Solid Oral Pharmaceutical Compositions for Isoxazoline Compounds

1 . A method of preparing solid oral 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;

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, am inocarbonyl, 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, comprising

a. dissolving the isoxazoline compound of formula (I) in a solvent;

b. adding the isoxazoline solution to a solid carrier and mix to form a first mixture;

c. adding all other dry excipients to the first mixture and mix to form a second mixture;

d. adding liquid ingredients, glycerol and soybean oil, to the second dry mixture;

e. mixing to form wet mass;

f. melting a polyethylene glycol forming agent and adding to the wet mass;

p. mixing to form the final bulk mass; and

h. forming soft chewable tablets in a forming machine.

2 . (canceled)

3 . The method of claim 1 wherein the solid carrier is microcrystalline cellulose.

4 . The method of any of claim 1 wherein the solvent is selected from 2-pyrrolidone, dimethyl acetamide or mixtures thereof.

5 . The method of claim 1 wherein the solvent is dimethyl acetamide.

6 . (canceled)

7 . The method of claim 1 wherein the isoxazoline compound is fluralaner.

8 . The method of claim 1 wherein the isoxazoline compound is 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N—[(Z)-(methoxyimino)methyl]-2-methyl-benzamide.

9 . The method of claim 1 wherein the isoxazoline compound is afoxolaner.

10 . The method of claim 1 wherein the isoxazoline compound is 5-[5-(3,5-Dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-3-methyl-N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]-2-thiophenecarboxamide.

11 . The method of claim 1 wherein the isoxazoline compound is 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-N-(thietan-3-yl)benzamide.

12 . The method of claim 1 wherein the method further comprises the addition of an additional pharmaceutically active compound.

13 . The method of claim 12 wherein the additional pharmaceutically active compound is a macrocyclic lactone selected from the group of ivermectin, milbemycin, and moxidectin.

14 - 29 . (canceled)

30 . The method of claim 1 , wherein n is an integer 1, 2 or 3.

31 . The method of claim 1 , wherein R 2 is CF 3 or CF 2 Cl.

32 . The method of claim 1 , wherein two adjacent radicals Y form together a three or four membered chain.

33 . The method of claim 1 , wherein Z A is CF 3 .