Solid oral pharmaceutical compositions for isoxazoline compounds

Abstract

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.