Solid forms of tin ethyl etiopurpurin and processes for producing such forms
AssigneeMiravant Pharmaceuticals, Inc.
InventorsG. Patrick Stahly, Barbara A. Garcia, Byron C. Robinson
Life of this patent
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Abstract
Solid forms of tin ethyl etiopurpurin (SnET2), including crystalline form I, crystalline Form II, disordered Form II, and an amorphous form are disclosed. Also disclosed are the 1,2-dichloroethane solvate of SnET2 and the N,N-dimethylformamide solvate of SnET2. These solid forms of SnET2 are useful as pharmaceuticals that exhibit pharmacological activity when irradiated with light and thus are useful in photodynamic therapy. Also disclosed are methods for making these solid forms of SnET2 and pharmaceuticals including these solid forms of SnET2.
Claims77
Crystalline Form I of tin ethyl etiopurpurin having an X-ray diffraction pattern with a powder diffraction line at 6.5 degrees 2θ measured with CuKα radiation.
Crystalline Form I of tin ethyl etiopurpurin having a solid state NMR resonance at 25.6 ppm.
Crystalline Form I of tin ethyl etiopurpurin having a solid state NMR delta of 16.2 ppm.
Crystalline Form II of tin ethyl etiopurpurin having an X-ray diffraction pattern with a powder diffraction line at 12.2 degrees 2θ measured with CuKα radiation.
Form II of tin ethyl etiopurpurin having a solid state NMR resonance at 29.8-29.9 ppm.
Form II of tin ethyl etiopurpurin having a solid state NMR delta of 21.1-21.4 ppm.
Crystalline Form II of tin ethyl etiopurpurin having substantially the solid state NMR spectrum of FIG. 4.
Disordered Form II of tin ethyl etiopurpurin having substantially the solid state NMR spectrum of FIG. 6.
Disordered Form II of tin ethyl etiopurpurin having an X-ray diffraction pattern with a powder diffraction line with a maxima at 11.5-13.5 degrees 2θ measured with CuKα radiation.
The 1,2-dichloroethane solvate of tin ethyl etiopurpurin having an X-ray diffraction pattern with a powder diffraction line at 10.0 degrees 2θ measured with CuKα radiation.
The 1,2-dichloroethane solvate of tin ethyl etiopurpurin having a solid state NMR resonance at 19.7 ppm.
The N,N-dimethylformamide solvate of tin ethyl etiopurpurin having an X-ray diffraction pattern with a powder diffraction line at 7.4 degrees 2θ measured with CuKα radiation.
The N,N-dimethylformamide solvate of tin ethyl etiopurpurin having a solid state NMR resonance at 8.2 ppm.
The N,N-dimethylformamide solvate of tin ethyl etiopurpurin having a solid state NMR delta of 2.8 ppm.
The desolvate of the 1,2-dichloroethane solvate of tin ethyl etiopurpurin.
The desolvate of the N,N-dimethylformamide solvate of tin ethyl etiopurpurin.
The amorphous form of tin ethyl etiopurpurin having an X-ray diffraction pattern with broad peaks at about 10 degrees and about 21 degrees 2θ measured with CuKα radiation.
A process for the preparation of crystalline Form I of tin ethyl etiopurpurin comprising:
- contacting tin ethyl etiopurpurin with a suitable solvent to form a solution thereof;
- and
- crystallizing tin ethyl etiopurpurin from said solution by evaporating said solvent from said solution under conditions sufficient to yield crystalline Form I of tin ethyl etiopurpurin.
A process for the preparation of crystalline Form I of tin ethyl etiopurpurin comprising:
- contacting tin ethyl etiopurpurin with a suitable solvent while heating to form a solution thereof;
- and
- crystallizing tin ethyl etiopurpurin from said solution by cooling said solution under conditions sufficient to yield crystalline Form I of tin ethyl etiopurpurin.
A process for the preparation of crystalline Form I of tin ethyl etiopurpurin comprising:
- contacting tin ethyl etiopurpurin with a suitable solvent to form a solution thereof;
- and
- crystallizing tin ethyl etiopurpurin from said solution by contacting said solution with a suitable antisolvent under conditions sufficient to cause crystalline Form I of tin ethyl etiopurpurin to precipitate from said solution.
A process for the preparation of crystalline Form II of tin ethyl etiopurpurin comprising:
- contacting tin ethyl etiopurpurin with a suitable solvent to form a solution thereof;
- and
- crystallizing tin ethyl etiopurpurin from said solution by evaporating said solvent from said solution under conditions sufficient to yield crystalline Form II of tin ethyl etiopurpurin.
A process for the preparation of crystalline Form II of tin ethyl etiopurpurin comprising:
- contacting tin ethyl etiopurpurin with a suitable solvent while heating to form a solution thereof;
- and
- crystallizing tin ethyl etiopurpurin from said solution by cooling said solution under conditions sufficient to yield crystalline Form II of tin ethyl etiopurpurin.
A process for the preparation of crystalline Form II of tin ethyl etiopurpurin comprising:
- contacting tin ethyl etiopurpurin with dichloromethane to form a slurry thereof;
- evaporating said dichloromethane from said slurry while treating the slurry with acetic acid to form a solid material;
- contacting said solid material with dichloromethane to form a solution thereof;
- and
- crystallizing tin ethyl etiopurpurin from said solution by evaporating said dichloromethane from said solution while treating the solution with acetone under conditions sufficient to yield crystalline Form II of tin ethyl etiopurpurin.
A process for the preparation of crystalline Form II of tin ethyl etiopurpurin comprising:
- contacting crystalline Form I of tin ethyl etiopurpurin with a suitable solvent to form a slurry thereof;
- and
- agitating said slurry under conditions sufficient to yield crystalline Form II of tin ethyl etiopurpurin.
A process for the preparation of crystalline Form II of tin ethyl etiopurpurin comprising:
- contacting a mixture of crystalline Form I of tin ethyl etiopurpurin and crystalline Form II of tin ethyl etiopurpurin with a suitable solvent to form a slurry thereof;
- and
- agitating said slurry under conditions sufficient to yield crystalline Form II of tin ethyl etiopurpurin.
A process for the preparation of disordered Form II of tin ethyl etiopurpurin comprising:
- contacting tin ethyl etiopurpurin with dichloromethane to form a slurry thereof;
- evaporating said dichloromethane from said slurry while treating the slurry with acetic acid to form a solid material;
- contacting said solid material with dichloromethane to form a solution thereof;
- and
- crystallizing tin ethyl etiopurpurin from said solution by evaporating said dichloromethane from said solution while treating the solution with acetone under conditions sufficient to yield disordered Form II of tin ethyl etiopurpurin.
A process for the preparation of the 1,2-dichloroethane solvate of tin ethyl etiopurpurin comprising:
- contacting tin ethyl etiopurpurin with 1,2-dichloroethane to form a mixture thereof;
- and
- evaporating said 1,2-dichloroethane from said mixture under conditions sufficient to yield the 1,2-dichloroethane solvate of tin ethyl etiopurpurin.
A process for the preparation of the N,N-dimethylformamide solvate of tin ethyl etiopurpurin comprising:
- contacting tin ethyl etiopurpurin with a suitable solvent to form a solution thereof;
- and
- treating said solution with N,N-dimethylformamide under conditions sufficient to cause the N,N-dimethylformamide solvate of tin ethyl etiopurpurin to precipitate from said solution.
A process for preparing amorphous tin ethyl etiopurpurin comprising grinding a solid form of tin ethyl etiopurpurin under conditions which produce the amorphous form.
A process for preparing amorphous tin ethyl etiopurpurin comprising:
- forming a solution of tin ethyl etiopurpurin in an appropriate solvent;
- and
- freeze drying, quench cooling, rapid evaporation or rapid cooling said solution under conditions sufficient to produce the amorphous form of tin ethyl etiopurpurin.
A tablet comprising crystalline Form I, crystalline Form II, disordered Form II, desolvates of the 1,2-dichloroethane solvate, desolvates of the N,N-dimethylformamide solvate or amorphous tin ethyl etiopurpurin or mixtures thereof together with at least one inert pharmaceutically acceptable carrier or diluent.
A capsule comprising crystalline Form I, crystalline Form II, disordered Form II, desolvates of the 1,2-dichloroethane solvate, desolvates of the N,N-dimethylformamide solvate or amorphous tin ethyl etiopurpurin or mixtures thereof together with at least one inert pharmaceutically acceptable carrier or diluent.
A powder comprising crystalline Form I, crystalline Form II, disordered Form II, desolvates of the 1,2-dichloroethane solvate, desolvates of the N,N-dimethylformamide solvate or amorphous tin ethyl etiopurpurin or mixtures thereof together with at least one inert pharmaceutically acceptable carrier or diluent.
A lozenge comprising crystalline Form I, crystalline Form II, disordered Form II, desolvates of the 1,2-dichloroethane solvate, desolvates of the N,N-dimethylformamide solvate or amorphous tin ethyl etiopurpurin or mixtures thereof together with at least one inert pharmaceutically acceptable carrier or diluent.
A suppository comprising crystalline Form I, crystalline Form II, disordered Form II, desolvates of the 1,2-dichloroethane solvate, desolvates of the N,N-dimethylformamide solvate or amorphous tin ethyl etiopurpurin or mixtures thereof together with at least one inert pharmaceutically acceptable carrier or diluent.
An ointment comprising crystalline Form I, crystalline Form II, disordered Form II, desolvates of the 1,2-dichloroethane solvate, desolvates of the N,N-dimethylformamide solvate or amorphous tin ethyl etiopurpurin or mixtures thereof together with at least one inert pharmaceutically acceptable carrier or diluent.
A patch or other controlled release device comprising crystalline Form I, crystalline Form II, disordered Form II, desolvates of the 1,2-dichloroethane solvate, desolvates of the N,N-dimethylformamide solvate or amorphous tin ethyl etiopurpurin or mixtures thereof together with at least one inert pharmaceutically acceptable carrier or diluent.
A process for producing a solution of tin ethyl etiopurpurin comprising combining crystalline Form I, crystalline Form II, disordered Form II, desolvates of the 1,2-dichloroethane solvate, desolvates of the N,N-dimethylformamide solvate, or amorphous tin ethyl etiopurpurin, or mixtures thereof, with at least one inert pharmaceutically acceptable carrier or diluent.
Dependencies are inferred from the claim text.