IP Library › Granted Patent US 8,796,451
Granted Patent B2
US 8,796,451 · App. 13/107,780 · Granted Aug 5, 2014

Crystalline pharmaceutical

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Quick Facts
Patent No.
US 8,796,451
App. No.
13/107,780
Granted
Aug 5, 2014
Kind
B2
Abstract

New crystalline forms of lopinavir are disclosed.

Claims (53)

1. A process for preparing a pharmaceutical composition comprising (2S,3S,5S)-2-(-2,6-dimethylphenoxyacetyl)-amino-3-hydroxy-5-(2-(1-tetrahydropyrimid-2-onyl)-3-methylbutanoyl)amino-1,6-diphenylhexane (lopinavir), said process comprising:

dissolving a crystalline form of lopinavir in a solvent, wherein said crystalline form of lopinavir is selected from the group consisting of:

a hydrated crystalline form of lopinavir with a peak in the solid state infrared spectrum at a position within the range 1652-1666 cm −1 and a peak in the solid state infrared spectrum at a position within the range 1606-1615 cm −1 , wherein said peaks have at least a moderately strong intensity;

a solvated crystalline form of lopinavir with a peak in the solid state infrared spectrum at a position within the range 1661-1673 cm −1 , a peak in the solid state infrared spectrum at a position within the range 1645-1653 cm −1 and a peak in the solid state infrared spectrum at a position within the range 1619-1629 cm −1 , wherein said peaks have at least a moderately strong intensity;

a non-solvated crystalline form of lopinavir with a peak in the solid state infrared spectrum at a position within the range 1661-1673 cm −1 , a peak in the solid state infrared spectrum at a position within the range 1645-1653 cm −1 and a peak in the solid state infrared spectrum at a position within the range 1619-1629 cm −1 , wherein said peaks have at least a moderately strong intensity;

a desolvated crystalline form of lopinavir with a peak in the solid state infrared spectrum at a position within the range 1661-1673 cm −1 , a peak in the solid state infrared spectrum at a position within the range 1645-1653 cm −1 and a peak in the solid state infrared spectrum at a position within the range 1619-1629 cm −1 , wherein said peaks have at least a moderately strong intensity;

a crystalline form of lopinavir with a peak in the solid state infrared spectrum at a position within the range 1655-1662 cm −1 , wherein said peaks have at least a moderately strong intensity;

a crystalline form of lopinavir with a peak in the solid state infrared spectrum at a position within the range 1655-1662 cm −1 and a peak in the solid state infrared spectrum at a position within the range 1636-1647 cm −1 , wherein said peaks have at least a moderately strong intensity;

a solvated crystalline form of lopinavir with a peak in the solid state infrared spectrum at a position within the range 1655-1662 cm −1 , wherein said peaks have at least a moderately strong intensity;

a solvated crystalline form of lopinavir with a peak in the solid state infrared spectrum at a position within the range 1655-1662 cm −1 and a peak in the solid state infrared spectrum at a position within the range 1636-1647 cm −1 , wherein said peaks have at least a moderately strong intensity;

a non-solvated crystalline form of lopinavir with a peak in the solid state infrared spectrum at a position within the range 1680-1685 cm −1 and a peak in the solid state infrared spectrum at a position within the range 1625-1630 cm −1 , wherein said peaks have at least a moderately strong intensity;

a non-solvated crystalline form of lopinavir with characteristic peaks in the powder X-ray diffraction pattern at values of two theta of 6.85°±0.1°, 9.14°±0.1°, 12.88°±0.1°, 15.09°±0.1°, 17.74°±0.1°, 18.01°±0.1° and 18.53°±0.1°;

a non-solvated crystalline form of lopinavir with characteristic peaks in the powder X-ray diffraction pattern at values of two theta of 6.85°±0.1°, 9.14°±0.1°, 1 0.80°±0.1°, 12.04°±0.1°, 12.88°±0.1°, 15.09°±0.1°, 17.74°±0.1°, 18.01°±0.1°, 18.26°±0.1°, 18.53°±0.1°, 20.47°±0.1° and 25.35°±0.1°;

a non-solvated crystalline form of lopinavir with a peak in the solid state infrared spectrum at a position within the range 1680-1685 cm −1 and a peak in the solid state infrared spectrum at a position within the range 1668-1674 cm −1 and a peak in the solid state infrared spectrum at a position within the range 1656-1662 cm −1 and a peak in the solid state infrared spectrum at a position within the range 1642-1648 cm −1 and a peak in the solid state infrared spectrum at a position within the range 1625-1630 cm −1 , wherein said peaks have at least a moderately strong intensity;

a desolvated crystalline form of lopinavir with a peak in the solid state infrared spectrum at a position within the range 1655-1662 cm −1 , wherein said peak has at least a moderately strong intensity;

a desolvated crystalline form of lopinavir with a peak in the solid state infrared spectrum at a position within the range 1655-1662 cm −1 and a peak in the solid state infrared spectrum at a position within the range 1636-1647 cm −1 , wherein said peaks have at least a moderately strong intensity;

a higher hydrated crystalline form of lopinavir with characteristic peaks in the powder X-ray diffraction pattern at values of two theta of 3.89°±0.1°, 6.55°±0.1°, 7.76°±0.1°, 8.55°±0.1°, 9.70°±0.1°, 10.56°±0.1°, 14.76°±0.1°, 15.57°±0.1°, 18.30°±0.1°, 18.95°±0.1° and 22.74°±0.1°; and a higher hydrated crystalline form of lopinavir with characteristic peaks in the powder X-ray diffraction pattern at values of two theta of 3.89°±0.1°, 6.55°±0.1°, 7.76°±0.1°, 8.55°±0.1°, 9.70°±0.1°, 10.56°±0.1°, 14.76°±0.1°, 15.06°±0.1°, 15.57°±0.1°, 16.49°±0.1°, 17.51°±0.1°, 18.30°±0.1°, 18.95°±0.1°, 21.73°±0.1° and 22.74°±0.1°.

2. The process of claim 1 , wherein the crystalline form of lopinavir is dissolved in an organic solvent.

3. The process of claim 1 , further comprising adding ritonavir to the pharmaceutical composition.

4. A process for preparing a pharmaceutical composition comprising lopinavir, said process comprising:

dissolving a crystalline form of lopinavir in a solvent, wherein said crystalline form of lopinavir is selected from the group consisting of:

a hydrated crystalline form of lopinavir with a peak in the solid state infrared spectrum at a position within the range 1652-1666 cm −1 and a peak in the solid state infrared spectrum at a position within the range 1606-1615 cm −1 , wherein said peaks have at least a moderately strong intensity;

a higher hydrated crystalline form of lopinavir with characteristic peaks in the powder X-ray diffraction pattern at values of two theta of 3.89°±0.1°, 6.55°±0.1°, 7.76°±0.1°, 8.55°±0.1°, 9.70°±0.1°, 10.56°±0.1°, 14.76°±0.1°, 15.57°±0.1°, 18.30°±0.1°, 18.95°±0.1° and 22.74°±0.1°; and

a higher hydrated crystalline form of lopinavir with characteristic peaks in the powder X-ray diffraction pattern at values of two theta of 3.89°±0.1°, 6.55°±0.1°, 7.76°±0.1°, 8.55°±0.1°, 9.70°±0.1°, 10.56°±0.1°, 14.76°±0.1°, 15.06°±0.1°, 15.57°±0.1°, 16.49°±0.1°, 17.51°±0.1°, 18.30°±0.1°, 18.95°±0.1°, 21.73°±0.1° and 22.74°±0.1°.

5. The process of claim 4 , wherein said hydrated crystalline form of lopinavir comprises from about 0.5 molecules of water per molecule of lopinavir to about 2 molecules of water per molecule of lopinavir.

6. The process of claim 5 , wherein said hydrated crystalline form of lopinavir comprises about 0.5 molecules of water per molecule of lopinavir.

7. The process of claim 4 , wherein the crystalline form of lopinavir is dissolved in a water miscible solvent.

8. The process of claim 4 , further comprising adding ritonavir to the pharmaceutical composition.

9. A process for preparing a pharmaceutical composition comprising lopinavir, said process comprising:

dissolving a crystalline form of lopinavir in a solvent, wherein said crystalline form of lopinavir is selected from the group consisting of:

a solvated crystalline form of lopinavir with a peak in the solid state infrared spectrum at a position within the range 1661-1673 cm −1 , a peak in the solid state infrared spectrum at a position within the range 1645-1653 cm −1 and a peak in the solid state infrared spectrum at a position within the range 1619-1629 cm −1 , wherein said peaks have at least a moderately strong intensity

a crystalline form of lopinavir with a peak in the solid state infrared spectrum at a position within the range 1661-1673 cm −1 a peak in the solid state infrared spectrum at a position within the range 1645-1653 cm −1 and a peak in the solid state infrared spectrum at a position within the range 1619-1629 cm −1 , wherein said peaks have at least a moderately strong intensity; and

a desolvated crystalline form of lopinavir with a peak in the solid state infrared spectrum at a position within the range 1661-1673 cm −1 , a peak in the solid state infrared spectrum at a position within the range 1645-1653 cm −1 and a peak in the solid state infrared spectrum at a position within the range 1619-1629 cm −1 , wherein said peaks have at least a moderately strong intensity.

10. The process of claim 9 , wherein the crystalline form of lopinavir is dissolved in a small polar organic solvent.

11. The process of claim 9 , further comprising adding ritonavir to the pharmaceutical composition.

12. A process for preparing a pharmaceutical composition comprising lopinavir, said process comprising:

dissolving a crystalline form of lopinavir in at least one solvent, wherein said crystalline form of lopinavir is selected from the group consisting of:

a solvated crystalline form of lopinavir with a peak in the solid state infrared spectrum at a position within the range 1655-1662 cm −1 , wherein said peak has at least a moderately strong intensity;

a solvated crystalline form of lopinavir with a peak in the solid state infrared spectrum at a position within the range 1655-1662 cm −1 and a peak in the solid state infrared spectrum at a position within the range 1636-1647 cm −1 , wherein said peaks have at least a moderately strong intensity;

a crystalline form of lopinavir with a peak in the solid state infrared spectrum at a position within the range 1655-1662 cm −1 , wherein said peak has at least a moderately strong intensity;

a crystalline form of lopinavir with a peak in the solid state infrared spectrum at a position within the range 1655-1662 cm −1 and a peak in the solid state infrared spectrum at a position within the range 1636-1647 cm −1 , wherein said peaks have at least a moderately strong intensity;

a desolvated crystalline form of lopinavir with a peak in the solid state infrared spectrum at a position within the range 1655-1662 cm −1 , wherein said peak has at least a moderately strong intensity; and

a desolvated crystalline form of lopinavir with a peak in the solid state infrared spectrum at a position within the range 1655-1662 cm −1 and a peak in the solid state infrared spectrum at a position within the range 1636-1647 cm −1 , wherein said peaks have at least a moderately strong intensity.

13. The process of claim 12 , wherein the crystalline form of lopinavir is dissolved in a hydrophobic organic solvent.

14. The process of claim 12 , further comprising adding ritonavir to the pharmaceutical composition.

15. A process for preparing a pharmaceutical composition comprising lopinavir, said process comprising:

dissolving a crystalline form of lopinavir in a solvent, wherein said crystalline form of lopinavir is selected from the group consisting of:

a non-solvated crystalline form of lopinavir with a peak in the solid state infrared spectrum at a position within the range 1680-1685 cm −1 and a peak in the solid state infrared spectrum at a position within the range 1625-1630 cm −1 , wherein said peaks have at least a moderately strong intensity;

a non-solvated crystalline form of lopinavir with characteristic peaks in the powder X-ray diffraction pattern at values of two theta of 6.85°±0.1°, 9.14°±0.1°, 12.88°±0.1°, 15.09°±0.1°, 17.74°±0.1°, 18.01°±0.1° and 18.53°±0.1°;

a non-solvated crystalline form of lopinavir with characteristic peaks in the powder X-ray diffraction pattern at values of two theta of 6.85°±0.1°, 9.14°±0.1°, 10.80°±0.1°, 12.04°±0.1°, 12.88°±0.1°, 15.09°±0.1°, 17.74°±0.1°, 18.01°±0.1°, 18.26°±0.1°, 18.53°±0.1°, 20.47°±0.1° and 25.35°±0.1°; and

a non-solvated crystalline form of lopinavir with a peak in the solid state infrared spectrum at a position within the range 1680-1685 cm −1 and a peak in the solid state infrared spectrum at a position within the range 1668-1674 cm −1 and a peak in the solid state infrared spectrum at a position within the range 1656-1662 cm −1 and a peak in the solid state infrared spectrum at a position within the range 1642-1648 cm −1 and a peak in the solid state infrared spectrum at a position within the range 1625-1630 cm −1 , wherein said peaks have at least a moderately strong intensity.

16. The process of claim 15 , wherein the crystalline form of lopinavir is dissolved in acetonitrile.

17. The process of claim 16 , further comprising adding ritonavir to the pharmaceutical composition.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 8, 2013
From: ABBOTT LABORATORIES
To: ABBVIE INC.
Reel/Frame 030167/0733 →