Polymorphic crystal forms of 5-(2-{[6-(2,2-difluoro-2-phenylethoxy)hexyl]amino}-1-(R)-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one, heminapadisytlate as agonist of the β2 adrenergic receptor

摘要

The present invention is directed to novel polymorphic crystal forms of a 5-(2-{[6-(2,2-difluoro-2-phenylethoxy)hexyl]amino}-1-(R)-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one, heminapadisylate. The invention is also directed to pharmaceutical compositions comprising said polymorphic crystal forms, methods of using them to treat respiratory diseases associated with β2 adrenergic receptor activity and a process for preparing such polymorphic crystal forms.

主权项

1. A crystalline polymorph of 5-(2-{[6-(2,2-difluoro-2-phenylethoxy)hexyl]amino}-1(R)-hydroxyethyl)-8-hydroxyquinolin-2(1H)-one heminapadisylate, which is chosen from (i) a hydrate polymorph, or (ii) a type β polymorph prepared by drying said hydrate polymorph,
wherein: the hydrate polymorph has: a) an X-Ray Powder Diffraction (XRPD) pattern with peaks at 13.3, 16.1 and 19.2 degrees 2θ (±0.1 degrees 2θ); and b) a Differential Scanning Calorimetry (DSC) pattern with a first endotherm in the range of 75-120° C. (±5° C.) and a second endotherm with an onset at 190° C. (±1° C.), the type β polymorph has: a) an X-Ray Powder Diffraction (XRPD) pattern with a peak at 19.1 degrees 2θ (±0.1 degrees 2θ); and b) a Differential Scanning Calorimetry (DSC) pattern with a first endotherm with an onset at 190° C. (±1° C.).