Anhydrous and hemihydrate crystalline forms of an (
View Patent ↗Crystalline (3R)-4-{[(1S)-2-methyl-1-(2-methylpropanoyloxyl)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid anhydrate and crystalline (3R)-4-{[(1S)-2-methyl-1-(2-methylpropanoyloxyl)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid hemihydrate, pharmaceutical compositions comprising such compounds, methods of making and methods of using the same are disclosed.
1. A method of treating a disease or disorder selected from spasticity, gastroesophageal reflux disease, emesis, cough, cocaine addiction and abuse, methamphetamine addiction and abuse, opioid addiction and abuse, alcohol addiction and abuse, nicotine addiction and abuse, neuropathic pain and musculoskeletal pain in a patient comprising administering to a patient in need of such treatment a therapeutically effective amount of crystalline (3R)-4-{[(1S)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid anhydrate exhibiting characteristic scattering angles (2θ) at least at 4.33°±0.2°, 4.76°±0.2°, 11.06°±0.2° and 11.61°±0.2° in an X-ray powder diffractogram measured using Cu-K α radiation.
2. The method of claim 1 , wherein the crystalline (3R)-4-{[(1S)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid anhydrate is in a sustained release oral dosage formulation.
3. A method of treating substance addition or abuse in a patient the substance is selected from the group of cocaine, methamphetamine, an opioid, alcohol and nicotine, comprising administering to a patient in need of such treatment a therapeutically effective amount of crystalline (3R)-4-{[(1S)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid anhydrate exhibiting characteristic scattering angles (2θ) at least at 4.33°±0.2°, 4.76°±0.2°, 11.06°±0.2° and 11.61°±0.2° in an X-ray powder diffractogram measured using Cu-K α radiation.
4. The method of claim 3 , wherein the crystalline (3R)-4-{[(1S)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid anhydrate is in a sustained release oral dosage formulation.
5. A method of treating alcohol addiction or abuse in a patient comprising administering to a patient in need of such treatment a therapeutically effective amount of crystalline (3R)-4-{[(1S)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid anhydrate exhibiting characteristic scattering angles (2θ) at least at 4.33°±0.2°, 4.76°±0.2°, 11.06°±0.2° and 11.61°±0.2° in an X-ray powder diffractogram measured using Cu-K α radiation.
6. The method according to claim 5 , wherein the crystalline (3R)-4-{[(1S)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid anhydrate is in a sustained release oral dosage formulation.
7. The method according to claim 5 , wherein the crystalline (3R)-4-{[(1S)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid anhydrate further exhibits characteristic scattering angles (2θ) at least at 5.83°±0.2°, 9.07°±0.2°, 9.46°±0.2°, 10.54°±0.2°, 12.94°±0.2°, 17.46°±0.2°, 17.84°±0.2°, 18.01°±0.2°, 19.36°±0.2°, 20.01°±0.2° and 21.26°±0.2° in an X-ray powder diffractogram measured using Cu-K α radiation.
8. The method according to claim 5 , wherein the crystalline (3R)-4-{[(1S)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid anhydrate further exhibits characteristic scattering angles (2θ) at least at 6.93°±0.2°, 15.25°±0.2°, 16.55°±0.2°, 18.41°±0.2°, 18.69°±0.2°, 18.93°±0.2°, 20.46°±0.2°, 21.75°±0.2°, 22.19°±0.2°, 22.56°±0.2°, 23.35°±0.2°, 23.85°±0.2°, 24.84°±0.2°, 25.96°±0.2°, 26.78°±0.2°, 27.29°±0.2°, 28.69°±0.2°, 29.39°±0.2°, 31.22°±0.2°, 32.35°±0.2°, 33.47°±0.2°, 34.62°±0.2° and 36.08°±0.2° in an X-ray powder diffractogram measured using Cu-K α radiation.
9. The method according to claim 5 , wherein the crystalline (3R)-4-{[(1S)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid anhydrate exhibits a strong characteristic Raman spectrum band at 119 cm −1 .
10. The method according to claim 5 , wherein the crystalline (3R)-4-{[(1S)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid anhydrate exhibits characteristic Raman spectrum bands at least at 119 cm −1 and 85 cm −1 .
11. The method according to claim 5 , wherein the crystalline (3R)-4-{[(1S)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid anhydrate exhibits characteristic Raman spectrum bands at least at 1599 cm −1 , 1447 cm −1 , 798 cm −1 , 119 cm −1 and 85 cm −1 .
12. The method according to claim 5 , wherein the crystalline (3R)-4-{[(1S)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid anhydrate exhibits characteristic Raman spectrum bands at least at 1747 cm −1 , 1599 cm −1 , 1447 cm −1 , 1412 cm −1 , 1335 cm −1 , 1203 cm −1 , 1092 cm −1 , 954 cm −1 , 868 cm −1 , 798 cm −1 , 637 cm −1 , 401 cm −1 , 348 cm −1 , 317 cm −1 , 244 cm −1 , 119 cm −1 and 85 cm −1 .
13. The method according to claim 5 , wherein the crystalline (3R)-4-{[(1S)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid anhydrate has a critical water activity of less than or equal to about 0.75±0.05.
14. The method according to claim 5 , wherein the crystalline (3R)-4-{[(1S)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid anhydrate undergoes thermal decomposition at a temperature ranging from about 170° C. to about 190° C. using a thermogravimetric analyzer coupled with a Fourier-transform infrared spectrometer at a scan rate of about 10 K/min.
15. The method according to claim 5 , wherein the crystalline (3R)-4-{[(1S)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid anhydrate undergoes a melt/phase transition at a temperature ranging from about 120° C. to about 140° C. using differential scanning calorimetry at a heating rate of 20 K/min.
16. The method according to claim 5 , wherein the crystalline (3R)-4-{[(1S)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid anhydrate has a melt/phase transition occurring at about 131° C. using differential scanning calorimetry at a heating rate of 20 K/min.
17. The method according to claim 5 , wherein the crystalline (3R)-4-{[(1S)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid anhydrate has a melt/phase transition occurring at about 131.3° C. using differential scanning calorimetry at a heating rate of 20 K/min.
18. The method according to claim 5 , wherein the crystalline (3R)-4-{[(1S)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid anhydrate contains less than about 0.05 wt % water at 50% relative humidity as measured by dynamic vapor sorption.
19. The method according to claim 5 , wherein the crystalline (3R)-4-{[(1S)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid anhydrate contains less than about 0.1 wt % water at 95% relative humidity as measured by dynamic vapor sorption.