Crystalline (2S,4R)-5-(5′-chloro-2′-fluoro-[1,1′-biphenyl]-4-yl)-2-(ethoxymethyl)-4-(3-hydroxyisoxazole-5-carboxamido)-2-methylpentanoic acid and uses thereof
In one aspect, the invention relates to a crystalline form of the structure: or a pharmaceutically acceptable salt thereof, having neprilysin inhibition activity. In another aspect, the invention relates to pharmaceutical compositions comprising this crystalline form; methods of using this crystalline form and its soluble form (I); and processes for preparing soluble (I) and crystalline (I′) forms.
1. A composition comprising a crystalline form of a compound or salt of Formula (I):
2. The composition of claim 1 , wherein the crystalline form is characterized by a powder x-ray diffraction pattern comprising peaks at 6.51±0.2 and 15.07±0.2 degrees 2θ.
3. The composition of claim 1 , wherein the crystalline form is characterized by a powder x-ray diffraction pattern comprising peaks at 11.62±0.2, 13.05±0.2, and 23.28±0.2 degrees 2θ.
4. The composition of claim 2 , wherein the powder x-ray diffraction pattern further comprises at least one peak selected from 11.62±0.2, 13.05±0.2, and 23.28±0.2 degrees 2θ.
5. The composition of claim 2 , wherein the powder x-ray diffraction pattern further comprises peaks at 11.62±0.2, 13.05±0.2, and 23.28±0.2 degrees 2θ.
6. The composition of claim 2 , wherein the powder x-ray diffraction pattern further comprises at least one peak selected from 15.72±0.2, 17.12±0.2, 18.77±0.2, 19.63±0.2, 20.79±0.2, and 24.48±0.2 degrees 2θ.
7. The composition of claim 2 , wherein the powder x-ray diffraction pattern further comprises peaks at 15.72±0.2, 17.12±0.2, 18.77±0.2, 19.63±0.2, 20.79±0.2, and 24.48±0.2 degrees 2θ.
8. The composition of claim 5 , wherein the powder x-ray diffraction pattern further comprises peaks at 15.72±0.2, 17.12±0.2, 18.77±0.2, 19.63±0.2, 20.79±0.2, and 24.48±0.2 degrees 2θ.
9. The composition of claim 1 , wherein the crystalline form is characterized by a differential scanning calorimetry thermogram comprising an endotherm in the range of about 214 to 218° C.
10. The composition of claim 5 , wherein the crystalline form is further characterized by a differential scanning calorimetry thermogram comprising an endotherm in the range of about 214 to 218° C.
11. The composition of claim 8 , wherein the crystalline form is further characterized by a differential scanning calorimetry thermogram comprising an endotherm in the range of about 214 to 218° C.
12. The composition of claim 1 , wherein the crystalline form is non-solvated.
13. The composition of claim 1 , wherein the compound of Formula (I) is a free acid.
14. A pharmaceutical composition comprising the composition of claim 1 and a pharmaceutically acceptable carrier.
15. A pharmaceutical composition comprising the composition of claim 2 and a pharmaceutically acceptable carrier.
16. A pharmaceutical composition comprising the composition of claim 10 and a pharmaceutically acceptable carrier.
17. The pharmaceutical composition of claim 16 , wherein the pharmaceutically acceptable carrier is magnesium stearate.
18. An oral dosage form comprising the composition of claim 1 .
19. An oral dosage form comprising the composition of claim 2 .
20. An oral dosage form comprising the composition of claim 10 .