PHARMACEUTICAL GLASS PACKAGING ASSURING PHARMACEUTICAL STERILITY

• US 20150157533A1
• Filed: 12/17/2014
• Published: 06/11/2015
• Est. Priority Date: 10/25/2011
• Status: Active Grant

• Current Assignee: Corning Incorporated
• Original Assignee: Corning Incorporated
• Inventors: DeMartino, Steven Edward, Schaut, Robert Anthony
• Granted Patent: US 10,350,139 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61J 1/00 Containers specially adapted for medical or pharmaceutical purposes capsules or the like for oral use A61J3/07; specially adapted for surgical or diagnostic appliances or instruments A61B50/30; containers for radioactive substances G21F5/00
• CPC Class Codes: B32B 17/06 comprising glass as the main or only constituent of a layer, next to another layer of a specific material
• CPC Class Codes: B65D 1/0215 multilayered B65D81/3837 takes precedence
• CPC Class Codes: C03B 27/065 Stresses, e.g. patterns, values or formulae
• CPC Class Codes: C03C 21/002 to perform ion-exchange between alkali ions C03C21/005 takes precedence
• CPC Class Codes: C03C 21/007 in gaseous phase
• CPC Class Codes: Y10T 29/49 Method of mechanical manufacture
• CPC Class Codes: Y10T 428/131 Glass, ceramic, or sintered, fused, fired, or calcined metal oxide or metal carbide containing [e.g., porcelain, brick, cement, etc.]
• CPC Class Codes: Y10T 428/1317 Multilayer [continuous layer]
• CPC Class Codes: Y10T 428/24802 Discontinuous or differential coating, impregnation or bond [e.g., artwork, printing, retouched photograph, etc.]
• CPC Class Codes: Y10T 428/315 Surface modified glass [e.g., tempered, strengthened, etc.]

Abstract

A sterile glass pharmaceutical container or vessel such as, but not limited to, vials for holding pharmaceutical products or vaccines in a hermetic and/or sterile state. The sterile glass pharmaceutical container undergoes a strengthening process that produces compression at the surface and tension within the container wall. The strengthening process is designed such that the tension within the wall is great enough to ensure catastrophic failure of the pharmaceutical container, thus rendering the product unusable, should sterility be compromised by a through-wall crack. The tension is greater than a threshold central tension, above which catastrophic failure of the pharmaceutical container is guaranteed, thus eliminating any potential for violation of pharmaceutical integrity or sterility (such as stable cracks) in the glass packaging which are not easily identifiable in an otherwise seemingly intact pharmaceutical container.

Claims

1. A sterile container comprising a glass having a Young'"'"'s modulus E and a Poisson'"'"'s ratio ν

, the sterile container having a thickness and first surface and a second surface, the glass has a first region under a compressive stress, the first region extending from at least one of the first surface and the second surface to a depth of layer in the glass, and a second region under a central tension greater than or equal to a threshold tensile stress of about 15 MPa, the second region extending from the depth of layer, and wherein the glass container remains sterile so long as a flaw does not extend into the second region, and wherein (CT²/E)·

(t−

2DOL)·

(1−

ν

)≧

3.0 MPa·

μ

m, where CT is the central tension, t is the thickness, and DOL is the depth of layer.

2. The sterile container of claim 1, wherein the glass comprises an alkali aluminosilicate glass.

3. The sterile container of claim 1, wherein the sterile container is adapted to hold a pharmaceutical product, a vaccine, a biologic, or a solution.

4. The sterile container of claim 1, wherein the threshold tensile stress is sufficient to allow self-propagation of a crack front through the thickness from the first surface to the second surface.

5. The sterile container of claim 4, wherein the self-propagation of the crack front from the first surface to the second surface further comprises bifurcation of the crack front across at least the first surface.

6. The sterile container of claim 4, wherein the self-propagation of the crack front from the first surface to the second surface further comprises self-propagation of the crack front laterally across at least the first surface, and wherein the self-propagation of the crack front renders the container unsuitable for its intended use.

7. The sterile container of claim 1, wherein (CT²/E)·

(t−

2DOL)·

(1−

ν

)≧

9.5 MPa·

μ

m.

8. The sterile container of claim 7, wherein (CT²/E)·

(t−

2DOL)·

(1−

ν

)≧

15.0 MPa·

μ

m.

9. The sterile container of claim 1, wherein the threshold tensile stress is greater than or equal to about 30 MPa.

10. The sterile container of claim 9, wherein the threshold tensile stress is greater than or equal to about 45 MPa.

11. The sterile container of claim 1, wherein the compressive stress is at least about 200 MPa.

12. The sterile container of claim 1, wherein the depth of layer is at least about 30 μ

m.

13. The sterile container of claim 1, wherein the depth of layer is in a range from about 15% to about 25% of the thickness.

14. The sterile container of claim 1, wherein the thickness is up to about 6 mm.

15. The sterile container of claim 14, wherein the thickness is in a range from about 0.3 mm to about 2.0 mm.

16. The sterile container of claim 1, wherein the glass is a strengthened glass.

17. The sterile container of claim 16, wherein the strengthened glass is ion exchanged or thermally tempered.

18. The sterile container of claim 1, wherein the glass comprises a laminate, the laminate comprising a first glass disposed on the first surface and a second glass disposed between the first glass and the second surface.

19. The sterile container of claim 18, wherein the first glass has a first CTE and the second glass is adjacent to the first glass and has a second CTE, wherein the first CTE is greater than the second CTE.

20. The sterile container of claim 18, wherein the first glass has a first Young'"'"'s modulus and the second glass is adjacent to the first glass and has a second Young'"'"'s modulus, wherein the first Young'"'"'s modulus is greater than the second Young'"'"'s modulus.

21. A sterile pharmaceutical container comprising a delamination resistant glass composition, the pharmaceutical container comprising:

a sterile pharmaceutical composition comprising an active pharmaceutical ingredient;

a first surface and a second surface separated by glass having a thickness;

a first region under a compressive stress, the first region extending from at least one of the first surface and the second surface to a depth of layer in the glass of at least about 10 μ

m;

a second region under a tensile stress of at least about 15 MPa, the second region extending from the depth of layer, wherein the central tension is greater than a threshold central tension that is sufficient to allow self-propagation of a crack front greater than the depth of layer from the first surface to the second surface which renders the pharmaceutical container unsuitable for its intended use such that the active pharmaceutical ingredient remains sterile.

22. The sterile pharmaceutical container of claim 21, wherein the delamination resistant glass composition comprises an alkali aluminosilicate glass.

23. The sterile pharmaceutical container of claim 21, wherein the sterile pharmaceutical composition is a vaccine, a biologic, or a solution.

24. The sterile pharmaceutical container of claim 21, wherein the threshold tensile stress is sufficient to allow self-propagation of a crack front through the thickness from the first surface to the second surface.

25. The sterile pharmaceutical container of claim 24, wherein the self-propagation of the crack front from the first surface to the second surface further comprises bifurcation of the crack front across at least the first surface.

26. The sterile pharmaceutical container of claim 24, wherein the self-propagation of the crack front from the first surface to the second surface further comprises self-propagation of the crack front laterally across at least the first surface, and wherein the self-propagation of the crack front renders the container unsuitable for its intended use.

27. The sterile pharmaceutical container of claim 21, wherein (CT²/E)·

(t−

2DOL)·

(1−

ν

)≧

9.5 MPa·

μ

m.

28. The sterile pharmaceutical container of claim 27, wherein (CT²/E)·

(t−

2DOL)·

(1−

ν

)≧

15.0 MPa·

μ

m.

29. The sterile pharmaceutical container of claim 21, wherein the threshold tensile stress is greater than or equal to about 30 MPa.

30. The sterile pharmaceutical container of claim 29, wherein the threshold tensile stress is greater than or equal to about 45 MPa.

31. The sterile pharmaceutical container of claim 21, wherein the compressive stress is at least about 200 MPa.

32. The sterile pharmaceutical container of claim 21, wherein the depth of layer is at least about 30 μ

m.

33. The sterile pharmaceutical container of claim 21, wherein the depth of layer is in a range from about 15% to about 25% of the thickness.

34. The sterile pharmaceutical container of claim 21, wherein the thickness is up to about 6 mm.

35. The sterile pharmaceutical container of claim 34, wherein the thickness is in a range from about 0.3 mm to about 2.0 mm.

36. The sterile pharmaceutical container of claim 21, wherein the delamination resistant glass composition is a strengthened glass composition.

37. The sterile pharmaceutical container of claim 36, wherein the strengthened glass composition is ion exchanged or thermally tempered.

38. The sterile pharmaceutical container of claim 21, wherein the delamination resistant glass composition comprises a laminate, the laminate comprising a first glass disposed on the first surface and a second glass disposed between the first glass and the second surface.

39. The sterile pharmaceutical container of claim 38, wherein the first glass has a first CTE and the second glass is adjacent to the first glass and has a second CTE, wherein the first CTE is greater than the second CTE.

40. The sterile pharmaceutical container of claim 38, wherein the first glass has a first Young'"'"'s modulus and the second glass is adjacent to the first glass and has a second Young'"'"'s modulus, wherein the first Young'"'"'s modulus is greater than the second Young'"'"'s modulus.

41. A pharmaceutical composition comprising:

an active pharmaceutical ingredient selected from the group consisting of the pharmaceutical compositions set forth in Table 2 or 3;

a pharmaceutically acceptable excipient; and

wherein the pharmaceutical composition is contained within a sterile glass pharmaceutical container comprising;

a first surface and a second surface separated by glass having a thickness;

a first region under a compressive stress, the first region extending from at least one of the first surface and the second surface to a depth of layer in the glass of at least about 10 μ

m; and

a second region under a tensile stress of at least about 15 MPa, the second region extending from the depth of layer, wherein the tensile stress is greater than a threshold tensile stress that is sufficient to allow self-propagation of a crack front greater than the depth of layer from the first surface to the second surface which renders the pharmaceutical container unsuitable for its intended use such that the active pharmaceutical ingredient remains sterile.

42. The pharmaceutical composition of claim 41, wherein the glass comprises an alkali aluminosilicate glass.

43. The pharmaceutical composition of claim 41, wherein the self-propagation of the crack front from the first surface to the second surface further comprises bifurcation of the crack front across at least the first surface.

44. The pharmaceutical composition of claim 43, wherein the self-propagation of the crack front from the first surface to the second surface further comprises self-propagation of the crack front laterally across at least the first surface, and wherein the self-propagation of the crack front renders the container unsuitable for its intended use.

45. The pharmaceutical composition of claim 41, wherein (CT²/E)·

(t−

2DOL)·

(1−

ν

)≧

9.5 MPa·

μ

m.

46. The pharmaceutical composition of claim 45, wherein (CT²/E)·

(t−

2DOL) (1−

ν

)≧

15.0 MPa·

μ

m.

47. The pharmaceutical composition of claim 41, wherein the threshold tensile stress is greater than or equal to about 30 MPa.

48. The pharmaceutical composition of claim 47, wherein the threshold tensile stress is greater than or equal to about 45 MPa.

49. The pharmaceutical composition of claim 41, wherein the compressive stress is at least about 200 MPa.

50. The pharmaceutical composition of claim 41, wherein the depth of layer is at least about 30 μ

m.

51. The pharmaceutical composition of claim 41, wherein the depth of layer is in a range from about 15% to about 25% of the thickness.

52. The pharmaceutical composition of claim 41, wherein the thickness is up to about 6 mm.

53. pharmaceutical composition of claim 52, wherein the thickness is in a range from about 0.3 mm to about 2.0 mm.

54. The pharmaceutical composition of claim 41, wherein the glass is a strengthened glass.

55. The pharmaceutical composition of claim 54, wherein the strengthened glass is ion exchanged or thermally tempered.

56. The pharmaceutical composition of claim 41, wherein the glass comprises a laminate, the laminate comprising a first glass disposed on the first surface and a second glass disposed between the first glass and the second surface.

57. The pharmaceutical composition of claim 56, wherein the first glass has a first CTE and the second glass is adjacent to the first glass and has a second CTE, wherein the first CTE is greater than the second CTE.

58. The pharmaceutical composition of claim 56, wherein the first glass has a first Young'"'"'s modulus and the second glass is adjacent to the first glass and has a second Young'"'"'s modulus, wherein the first Young'"'"'s modulus is greater than the second Young'"'"'s modulus.

59. A method of assuring a sterile condition of a pharmaceutical ingredient contained within a pharmaceutical container, the method comprising:

providing the pharmaceutical container, the pharmaceutical container comprising a glass, the pharmaceutical container having a thickness and first surface and a second surface, wherein the glass has a first region under a compressive stress, the first region extending from at least one of the first surface and the second surface to a depth of layer in the glass, and a second region under a tensile stress of at least 15 MPa, the second region extending from the depth of layer, wherein the central tension is greater than a threshold tensile stress that is sufficient to allow self-propagation of a crack front through the thickness from the first surface to the second surface, and wherein the self-propagation of the crack front from the first surface to the second surface renders the pharmaceutical container unsuitable for its intended use such that a user is assured that the pharmaceutical ingredient remains sterile within the pharmaceutical container.

60. The method of claim 59, wherein the self-propagation of the crack front from the first surface to the second surface further comprises bifurcation of the crack front across at least the first surface.

61. The method of claim 59, wherein the glass comprises a delamination resistant glass.