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-9708261-B2
Publication Date
2017-07-18
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 disclosure describes crystalline polymorphs of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride, including Crystalline Forms A through F. The crystalline forms are characterized by XRPD fingerprints and solid-state characterization including DSC, TGA, and DVS, with unit cell and space group information reported for at least Crystalline Form A and Crystalline Form B.
Forms A, B, and C are described as anhydrous enantiotropes, and thermodynamic transition temperatures are reported for C to B, B to A, and C to A. Crystalline Form A is presented as surprisingly kinetically stable, including behavior where it does not convert to Form B under solvent and solid aging, while Form C does under stress conditions.
The disclosure also extends the crystalline forms to pharmaceutical compositions, including compositions having sustained release, and to use in treating CNS disorders with therapeutically effective amounts. Attention deficit hyperactivity disorder is specifically noted as an example of such treatment use.
Claims Coverage
The independent claims center on specific crystalline forms of (1R,5S)-1-(naphthalen-2-yl)-3-azabicyclo[3.1.0]hexane hydrochloride and their crystallographic identity. Four inventive features are identifiable across the claims: unit cell and space group definition, XRPD 2-theta definition, XRPD d-spacing definition for Form A, and XRPD d-spacing definition for Form B.
Crystalline form a or crystalline form b defined by p21 and unit cell parameters
Crystalline Form A or Crystalline Form B belongs to the P21 space group and has specified unit cell parameters with right-angle angles.
Crystalline form a defined by xrpd 2-theta peak values measured with cu kα radiation
Crystalline Form A exhibits an XRPD pattern comprising specified 2-theta values, with measurement using Cu Kα radiation of wavelength 1.54059 Å.
Crystalline form a defined by xrpd d-spacing values
Crystalline Form A exhibits an XRPD pattern comprising specified d-spacing values.
Crystalline form b defined by xrpd d-spacing values
Crystalline Form B exhibits an XRPD pattern comprising specified d-spacing values.
Claim coverage is focused on defining specific crystalline forms through crystallographic parameters and XRPD solid-state fingerprints. Dependent claims extend coverage to pharmaceutical compositions containing the crystalline forms and to treating attention deficit hyperactivity disorder by administering a therapeutically effective amount.
Stated Advantages
Crystalline Form A is surprisingly kinetically stable and does not convert to Form B under solvent and solid aging, while Form C does under stress conditions.
Documented Applications
Treatment of attention deficit hyperactivity disorder (ADHD) by administering a therapeutically effective amount of Crystalline Form A to a patient in need.
Pharmaceutical compositions containing Crystalline Form A, including use with pharmaceutically acceptable diluent or carrier.
Pharmaceutical compositions containing Crystalline Form B, including use with pharmaceutically acceptable diluent or carrier.
Pharmaceutical compositions having sustained release.
Use in treating CNS disorders.
Interested in licensing this patent?