Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients

1. A delamination resistant pharmaceutical container comprising a pharmaceutical composition stored within the container, 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. % relative to the glass composition, 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, and

wherein the pharmaceutical composition comprises one of: an antidiabetic, an anti-neoplastic Mab, an antirheumatic, an antibacterial, a cytostatic, a vaccine, an immunosuppressant, an anti-fibrinolytic, an eye preparation, a MS therapeutic, a bone calcium regulator, an anti-coagulant, an anti-psychotic, an anti-metabolite, a radiopharmaceutical, an immunostimulant, a cytotoxic antibiotic, a cerebral and peripheral vasotherapeutic, a muscoskeletal agent, a nootropic, a CNS drug, a dermatological, an angiotensin II antagonist, a serelaxin, an anti-spasmodic, an anti-cholinergic, an interferon, an anti-anaemic, an anti-psoriasis agent, an anti-hyperlipidaemic, a cardiac therapeutic, an alkylating agent, a bronchodilator, a gastro-intestinal anti-inflammatory, a growth hormone, a hormone preparation, a non-narcotic analgesic, a diagnostic imaging agent, a haematological, a peripheral muscle relaxant, a growth hormone (human), or an immune globulin.

2. A delamination resistant pharmaceutical container comprising a pharmaceutical composition stored within the container, 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, and

wherein the pharmaceutical composition comprises one of: of an antidiabetic, an anti-neoplastic Mab, an antirheumatic, an antibacterial, a cytostatic, a vaccine, an immunosuppressant, an anti-fibrinolytic, an eye preparation, a MS therapeutic, a bone calcium regulator, an anti-coagulant, an anti-psychotic, an anti-metabolite, a radiopharmaceutical, an immunostimulant, a cytotoxic antibiotic, a cerebral and peripheral vasotherapeutic, a muscoskeletal agent, a nootropic, a CNS drug, a dermatological, an angiotensin II antagonist, a serelaxin, an anti-spasmodic, an anti-cholinergic, an interferon, an anti-anaemic, an anti-psoriasis agent, an anti-hyperlipidaemic, a cardiac therapeutic, an alkylating agent, a bronchodilator, a gastro-intestinal anti-inflammatory, a growth hormone, a hormone preparation, a non-narcotic analgesic, a diagnostic imaging agent, a haematological, a peripheral muscle relaxant, a growth hormone (human) or an immune globulin.

3. A delamination resistant pharmaceutical container comprising a pharmaceutical composition stored within the container, 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. % relative to the glass composition, 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, and

wherein the pharmaceutical composition comprises one of: an antidiabetic, an anti-neoplastic Mab, an antirheumatic, an antibacterial, a cytostatic, a vaccine, an immunosuppressant, an anti-fibrinolytic, an eye preparation, a MS therapeutic, a bone calcium regulator, an anti-coagulant, an anti-psychotic, an anti-metabolite, a radiopharmaceutical, an immunostimulant, a cytotoxic antibiotic, a cerebral and peripheral vasotherapeutic, a muscoskeletal agent, a nootropic, a CNS drug, a dermatological, an angiotensin II antagonist, a serelaxin, an anti-spasmodic, an anti-cholinergic, an interferon, an anti-anaemic, an anti-psoriasis agent, an anti-hyperlipidaemic, a cardiac therapeutic, an alkylating agent, a bronchodilator, a gastro-intestinal anti-inflammatory, a growth hormone, a hormone preparation, a non-narcotic analgesic, a diagnostic imaging agent, a haematological, a peripheral muscle relaxant, a growth hormone (human) or an immune globulin.

4. The pharmaceutical container of claim 1 , wherein the container comprises a vial, cartridge, syringe, ampoule, bottle, flask, or vacutainer.

5. The pharmaceutical container of claim 1 , wherein the container is delamination resistant.

6. The pharmaceutical container of claim 1 , wherein the container has a delamination factor of 1.

7. The pharmaceutical container of any one of 1 , 2 , and 3 , wherein

(i) the antidiabetic is selected from the group consisting of insulin aspart; insulin degludec; insulin glargine recombinant; dulaglutide; lixisenatide; hyaluronidase (human); insulin; liraglutide; insulin glargine; albiglutide; insulin lispro recombinant; insulin (human); insulin detemir; exenatide synthetic; insulin aspart and insulin aspart protamine; insulin aspart and insulin degludec; hyaluronidase (human) and insulin lispro/insulin aspart; insulin glargine and lixisenatide; and insulin degludec and liraglutide;

(ii) the antineoplastic is selected from the group consisting of Bavituximab, Onartuzumab, yttrium Y-90 clivatuzumab tetraxetan, obinutuzumab, cixutumumab, necitumumab, pertuzumab, brentuximab vedotin, nivolumab, trastuzumab emtansine, siltuximab, elotuzumab, ramucirumab, Ipilimumab, Rituximab, Trastuzumab, and bevacizumab;

(iii) the antirheumatic is selected from the group consisting of tabalumab, sarilumab, Tocilizumab, Infliximab, Etanercept, Abatacept, certolizumab pegol, Golimumab, and Adalimumab;

(iv) the antibacterial is selected from the group consisting of ceftolozane sulfate, and tazobactam sodium, ceftaroline fosamil, brilacidin, and tedizolid phosphate;

(v) the cytostatic is selected from the group consisting of CT-107, ganetespib, CUDC-101, Reolysin, AEZS-108, velimogene aliplasmid, imetelstat sodium, algenpantucel-L, retaspimycin hydrochloride, astuprotimut-R, vosaroxin, BiovaxID, iniparib, Bortezomib, and carfilzomib;

(vi) the vaccine is selected from the group consisting of meningococcal B vaccine; herpes zoster vaccine; hepatitis B vaccine; human papillomavirus (HPV) vaccine; pneumococcal vaccine; DTPw; influenza vaccine; hepatitis A and B vaccine; DTP, hepatitis B, and polio vaccine; and PENTAct-H1B;

(vii) the immunosuppressant is selected from the group consisting of epratuzumab, eritoran tetrasodium, blisibimod, and ustekinumab;

(viii) the anti-fibrinolytic is selected from the group consisting of turoctocog alfa, vonicog alfa, factor VIII, eptacog alfa, and octocog alfa;

(ix) the eye preparation is selected from the group consisting of Ocriplasmin, Aflibercept, and Ranibizumab;

(x) the MS therapeutic is selected from the group consisting of Alemtuzumab, ocrelizumab, daclizumab, peginterferon beta-1a, Natalizumab, glatiramer acetate, and interferon beta-1a;

(xi) the bone calcium regulator is selected from the group consisting of romosozumab, Denosumab, and recombinant human teriparatide;

(xii) the anti-coagulant is selected from the group consisting of semuloparin sodium, otamixaban, and enoxaparin sodium

(xiii) the anti-psychotic is aripiprazole;

(xiv) the anti-metabolite is gemcitabine elaidate;

(xv) the radiopharmaceutical is radium Ra-223 chloride;

(xvi) the immunostimulant is Pegfilgrastim;

(xvii) the cytotoxic antibiotic is doxorubicin hydrochloride;

(xviii) the cerebral and peripheral vasotherapeutic is defibrotide;

(xix) the musculoskeletal agent is selected from the group consisting of Drisapersen, eteplirsen, and asfotase alfa;

(xx) the nootropic is solanezumab;

(xxi) the CNS drug is neural stem cells;

(xxii) the dermatological is secukinumab;

(xxiii) the angiotensin II antagonist is serelaxin;

(xxiv) the anti-spasmodic or anti-cholinergic is teduglutide;

(xxv) the interferon is peginterferon lambda-1a or peginterferon alfa-2a;

(xxvi) the anti-anaemic is ferric pyrophosphate or darbepoetin alfa;

(xxvii) the anti-psoriasis agent is ixekizumab;

(xxviii) the anti-hyperlipidaemic is alirocumab;

(xxix) the cardiac therapeutic is cenderitide;

(xxx) the alkylating agent is palifosfamide;

(xxxi) the bronchodilator is lebrikizumab;

(xxxii) the gastro-intestinal anti-inflammatory is vedolizumab;

(xxxiii) the hormone preparation is parathyroid hormone 1-84;

(xxxiv) the non-narcotic analgesic is fulranumab;

(xxxv) the diagnostic imaging agent is Minretumomab;

(xxxvi) the haematological is Eculizumab

(xxxvii) the peripheral muscle relaxant is botulinum toxin type A; and

(xxxviii) the pharmaceutical composition comprises an agent selected from the group consisting of elosulfase alfa, Protectan CBLB502, HGT-1410, HGT 1110, and sebelipase alfa.

8. The pharmaceutical container of claim 1 , wherein the pharmaceutical composition comprises a citrate buffer or a phosphate buffer.

9. The pharmaceutical container of claim 8 , wherein the buffer is selected from the group consisting of sodium citrate, saline-sodium citrate (SSC), monosodium phosphate and disodium phosphate.

10. The pharmaceutical container of claim 1 , wherein the pharmaceutical composition is a solution having a pH between about 7 and about 11.

11. The pharmaceutical container of claim 1 , wherein the concentration of SiO 2 is less than or equal to about 80 mol. %.

12. The pharmaceutical container of claim 1 , wherein the glass composition is free from phosphorous and compounds of phosphorous.

13. The pharmaceutical container of claim 1 , further comprising X mol. % Al 2 O 3 , wherein a ratio of Y:X is greater than 1.

14. The pharmaceutical container of claim 13 , wherein the ratio of Y:X is less than or equal to 2.

15. The pharmaceutical container of claim 13 , wherein X is greater than or equal to about 2 mol. % and less than or equal to about 10 mol. %.

16. The pharmaceutical container of claim 1 , wherein the alkaline earth oxide is present in an amount from about 3 mol. % to about 13 mol. %.

17. The pharmaceutical container of claim 13 , wherein the ratio of Y:X is greater than or equal 1.3 and less than or equal to 2.

18. The pharmaceutical container of claim 13 , wherein X is greater than or equal to about 5 mol. % and less than or equal to about 7 mol. %.

19. The pharmaceutical container of claim 1 , wherein the ratio (CaO (mol. %)/(CaO (mol. %)+MgO (mol. %))) is less than or equal to 0.3.

20. The pharmaceutical container of claim 1 , further comprising SnO 2 .

21. The pharmaceutical container of claim 2 , wherein the ratio of Y:X is less than or equal to about 2.

22. The pharmaceutical container of claim 2 , wherein the ratio of Y:X is greater than or equal to about 1.3 and less than or equal to about 2.0.

23. The pharmaceutical container of claim 2 , wherein the ratio (CaO (mol. %)/(CaO (mol. %)+MgO (mol. %))) is less than or equal to 0.1.

24. The pharmaceutical container of claim 2 , wherein the alkaline earth oxide comprises from about 3 mol. % to about 7 mol. % MgO.

25. The pharmaceutical container of claim 2 , 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. %.

26. The pharmaceutical container of claim 2 , 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. %.

27. The pharmaceutical container of claim 2 , wherein X is greater than or equal to about 5 mol. % and less than or equal to about 7 mol. %.

28. The pharmaceutical container of claim 3 , wherein the ratio of Y:X is less than or equal to 2.

29. The pharmaceutical container of claim 3 , wherein the ratio of Y:X is greater than or equal to 1.3 and less than or equal to 2.0.

30. The pharmaceutical container of claim 3 , wherein the ratio (CaO (mol. %)/(CaO (mol. %)+MgO (mol. %))) is less than or equal to 0.1.

31. The pharmaceutical container of claim 3 , wherein the glass composition is free of phosphorous and compounds of phosphorous.

32. The pharmaceutical container of claim 3 , wherein the alkali oxide further comprises Na 2 O in an amount greater than about 8 mol. %.

33. The pharmaceutical container of claim 3 , 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. %.

34. The pharmaceutical container of claim 3 , wherein the alkali oxide further comprises from about 9 mol. % to about 13 mol. % Na 2 O.

35. The pharmaceutical container of claim 3 , wherein X is greater than or equal to about 5 mol. % and less than or equal to about 7 mol. %.