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(12) Patent Application Publication (10) Pub. No.: US 2013/0216742 A1 Demartino Et Al

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(12) Patent Application Publication (10) Pub. No.: US 2013/0216742 A1 Demartino Et Al US 2013 0216742A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2013/0216742 A1 DeMartino et al. (43) Pub. Date: Aug. 22, 2013 (54) DELAMINATION RESISTANT Related U.S. Application Data PHARMACEUTICAL, GLASS CONTAINERS (60) Provisional application No. 61/551,163, filed on Oct. CONTAINING ACTIVE PHARMACEUTICAL 25, 2011, provisional application No. 61/656,998, INGREDIENTS filed on Jun. 7, 2012. (71) Applicants: Steven Edward DeMartino, Painted Publication Classification Post, NY (US); John Stephen Peanasky, Big Flats, NY (US); Robert (51) Int. Cl. Anthony Schaut, Painted Post, NY A61. I/00 (2006.01) (US); Wendell P. Weeks, Corning, NY CO3C 4/20 (2006.01) (US) (52) U.S. Cl. (72) Inventors: Steven Edward DeMartino, Painted CPC. A61J I/00 (2013.01); C03C4/20 (2013.01) Post, NY (US); John Stephen USPC ......................................................... 428/34.4 Peanasky, Big Flats, NY (US); Robert (57) ABSTRACT Anthony Schaut, Painted Post, NY The present invention is based, at least in part, on the identi (US); Wendell P. Weeks, Corning, NY fication of a pharmaceutical container formed, at least in part, (US) of a glass composition which exhibits a reduced propensity to delaminate, i.e., a reduced propensity to shed glass particu (21) Appl. No.: 13/660,680 lates. As a result, the presently claimed containers are par ticularly Suited for storage of pharmaceutical compositions and, specifically, a pharmaceutical solution comprising a (22) Filed: Oct. 25, 2012 pharmaceutically active ingredient. Patent Application Publication Aug. 22, 2013 Sheet 1 of 9 US 2013/0216742 A1 Fis, 8, 2 Patent Application Publication Aug. 22, 2013 Sheet 2 of 9 US 2013/0216742 A1 ***, F & 3 - -i Patent Application Publication Aug. 22, 2013 Sheet 3 of 9 US 2013/0216742 A1 8. Patent Application Publication Aug. 22, 2013 Sheet 4 of 9 US 2013/0216742 A1 ^www.www.w3.33%YYYYYYYYYYYYYYYYYYYYYYYY. Patent Application Publication Aug. 22, 2013 Sheet 5 of 9 US 2013/0216742 A1 FES 8 Patent Application Publication Aug. 22, 2013 Sheet 6 of 9 US 2013/0216742 A1 SS, 9 Patent Application Publication Aug. 22, 2013 Sheet 7 of 9 US 2013/0216742 A1 --- is raia 3-sy-in-e-is-Sei-asi-Wai-Sér N S *8-Si-ys-Ala-ai-s: Yety-six-is-yr-Sei is-àia-its-i.e.-ya-ai-Siya-a-3:y-8- Patent Application Publication Aug. 22, 2013 Sheet 8 of 9 US 2013/0216742 A1 Patent Application Publication Aug. 22, 2013 Sheet 9 of 9 US 2013/0216742 A1 is: & is is 3-; its in 38-3s-is-Sire 38-3ris: Tyr Caria: 3: Air "3rt: 8 l s w Fis' 3-arcitriis-is-e-is-isia; 3-3rsia isra is 8-a-fiy ?it &gtiy Berite-'3-iriit |is 8. US 2013/0216742 A1 Aug. 22, 2013 DELAMINATION RESISTANT package. Thermal tempering strengthens glass by inducing a PHARMACEUTICAL, GLASS CONTAINERS Surface compressive stress during rapid cooling after form CONTAINING ACTIVE PHARMACEUTICAL ing. This technique works well for glass articles with flat INGREDIENTS geometries (such as windows), glass articles with thicknesses >2 mm, and glass compositions with high thermal expansion. CROSS REFERENCE TO RELATED However, pharmaceutical glass packages typically have com APPLICATIONS plex geometries (vial, tubular, ampoule, etc.), thin walls (~1- 0001. The present application claims priority to U.S. Pro 1.5 mm), and are produced from low expansion glasses (30 visional Patent Application Ser. No. 61/551,163, filed Oct. 55x10'K') making glass pharmaceutical packages 25, 2011, entitled “Glass Compositions With Improved unsuitable for strengthening by thermal tempering. Chemical and Mechanical Durability,” and U.S. Provisional 0009 Chemical tempering also strengthens glass by the Patent Application No. 61/656,998, filed Jun. 7, 2012, introduction of surface compressive stress. The stress is intro entitled “De-lamination Resistant Glass Containers'; the duced by Submerging the article in a molten salt bath. As ions entirety of each of which are hereby incorporated by refer from the glass are replaced by larger ions from the molten salt, ence herein. a compressive stress is induced in the Surface of the glass. The advantage of chemical tempering is that it can be used on SEQUENCE LISTING complex geometries, thin samples, and is relatively insensi tive to the thermal expansion characteristics of the glass Sub 0002 The instant application contains a Sequence Listing strate. However, glass compositions which exhibit a moderate which has been submitted in ASCII format via EFS-Web and Susceptibility to chemical tempering generally exhibit poor is hereby incorporated by reference in its entirety. Said ASCII chemical durability and vice-versa. copy, created on Dec. 19, 2012, is named 12246711.txt and is 0010 Finally, glass compositions commonly used in phar 3,629 bytes in size. maceutical packages, e.g., Type 1a and Type 1b glass, further suffer from a tendency for the interior surfaces of the phar FIELD OF THE INVENTION maceutical package to shed glass particulates or 'delaminate' 0003. The present specification generally relates to phar following exposure to pharmaceutical Solutions. Such maceutical containers and, more specifically, to chemically delamination often destabilizes the active pharmaceutical and mechanically durable pharmaceutical containers that are ingredient (API) present in the solution, thereby rendering the delamination resistant and formed, at least in part, of a glass API therapeutically ineffective or unsuitable for therapeutic composition. SC. 0011 Delamination has caused the recall of multiple drug BACKGROUND products over the last few years (see, for example, Reynolds et al., (2011) BioProcess International 9(11) pp. 52-57). In 0004 The design of a packaged pharmaceutical composi response to the growing delamination problem, the U.S. Food tion generally seeks to provide an active pharmaceutical and Drug Administration (FDA) has issued an advisory indi ingredient (API) in a suitable package that is convenient to cating that the presence of glass particulate in injectable drugs use, that maintains the stability of the API over prolonged can pose a risk. storage, and that ultimately allows for the delivery of effica 0012. The advisory states that, “there is potential for cious, stable, active, nontoxic and nondegraded API. drugs administered intravenously that contain these frag 0005 Most packaged formulations are complex physico ments to cause embolic, thrombotic and other vascular chemical systems, through which the API is subject to dete events; and Subcutaneously to the development of foreign rioration by a variety of chemical, physical, and microbial body granuloma, local injections site reactions and increased reactions. Interactions between drugs, adjuvants, containers, immunogenicity.” and/or closures may occur, which can lead to the inactivation, decomposition and/or degradation of the API. 0013. Accordingly, a recognized need exists for alterna 0006. Historically, glass has been used as the preferred tive glass containers for packaging of pharmaceutical com material for packaging pharmaceuticals because of its herme positions which exhibit a reduced propensity to delaminate. ticity, optical clarity and excellent chemical durability rela SUMMARY tive to other materials. Specifically, the glass used in pharma ceutical packaging must have adequate chemical durability 0014. The inventors of the instant application have devel So as not to affect the stability of the pharmaceutical compo oped delamination resistant pharmaceutical containers with sitions contained therein. Glasses having Suitable chemical improved mechanical properties that impart, for example, durability include those glass compositions within the ASTM improved safety and efficacy on active pharmaceutical ingre standard Type 1B glass compositions which have a proven dients stored within the containers. history of chemical durability. 00.15 one aspect, the present invention is directed to a 0007. However, use of glass for such applications is lim delamination resistant pharmaceutical container formed, at ited by the mechanical performance of the glass. Specifically, least in part, of a glass composition including from about 70 in the pharmaceutical industry, glass breakage is a safety mol.% to about 80 mol.% SiO, from about 3 mol.% to about concern for the end user as the broken package and/or the 13 mol.% alkaline earth oxide; X mol.% Al-O; and Y mol. contents of the package may injure the end user. Further, % alkali oxide, wherein the alkali oxide comprises Na-O in an non-catastrophic breakage (i.e., when the glass cracks but amount greater than about 8 mol.%, a ratio of Y:X is greater does not break) may cause the contents to lose their sterility than 1, and the glass composition is free of boron and com which, in turn, may result in costly product recalls. pounds of boron. 0008. One approach to improving the mechanical durabil 0016. In one embodiment, the SiO is present in an amount ity of the glass package is to thermally temper the glass less than or equal to 78 mol.%. US 2013/0216742 A1 Aug. 22, 2013 0017. In one embodiment, the amount of the alkaline earth 0028. In another aspect, the present invention provides a oxide is greater than or equal to about 4 mol.% and less than delamination resistant pharmaceutical container formed, at or equal to about 8 mol.%. In a particular embodiment, the least in part, of a glass composition including from about 68 alkaline earth oxide includes MgO and CaO and has a ratio mol.% to about 80 mol.% SiO; from about 3 mol.% to about (CaO (mol.%)/(CaO (mol.%)+MgO (mol.%))) that is less 13 mol.% alkaline earth oxide; X mol.%. Al-O: Y mol.% than or equal to 0.5. In a particular embodient, the alkaline alkali oxide, wherein the alkali oxide includes NaO in an earth oxide includes from about 0.1 mol. 96 to less than or amount greater than about 8 mol. 96; and BO, wherein a equal to about 1.0 mol.% CaO. In a particular embodiment, ratio (B.O.
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