Crystalline freebase forms of a biphenyl compound

Patent metadata

Field	Value
Publication number	US-2016143897-A1
Application number	US-201514955515-A
Country	US
Kind code	A1
Filing date	Dec 1, 2015
Priority date	Jul 15, 2009
Publication date	May 26, 2016
Grant date	—

Abstract

The invention provides two crystalline freebase forms of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester. The invention also provides pharmaceutical compositions comprising the crystalline freebase or prepared using the crystalline freebases; processes and intermediates for preparing the crystalline freebases; and methods of using the crystalline freebases to treat a pulmonary disorder.

First claim

1 - 2 . (canceled)

3 . The composition of claim 13 , wherein the crystalline compound is characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values selected from 6.6±0.1, 11.4±0.1, 13.1±0.1, 16.1±0.1, 17.5±0.1, 18.2±0.1, 18.6±0.1, 19.3±0.1, 19.7±0.1, 19.9±0.1, 20.2±0.1, 20.8±0.1, 21.1±0.1, 21.7±0.1, and 22.3±0.1.

4 - 11 . (canceled)

12 . A pharmaceutical composition comprising a pharmaceutically acceptable dry powder excipient and a crystalline freebase of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 6.6±0.1, 13.1±0.1, 18.6±0.1, 19.7±0.1, and 20.2±0.1; and further characterized by having five or more additional diffraction peaks at 2θ values selected from 8.8±0.1, 10.1±0.1, 11.4±0.1, 11.6±0.1, 14.8±0.1, 15.2±0.1, 16.1±0.1, 16.4±0.1, 16.9±0.1, 17.5±0.1, 18.2±0.1, 19.3±0.1, 19.9±0.1, 20.8±0.1, 21.1±0.1, 21.7±0.1, and 22.3±0.1.

13 . The composition of claim 12 , which further comprises an agent selected from β 2 adrenergic receptor agonists, steroidal anti-inflammatory agents, phosphodiesterase-4 inhibitors, and combinations thereof; wherein the crystalline form and the agent are formulated together or separately.

14 . The composition of claim 13 , which comprises a β 2 adrenergic receptor agonist and a steroidal anti-inflammatory agent.

15 . The composition of claim 12 , wherein the crystalline compound is in micronized form.

16 - 20 . (canceled)

21 . The composition of claim 12 , wherein the excipient is selected from lactose, starch, mannitol, dextrose, polylactic acid, polylactide-co-glycolide, and combinations thereof.

22 . The composition of claim 12 , wherein the excipient is lactose.

23 . The composition of claim 13 , which comprises a β 2 adrenergic receptor agonist.

24 . The composition of claim 13 , which comprises a steroidal anti-inflammatory agent.

25 . The composition of claim 13 , which comprises a phosphodiesterase-4 inhibitor.

26 . A pharmaceutical composition comprising dry lactose having a particle size between about 1 μm and about 100 μm and micronized particles of a crystalline freebase of biphenyl-2-ylcarbamic acid 1-(2-{[4-(4-carbamoylpiperidin-1-ylmethyl)benzoyl]methylamino}ethyl)piperidin-4-yl ester characterized by a powder x-ray diffraction pattern comprising diffraction peaks at 2θ values of 6.6±0.1, 13.1±0.1, 18.6±0.1, 19.7±0.1, and 20.2±0.1; and further characterized by having five or more additional diffraction peaks at 2θ values selected from 8.8±0.1, 10.1±0.1, 11.4±0.1, 11.6±0.1, 14.8±0.1, 15.2±0.1, 16.1±0.1, 16.4±0.1, 16.9±0.1, 17.5±0.1, 18.2±0.1, 19.3±0.1, 19.9±0.1, 20.8±0.1, 21.1±0.1, 21.7±0.1, and 22.3±0.1.

Assignees

• Woollam Grahame
• Theravance Biopharma R&D Ip Llc

Inventors

• Woollam Grahame

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• A61P11/06

  Antiasthmatics · CPC title

• A61P11/08

  Bronchodilators · CPC title

• A61K9/1623

  Sugars or sugar alcohols, e.g. lactose; Derivatives thereof; Homeopathic globules · CPC title