IP Library › Granted Patent US 8,058,433
Granted Patent B2
US 8,058,433 · App. 11/542,075 · Granted Nov 15, 2011

Crystalline pharmaceutical

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Quick Facts
Patent No.
US 8,058,433
App. No.
11/542,075
Granted
Nov 15, 2011
Kind
B2
Abstract

New crystalline forms of lopinavir are disclosed.

Claims (76)

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

combining a crystalline form of lopinavir and additional ingredients,

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 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 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 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°;

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 according to claim 1 , wherein said additional ingredients comprise ritonavir.

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

combining lopinavir that comprises a crystalline form of lopinavir with additional ingredients,

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 crystalline form of lopinavir with a peak in the solid state infrared spectrum at a position within the range 1655-1662 cm −1 ;

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 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 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°;

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°.

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

combining a hydrated crystalline form of lopinavir and additional ingredients,

wherein said hydrated 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 about 0.5 molecules of water per molecule of lopinavir.

6. 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.

7. The process according to claim 1 , wherein said crystalline form of lopinavir is 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.

8. The process according to claim 1 , wherein said crystalline form of lopinavir is 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.

9. The process according to claim 1 , wherein said crystalline form of lopinavir is 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.

10. The process according to claim 1 , wherein said crystalline form of lopinavir is 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.

11. The process according to claim 1 , wherein said crystalline form of lopinavir is 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.

12. The process according to claim 1 , wherein said crystalline form of lopinavir is 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.

13. The process according to claim 1 , wherein said crystalline form of lopinavir is 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.

14. The process according to claim 1 , wherein said crystalline form of lopinavir is 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°.

15. The process according to claim 1 , wherein said crystalline form of lopinavir is 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°.

16. The process according to claim 1 , wherein said crystalline form of lopinavir is 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.

17. The process according to claim 1 , wherein said crystalline form of lopinavir is 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.

18. The process according to claim 1 , wherein said crystalline form of lopinavir is 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.

19. The process according to claim 1 , wherein said crystalline form of lopinavir is 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°.

20. The process according to claim 1 , wherein said crystalline form of lopinavir is 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°.

21. The process according to claim 3 , wherein said crystalline form of lopinavir is 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.

22. The process according to claim 3 , wherein said crystalline form of lopinavir is 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.

23. The process according to claim 3 , wherein said crystalline form of lopinavir is 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.

24. The process according to claim 3 , wherein said crystalline form of lopinavir is 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.

25. The process according to claim 3 , wherein said crystalline form of lopinavir is 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.

26. The process according to claim 3 , wherein said crystalline form of lopinavir is 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.

27. The process according to claim 3 , wherein said crystalline form of lopinavir is 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.

28. The process according to claim 3 , wherein said crystalline form of lopinavir is 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°.

29. The process according to claim 3 , wherein said crystalline form of lopinavir is 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°.

30. The process according to claim 3 , wherein said crystalline form of lopinavir is 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.

31. The process according to claim 3 , wherein said crystalline form of lopinavir is 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.

32. The process according to claim 3 , wherein said crystalline form of lopinavir is 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.

33. The process according to claim 3 , wherein said crystalline form of lopinavir is 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°.

34. The process according to claim 3 , wherein said crystalline form of lopinavir is 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°.

35. The process according to claim 3 , wherein said additional ingredients comprise ritonavir.

36. The process according to claim 4 , wherein said hydrated crystalline form of lopinavir is 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.

37. The process according to claim 4 , wherein said hydrated crystalline form of lopinavir is 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°.

38. The process according to claim 4 , wherein said hydrated crystalline form of lopinavir is 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°.

39. The process according to claim 4 , wherein said additional ingredients comprise ritonavir.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 8, 2013
From: ABBOTT LABORATORIES
To: ABBVIE INC.
Reel/Frame 030167/0733 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 2, 2006
From: DICKMAN, DANIEL A.; CHEMBURKAR, SANJAY; FORT, JAMES J.; HENRY, RODGER F.; LECHUGA-BALLESTEROS, DAVID; NIU, YUPING; PORTER, WILLIAM
To: ABBOTT LABORATORIES
Reel/Frame 018406/0580 →