TABLETS COMPRISING 2-HYDROXY-6-((2-(1-ISOPROPYL-1H-PYRAZOL-5-YL)PYRIDIN-3-YL)METHOXY)BENZALDEHYDE

1 . A tablet comprising about 50% to about 70% by weight of 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde and a microcrystalline cellulose as a filler provided that at least one microcrystalline cellulose is a high-compactable microcrystalline cellulose and wherein the % by weight is relative to the total weight of the tablet.

2 . The tablet of claim 1 , wherein the amount of 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde comprises from about 50% to about 65% by weight of the tablet.

3 . The tablet of claim 1 , wherein 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde comprises about 65% by weight of the tablet.

4 . The tablet of claim 1 , wherein 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde comprises about 60%±2% by weight of the tablet.

5 . The tablet of any one of claims 1-4 , wherein the high-compactable microcrystalline cellulose comprises from about 20% to about 40% by weight of the tablet.

6 . The tablet of claim 5 , wherein the high-compactable microcrystalline cellulose comprises about 30% by weight of the tablet.

7 . The tablet of claim 5 , wherein the high-compactable microcrystalline cellulose comprises 35%±2% by weight of the tablet.

8 . The tablet of any one of claims 1-7 , wherein the high-compactable microcrystalline cellulose is Ceolus™ UF-711.

9 . The tablet of any one of claims 1-7 , wherein the high-compactable microcrystalline cellulose is Ceolus™ KG-1000 or KG-802.

10 . The tablet of any one of claims 1-9 , wherein 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde is in a substantially pure crystalline ansolvate form characterized by at least two X-ray powder diffraction peaks (Cu Kα radiation) selected from 13.37°, 14.37°, 19.950 and 23.92°2θ (each ±0.2 °2θ).

11 . The tablet of any one of claims 1-9 , consisting essentially of 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde as a crystalline ansolvate form characterized by at least two X-ray powder diffraction peaks (Cu Kα radiation) selected from 13.37°, 14.37°, 19.95° and 23.92°2θ (each ±0.2 °2θ).

12 . The tablet of claim 10 or 11 , wherein the crystalline ansolvate form of 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde is characterized by at least three X-ray powder diffraction peaks (Cu Kα radiation) selected from 13.37°, 14.37°, 19.95° and 23.92°2θ (each ±0.2 °2θ).

13 . The tablet of any one of claims 1-9 , wherein the 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde comprises 95% by weight Form II characterized by X-ray powder diffraction peaks (Cu Kα radiation) selected from 13.37°, 14.37°, 19.95° and 23.92°2θ (each ±0.2 °2θ) and 5% by weight 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)-pyridin-3-yl)methoxy)benzaldehyde is Form I and/or Form N.

14 . The tablet of any one of claims 1-13 , wherein the tablet further comprises a disintegrant from 0% to about 10% by weight of the tablet.

15 . The tablet of claim 14 , wherein the disintegrant comprises about 0.75% to about 1.5% by weight of the tablet.

16 . The tablet of claim 14 , wherein the disintegrant comprises about 1% to about 1.5% by weight of the tablet.

17 . The tablet of any one of claims 14-16 , wherein the disintegrant is croscarmellose sodium.

18 . The tablet of any one of claims 1-17 , wherein the tablet further comprises a lubricant from about 1.75% to about 2.75% by weight of the tablet.

19 . The tablet of claim 18 , wherein the lubricant comprises about 2.0% to about 2.5% by weight of the tablet.

20 . The tablet of claim 18 or 19 , wherein the lubricant is magnesium stearate.

21 . The tablet of any of claims 1-20 , wherein the tablet comprises from about 300 mg to about 900 mg of 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde.

22 . The tablet of any of claims 1-20 , wherein the tablet comprises 300 mg of 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde.

23 . The tablet of any one of claims 1-22 , wherein the tablet further comprises a surfactant from about 1% to about 2% by weight of the tablet.

24 . The tablet of claim 23 , wherein the surfactant comprises about 1.5% by weight of the tablet.

25 . The tablet of claim 23 or 24 , wherein the surfactant is sodium lauryl sulfate.

26 . A tablet comprising a granular component wherein the granular component comprises:

(i) about 60% by weight of 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde;

(ii) a high-compactable microcrystalline cellulose;

(iii) optionally a disintegrant;

(iv) a lubricant;

(v) optionally a surfactant; and

(vi) optionally a binder;

wherein the percentage by weight is relative to the total weight of the tablet.

27 . The tablet of claim 26 , wherein the granular component comprises:

(i) a high-compactable microcrystalline cellulose in the amount of about 27.50% by weight of the tablet;

(ii) a disintegrant in the amount of about 1% by weight of the tablet;

(iii) a lubricant in the amount of about 1.50% by weight of the tablet; and

(iv) optionally a surfactant in the amount of about 1.5% by weight of the tablet.

28 . The tablet of claim 27 , wherein the high-compactable microcrystalline cellulose is Ceolus™ UF-711; the disintegrant is croscarmellose sodium; the lubricant is magnesium stearate; 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde is a substantially pure crystalline ansolvate form characterized by at least two X-ray powder diffraction peaks (Cu Kα radiation) selected from 13.37°, 14.37°, 19.95° and 23.92°2θ (each ±0.2 °2θ); and the surfactant is absent.

29 . A tablet comprising a granular component wherein the granular component consists essentially of:

(i) about 60% by weight 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde;

(ii) a high-compactable microcrystalline cellulose;

(iii) optionally a disintegrant;

(iv) a lubricant;

(v) optionally a surfactant; and

(vi) optionally a binder;

wherein the percentage by weight is relative to the total weight of the tablet.

30 . The tablet of claim 29 , wherein:

(i) the amount of high-compactable microcrystalline cellulose is about 27.50% by weight of the tablet;

(ii) the amount of disintegrant is about 1% by weight of the tablet;

(iii) the amount of lubricant is about 1.50% by weight of the tablet; and

(iv) optionally, the amount of surfactant is about 1.5% by weight of the tablet.

31 . The tablet of claim 30 , wherein the high-compactable microcrystalline cellulose is Ceolus™ UF-711; the disintegrant is croscarmellose sodium; the lubricant is magnesium stearate; 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde is a substantially pure crystalline ansolvate form characterized by at least two X-ray powder diffraction peaks (Cu Kα radiation) selected from 13.37°, 14.37°, 19.95° and 23.92°2θ (each ±0.2 °2θ); and the surfactant is absent.

32 . The tablet of any one of claims 26-31 , further comprising an extragranular component.

33 . The tablet of claim 32 , wherein the extragranular component comprises:

(i) a microcrystalline cellulose;

(ii) a disintegrant;

(iii) optionally a surfactant;

(iv) a lubricant; and

(v) optionally a coating;

provided that at least one of the intragranular or extragranular components of the tablet comprises a surfactant.

34 . The tablet of claim 33 , wherein:

(i) the amount of extragranular microcrystalline cellulose comprises about 7.50% by weight of the tablet;

(ii) the amount of extragranular disintegrant comprises about 0.25% by weight of the tablet;

(iii) the amount of extragranular surfactant comprises about 1.50% by weight of the tablet; and

(iv) the amount of extragranular lubricant comprises about 0.75% by weight of the tablet.

35 . The tablet of claim 34 , wherein the extragranular microcrystalline cellulose is high-compactable microcrystalline cellulose, the extragranular disintegrant is croscarmellose sodium, the extragranular lubricant is magnesium stearate; and the extragranular surfactant is present and is sodium lauryl sulfate.

36 . The tablet of claim 35 , wherein the high-compactable microcrystalline cellulose is Ceolus™ UF-711.

37 . The tablet of claim 32 , wherein the extragranular component consists essentially of:

(i) a microcrystalline cellulose;

(ii) a disintegrant;

(iii) optionally a surfactant;

(iv) a lubricant; and

(v) optionally a coating;

provided that at least one of intragranular or extragranular component of the tablet contains a surfactant.

38 . The tablet of any of claims 26-37 , wherein the tablet comprises from about 300 to about 900 mg of 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde.

39 . The tablet of claim 38 , wherein the tablet comprises 300 mg of 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde.

40 . The tablet of claim 38 , wherein the tablet comprises 900 mg of 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde.

41 . The tablet of any one of claims 1-40 , further comprising a glidant in an amount of less than about 2% by weight of the tablet.

42 . The tablet of claim 41 , wherein the glidant is in an amount of about 0.75% by weight of the tablet.

43 . The tablet of claim 41 or 42 , wherein the glidant is colloidal silicon dioxide.

44 . A tablet comprising:

(i) an intragranular component comprising:

(a) 60% by weight of 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde as a crystalline form characterized by two, three or four X-ray powder diffraction peaks (Cu Kα radiation) selected from 13.37°, 14.37°, 19.95° and 23.92°2θ (each ±0.2 °2θ);

(b) 27.50% by weight of microcrystalline cellulose Ceolus™ UF-711;

(c) 1.0% by weight of Croscarmellose Sodium; and

(d) 1.50% by weight of Magnesium Stearate; and

(ii) an extragranular component comprising:

(a) 9.0% by weight of microcrystalline cellulose Ceolus™ UF-711;

(b) 0.25% by weight of Croscarmellose Sodium; and

(c) 0.75% by weight of Magnesium Stearate;

wherein the percentage by weight is relative to the total weight of the tablet.

45 . A tablet comprising:

(i) an intragranular component comprising:

(a) 60% by weight of 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde as a crystalline form characterized by two, three or four X-ray powder diffraction peaks (Cu Kα radiation) selected from 13.37°, 14.37°, 19.950 and 23.92°2θ (each ±0.2 °2θ);

(b) 27.50% by weight of microcrystalline cellulose Ceolus™ UF-711;

(c) 1.0% by weight of Croscarmellose Sodium; and

(d) 1.50% by weight of Magnesium Stearate; and

(ii) an extragranular component comprising:

(a) 7.50% by weight of microcrystalline cellulose Ceolus™ UF-711;

(b) 0.25% by weight of Croscarmellose Sodium;

(c) 0.75% by weight of Magnesium Stearate; and

(d) 1.50% by weight Sodium Lauryl Sulfate;

wherein the percentage by weight is relative to the total weight of the tablet.

46 . A dispersible tablet comprising:

(i) about 30% to about 70% by weight of Compound 1;

(ii) filler;

(iii) disintegrant;

(iv) glidant; and

(v) a lubricant;

wherein the percentage by weight is relative to the total weight of the tablet.

47 . A dispersible tablet comprising:

(i) about 30% to about 70% by weight of Compound 1;

(ii) a filler;

(iii) a disintegrant;

(iv) a glidant;

(v) a lubricant;

(vi) a surfactant; and

(vii) optionally a binder;

wherein the amount of disintegrant to filler is in a ratio of about 1:28, and wherein the percentage by weight is relative to the total weight of the tablet.

48 . A tablet comprising:

(i) about 30% to about 70% by weight of Compound 1;

(ii) a filler;

(iii) less than about 2% by weight of disintegrant;

(iv) a glidant;

(v) a lubricant;

(vi) a surfactant; and

(vii) optionally a binder;

wherein the amount of disintegrant to filler is in a ratio of about 1:28 and wherein the percentage by weight is relative to the total weight of the tablet.

49 . A dispersible tablet comprising:

(i) about 60% by weight of Compound 1 Form II;

(ii) about 20% to about 35% by weight of microcrystalline cellulose;

(iii) about 1% to about 2% by weight of croscarmellose sodium;

(iv) less than about 2% by weight of colloidal silicon dioxide;

(v) about 1% to about 5% by weight of magnesium stearate;

(vi) a sweetener;

(vii) a flavoring agent; and

(viii) a coloring agent;

wherein the percentage by weight is relative to the total weight of the tablet and wherein the dispersible tablet disintegrates in a liquid in less than 1 minute.

50 . A method for treating a condition associated with oxygen deficiency in a patient, the method comprising administering to the patient having a condition associated with oxygen deficiency a tablet of any one of claims 1-49 , wherein the tablet comprises a therapeutically effective amount of 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde.

51 . The method of claim 50 , wherein the condition is sickle cell disease, cancer, a pulmonary disorder such as idiopathic pulmonary fibrosis, stroke, high altitude sickness, an ulcer, a pressure sore, Alzheimer's disease, acute respiratory disease syndrome, acute lung injury, or a wound.

52 . The method of claim 51 , wherein the condition is sickle cell disease.

53 . The method of claim 51 , wherein the condition is a pulmonary disorder.

54 . The method of claim 51 , wherein the condition is idiopathic pulmonary fibrosis.

55 . The method of any one of claims 50-54 , wherein the therapeutically effective amount of 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde is from 600 to 2000 mg once a day.

56 . The method of any one of claims 50-54 , wherein the therapeutically effective amount of 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde is 900 mg or 1500 mg once a day.

57 . The method of any one of claims 50-54 , wherein the tablet contains 300, 750 or 900 mg of 2-hydroxy-6-((2-(1-isopropyl-1H-pyrazol-5-yl)pyridin-3-yl)methoxy)benzaldehyde.