Crystalline compounds
Inventors
McKINNEY, Anthony Alexander • BYMASTER, Franklin • Piskorski, Walter • Fleitz, Fred J. • Yang, Yonglai • Engers, David A. • Smolenskaya, Valeriya • Kusukuntla, Venkat
Assignees
Interested in licensing this patent?
MTEC can help explore whether this patent might be available for licensing for your application.
Publication Number
US-11299458-B2
Publication Date
2022-04-12
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 disclosed invention relates to crystalline hydrochloride addition salt polymorphs of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane, including Crystalline Forms A–F. The document characterizes these crystalline forms using X-ray powder diffraction (XRPD), including d-spacing (Å) values and 2-theta (°) peak information, and associates each form with defined crystallographic parameters such as space group and unit cell parameters.
XRPD characterization is supported by solid-state characterization methods including DSC endotherms and TGA weight loss and onset decomposition. The invention further links the crystalline forms to solid-state stability and polymorph transformation behavior, including stability and transition behavior among Forms A, B, and C, kinetic persistence of Form A, and conversion behavior involving Form C under stress.
The document describes crystallization and isolation workflows for (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride to obtain specific crystalline forms, including Crystalline Form B. The crystalline forms are used in pharmaceutical contexts, including pharmaceutical formulations and therapeutic use, and are described in relation to sustained release and to therapeutic activity connected to triple reuptake inhibition, including norepinephrine (NE), dopamine (DA), and serotonin (5-HT).
Claims Coverage
The independent claims cover two related processes grounded on Crystalline Form B of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride, with Crystalline Form B defined by a specific XRPD pattern having five d-spacing values. The core inventive features focus on seeding-based preparation of Crystalline Form B and its use in forming a pharmaceutical composition by isolating and admixing the crystalline form with a pharmaceutically acceptable diluent or carrier.
Seeding a solution or slurry with Crystalline Form B
A process for making Crystalline Form B of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride by seeding a solution or slurry of the hydrochloride with Crystalline Form B, wherein the Crystalline Form B exhibits an XRPD pattern comprising d-spacing values of 14.6, 5.1, 4.7, 4.6, and 3.6.
Isolating Crystalline Form B and admixing with a pharmaceutically acceptable diluent or carrier
A process for making a pharmaceutical composition comprising Crystalline Form B of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride by isolating Crystalline Form B and admixing the isolated Crystalline Form B with a pharmaceutically acceptable diluent or carrier, wherein the Crystalline Form B exhibits an XRPD pattern comprising d-spacing values of 14.6, 5.1, 4.7, 4.6, and 3.6.
Overall, the claims are directed to preparing Crystalline Form B by seeding and using isolated Crystalline Form B to produce a pharmaceutical composition by admixing with a pharmaceutically acceptable diluent or carrier, with Form B defined by an XRPD pattern containing the specified d-spacing values.
Stated Advantages
Documented Applications
No documented applications found
Interested in licensing this patent?