Pharmaceutical composition comprising ibuprofen and arginine

1 . A pharmaceutical composition to be applied on the pulmonary epithelium for the treatment of respiratory diseases, comprising ibuprofen, arginine, solubilized in a hypertonic aqueous solution at a pH between 7.5 and 9.5 wherein the arginine/ibuprofen molar ratio is lower than 6.5.

2 . The pharmaceutical composition of claim 1 , wherein the arginine/ibuprofen molar ratio is greater than 1.

3 . The pharmaceutical composition of claim 1 , wherein the ibuprofen is in a concentration from 10 mM to 50 mM.

4 . The pharmaceutical composition of claim 1 , wherein the ibuprofen is racemic.

5 . The pharmaceutical composition of claim 1 , wherein the ibuprofen is the S enantiomer.

6 . The pharmaceutical composition of claim 1 , wherein the ibuprofen is the R enantiomer.

7 . The pharmaceutical composition of claim 1 , wherein said ibuprofen comprises as a counterion the monovalent cation selected from the group consisting of sodium, potassium, lithium, arginate, lysinate, histidinate and combinations thereof.

8 . The pharmaceutical composition of claim 1 , wherein said arginine comprises a concentration from 10 mM to 250 mM.

9 . The pharmaceutical composition of claim 1 , further comprising a pH in aqueous solution from 8.0 to 9.0.

10 . The pharmaceutical composition of claim 9 , wherein the pH in aqueous solution is 8.5.

11 . The pharmaceutical composition of claim 1 , wherein the composition is in nebulizer or inhalation form.

12 . The pharmaceutical composition of claim 1 , wherein the composition is in liquid, powder or lyophilized state.

13 . The pharmaceutical composition of claim 1 , wherein said composition is hypertonic comprising a salt in a concentration from 0.3 to 2.0 M.

14 . The pharmaceutical composition of claim 1 , wherein said composition is hypertonic comprising a salt in a concentration from 0.4 to 1.1 M.

15 . The pharmaceutical composition of claim 1 , wherein said composition is hypertonic comprising a salt in a concentration from 0.5 to 1.0 M.

16 . The pharmaceutical composition of claim 13 , wherein said salt is selected from the group consisting of sodium chloride, potassium chloride, sodium carbonate and combinations thereof.

17 . The pharmaceutical composition of claim 16 , wherein said salt is NaCl.

18 . A manufacturing process of a pharmaceutical composition of claim 1 , wherein said process comprises the following steps:

a) mixing said ibuprofen in its acid state with aqueous solution of Na 2 CO 3 at more than 40° C. and stirring to maintain its suspension;

b) adding said arginine on the step a);

c) adding NaOH or Na 2 CO 3 to reach a pH value from 7.5 to 9.5 and stirring to allow a complete solubilization of said ibuprofen and arginine to obtain a concentration between 1 and 100 mg/mL for ibuprofen and between 5 and 100 mg/mL for basic amino acid;

d) adding said salt suitable for human consumption to the preparation of said step c), in a concentration from 0.3 to 1.0 M and;

e) filtering the preparation in said step d), through a 0.22 micron pore filter.

19 . The process of claim 18 , further comprising the following step:

f) lyophilizing the filtered solution in said step e).

20 . The process of claim 19 , further comprising the following step:

g) at the time to be applied to a patient in need thereof, resuspending the lyophilized composition of said step f) in water or in a 2.5% of glucose solution.

21 . A method for treating lung disease comprising administering an effective amount of the pharmaceutical composition of claim 1 to the pulmonary epithelium of the subject in need thereof.

22 . The method of claim 21 , wherein said pharmaceutical composition is administered to the subject as a nebulized solution.

23 . The method of claim 22 , wherein between 1 mL and 25 mL of said pharmaceutical composition is administered to the subject.

24 . The method of claim 22 , wherein between 1 mL and 10 mL of said pharmaceutical composition is administered to the subject.

25 . The method of claim 22 , wherein between 1 mL and 5 mL of said pharmaceutical composition is administered to the subject.

26 . The method of claim 22 , wherein 3 mL of said pharmaceutical composition is administered to the subject.

27 . The method of claim 21 , wherein said lung disease is selected from the group consisting of asthma, chronic obstructive pulmonary disease (COPD), cystic fibrosis (CF), pulmonary hypertension, bronchopulmonary dysplasia, acute respiratory distress syndrome (ARDS), respiratory syndrome coronavirus 2 (SARS-CoV-2), respiratory viral, mycotic or bacterial infection, bilateral pneumonia, and bronchiectasis.

28 . The method of claim 21 , wherein the subject is hypoxic.

29 . The method of claim 28 , wherein the subject has a pulse-oximetry blood-oxygen saturation level of less than 92%.

30 . The method of claim 21 , wherein the subject has a respiratory rate of 21-25 breaths/minute.

31 . The method of claim 21 , wherein the subject has a respiratory rate of 25-30 breaths/minute.

32 . The method of claim 21 , wherein the subject has a respiratory rate of 30-40 breaths/minute.

33 . The method of claim 21 , wherein the subject has a respiratory rate over 41 breaths/minute.

34 . The method of claim 21 , wherein the subject has a pulse rate of 91-110 beats/minute.

35 . The method of claim 21 , wherein the subject has a pulse rate of 111-130 beats/minute.

36 . The method of claim 21 , wherein the subject has a pulse rate of over 131 beats/minute.

37 . The method of claim 21 , wherein the subject has a NEWS2 Score of 0-4.

38 . The method of claim 21 , wherein the subject has a NEWS2 Score of 5-6.

39 . The method of claim 21 , wherein the subject has a NEWS2 Score of 7 or greater.

40 . The method of claim 21 , wherein the subject is intubated.

41 . The method of claim 21 , wherein the subject is pre-intubation.

42 . The method of claim 21 , wherein the subject is non-hypoxic.