Crystalline compounds
Inventors
McKINNEY, Anthony Alexander • BYMASTER, Franklin • Piskorski, Walter • Fleitz, Fred J. • Yang, Yonglai • Engers, David A. • Smolenskaya, Valeriya • Kusukuntla, Venkat
Assignees
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Publication Number
US-10800740-B2
Publication Date
2020-10-13
Expiration Date
Abstract
The present invention relates to crystalline forms of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride and compositions comprising the same and methods of making and using the same.
Core Innovation
The invention is directed to crystalline Form A of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride, characterized by an X-ray powder diffraction (XRPD) pattern comprising at least three selected 2-theta values measured using an incident beam of Cu radiation. Crystalline Form A is also described with specific unit cell/space group information and XRPD signature data, together with solid-state characterization including DSC, TGA, and dynamic vapor sorption.
The document further describes enantiotropic polymorph relationships among Crystalline Forms A-C, including solid-state behavior under conditions that produce kinetic stability and conversion between forms. The polymorph set is expanded to additional crystalline forms including Crystalline Forms B-F, with definitions that include substantially free, solvate, and amorphous.
The crystalline forms are linked to pharmaceutical compositions, including compositions with pharmaceutically acceptable diluent or carrier and formulations described as sustained release. The document associates the crystalline Form A material with CNS indications, including attention deficit hyperactivity disorder (ADHD) and related disorders, described in connection with reuptake inhibition and administration to a patient.
Claims Coverage
The independent claim set defines Crystalline Form A, a pharmaceutical composition including Crystalline Form A, and a method of treating attention deficit hyperactivity disorder using Crystalline Form A. Across the independent claims, the main inventive feature is a quantitative XRPD-based definition of Crystalline Form A by specifying at least three selected 2-theta values under Cu radiation measurement conditions.
Crystalline Form A XRPD signature
Crystalline Form A of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride, wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising at least three 2-theta (°) values selected from the group consisting of 6.87±0.20, 12.26±0.20, 13.78±0.20, 14.49±0.20, 15.42±0.20, 16.55±0.20, 17.15±0.20, 18.19±0.20, 18.50±0.20, 19.45±0.20, 20.06±0.20, 20.46±0.20, 20.68±0.20, 20.96±0.20, 21.54±0.20, 22.90±0.20, 24.69±0.20, 25.17±0.20, 25.44±0.20, 25.69±0.20, 26.36±0.20, 27.52±0.20, and 27.76±0.20, wherein the XRPD is measured using an incident beam of Cu radiation.
Pharmaceutical composition with Crystalline Form A
A pharmaceutical composition comprising Crystalline Form A of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride and a pharmaceutically acceptable diluent or carrier, wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising at least three 2-theta (°) values selected from the group consisting of 6.87±0.20, 12.26±0.20, 13.78±0.20, 14.49±0.20, 15.42±0.20, 16.55±0.20, 17.15±0.20, 18.19±0.20, 18.50±0.20, 19.45±0.20, 20.06±0.20, 20.46±0.20, 20.68±0.20, 20.96±0.20, 21.54±0.20, 22.90±0.20, 24.69±0.20, 25.17±0.20, 25.44±0.20, 25.69±0.20, 26.36±0.20, 27.52±0.20, and 27.76±0.20, wherein the XRPD is measured using an incident beam of Cu radiation.
Treatment of ADHD by administering Crystalline Form A
A method for treatment of attention deficit hyperactivity disorder in a patient in need thereof, wherein the method comprises administering to the patient Crystalline Form A of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride, wherein the Crystalline Form A exhibits an X-ray powder diffraction (XRPD) pattern comprising at least three 2-theta (°) values selected from the group consisting of 6.87±0.20, 12.26±0.20, 13.78±0.20, 14.49±0.20, 15.42±0.20, 16.55±0.20, 17.15±0.20, 18.19±0.20, 18.50±0.20, 19.45±0.20, 20.06±0.20, 20.46±0.20, 20.68±0.20, 20.96±0.20, 21.54±0.20, 22.90±0.20, 24.69±0.20, 25.17±0.20, 25.44±0.20, 25.69±0.20, 26.36±0.20, 27.52±0.20, and 27.76±0.20, wherein the XRPD is measured using an incident beam of Cu radiation.
Across the independent claims, Crystalline Form A is defined by a quantitative XRPD pattern with at least three specified 2-theta values under Cu radiation. This XRPD-defined crystalline material is incorporated into a pharmaceutical composition and used to treat attention deficit hyperactivity disorder by administration to a patient.
Stated Advantages
Not explicitly described in patent.
Documented Applications
A pharmaceutical composition comprising Crystalline Form A for administration to a patient.
Treatment of attention deficit hyperactivity disorder (ADHD) by administering the pharmaceutical composition to a patient in need thereof.
Treatment of fragile X-associated disorder, autism spectrum disorder, or substance abuse disorder by administering the pharmaceutical composition to a patient in need thereof.
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