Stable ibuprofen injectable composition

Abstract

The present invention relates to a composition for injectable formulation, the composition comprising: —An aqueous solution of ibuprofen and arginine with a molar ratio of ibuprofen:arginine comprised between 1:1.1 and 1:2.1; —An aqueous solution of a diuretic compound comprising between 3.9% and 4.35% w/v of the diuretic compound. The present invention also concerns a pharmaceutical composition comprising said composition and the use of said composition and said pharmaceutical composition.

Claims

1. Aqueous ibuprofen injectable formulation consisting of arginine and solubilized ibuprofen in a diuretic solution of mannitol in water for injection (WFI); wherein the molar ratio of ibuprofen:arginine is between 1:1.22388 and 1:1.9908 or between 1:1.22 and 1:1.99, the diuretic solution of mannitol comprises between 4.05% to 4.25% w/v of mannitol and the concentration of ibuprofen is between 1 mg/mL and 8 mg/m/L or between 25 mg/mL and 200 mg/mL.

2. The aqueous ibuprofen injectable formulation according to claim 1, wherein the pH of the injectable formulation is 7.47 at 37° C., 7.41 at 38° C. and 7.38 at 39° C., measured as per requirement of European Pharmacopeia.

3. The aqueous ibuprofen injectable formulation according to claim 1, wherein the pH of the injectable formulation is 8.20 at 20° C., measured as per requirement of European Pharmacopeia.

4. The aqueous ibuprofen injectable formulation according to claim 1, wherein the molar ratio of ibuprofen:arginine is between 1:1.22388 and 1:1.22.

5. The aqueous ibuprofen injectable formulation according to claim 4, wherein the molar ratio of ibuprofen:arginine is 1:1.22388 or 1:1.22.

6. Pharmaceutical composition consisting of the injectable ibuprofen formulation according to claim 1, wherein the concentration of ibuprofen is between 1 mg/mL-8 mg/mL.

7. Pharmaceutical composition consisting of the injectable ibuprofen formulation according to claim 1, wherein the concentration of ibuprofen is between 25 mg/mL-200 mg/mL.

8. The pharmaceutical composition according to claim 6, wherein the pharmaceutical composition is stable for 48 months in glass bottle with a stopper selected from a rubber or aluminum cap.

9. The pharmaceutical composition according to claim 6, wherein the pharmaceutical composition is stable for 48 months in a plastic bottle.

10. The pharmaceutical composition according to claim 6, wherein the pharmaceutical composition is stable for 48 months in polymer bags.

11. The pharmaceutical composition according to claim 6, wherein said pharmaceutical composition is prepared aseptically.

12. The pharmaceutical composition according to claim 6, wherein said pharmaceutical composition is autoclavable at a temperature around 121° C.

13. The aqueous ibuprofen injectable formulation according to claim 1 or pharmaceutical composition according to claim 6, for use in an analgesic treatment of a patient.

14. The pharmaceutical composition according to claim 7, wherein the pharmaceutical composition is stable for 48 months in a glass bottle with stopper selected from a rubber or aluminum cap.

15. The pharmaceutical composition according to claim 7, wherein the pharmaceutical composition is stable for 48 months in a plastic bottle.

16. The pharmaceutical composition according to claim 7, wherein the pharmaceutical composition is stable for 48 months in polymer bags.

17. The pharmaceutical composition according to claim 7, wherein said pharmaceutical composition is prepared aseptically.

18. The pharmaceutical composition according to claim 7, wherein said pharmaceutical composition is autoclavable at a temperature around 121° C.

19. The aqueous ibuprofen injectable formulation according to claim 1, wherein the pH of the injectable formulation is between 7.4 and 8.2 within the temperature range of 20° C. to 39° C., measured as per requirement of European Pharmacopeia.

20. The pharmaceutical composition according to claim 9, wherein the plastic bottle is made of LDPE, HDPE, PP or COC.

21. The pharmaceutical composition according to claim 15, wherein the plastic bottle is made of LDPE, HDPE, PP or COC.

Description

SUMMARY OF INVENTION

(1) The composition according to the independent claims provides a composition or a pharmaceutical composition exempt from, or minimizing the drawbacks of the known composition of above mentioned problems. Dependent claims describes optional features.

(2) The present invention provides a composition with a solubilized ibuprofen thanks to an aqueous solution of ibuprofen and arginine with a molar ratio of ibuprofen:arginine comprised between 1:1.1 and 1:2.1, in combination with a aqueous solution of a diuretic compound comprising between 3.9% and 4.35% w/v of the diuretic compound.

(3) Advantageously, the composition according to the present invention comprises a perfect combination ratio of Ibuprofen and Arginine in diuretic solution that eliminates the requirement of any buffer and pH adjustment or other additive and the known drawbacks related thereof.

(4) The composition according to the invention also provides a stable ibuprofen composition for injectable formulation.

(5) The present invention is an excellent analgesic treatment, for use in hospitals, for post operative pain and fever. The present invention, due to its rout of administration, can provide the patient an early recovery, as well as reduce the time of hospitalization and cost associated to the patient care.

(6) The current invention is sodium free, dextrose free and buffer free stable Ibuprofen intravenous injection or infusion. Sodium free, dextrose free and buffer free stable Ibuprofen intravenous injection or infusion increases the scope of application of current invention over existing marketed Ibuprofen injectable products and can help to optimize the safety and clinical efficacy of the patient as well as reduce the risk of disorders that may associated with cardiovascular system, hypertension, diabetic, perivascular infiltration and local tissue damage.

(7) For usage of present invention in high fever and normal body temperature pH of solution is very near to blood pH. At 37° C. pH is 7.47, at 38° C. pH is 7.41, at 39° C. pH is 7.38. Present invention is stable at real time and accelerated stability conditions as per ICH guidelines.

(8) In one embodiment, the composition comprises mannitol as osmotic agent making current invention Sodium free and dextrose free.

(9) In one embodiment, the pH for stability Ibuprofen infusion solution is 8.20 at 20° C. (measured as per requirement of European Pharmacopeia) 8.04 at 25° C. and 7.87 at 30° C.

(10) In one embodiment, the composition is an aqueous, sodium free, dextrose free and buffer free stable Ibuprofen Injectable formulation with molar concentration of ibuprofen to arginine (1:1.9908-1:1.22388) in 4.05%-4.25% w/v solution of mannitol in WFI with temperature dependent pH.

(11) In one embodiment, arginine is replaced by another nitrous oxide or nitric oxide precursor.

(12) In one embodiment, ibuprofen is replaced by another analgesic compound, for instance ibuprofen derivatives, or analgesic compound with similar solubility's properties.