Soft Chewable Pharmaceutical Products

Abstract

A soft chewable pharmaceutical product for delivery of a pharmaceutically acceptable active ingredient to an animal comprising pamoic acid or a pharmaceutically acceptable salt and a process for the manufacture of such soft chewable pharmaceutical product.

1 . A soft chewable veterinary pharmaceutical product comprising as ingredients,
 pamoic acid or a pharmaceutically acceptable salt thereof,   one or more active pharmaceutical ingredient,   a liquid component, and   a forming agent.   
     
     
         2 . The product according to  claim 1  wherein the product comprises sodium pamoate. 
     
     
         3 . The product according to  claim 1  wherein the amount of pamoic acid or the pharmaceutically acceptable salt thereof is between 1.5 and 30% w/w. 
     
     
         4 . The product according to  claim 3  wherein the amount of pamoic acid or the pharmaceutically acceptable salt thereof is between 2 and 5% w/w. 
     
     
         5 . (canceled) 
     
     
         6 . The product according to  claim 1 , additionally comprising one or more of the following excipients:
 a filler,   a stabilizer component,   a flavoring component, and   a sugar component.   
     
     
         7 . The product according to  claim 1  wherein the active pharmaceutical ingredient is 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 (CF 3 ); 
         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. 
       
     
     
         8 . The product according to  claim 7  wherein the active pharmaceutical ingredient is 4-[5-(3,5-Dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]-2-methyl-N-[(2,2,2-trifluoro-ethylcarbamoyl)-methyl]-benzamide. 
     
     
         9 . The product according to  claim 7  wherein the active pharmaceutical ingredient is 4-[5-[3-Chloro-5-(trifluoromethyl)phenyl]-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N-[2-oxo-2-[(2,2,2-trifluoroethyl)amino]ethyl]-1-naphthalenecarboxamide. 
     
     
         10 . The product according to  claim 7  wherein the active pharmaceutical ingredient is 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-N-(thietan-3-yl)benzamide. 
     
     
         11 . The product according to  claim 7  wherein the active pharmaceutical ingredient 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. 
     
     
         12 . The product according to  claim 1  wherein more than one active pharmaceutical ingredient is present. 
     
     
         13 . The product according to  claim 12  wherein the combination of active pharmaceutical ingredients comprises one or more antiparasitics. 
     
     
         14 . A process for the manufacture of a product according to  claim 1  in a forming machine comprising the steps of
 a) mixing the ingredients into a dough, 
 b) filling a mold with dough, and 
 c) removing the dough from the mold, 
 
       wherein in the mixing step a) the pamoic acid or the pharmaceutically acceptable salt thereof is mixed with the other ingredients. 
     
     
         15 . The process of  claim 14 , wherein the lubricity of a product is increased when filling the mold with dough or when removing the dough from the mold or both. 
     
     
         16 - 17 . (canceled) 
     
     
         18 . A method of controlling a parasitic insect, acarid or nematode infestation of an animal comprising administering to the animal a soft chewable veterinary pharmaceutical composition comprising
 4-[5-(3,5-Dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]-2-methyl-N-[(2,2,2-trifluoro-ethylcarbamoyl)-methyl]-benzamide;   pamoic acid or a pharmaceutically acceptable salt thereof,   a liquid component, and   a forming agent.   
     
     
         19 . The method according to  claim 18 , wherein the liquid component comprises one or more oils, one or more non-aqueous solvents and one or more humectants. 
     
     
         20 . The method according to  claim 19 , wherein the humectant is glycerol. 
     
     
         21 . The method according to  claim 19 , wherein the oil is soybean oil. 
     
     
         22 . The method according to  claim 18 , wherein the forming agent comprises a polyethylene glycol. 
     
     
         23 . The method according to  claim 18 , wherein in the composition comprises soy bean oil, glycerol and polyethylene glycol 3350. 
     
     
         24 . A chewable veterinary pharmaceutical product comprising as ingredients, -4-[5-(3,5-Dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]-2-methyl-N-[(2,2,2-trifluoro-ethylcarbamoyl)-methyl]-benzamide;
 sodium pamoate;   a liquid component comprising one or more oils, one or more non-aqueous solvents and one or more humectants; and   a forming agent.   
     
     
         25 . The product according to  claim 24  comprising soy bean oil, glycerol and polyethylene glycol 3350. 
     
     
         26 . The product of  claim 1 , further comprising one or more excipients. 
     
     
         27 . The product of  claim 1 , wherein the active pharmaceutical ingredient is 4-[5-(3,5-dichlorophenyl)-4,5-dihydro-5-(trifluoromethyl)-3-isoxazolyl]-N—[(Z)-(methoxyimino)methyl]-2-methyl-benzamide. 
     
     
         28 . The product of  claim 7 , wherein n is an integer 1, 2 or 3. 
     
     
         29 . The product of  claim 7 , wherein R 2  is CF 3  or CF 2 Cl. 
     
     
         30 . The product of  claim 7 , wherein two adjacent radicals Y form together a three or four member chain.