Polymorphic forms of naltrexone
AssigneeAlkermes Controlled Therapeutics Inc. II
InventorsHarry Brittain, David Dickason, Joyce Hotz, Shawn Lyons, J. Ramstack, Steven Wright
Life of this patent
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Abstract
This invention relates to the discovery of novel polymorphic forms of naltrexone, including solvates, hydrates, anhydrous and other crystalline forms and combinations thereof. These novel forms of naltrexone impart advantages in pharmaceutical formulations incorporating them, including sustained release, or long acting, formulations.
Claims60
A polymorphic form of naltrexone ethanolate characterized by an X-ray powder diffraction with a characteristic peak at about 9° (2θ).
A polymorphic form of naltrexone benzyl alcohol solvate which is characterized by an X-ray powder diffraction with a characteristic peak at about 5-6° (2θ).
A polymorphic form of naltrexone dimethylformamide solvate which is characterized by an X-ray powder diffraction pattern of FIG. 2.
A polymorphic form of naltrexone methanol solvate which is characterized by the X-ray powder diffraction pattern of FIG. 4.
A polymorphic form of naltrexone dichloromethane which is characterized by the X-ray powder diffraction pattern of FIG. 7.
A polymorphic form of naltrexone acetone solvate which is characterized by the X-ray powder diffraction pattern of FIG. 8.
A polymorphic form of naltrexone ethylacetate solvate which is characterized by the X-ray powder diffraction pattern of FIG. 9.
A polymorphic form of naltrexone toluene solvate which is characterized by the X-ray powder diffraction pattern of FIG. 11.
A polymorphic form of naltrexone hexane solvate which is characterized by the X-ray powder diffraction pattern of FIG. 12.
A method of making a polymorphic form of naltrexone comprising:
- (i) mixing a naltrexone base anhydrous or a naltrexone salt with a solvent or solvent system selected from the group consisting of acetonitrile, dimethyl formamide, water, methanol, ethanol, benzyl alcohol, dichloromethane, acetone, ethyl acetate, methyl ethyl ketone, toluene and hexane and combinations thereof;
- (ii) heating the mixture to prepare a nearly saturated solution;
- (iii) cooling the nearly saturated solution to room temperature at a rate not greater than 1-2° C./min thereby forming the polymorphic form;
- and
- (iv) harvesting the polymorphic form.
A method of making a polymorphic form of naltrexone comprising:
- (i) mixing a naltrexone base anhydrous or a naltrexone salt with a solvent or solvent system selected from the group consisting of acetonitrile, dimethyl formamide, water, methanol, ethanol, benzyl alcohol, dichloromethane, acetone, ethyl acetate, methyl ethyl ketone, toluene and hexane and combinations thereof;
- to form a mixture;
- (ii) heating the mixture to prepare a nearly saturated solution;
- (iii) cooling the nearly saturated solution to room temperature as rapidly as possible thereby forming the polymorphic form;
- and (iv) harvesting the polymorphic form.
A composition comprising at least 35% by weight naltrexone wherein the naltrexone is characterized by at less than about 45% crystallinity in a non-crystalline state.
Dependencies are inferred from the claim text.