Crystalline Forms of (-)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride
AssigneeGruenenthal GmbH
InventorsAndreas Fischer, Helmut Buschmann, Michael Gruss, Dagmar Lischke
Life of this patent
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Abstract
A hitherto unknown crystalline form of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride, pharmaceutical compositions containing the new crystalline form, methods of producing the new crystalline form, and a related method of use including treatment of, e.g., pain and/or urinary incontinence.
Claims28
A crystalline Form A of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Kα radiation at 15.1±0.2, 16.0±0.2, 18.9±0.2, 20.4±0.2, 22.5±0.2, 27.3±0.2, 29.3±0.2 and 30.4±0.2.
A process for producing a (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A, said process comprising:
- dissolving a (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form B in acetone, acetonitrile or isopropanol to form a solution;
- leaving the solution to crystallize and
- isolating crystals of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of crystalline Form A.
A process for producing crystalline Form A of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride comprising the step of cooling (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-hydrochloride phenol of Form B for a time between 24 hours and 168 hours at a temperature of between −4° C. and −80° C.
A crystalline Form A of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride produced by the process of:
- dissolving (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form B in acetonitrile together with active carbon,
- heating the solution to the boiling point,
- removing the active carbon by filtering,
- stirring the solution at a temperature below 40° C.,
- removing insoluble residue by filtering and removing part of the solvent, leaving (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form A to crystallize,
- redissolving the resulting crystals in acetonitrile,
- removing insoluble residue by filtering and removing part of the solvent, and leaving (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form A to crystallize.
A pharmaceutical composition comprising, as an active ingredient, a crystalline Form A of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Kα radiation at 15.1±0.2, 16.0±0.2, 18.9±0.2, 20.4±0.2, 22.5±0.2, 27.3±0.2, 29.3±0.2 and 30.4±0.2, and at least one suitable additive or auxiliary substance.
A pharmaceutical composition comprising, as an active ingredient, a crystalline Form A of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride produced by the process of
- dissolving (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form B in acetonitrile together with active carbon,
- heating the solution to the boiling point,
- removing the active carbon by filtering,
- stirring the solution at a temperature below 40° C.,
- removing insoluble residue by filtering and removing part of the solvent, leaving (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form A to crystallize,
- redissolving the resulting crystals in acetonitrile,
- removing insoluble residue by filtering and removing part of the solvent, and leaving (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride of Form A to crystallize, and
- at least one suitable additive or auxiliary substance.
A method of treating or inhibiting pain or urinary incontinence, said method comprising the step of administering a pharmaceutically effective amount of a crystalline Form A of (−)-(1R,2R)-3-(3-dimethylamino-1-ethyl-2-methylpropyl)-phenol hydrochloride exhibiting at least X-ray lines (2-theta values) in a powder diffraction pattern when measured using Cu Kα radiation at 15.1±0.2, 16.0±0.2, 18.9±0.2, 20.4±0.2, 22.5±0.2, 27.3±0.2, 29.3±0.2 and 30.4±0.2 to a subject in need thereof.
Dependencies are inferred from the claim text.