Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients
The present invention is based, at least in part, on the identification of a pharmaceutical container formed, at least in part, of a glass composition which exhibits a reduced propensity to delaminate, i.e., a reduced propensity to shed glass particulates. As a result, the presently claimed containers are particularly suited for storage of pharmaceutical compositions and, specifically, a pharmaceutical solution comprising a pharmaceutically active ingredient, for example, LEVEMIR, NOVOLOG, NOVOLIN 70-30, NOVOLIN R, NOVOLIN N, NOVOLOG MIX 70-30 and NOVOLIN L.
1. A delamination resistant pharmaceutical container comprising a pharmaceutical composition, wherein the pharmaceutical container comprises a glass composition comprising:
SiO 2 in a concentration greater than about 74 mol. %;
alkaline earth oxide comprising MgO and CaO, wherein CaO is present in an amount greater than or equal to about 0.1 mol. % and less than or equal to about 1.0 mol. %, and a ratio (CaO (mol. %)/(CaO (mol. %)+MgO (mol. %))) is less than or equal to 0.5; and
Y mol. % alkali oxide, wherein the alkali oxide comprises Na 2 O in an amount greater than about 8 mol. %, wherein the glass composition is free of boron and compounds of boron, wherein the pharmaceutical composition comprises one of human insulin detemir, human insulin aspart, 70% human insulin isophane suspension and 30% regular human insulin, regular human insulin, human insulin isophane suspension, 70% human insulin aspart protamine suspension and 30% human insulin aspart, lente insulin or an insulin analog.
2. The pharmaceutical container of claim 1 , wherein the pharmaceutical composition comprises a citrate or phosphate buffer.
3. The pharmaceutical container of claim 2 , wherein the buffer is selected from the group consisting of sodium citrate, SSC, monosodium phosphate and disodium phosphate.
4. The pharmaceutical container of claim 1 , wherein the pharmaceutical composition is a solution having a pH between about 7 and about 11.
5. The pharmaceutical container of claim 1 , wherein the pharmaceutical composition comprises an insulin analog.
6. The pharmaceutical container of claim 1 , wherein the pharmaceutical composition is selected from the group consisting of human insulin detemir, human insulin aspart, 70% human insulin isophane suspension and 30% regular human insulin, regular human insulin, human insulin isophane suspension, 70% human insulin aspart protamine suspension and 30% human insulin aspart and lente insulin.
7. The pharmaceutical container of claim 1 , wherein the pharmaceutical composition is human insulin detemir.
8. The pharmaceutical container of claim 1 , wherein the pharmaceutical composition is human insulin aspart.
9. The pharmaceutical container of claim 1 , wherein the pharmaceutical composition is 70% human insulin isophane suspension and 30% regular human insulin.
10. The pharmaceutical container of claim 1 , wherein the pharmaceutical composition is regular human insulin.
11. The pharmaceutical container of claim 1 , wherein the pharmaceutical composition is human insulin isophane suspension.
12. The pharmaceutical container of claim 1 , wherein the pharmaceutical composition is 70% human insulin aspart protamine suspension and 30% human insulin aspart.
13. The pharmaceutical container of claim 1 , wherein the pharmaceutical composition is lente insulin.
14. The pharmaceutical container of claim 1 , wherein the concentration of SiO 2 is less than or equal to about 80 mol. %.
15. The pharmaceutical container of claim 1 , wherein the glass composition is free from phosphorous and compounds of phosphorous.
16. The pharmaceutical container of claim 1 , further comprising X mol. % Al 2 O 3 , wherein a ratio of Y:X is greater than 1.
17. The pharmaceutical container of claim 16 , wherein the ratio of Y:X is less than or equal to 2.
18. The pharmaceutical container of claim 16 , wherein X is greater than or equal to about 2 mol. % and less than or equal to about 10 mol. %.
19. The pharmaceutical container of claim 16 , wherein the alkaline earth oxide is present in an amount from about 3 mol. % to about 13 mol. %.
20. The pharmaceutical container of claim 16 , wherein the ratio of Y:X is greater than or equal 1.3 and less than or equal to 2.
21. The pharmaceutical container of claim 16 , wherein X is greater than or equal to about 5 mol. % and less than or equal to about 7 mol. %.
22. The pharmaceutical container of claim 1 , wherein the ratio (CaO (mol. %)/(CaO (mol. %)+MgO (mol. %))) is less than or equal to 0.3.
23. The pharmaceutical container of claim 1 , further comprising SnO 2 .
24. A delamination resistant pharmaceutical container comprising a pharmaceutical composition, wherein the pharmaceutical container comprises a glass composition comprising:
from about 74 mol. % to about 78 mol. % SiO 2 ;
from about 4 mol. % to about 8 mol. % alkaline earth oxide, wherein the alkaline earth oxide comprises both MgO and CaO and a ratio (CaO (mol. %)/(CaO (mol. %)+MgO (mol. %))) is less than or equal to 0.5;
X mol. % Al 2 O 3 , wherein X is greater than or equal to about 2 mol. % and less than or equal to about 10 mol. %; and
Y mol. % alkali oxide, wherein the alkali oxide comprises Na 2 O in an amount greater than or equal to about 9 mol. % and less than or equal to about 15 mol. %, a ratio of Y:X is greater than 1, and the glass composition is free of boron and compounds of boron, wherein the pharmaceutical composition comprises one of human insulin detemir, human insulin aspart, 70% human insulin isophane suspension and 30% regular human insulin, regular human insulin, human insulin isophane suspension, 70% human insulin aspart protamine suspension and 30% human insulin aspart, lente insulin or an insulin analog.
25. The pharmaceutical container of claim 24 , wherein the ratio of Y:X is less than or equal to about 2.
26. The pharmaceutical container of claim 24 , wherein the ratio of Y:X is greater than or equal to about 1.3 and less than or equal to about 2.0.
27. The pharmaceutical container of claim 24 , wherein the ratio (CaO (mol. %)/(CaO (mol. %)+MgO (mol. %))) is less than or equal to 0.1.
28. The pharmaceutical container of claim 24 , wherein the alkaline earth oxide comprises from about 3 mol. % to about 7 mol. % MgO.
29. The pharmaceutical container of claim 24 , wherein the alkaline earth oxide comprises CaO in an amount greater than or equal to about 0.1 mol. % and less than or equal to about 1.0 mol. %.
30. The pharmaceutical container of claim 24 , wherein the alkali oxide further comprises K 2 O in an amount greater than or equal to about 0.01 mol. % and less than or equal to about 1.0 mol. %.
31. The pharmaceutical container of claim 24 , wherein X is greater than or equal to about 5 mol. % and less than or equal to about 7 mol. %.
32. A delamination resistant pharmaceutical container comprising a pharmaceutical composition, wherein the pharmaceutical container comprises a glass composition comprising:
from about 74 mol. % to about 78 mol. % SiO 2 ,
alkaline earth oxide comprising both CaO and MgO, wherein the alkaline earth oxide comprises CaO in an amount greater than or equal to about 0.1 mol. % and less than or equal to about 1.0 mol. %, and a ratio (CaO (mol. %)/(CaO (mol. %)+MgO (mol. %))) is less than or equal to 0.5;
X mol. % Al 2 O 3 , wherein X is greater than or equal to about 2 mol. % and less than or equal to about 10 mol. %; and
Y mol. % alkali oxide, wherein the alkali oxide comprises from about 0.01 mol. % to about 1.0 mol. % K 2 O and a ratio of Y:X is greater than 1, and the glass composition is free of boron and compounds of boron, wherein the pharmaceutical composition comprises one of LEVEMIR® human insulin detemir, human insulin aspart, 70% human insulin isophane suspension and 30% regular human insulin, regular human insulin, human insulin isophane suspension, 70% human insulin aspart protamine suspension and 30% human insulin aspart, lente insulin or an insulin analog.
33. The pharmaceutical container of claim 32 , wherein the ratio of Y:X is less than or equal to 2.
34. The pharmaceutical container of claim 32 , wherein the ratio of Y:X is greater than or equal to 1.3 and less than or equal to 2.0.
35. The pharmaceutical container of claim 32 , wherein the ratio (CaO (mol. %)/(CaO (mol. %)+MgO (mol. %))) is less than or equal to 0.1.
36. The pharmaceutical container of claim 32 , wherein the glass composition is free of phosphorous and compounds of phosphorous.
37. The pharmaceutical container of claim 32 , wherein the alkali oxide further comprises Na 2 O in an amount greater than about 8 mol. %.
38. The pharmaceutical container of claim 32 , wherein the alkali oxide further comprises Na 2 O in an amount greater than or equal to about 2 mol. % and less than or equal to about 15 mol. %.
39. The pharmaceutical container of claim 32 , wherein the alkali oxide further comprises from about 9 mol. % to about 13 mol. % Na 2 O.
40. The pharmaceutical container of claim 32 , wherein X is greater than or equal to about 5 mol. % and less than or equal to about 7 mol. %.