Pharmaceutical dronedarone composition for parenteral administration
View Patent ↗A subject-matter of the invention is a pharmaceutical composition for parenteral administration, characterized in that it comprises: dronedarone or one of its pharmaceutically acceptable salts as active principle; a physiologically acceptable buffer solution capable of maintaining the pH of the composition between 3 and 5; a physiologically acceptable water-soluble β-cyclodextrin derivative.
1. A pharmaceutical composition for parenteral administration comprising:
dronedarone or one of its pharmaceutically acceptable salts as active principle,
a physiologically acceptable buffer solution capable of maintaining the pH of the composition between 3 and 5,
a physiologically acceptable water-soluble β-cyclodextrin derivative.
2. A pharmaceutical composition according to claim 1 comprising from 0.01% to 4% of active principle.
3. A pharmaceutical composition according to claim 2 comprising from 0.4 to 0.8% of active principle.
4. A pharmaceutical composition according to claim 3 wherein the buffer solution is an aqueous solution comprising a buffer system chosen from the following:
acetic acid/alkali metal acetate,
fumaric acid/alkali metal fumarate,
succinic acid/alkali metal succinate,
citric acid/alkali metal citrate,
tartaric acid/alkali metal tartrate,
lactic acid/alkali metal lactate,
maleic acid/alkali metal maleate,
methanesulphonic acid/alkali metal methanesulphonate, or
monoalkali metal phosphate.
5. A pharmaceutical composition according to claim 4 wherein the buffer system is a monoalkali metal phosphate.
6. A pharmaceutical composition according to claim 5 wherein the monoalkali metal phosphate buffer solution maintains the pH at 4.5.
7. A pharmaceutical composition according to claim 6 wherein the ionic strength of the buffer solution is between 0.005 molar and 0.5 molar.
8. A pharmaceutical composition according to claim 7 wherein the ionic strength of the buffer solution is between 0.01 molar and 0.2 molar.
9. A pharmaceutical composition according to claim 8 wherein the ionic strength of the buffer solution is between 0.05 and 0.15 molar.
10. A pharmaceutical composition according to claim 9 wherein the buffer solution is a 0.05 to 0.15 molar aqueous solution of monoalkali metal phosphate.
11. A pharmaceutical composition according to claim 10 , wherein the alkali metal is sodium or potassium.
12. A pharmaceutical composition according to claim 11 wherein the water-soluble β-cyclodextrin derivative is chosen from hydroxypropyl-β-cyclodextrin, the sulphobutyl ether derivative of β-cyclodextrin, dimethyl-β-cyclodextrin, trimethyl-β-cyclodextrin, and their mixtures.
13. A pharmaceutical composition according to claim 12 wherein the water-soluble β-cyclodextrin derivative is hydroxypropyl-β-cyclodextrin.
14. A pharmaceutical composition according to claim 13 wherein the hydroxypropyl-β-cyclodextrin is present in a proportion of 0.5 to 50%.
15. A pharmaceutical composition according to claim 14 wherein the hydroxypropyl-β-cyclodextrin is present in a proportion of 5 to 20 times the weight of dronedarone or of one of its pharmaceutically acceptable salts.
16. A pharmaceutical composition according to claim 15 wherein the hydroxypropyl-β-cyclodextrin is present in a proportion of 12 to 13 times the weight of dronedarone or of one of its pharmaceutically acceptable salts.
17. A pharmaceutical composition according to claim 16 additionally comprising a preservative.
18. A pharmaceutical composition according to claim 16 additionally comprising a compound which makes it possible to maintain the isotonicity.
19. A pharmaceutical composition according to claim 1 wherein the active principle is dronedarone hydrochloride.
20. A pharmaceutical composition according to claim 1 wherein the buffer solution is an aqueous solution comprising a buffer system chosen from the following:
acetic acid/alkali metal acetate,
fumaric acid/alkali metal fumarate,
succinic acid/alkali metal succinate,
citric acid/alkali metal citrate,
tartaric acid/alkali metal tartrate,
lactic acid/alkali metal lactate,
maleic acid/alkali metal maleate,
methanesulphonic acid/alkali metal methanesulphonate, or
monoalkali metal phosphate.
21. A pharmaceutical composition according to claim 11 wherein the water-soluble β-cyclodextrin derivative is chosen from hydroxypropyl-β-cyclodextrin, the sulphobutyl ether derivative of β-cyclodextrin, dimethyl-β-cyclodextrin, trimethyl-β-cyclodextrin, and their mixtures.
22. A pharmaceutical composition according to claim 1 wherein the water-soluble β-cyclodextrin derivative is hydroxypropyl-β-cyclodextrin.
23. A pharmaceutical composition according to claim 1 additionally comprising a preservative.
24. A pharmaceutical composition according to claim 1 additionally comprising a compound which makes it possible to maintain the isotonicity.
25. A pharmaceutical composition according to claim 3 wherein the active principle is dronedarone hydrochloride.
26. A pharmaceutical composition according to claim 4 wherein the ionic strength of the buffer solution is between 0.005 molar and 0.5 molar.
27. A pharmaceutical composition according to claim 4 wherein the buffer solution is a 0.05 to 0.15 molar aqueous solution of monoalkali metal phosphate.
28. A pharmaceutical composition according to claim 5 , wherein the alkali metal is sodium or potassium.
29. A pharmaceutical composition according to claim 11 wherein the active principle is dronedarone hydrochloride.
30. A pharmaceutical composition according to claim 13 wherein the active principle is dronedarone hydrochloride.
31. A pharmaceutical composition according to claim 14 wherein the active principle is dronedarone hydrochloride.
32. A pharmaceutical composition according to claim 16 wherein the active principle is dronedarone hydrochloride.
33. A pharmaceutical composition according to claim 20 wherein the water-soluble β-cyclodextrin derivative is chosen from hydroxypropyl-β-cyclodextrin, the sulphobutyl ether derivative of β-cyclodextrin, dimethyl-β-cyclodextrin, trimethyl-β-cyclodextrin, and their mixtures.
34. A pharmaceutical composition according to claim 22 wherein the hydroxypropyl-β-cyclodextrin is present in a proportion of 0.5 to 50%.
35. A pharmaceutical composition according to claim 1 comprising:
4.26 mg of dronedarone hydrochloride;
50.00 mg of hydroxypropyl-β-cyclodextrin;
15.60 mg of monosodium phosphate dihydrate; and
8.00 mg of mannitol.
36. A pharmaceutical composition according to claim 1 comprising:
4.26 mg of dronedarone hydrochloride;
50.00 mg of hydroxypropyl-β-cyclodextrin;
12.00 mg of anhydrous monosodium phosphate; and
8.00 mg of mannitol.
37. A pharmaceutical composition according to claim 1 comprising:
1.065 mg of dronedarone hydrochloride;
50.00 mg of hydroxypropyl-β-cyclodextrin;
12.00 mg of anhydrous monosodium phosphate; and
8.00 mg of mannitol.
38. A pharmaceutical composition according to claim 1 additionally comprising a bactericide.