaminocarbonylmethyl, haloethylaminocarbonylcyclopropyl,
wherein Z A =hydrogen, halogen, cyano, halomethyl;
R 4 =hydrogen, ethyl, methoxymethyl, halomethoxymethyl, ethoxymethyl, haloethoxymethyl, propoxymethyl, methylcarbonyl, ethylcarbonyl, propylcarbonyl, cyclopropylcarbonyl, methoxycarbonyl, methoxymethylcarbonyl, aminocarbonyl, ethylaminocarbonylmethyl, ethylaminocarbonylethyl, dimethoxyethyl, propynylaminocarbonylmethyl, haloethylaminocarbonylmethyl, cyanomethylaminocarbonylmethyl, or haloethylaminocarbonylethyl;
Or R 3 and R 4 together form a substituent selected from the group consisting of:
or a salt or solvate thereof, a solid carrier and a solvent wherein the solvent is 2.0-35.0% w/w of the composition with solubility for the isoxazoline compound and wherein the solid carrier is microcrystalline cellulose.
31 . The soft chewable veterinary pharmaceutical composition of claim 30 further comprising pamoic acid or a pharmaceutically acceptable salt thereof.
32 . The soft chewable veterinary pharmaceutical composition of claim 30 wherein the isoxazoline compound is fluralaner.
33 . The soft chewable veterinary pharmaceutical composition of claim 30 wherein the composition comprises an additional pharmaceutically active compound.
34 . A method of controlling parasite infestation in an animal comprising administering to the animal a therapeutically effective amount of the composition of claim 30 .
35 . A soft chewable veterinary pharmaceutical composition comprising an isoxazoline compound of Formula (I)
wherein
R 1 =halogen, CF 3 , OCF 3 , CN,
n=integer from 0 to 3,
R 2 =C 1 -C 3 -haloalkyl,
T=5- or 6-membered ring, which is optionally substituted by one or more radicals Y,
Y=methyl, halomethyl, halogen, CN, NO 2 , NH 2 —C═S, or two adjacent radicals Y form together a chain, especially a three or four membered chain;
Q=X—NR 3 R 4 or a 5-membered N-heteroaryl ring, which is optionally substituted by one or more radicals;
X=CH 2 , CH(CH 3 ), CH(CN), CO, CS,
R 3 =hydrogen, methyl, haloethyl, halopropyl, halobutyl,
methoxymethyl, methoxyethyl, halomethoxymethyl, ethoxymethyl, haloethoxymethyl, propoxymethyl, ethylaminocarbonylmethyl, ethylaminocarbonylethyl, dimethoxyethyl, propynylaminocarbonylmethyl, N-phenyl-N-methyl-amino, haloethylaminocarbonylmethyl, haloethylaminocarbonylethyl, tetrahydrofuryl, methylaminocarbonylmethyl, (N,N-dimethylamino)-carbonylmethyl, propylaminocarbonylmethyl, cyclopropylaminocarbonylmethyl, propenylaminocarbonylmethyl, haloethylaminocarbonylcyclopropyl,
wherein Z A =hydrogen, halogen, cyano, halomethyl;
R 4 =hydrogen, ethyl, methoxymethyl, halomethoxymethyl, ethoxymethyl, haloethoxymethyl, propoxymethyl, methylcarbonyl, ethylcarbonyl, propylcarbonyl, cyclopropylcarbonyl, methoxycarbonyl, methoxymethylcarbonyl, aminocarbonyl, ethylaminocarbonylmethyl, ethylaminocarbonylethyl, dimethoxyethyl, propynylaminocarbonylmethyl, haloethylaminocarbonylmethyl, cyanomethylaminocarbonylmethyl, or haloethylaminocarbonylethyl;
Or R 3 and R 4 together form a substituent selected from the group consisting of:
or a salt or solvate thereof, a solid carrier and a solvent wherein the solvent is 2.0-35.0% w/w of the composition with solubility for the isoxazoline compound and wherein the solvent is 2-pyrrolidone.
36 . The soft chewable veterinary pharmaceutical composition of claim 35 further comprising pamoic acid or a pharmaceutically acceptable salt thereof.
37 . The soft chewable veterinary pharmaceutical composition of claim 35 wherein the isoxazoline compound is fluralaner.
38 . The soft chewable veterinary pharmaceutical composition of claim 35 wherein the composition comprises an additional pharmaceutically active compound.
39 . A method of controlling parasite infestation in an animal comprising administering to the animal a therapeutically effective amount of the composition of claim 35 .
40 . A method of preparing the composition of claim 30 comprising dissolving the isoxazoline compound in the solvent and then adsorbing the resulting solution on to the solid carrier excipient.
41 . The method of claim 40 , where the solvent is 2-pyrrolidone or dimethyl acetamide.
42 . The method of claim 40 , where the solvent is 2-pyrrolidone.
43 . The method of claim 40 , where the solvent is dimethyl acetamide.
44 . A method of preparing the composition of claim 35 comprising dissolving the isoxazoline compound in the solvent and then adsorbing the resulting solution on to the solid carrier excipient.
45 . The method of claim 44 , wherein the solid carrier is microcrystalline cellulose.