Forms of oxymorphone hydrochloride

1. A form of oxymorphone hydrochloride selected from the group consisting of Form C, Form D, Form E, Form F, Form G and Form H; wherein:

Form C has an X-ray powder diffraction pattern comprising peaks, in terms of 2-theta, at about 7.87 and about 23.73;

Form D has an X-ray powder diffraction pattern comprising peaks, in terms of 2-theta, at about 9.4 and about 10.29;

Form E has an X-ray powder diffraction pattern comprising peaks, in terms of 2-theta, at about 9.21 and about 12.69;

Form F has an X-ray powder diffraction pattern comprising peaks, in terms of 2-theta, at about 9.2, about 11.8 and about 16.04;

Form G has an X-ray powder diffraction pattern comprising peaks, in terms of 2-theta, at about 9.65 and about 16.16; and

Form H has an X-ray powder diffraction pattern comprising peaks, in terms of 2-theta, at about 7.95 and about 9.04.

2. A form of oxymorphone hydrochloride according to claim 1 , wherein:

Form C has an X-ray powder diffraction pattern further comprising peaks, in terms of 2-theta, at about 16.27 and about 18.09;

Form D has an X-ray powder diffraction pattern further comprising peaks, in terms of 2-theta, at about 13.14, about 17.39, about 19.69 and about 25.05;

Form E has an X-ray powder diffraction pattern further comprising peaks, in terms of 2-theta, at about 15.44, about 16.24 and about 19.93;

Form F has an X-ray powder diffraction pattern further comprising peaks, in terms of 2-theta, at about 11.47, about 19.97 and about 20.93;

Form G has an X-ray powder diffraction pattern further comprising peaks, in terms of 2-theta, at about 12.68 and about 17.2; and

Form H has an X-ray powder diffraction pattern further comprising a peak, in terms of 2-theta, at about 23.87.

3. A form of oxymorphone hydrochloride selected from the group consisting of Form C, Form D, Form E, Form F, Form G and Form H; wherein:

Form C has an X-ray powder diffraction pattern substantially as shown in FIG. 3 ;

Form D has an X-ray powder diffraction pattern substantially as shown in FIG. 4 ;

Form E has an X-ray powder diffraction pattern substantially as shown in FIG. 5 ;

Form F has an X-ray powder diffraction pattern substantially as shown in FIG. 6 ;

Form G has an X-ray powder diffraction pattern substantially as shown in FIG. 7 ; and

Form H has an X-ray powder diffraction pattern substantially as shown in FIG. 8 .

4. A form of oxymorphone hydrochloride selected from the group consisting of Form C, Form D, Form E, Form F, Form G and Form H; wherein:

Form C has an X-ray powder diffraction pattern comprising peaks at d-spacing, in terms of Angstroms, of about 11.224 and about 3.747;

Form D has an X-ray powder diffraction pattern comprising peaks at d-spacing, in terms of Angstroms, of about 9.400 and about 8.592;

Form E has an X-ray powder diffraction pattern comprising peaks at d-spacing, in terms of Angstroms, of about 9.600 and about 6.968;

Form F has an X-ray powder diffraction pattern comprising peaks at d-spacing, in terms of Angstroms, of about 9.607, about 7.492 and about 5.521;

Form G has an X-ray powder diffraction pattern comprising peaks at d-spacing, in terms of Angstroms, of about 9.160 and about 5.480; and

Form H has an X-ray powder diffraction pattern comprising peaks at d-spacing, in terms of Angstroms, of about 11.106 and about 9.774.

5. A form of oxymorphone hydrochloride according to claim 4 , wherein:

Form C has an X-ray powder diffraction pattern further comprising peaks at d-spacing, in terms of Angstroms, of about 5.445 and about 4.899;

Form D has an X-ray powder diffraction pattern further comprising peaks at d-spacing, in terms of Angstroms, of about 6.733, about 5.097, about 4.506 and about 3.552;

Form E has an X-ray powder diffraction pattern further comprising peaks at d-spacing, in terms of Angstroms, of about 5.736, about 5.453 and about 4.451;

Form F has an X-ray powder diffraction pattern further comprising peaks at d-spacing, in terms of Angstroms, of about 7.710, about 4.442 and about 4.241;

Form G has an X-ray powder diffraction pattern further comprising peaks at d-spacing, in terms of Angstroms, of about 6.977 and about 5.151; and

Form H has an X-ray powder diffraction pattern comprising further a peak at d-spacing, in terms of Angstroms, of about 3.725.

6. A form of oxymorphone hydrochloride according to claim 1 , wherein, as measured by differential scanning calorimetry:

Form D is characterized by an endotherm at about 93° C.;

Form E is characterized by an endotherm at about 286° C.;

Form F is characterized by an endotherm at about 122° C.;

Form G is characterized by an endotherm at about 105° C.; and

Form H is characterized by an endotherm at about 96° C.

7. A form of oxymorphone hydrochloride according to claim 1 , wherein:

Form D is characterized by a differential scanning calorimetry pattern substantially as shown in FIG. 9 ;

Form E is characterized by a differential scanning calorimetry pattern substantially as shown in FIG. 10 ;

Form F is characterized by a differential scanning calorimetry pattern substantially as shown in FIG. 11 ;

Form G is characterized by a differential scanning calorimetry pattern substantially as shown in FIG. 12 ; and

Form H is characterized by a differential scanning calorimetry pattern substantially as shown in FIG. 13 .

8. A form of oxymorphone hydrochloride according to claim 1 , wherein:

Form D is characterized by a thermal gravimetric analysis pattern substantially as shown in FIG. 14 ;

Form E is characterized by a thermal gravimetric analysis pattern substantially as shown in FIG. 15 ; and

Form F is characterized by a thermal gravimetric analysis pattern substantially as shown in FIG. 16 .

9. A pharmaceutical formulation comprising at least one pharmaceutically acceptable excipient and oxymorphone hydrochloride according to claim 1 .

10. A pharmaceutical formulation according to claim 9 , wherein the formulation is a tamper resistant or abuse proof dosage form.

11. The pharmaceutical formulation according to claim 9 , wherein the formulation is an extended release or sustained release dosage form.

12. A method of treating pain comprising administering a pharmaceutical formulation according to claim 9 to a patient in need thereof.

13. A method of making oxymorphone hydrochloride Form C according to claim 1 , comprising exposing a starting material comprising oxymorphone hydrochloride Form A to acetone at a temperature in the range of about 0 to 20° C. for a time sufficient to yield oxymorphone hydrochloride Form C.

14. A method of making oxymorphone hydrochloride Form D according to claim 1 , comprising exposing a starting material comprising oxymorphone hydrochloride Form A to a mixture of ethanol and water at a temperature in the range of about 0 to 20° C. for a time sufficient to yield oxymorphone hydrochloride Form D.

15. A method of making oxymorphone hydrochloride Form E according to claim 1 , comprising exposing a starting material comprising oxymorphone hydrochloride Form A to ethyl acetate at a temperature in the range of about 40 to 55° C. for a time sufficient to yield oxymorphone hydrochloride Form E.

16. A method of making oxymorphone hydrochloride Form E according to claim 1 , comprising exposing a starting material comprising oxymorphone hydrochloride Form A to acetone at a temperature in the range of about 40 to 55° C. for a time sufficient to yield oxymorphone hydrochloride Form E.

17. A method of making oxymorphone hydrochloride Form E according to claim 1 , comprising exposing a starting material comprising oxymorphone hydrochloride Form A to acetronitrile at a temperature in the range of about 40 to 55° C. for a time sufficient to yield oxymorphone hydrochloride Form E.

18. A method of making oxymorphone hydrochloride Form F according to claim 1 , comprising drying a starting material comprising oxymorphone hydrochloride Form A at a temperature in the range of about 45 to 65° C. for a time sufficient to yield oxymorphone hydrochloride Form F.

19. A method of making oxymorphone hydrochloride Form G according to claim 1 , comprising drying a starting material comprising oxymorphone hydrochloride Form B at a temperature in the range of about 45 to 65° C. for a time sufficient to yield oxymorphone hydrochloride Form G.

20. A method of making oxymorphone hydrochloride Form H according to claim 1 , comprising the steps of:

dissolving oxymorphone freebase in a mixture comprising water, ethanol and hydrochloric acid at a temperature in the range of about 60 to 70° C.;

removing a portion of the solvent;

adding ethanol to the mixture;

removing an additional portion of the solvent; and

adding additional ethanol to the mixture to yield oxymorphone hydrochloride Form H.