Soft chewable pharmaceutical products
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,
sodium pamoate,
one or more active pharmaceutical ingredient,
a liquid component, and
a forming agent;
wherein the amount of sodium pamoate is between 1.5 and 30% w/w.
2. The product according to claim 1 wherein the amount of sodium pamoate is between 2 and 5% w/w.
3. 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.
4. 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, 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.
5. The product according to claim 4 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.
6. The product according to claim 4 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.
7. The product according to claim 4 wherein the active pharmaceutical ingredient is 4-[5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4H-isoxazol-3-yl]-2-methyl-N-(thietan-3-yl)benzamide.
8. The product according to claim 4 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.
9. The product according to claim 1 wherein more than one active pharmaceutical ingredient is present.
10. The product according to claim 9 wherein the combination of active pharmaceutical ingredients comprises one or more antiparasitics.
11. The product of claim 1 , further comprising one or more excipients.
12. 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.
13. The product of claim 4 , wherein n is an integer 1, 2 or 3.
14. The product of claim 4 , wherein R 2 is CF 3 or CF 2 Cl.
15. The product of claim 4 , wherein two adjacent radicals Y form together a three or four member chain.
16. The product of claim 5 , wherein the isoxazoline compound is an enantiomer of 4-[5-(3,5-Dichlorophenyl)-5-trifluoromethyl-4,5-dihydroisoxazol-3-yl]-2-methyl-N-[(2,2,2-trifluoro-ethylcarbamoyl)-methyl]-benzamide.
17. 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;
wherein the amount of sodium pamoate is between 1.5 and 30% w/w.
18. The product according to claim 17 comprising soy bean oil, glycerol and polyethylene glycol 3350.
19. 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 sodium pamoate is mixed with the other ingredients;
wherein the amount of sodium pamoate is between 1.5 and 30% w/w.
20. The process of claim 19 , wherein the lubricity of a product is increased when filling the mold with dough or when removing the dough from the mold or both.
21. 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;
sodium pamoate,
a liquid component, and
a forming agent;
wherein the amount of sodium pamoate is between 1.5 and 30% w/w.
22. The method according to claim 21 , wherein the liquid component comprises one or more oils, one or more non-aqueous solvents and one or more humectants.
23. The method according to claim 22 , wherein the humectant is glycerol.
24. The method according to claim 22 , wherein the oil is soybean oil.
25. The method according to claim 21 , wherein the forming agent comprises a polyethylene glycol.
26. The method according to claim 21 , wherein in the composition comprises soy bean oil, glycerol and polyethylene glycol 3350.