Crystalline form of a 4-[2-(2-fluorophenoxymethyl)phenyl]piperidine compound

Patent metadata

Field	Value
Publication number	US-10946006-B2
Application number	US-202016744551-A
Country	US
Kind code	B2
Filing date	Jan 16, 2020
Priority date	Nov 14, 2008
Publication date	Mar 16, 2021
Grant date	Mar 16, 2021

Abstract

The invention provides a crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine. This invention also provides pharmaceutical compositions comprising the crystalline salt, processes and intermediates for preparing the crystalline salt, and methods of using the crystalline salt to treat diseases.

First claim

What is claimed is:

1. A pharmaceutical composition in unit dosage form comprising a pharmaceutically acceptable carrier and about 1 mg to about 20 mg of a crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine characterized by (a) a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 4.44±0.20, 10.22±0.20, 16.06±0.20, 21.78±0.20, 23.76±0.20, 26.32±0.20, 27.24±0.20, 29.60±0.20, and 31.94±0.20; or (b) a differential scanning calorimetry trace which has a melting point of about 196.9° C.; wherein the unit dosage form is a capsule or a tablet.

2. The pharmaceutical composition of claim 1 , wherein the unit dosage form is a tablet.

3. The pharmaceutical composition of claim 1 , wherein the unit dosage form is a capsule.

4. The pharmaceutical composition of claim 1 , wherein the crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine is characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 20 values of 4.44±0.20, 10.22±0.20, 16.06±0.20, 21.78±0.20, 23.76±0.20, 26.32±0.20, 27.24±0.20, 29.60±0.20, and 31.94±0.20.

5. The pharmaceutical composition of claim 1 , wherein the crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine is characterized by a differential scanning calorimetry trace which has a melting point of about 196.9° C.

6. The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable carrier comprises microcrystalline cellulose.

7. The pharmaceutical composition of claim 1 , wherein the pharmaceutically acceptable carrier comprises lactose.

8. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises a lubricant selected from talc, calcium stearate, magnesium stearate, solid polyethylene glycol, sodium lauryl sulfate and mixtures thereof.

9. The pharmaceutical composition of claim 8 , wherein the lubricant is magnesium stearate.

10. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition contains about 1 milligram to about 15 milligrams of the crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine.

11. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition contains about 1 milligram to about 10 milligrams of the crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine.

12. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition contains about 5 milligrams to about 20 milligrams of the crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine.

13. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition contains about 7.5 milligrams to about 15 milligrams of the crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine.

14. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition contains about 10 milligrams of the crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine.

15. A tablet comprising:
(a) about 1 mg to about 20 mg of a crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine characterized by (a) a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 4.44±0.20, 10.22±0.20, 16.06±0.20, 21.78±0.20, 23.76±0.20, 26.32±0.20, 27.24±0.20, 29.60±0.20, and 31.94±0.20; or (b) a differential scanning calorimetry trace which has a melting point of about 196.9° C.;
(b) a pharmaceutically acceptable carrier selected from starch, microcrystalline cellulose, lactose, sucrose, glucose, mannitol, silicic acid and mixtures thereof; and
(c) a lubricant selected from talc, calcium stearate, magnesium stearate, solid polyethylene glycol, sodium lauryl sulfate and mixtures thereof.

16. The tablet of claim 15 , wherein the crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine is characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 4.44±0.20, 10.22±0.20, 16.06±0.20, 21.78±0.20, 23.76±0.20, 26.32±0.20, 27.24±0.20, 29.60±0.20, and 31.94±0.20.

17. The tablet of claim 15 , wherein the crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine is characterized by a differential scanning calorimetry trace which has a melting point of about 196.9° C.

18. The tablet of claim 15 , wherein the tablet contains about 1 milligram to about 15 milligrams of the crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine.

19. The tablet of claim 15 , wherein the tablet contains about 1 milligram to about 10 milligrams of the crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine.

20. The tablet of claim 15 , wherein the tablet contains about 5 milligrams to about 20 milligrams of the crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine.

21. The tablet of claim 15 , wherein the pharmaceutical composition contains about 7.5 milligrams to about 15 milligrams of the crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)phenyl]piperidine.

22. The tablet of claim 15 , wherein the tablet contains about 10 milligrams of the crystalline hydrochloride salt of 4-[2-(2,4,6-trifluorophenoxymethyl)-phenyl]piperidine.

23. The tablet of claim 15 , wherein the pharmaceutically acceptable carrier contains microcrystalline cellulose.

24. The tablet of claim 15 , wherein the pharmaceutically acceptable carrier contains lactose.

25. The tablet of claim 15 , wherein the lubricant is magnesium stearate.

Assignees

• Theravance Biopharma R&D Ip Llc

Inventors

• Patterson Lori Jean
• Chao Robert S
• Rapta Miroslav

Classifications

• A61P21/00

  Drugs for disorders of the muscular or neuromuscular system · CPC title

• A61K31/4465 Primary

  only substituted in position 4 · CPC title

• A61K31/4409

  only substituted in position 4, e.g. isoniazid, iproniazid · CPC title

• C07D211/10

  with radicals containing only carbon and hydrogen atoms attached to ring carbon atoms · CPC title

• A61P25/30

  for treating abuse or dependence · CPC title