Solvate form of (R)-2-amino-3-phenylpropyl carbamate
View Patent ↗The present invention relates to a newly identified solvate form of (i?)-2-amino-3-phenylpropyl carbamate (APC) hydrochloride, a method of preparing APC hydrochloride, and methods of using the same to treat disorders. The invention further relates to methods of producing APC hydrochloride with increased purity.
1. A solvate form of (R)-2-amino-3-phenylpropyl carbamate hydrochloride characterized by a powder x-ray diffraction pattern substantially the same as that shown in FIG. 1 Form B.
2. The solvate form of claim 1 , further characterized by differential scanning calorimetry as having a broad endotherm with onset at 69.1° C. and peak at 71.7° C. and a sharp endotherm with onset at 182.5° C. and peak at 183.6° C.
3. The solvate form of claim 1 , wherein the solvate form is a hemihydrate.
4. The solvate form of claim 1 , further characterized as being produced by slurrying (R)-2-amino-3-phenylpropyl carbamate hydrochloride in acetonitrile/water (95%/5% v/v).
5. A process of preparing a solvate form of (R)-2-amino-3-phenylpropyl carbamate hydrochloride, comprising slurrying (R)-2-amino-3-phenylpropyl carbamate hydrochloride in acetonitrile/water (95%/5% v/v) and collecting the solvate by vacuum filtration.
6. The process of claim 5 , wherein the slurrying is performed at about room temperature.
7. The process of claim 5 , wherein the slurrying is performed for at least about 20 hours.
8. A composition comprising (R)-2-amino-3-phenylpropyl carbamate hydrochloride, wherein at least 30% of the (R)-2-amino-3-phenylpropyl carbamate hydrochloride is the solvate form of claim 1 .
9. The composition of claim 8 , wherein the composition is a dosage form.
10. The composition of claim 9 , wherein the composition is an immediate release oral dosage form.
11. The composition of claim 10 , wherein the composition is a tablet or a capsule.
12. A method of treating narcolepsy, cataplexy, excessive daytime sleepiness, drug addiction, sexual dysfunction, fatigue, fibromyalgia, attention deficit/hyperactivity disorder, restless legs syndrome, depression, bipolar disorder, or obesity in a subject in need thereof, or promoting smoking cessation in a subject in need thereof, comprising administering to the subject the composition of claim 8 .
13. A method of preparing (R)-2-amino-3-phenylpropyl carbamate hydrochloride while minimizing contamination with 2-chloropropane, the method comprising crystallizing (R)-2-amino-3-phenylpropyl carbamate in the presence of aqueous HCl, thereby producing crystals of (R)-2-amino-3-phenylpropyl carbamate hydrochloride.
14. The method of claim 13 , wherein the crystallizing is performed at a temperature of about 25° C. to about 30° C.
15. The method of claim 12 , wherein the subject has excessive daytime sleepiness.
16. The method of claim 13 , further comprising drying the crystals of (R)-2-amino-3-phenylpropyl carbamate hydrochloride at a temperature of about 35° C. or less.
17. The method of claim 13 , wherein the amount of 2-chloropropane in the (R)-2-amino-3-phenylpropyl carbamate hydrochloride is less than about 5 ppm.
18. A solvate form of (R)-2-amino-3-phenylpropyl carbamate hydrochloride characterized by a powder x-ray diffraction pattern having peaks at about 7.0, 13.6, 16.2, 17.4, 17.8, 18.5, 21.0, 21.7, 22.7, 23.0, 24.0, and 27.3±0.2 °2θ.
19. The solvate form of claim 18 , further characterized by differential scanning calorimetry as having a broad endotherm with onset at 69.1° C. and peak at 71.7° C. and a sharp endotherm with onset at 182.5° C. and peak at 183.6° C.
20. The solvate form of claim 18 , wherein the solvate form is a hemihydrate.
21. The solvate form of claim 18 , further characterized as being produced by slurrying (R)-2-amino-3-phenylpropyl carbamate hydrochloride in acetonitrile/water (95%/5% v/v).
22. A composition comprising (R)-2-amino-3-phenylpropyl carbamate hydrochloride, wherein at least 30% of the (R)-2-amino-3-phenylpropyl carbamate hydrochloride is the solvate form of claim 18 .
23. The composition of claim 22 , wherein the composition is a dosage form.
24. The composition of claim 23 , wherein the composition is an immediate release oral dosage form.
25. The composition of claim 24 , wherein the composition is a tablet or a capsule.
26. A method of treating narcolepsy, cataplexy, excessive daytime sleepiness, drug addiction, sexual dysfunction, fatigue, fibromyalgia, attention deficit/hyperactivity disorder, restless legs syndrome, depression, bipolar disorder, or obesity in a subject in need thereof, or promoting smoking cessation in a subject in need thereof, comprising administering to the subject the composition of claim 22 .
27. The method of claim 26 , wherein the subject has excessive daytime sleepiness.