WO2025090291A1

WO2025090291A1 - Glass containers and pharmaceutical compositions with reduced boron interaction

Info

Publication number: WO2025090291A1
Application number: PCT/US2024/050644
Authority: WO
Inventors: Pei-Chen Chiang; Ye Fang; Robert Anthony Schaut; Ross Johnson STEWART; Steven Alvin Tietje
Original assignee: Corning Inc
Current assignee: Corning Inc
Priority date: 2023-10-24
Filing date: 2024-10-10
Publication date: 2025-05-01
Anticipated expiration: 2026-04-24

Abstract

A glass container may comprise a glass body comprising a sidewall enclosing an interior volume, the sidewall of the glass body comprising a first layer and the first layer comprising an inner surface; and a pharmaceutical composition disposed in the interior volume, the pharmaceutical composition is in contact with the inner surface; and the pharmaceutical composition comprises a molecule that reacts with boron and compounds of boron. The glass body may meet Type 1 criteria according to USP <660>, Class HGA 1 hydrolytic resistance when tested according to the ISO 720-1985 testing standard, or both; the first layer may comprise less than 1 mol. % of boron and compounds of boron; or both.

Description

GLASS CONTAINERS AND PHARMACEUTICAL COMPOSITIONS WITH REDUCED

BORON INTERACTION

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority under 35 U.S.C. § 1 19 of U.S. Provisional Application Serial No. 63/545,429 filed on October 24, 2023, the content of which is relied upon and incorporated herein by reference in its entirety.

Field

[0002] The present specification generally relates to glass containers for storing pharmaceutical compositions and, more specifically, to glass containers comprising pharmaceutical compositions including at least one molecule that reacts with boron and compounds of boron.

Technical Background

[0003] Pharmaceutical manufacturers demand high quality packaging to ensure the safety, purity, and stability of drug products. In fact, the FDA, US law, and other international regulatory bodies require that “drug product containers and closures shall not be reactive, additive, or absorptive so as to alter the safety, identity, strength, quality or purity of the drug beyond the official or established requirements.” and “container closure systems shall provide adequate protection against foreseeable external factors in storage and use that can cause deterioration or contamination of the drug product.” [21 CFR 211.94] This means that drug manufacturers and their suppliers must assure that no unintended or unnecessary contamination is present in the contained drug product throughout its shelflife and that any known interactions do not significantly impact the potency, stability, and efficacy of the drug product.

[0004] Extractable and leachable (E&L) elements from glass containers begin to enter aqueous solutions as soon as the pharmaceutical compound is introduced to the container and increase in concentration throughout the product's shelf life. In some cases, these elements reach concentrations where they interact with the drug product and cause degradation or alter the chemical identity of the drug product. If the drug product has changed in appearance, function, potency, concentration, or efficacy, it may be deemed unstable, degraded, or adulterated. [0005] Borosilicate glasses, such as the borosilicate glasses meeting hydrolytic criteria of USP <660> and defined in ASTM E438-92 (2018), have been used to package pharmaceutical solutions for more than 100 years. Boron is a common extractable element with high solubility in aqueous solutions. For many drug products and for many glass containers, the concentration of boron observed in solution is low (Ippm to 100 ppm B) and no interactions with the drug product occur. But in certain drug products, degradation may occur. Such degradation may be related to the presence of boron that entered the drug product from the primary glass packaging during its filling and storage period.

SUMMARY

[0006] Accordingly, glass packaging which does not leach boron into pharmaceutical compositions is desired. Embodiments of the present disclosure meet this need by providing glass containers comprising pharmaceutical compositions which react with boron and compounds of boron. The pharmaceutical compositions are contained within a glass body. The glass bodies release minimal amounts of boron and compounds of boron into the pharmaceutical composition. The glass bodies may accomplish this release of minimal amounts of boron and compounds of boron through the use of specific glass compositions, surface treatments, barrier coatings, or combinations thereof.

[0007] According to one embodiment, a glass container may comprise: a glass body comprising a sidewall enclosing an interior volume, the sidewall of the glass body comprising a first layer and the first layer comprising an inner surface; and a pharmaceutical composition disposed in the interior volume, wherein: the glass body meets Type 1 criteria according to USP <660>, Class HGA 1 hydrolytic resistance when tested according to the ISO 720-1985 testing standard, or both; the pharmaceutical composition is in contact with the inner surface; and the pharmaceutical composition comprises a molecule that reacts with boron and compounds of boron.

[0008] According to one embodiment, a glass container may comprise glass body comprising a sidewall enclosing an interior volume, the sidewall of the glass body comprising a first layer and the first layer comprising an inner surface; and a pharmaceutical composition disposed in the interior volume, wherein: the first layer comprises less than 1 mol. % of boron and compounds of boron; the pharmaceutical composition is in contact with the first layer of the inner surface; and the pharmaceutical composition comprises a molecule that reacts with boron and compounds of boron. [0009] According to one embodiment of a method of using a glass container, the glass container may comprise: a glass body comprising a sidewall enclosing an interior volume, the sidewall of the glass body comprising an inner surface; and a pharmaceutical composition disposed in the interior volume, wherein: the pharmaceutical composition comprises a molecule that reacts with boron and compounds of boron. The method may comprise: storing the pharmaceutical container for from 18 months to 10 years, thereby leaching boron out of the glass container into the pharmaceutical composition to yield a final concentration of boron; and the final concentration of boron in the pharmaceutical composition is less than 100 % of a concentration of the molecule.

[0010] Additional features and advantages of the embodiments of the glass containers described herein will be set forth in the detailed description which follows, and in part will be readily apparent to those skilled in the art from that description or recognized by practicing the embodiments described herein, including the detailed description which follows, the claims, as well as the appended drawings.

[0011] It is to be understood that both the foregoing general description and the following detailed description describe various embodiments and are intended to provide an overview or framework for understanding the nature and character of the claimed subject matter. The accompanying drawings are included to provide a further understanding of the various embodiments, and are incorporated into and constitute a part of this specification. The drawings illustrate the various embodiments described herein, and together with the description serve to explain the principles and operations of the claimed subject matter.

BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWINGS

[0012] FIG. 1 schematically depicts a cross section of a glass container according to embodiments disclosed and described herein.

[0013] FIG. 2 schematically depicts a portion of the sidewall of the glass container of FIG. 1.

[0014] FIG. 3 schematically depicts a cross section of a glass container according to embodiments disclosed and described herein.

[0015] FIG. 4 schematically depicts a portion of the sidewall of the glass container of FIG.

3. DETAILED DESCRIPTION

[0016] Reference will now be made in detail to embodiments of the glass containers of the present disclosure, various embodiments of which will be described herein with specific reference to the accompanying drawings. Whenever possible, the same reference numerals will be used throughout the drawings to refer to the same or like parts. One embodiment of a glass container containing a pharmaceutical composition is schematically depicted in FIG. 1. In embodiments, a glass container 100 may comprise a glass body 102 comprising a sidewall 104 enclosing an interior volume 106. The sidewall 104 of the glass body 102 may comprise a first layer 112 and the first layer may comprise an inner surface 108. The glass container 100 may further comprise a pharmaceutical composition 110 disposed in the interior volume 106, in contact with the inner surface 108, and comprising a molecule that reacts with boron and compounds of boron. The glass body 102 may meet Type 1 criteria according to USP <660>, Class HGA 1 hydrolytic resistance when tested according to the ISO 720-1985 testing standard, or both; the first layer may comprise less than 1 mol. % of boron and compounds of boron; or both. Various embodiments of glass containers comprising pharmaceutical compositions will be described herein with specific reference to the appended drawings.

[0017] In the following detailed description, numerous specific details may be set forth in order to provide a thorough understanding of embodiments described herein. However, it will be clear to one skilled in the art when embodiments may be practiced without some or all of these specific details. In other instances, well-known features or processes may not be described in detail so as not to unnecessarily obscure the disclosure. In addition, like or identical reference numerals may be used to identify common or similar elements. Moreover, unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. In case of conflict, the present specification, including the definitions herein, will control.

[0018] Unless otherwise expressly stated, it is in no way intended that any method set forth herein be construed as requiring that its steps be performed in a specific order, nor that with any apparatus specific orientations be required. Accordingly, where a method claim does not actually recite an order to be followed by its steps, or that any apparatus claim does not actually recite an order or orientation to individual components, or it is not otherwise specifically stated in the claims or description that the steps are to be limited to a specific order, or that a specific order or orientation to components of an apparatus is not recited, it is in no way intended that an order or orientation be inferred, in any respect. This holds for any possible non-express basis for interpretation, including: matters of logic with respect to arrangement of steps, operational flow, order of components, or orientation of components; plain meaning derived from grammatical organization or punctuation; and the number or type of embodiments described in the specification.

[0019] As used herein, a glass or glass ceramic composition having 0 mol % or 0 wt. % of a compound is defined as meaning that the compound, molecule, or element was not purposefully added to the composition, but the composition may still comprise the compound, typically in tramp ortrace amounts. Similarly, "iron-free," "sodium-free," "lithium-free," "zirconium-free," "alkali earth metal-free," "heavy metal -free" or the like are defined to mean that the compound, molecule, or element was not purposefully added to the composition, but the composition may still comprise iron, sodium, lithium, zirconium, alkali earth metals, or heavy metals, etc., but in approximately tramp or trace amounts.

[0020] In the embodiments of the glass compositions described herein, the concentration of constituent components (e.g., SiCh, AI2O3, B2O3 and the like) are specified in mole percent (mol. %) on an oxide basis, unless otherwise specified.

[0021] The term “substantially free,” when used to describe the concentration and/or absence of a particular constituent component in a glass composition, means that the constituent component is not intentionally added to the glass composition. However, the glass composition may contain traces of the constituent component as a contaminant or tramp in amounts of less than 0.1 mol. %.

[0022] As previously discussed, borosilicate glasses have long been used as pharmaceutical containers, despite the drawback of boron leaching into the pharmaceutical compositions contained therein. Accordingly, combinations of glass containers and pharmaceutical compositions which exhibit reduced interaction between boron and the pharmaceutical compositions are desired. Embodiments of the present disclosure meet this need by providing glass containers with reduced leachability of boron. Embodiments of the present disclosure meet this need by providing boron free glass containers. Further embodiments meet this need by providing glass containers comprising a first layer where the first layer is free of boron.

[0023] Referring now to FIG. 1 - FIG. 4, embodiments of the present disclosure provide a glass container 100, 300 which may comprise a glass body 102, 302. The glass body 102, 302 may comprise a sidewall 104, 304 enclosing an interior volume 106, 306. The sidewall 104, 304 of the glass body 102, 302 may comprise an inner surface 108, 308. A pharmaceutical composition 110, 310 may be disposed in the interior volume 106, 306. The pharmaceutical composition 110, 310 may be in contact with the inner surface 108, 308. The pharmaceutical composition 110, 310 may comprise a molecule which reacts with boron and compounds of boron.

[0024] While the glass container 100, 300 is depicted in FIG. 1 and FIG. 3 as having a specific shape form (i.e., a vial), it should be understood that the glass container 100, 300 may have other shape forms, including, without limitation, Vacutainers®, cartridges, syringes, ampoules, bottles, flasks, phials, tubes, beakers, or the like. Further, it should be understood that the glass containers described herein may be used for a variety of applications including, without limitation, as pharmaceutical packages, beverage containers, or the like.

[0025] As described in more detail below, the pharmaceutical composition 110, 310 such as an aqueous pharmaceutical composition, may leach boron out of the glass body 102, 302 and into the pharmaceutical composition 110, 310. This leaching process may result in the pharmaceutical composition 110, 310 having a concentration of boron. It should be understood that the concentration of boron in the pharmaceutical composition 110, 310 refers to the concentration of boron and all compounds which include boron atoms (e.g. B2O3 or molecules in the pharmaceutical composition 110, 310 which have reacted with boron).

[0026] The combinations of pharmaceutical compositions and glass containers described herein may reduce or mitigate the degradation of the pharmaceutical compositions by limiting the leachability of boron (either through the use of a boron-free glass container, a glass container with a barrier layer, or a glass container with a leached layer). For example, after an extended period of leaching (e.g. 6 months, 1 year, 18 months, 2 years, 3 years, or 4 years), a concentration of boron in the pharmaceutical composition 110, 310 may be less than a concentration of the molecule. As described above, when the concentration of boron in the pharmaceutical composition 110, 310 reaches a high enough level, it may change the appearance, function, potency, concentration, or efficacy of the pharmaceutical composition 110, 310 enough that the pharmaceutical composition 110, 310 no longer delivers the original performance or is otherwise unstable, degraded, or adulterated. A concentration of boron which is likely to have these deleterious effects may be determined in relation to the concentration of the molecule in the pharmaceutical composition 110, 310. It should be understood that if the concentration of boron is less than (or substantially less than) a concentration of the molecule, interactions between the molecule and boron are unlikely and any degradation of the molecule due to boron will be minimal. In embodiments, after the extended period of leaching at room temperature, the concentration of boron in the pharmaceutical composition 110, 310 may be less than 100 % of a concentration of the molecule in the pharmaceutical composition 110, 310, on a molar basis to avoid degradation of the pharmaceutical composition. Accordingly, it should be understood that the glass containers 100, 300 described herein reduce or even mitigate the leaching of boron and compounds of boron in the pharmaceutical composition 110, 310 contained therein. In embodiments, after the extended period of leaching at room temperature, the concentration of boron in the pharmaceutical composition 110, 310 may be less than 75 %, less than 50 %, less than 25 %, less than 20 %, less than 15 %, less than 10 %, less than 5 %, less than 2.5 %, less than 2 %, less than 1.50 %, less than 1.00 %, less than less than 0.50 %, less than 0.25 %, or even less than 0. 1 % of a concentration of the molecule in the pharmaceutical composition, on a molar basis.

[0027] After an extended period of leaching (e.g. 6 months, 1 year, 18 months, 2 years, 3 years, or 4 years) at room temperature in the pharmaceutical composition 110, 310 the concentration of boron in the pharmaceutical composition 110, 310 may be less than 3 pg B/cm², such as less than 2 pg B/cm², less than 1 pg B/cm², less than 0.5 pg B/cm², less than 0.25 pg B/cm², less than 0.2 pg B/cm², or less than 0.15 pg B/cm², on the basis of the total contact surface area between the inner surface 108, 308 and the pharmaceutical composition 110, 310.

[0028] After an extended period of leaching (e.g. 6 months, 1 year, 18 months, 2 years, 3 years, or 4 years) at room temperature in the glass container 100, 300 the concentration of boron in the pharmaceutical composition 110, 310 may be less than 500 pg/mL, such as less than 250 pg/ mb, less than 125 pg/ mb, less than 75 pg/ mb, less than 50 pg/ mb, less than 25 pg/ mb, less than 10 pg/ mb, less than 1 pg/ mb, less than 0.5 pg/ mb, or even less than 0.1 pg/ mb, on the basis of the volume of the pharmaceutical composition 110, 310. The concentration of boron and compounds of boron in the pharmaceutical compositions 110, 310 may be determined by any standard analytical technique, such as inductively coupled mass spectrometry (ICP-MS).

[0029] To rapidly assess the long-term resistance of the glass container 100, 300 to the release of boron into a pharmaceutical composition 110, 310 contained therein, an accelerated boron leaching test may be utilized. The test may be performed on any of the embodiments of the glass containers 100, 300 described herein. The test includes washing the glass container at room temperature with purified water at least twice to remove debris for less than 20 minutes. Thereafter a test solution of deionized, distilled, or carbon-dioxide free water is placed in the glass container to 90% brimful fill, the glass container is covered loosely to minimize evaporation loss, and the glass container is placed in an autoclave and heated to 100 °C, then the temperature is increased from 100 °C to 121 °C at a ramp rate of 1 °C/min at a pressure of 2 atmospheres. The glass container and solution are held at this temperature for 60 minutes, then cooled to 95 °C at a rate of 0.5 °C /min, followed by rapid cooling to room temperature. A minimum of 2 mb of solution is tested from each individual vial. At least 3 individual vials are randomly selected to account for vial-to-vial variability. The individual concentrations are averaged over multiple containers to account for potential variations in the boron leachability of individual containers.

[0030] The concentration of boron and compounds of boron in the test solution after the accelerated boron-leaching test may be referred to herein as the accelerated boron leaching score. The glass containers 100, 300 may have an accelerated boron leaching score of less than less than 10 pg/ mL, less than 1 pg/ mL, less than 0.5 pg/ mb, less than 0.1 pg/ mL, less than 0.01 pg/ mL, or even less than 0.001 pg/ mL on the basis of the test solution In embodiments, the glass containers 100, 300 may have a volume of from 0.5 mL to 2 L, such as from 0.5 mL to 1.5 L, from 0.5 mL to 1 L, from 0.5 mL to 750 mL, from 0.5 mL to 500 mL, from 0.5 mL to 250 mL, from 0.5 mL to 250 mL, from 0.5 mL to 100 mL, from 0.5 mL to 50 mL, from 0.5 mL to 25 mL, or from 0.5 mL to 10 mL, and may have an accelerated boron leaching score of less than 10 pg/ mL, less than 1 pg/ mL, less than 0.5 pg/ mL, less than 0.1 pg/ mL, less than 0.01 pg/ mL, or even less than 0.001 pg/ mL on the basis of the test solution.

[0031] Still referring to FIG. 1 to FIG. 4, in embodiments, the glass body 102, 302 may be formed from one of a borosilicate glass composition that meets Type 1 criteria according to USP <660> or an alkali aluminosilicate glass having a class HGA1 hydrolytic resistance when tested according to the ISO 720-1985 testing standard.

[0032] In embodiments, the glass body 102, 302 may be formed from an alkali aluminosilicate glass. The glass body 102, 302 may have a class HGA1 hydrolytic resistance. [0033] The glass compositions from which the glass bodies 102, 302 are formed may be chemically durable and resistant to degradation. Chemical durability and resistance to degradation may be determined by the ISO 720 standard. The ISO 720 standard is a measure of the resistance of the glass to degradation in distilled water (i.e., the hydrolytic resistance of the glass). The ISO 720 standard is broken into individual types. Type HGA1 is indicative of up to 62 pg extracted equivalent of Na20; Type HGA2 is indicative of more than 62 pg and up to 5 1 pg extracted equivalent of Na20; and Type HGA3 is indicative of more than 527 pg and up to 930 pg extracted equivalent of Na20. The glass compositions described herein may have an ISO 720 hydrolytic resistance of type HGA1 or better. It should be understood that lower class rankings have improved hydrolytic resistance performance. Accordingly, a composition classified at HGA1 has better hydrolytic resistance than a composition classified at HGA2.

[0034] The glass compositions from which the glass bodies 102, 302 are formed may also be chemically durable and resistant to degradation as determined by the ISO 719 standard. The ISO 719 standard is a measure of the resistance of the glass to degradation in distilled water (i.e., the hydrolytic resistance of the glass). The ISO 719 standard is broken into individual types. Type HGB1 is indicative of up to 31 pg extracted equivalent of Na2O; Type HGB2 is indicative of more than 31 pg and up to 62 pg extracted equivalent of Na2O; Type HGB3 is indicative of more than 62 pg and up to 264 pg extracted equivalent of Na2O; Type HGB4 is indicative of more than 264 pg and up to 620 pg extracted equivalent of Na2O; and Type HGB5 is indicative of more than 620 pg and up to 1085 pg extracted equivalent of Na2O. The glass compositions described herein may have an ISO 719 hydrolytic resistance of type HGB2 or better with some embodiments having a type HGB1 hydrolytic resistance. Is should be understood that lower class rankings have improved hydrolytic resistance performance. Accordingly, a composition classified at HGB1 has better hydrolytic resistance than a composition classified at HGB2.

[0035] Referring now to FIG. 1, the glass body 102 may be formed from a borosilicate glass composition. The borosilicate glass composition may meet Type 1 criteria according to USP <660>. Type I, Class A (Type IA) or Type I, Class B (Type IB) glasses under ASTM Standard E438-92 (2018) entitled “Standard Specification for Glasses in Laboratory Apparatus”. Borosilicate glasses meeting the Type I (A or B) criteria are routinely used for pharmaceutical packaging. The USP <660> test is performed on intact glass containers rather than crushed grains of glass and, as such, the USP <660> may be used to directly assess the chemical durability of the inner surface of the glass containers. Examples of borosilicate glass include, without limitation, Coming® Pyrex® 7740, 7800; Coming® C33, C51A, C51C, C51D, C51L, C5IV^; Wheaton 180, 200, and 400, Schott Duran®’ Schott Fiolax®, KIMAX® N-51A, Gerresheimer GX-51 Flint and others.

[0036] It should be understood that, when referring to the above referenced classifications according to <USP <660>, ISO 719, and ISO 720, a glass composition or glass article which has a specified classification “or better” means that the performance of the glass composition is as good as or better than the specified classification. For example, a glass article which has an ISO 720 hydrolytic resistance of “HGA2” or better may have an ISO 720 classification of either HGA2 or HGA 1.

[0037] Referring again to FIG. 1 to FIG. 4, the pharmaceutical composition 110, 310 may be in contact with an inner surface 108, 308 of the glass body 102, 302. The inner surface 108, 308 of the glass body 102, 302 may be on a first layer 112, 312 of the glass body 102, 302. Referring first to FIG. 1 and FIG. 2, the first layer 112 may be a layer distinct from the sidewall 104. In some embodiments of FIG. 1, the first layer 112 may refer to a layer within the glass body 102 from which boron and compounds of boron have been removed, such as when boron and compounds of boron have been previously leached from the glass body 102 such as during manufacture of the glass container 100. Thus, the first layer 112 forms a portion of the sidewall 104. Alternatively, the first layer 112 may refer to a layer which has been deposited on a surface of the glass body 102, such as an organic or inorganic barrier layer. Embodiments which combine both a leached first layer and a deposited barrier layer are also contemplated.

[0038] Referring now to FIG. 3, in an alternative embodiment, the first layer 312 extends through the entire thickness 314 of the sidewall 304 and may be coterminous with the side wall 304 of the glass body 302. For example, in such embodiments, the sidewall 304 of the glass body 302 may be formed from a glass composition which is substantially homogenous through the thickness of the sidewall 304 (i.e., the composition of the glass at the inner surface 308 is substantially the same as the composition of glass at the midpoint through the thickness 314 of the sidewall 304.

[0039] Referring again to FIG. 1 to FIG. 4, the first layer may comprise less than 14 mol. % of boron and compounds of boron, on an oxide basis. In embodiments, the first layer 112, 312 may comprise less than 12 mol. %, less than 10 mol. %, less than 8 mol. %, less than 6 mol. %, less than 4 mol. %, less than 2 mol. %, less than 1 mol. %, less than 0.5 mol. %, less than 0.1 mol. %, less than 0.01 mol. %, from 0 mol. % to 14 mol. %, from 0 mol. % to 8 mol. %, from 0 mol. % to 2 mol. %, from 0 mol. % to 0.5 mol. %, from 0 mol. % to 0.1 mol. %, or even from 0 mol. % to 0.001 mol. % of boron and compounds of boron, on an oxide basis. In embodiments, the first layer 112, 312 may be free of boron and compounds of boron or substantially free of boron and compounds of boron.

[0040] As noted herein, in embodiments, the glass body 102, 302 may be formed from alkali aluminosilicate glass compositions. The presence of silica in the glass composition improves the chemical durability of the glass composition. In embodiments the alkali aluminosilicate glass composition may comprise SiCh in an amount greater than or equal to about 65 mol. % and less than or equal to about 75 mol. %. In some embodiments SiC>2 is present in the alkali aluminosilicate glass composition in an amount greater than or equal to about 67 mol. % and less than or equal to about 75 mol. %. In some other embodiments, Si O2 is present in the alkali aluminosilicate glass composition in an amount greater than or equal to about 67 mol. % and less than or equal to about 73 mol . %. In each of these embodiments, the amount of SiCh present in the alkali aluminosilicate glass composition may be greater than or equal to about 70 mol. % or even greater than or equal to about 72 mol. %, on an oxide basis.

[0041] In embodiments, the alkali aluminosilicate glass composition includes AI2O3. AI2O3, in conjunction with alkali oxides present in the alkali aluminosilicate glass compositions such as Na2O or the like, improves the susceptibility of the glass to ion exchange strengthening. Moreover, additions of AI2O3 to the composition reduce the propensity of alkali constituents (such as Na and K) from leaching out of the glass and, as such, additions of AI2O3 increase the resistance of the composition to hydrolytic degradation. Moreover, additions of AI2O3 greater than about 12.5 mol. % may also increase the softening point of the glass thereby reducing the formability of the glass. Accordingly, the alkali aluminosilicate glass compositions described herein generally include AI2O3 in an amount greater than or equal to about 6 mol. % and less than or equal to about 12.5 mol. %. In some embodiments, the amount of AI2O3 in the alkali aluminosilicate glass composition is greater than or equal to about 6 mol. % and less than or equal to about 10 mol. %. In some other embodiments, the amount of AI2O3 in the alkali aluminosilicate glass composition is greater than or equal to about 7 mol. % and less than or equal to about 10 mol. %, on an oxide basis. [0042] In embodiments, the alkali aluminosilicate glass composition may also include at least two alkali oxides. The alkali oxides facilitate the ion exchangeability of the glass composition and, as such, facilitate chemically strengthening the glass. The alkali oxides also lower the softening point of the glass, thereby offsetting the increase in the softening point due to higher concentrations of SiCh in the glass composition. The alkali oxides also assist in improving the chemical durability of the glass composition. The alkali oxides are generally present in the alkali aluminosilicate glass composition in an amount greater than or equal to about 5 mol. % and less than or equal to about 12 mol. %. In some of these embodiments, the amount of alkali oxides may be greater than or equal to about 5 mol. % and less than or equal to about 10 mol. %. In some other embodiments, the amount of alkali oxide may be greater than or equal to about 5 mol. % and less than or equal to about 8 mol. %, on an oxide basis. In some of the alkali aluminosilicate glass compositions described herein, the alkali oxides comprise at least Na2O. In some embodiments, the alkali oxides further comprise Li2O and/or K2O.

[0043] In embodiments, the alkali aluminosilicate glass compositions include Na2O in an amount greater than or equal to about 2.5 mol. % and less than or equal to about 10 mol. %, on an oxide basis. In some embodiments, the alkali aluminosilicate glass composition may include Na2O in an amount greater than or equal to about 3.5 mol. % and less than or equal to about 8 mol. %. In some of these embodiments, the alkali aluminosilicate glass composition may include Na2O in an amount greater than or equal to about 6 mol. % and less than or equal to about 8 mol. %, on an oxide basis.

[0044] As noted above, the alkali oxides in the alkali aluminosilicate glass composition also include K2O. The amount of K2O present in the alkali aluminosilicate glass composition also relates to the ion exchangeability of the alkali aluminosilicate glass composition. Specifically, as the amount of K2O present in the alkali aluminosilicate glass composition increases, the compressive stress obtainable through ion exchange decreases. Accordingly, it is desirable to limit the amount of K2O present in the glass composition. In some embodiments, the amount of K2O is greater than 0 mol. % and less than or equal to about 2.5 mol. %, on an oxide basis. In some of these embodiments, the amount of K2O present in the alkali aluminosilicate glass composition is less than or equal to about 0.5 mol. %, on an oxide basis.

[0045] In some embodiments, the alkali oxide in the alkali aluminosilicate glass composition further comprises Li2O. Including Li2O in the alkali aluminosilicate glass composition further decreases the softening point of the alkali aluminosilicate glass. In embodiments where the alkali oxide includes Li2O, the Li2O may be present in an amount greater than or equal to about 1 mol. % and less than or equal to about 3 mol. %, on an oxide basis. In some embodiments, Li2O may be present in the alkali aluminosilicate glass composition in an amount which is greater than about 2 mol. % and less than or equal to about 3 mol. %, on an oxide basis. However, in some other embodiments, the alkali aluminosilicate glass composition may be substantially free of lithium and compounds containing lithium.

[0046] In embodiments, the glass composition may further comprise alkaline earth oxides. Additions of alkaline earth oxides in the alkali aluminosilicate glass composition improve the meltability of the glass batch materials and increase the chemical durability of the glass composition. The presence of alkaline earth oxides in the glass composition also reduces the susceptibility of the glass to delamination. In the alkali aluminosilicate glass compositions described herein, the glass compositions generally include at least one alkaline earth oxide in a concentration greater than or equal to about 8 mol. % or even 8.5 mol. % and less than or equal to about 15 mol. %. In some embodiments, the alkali aluminosilicate glass composition may comprise from about 9 mol. % to about 15 mol. % of alkaline earth oxide. In some of these embodiments, the amount of alkaline earth oxide in the alkali aluminosilicate glass composition may be from about 10 mol. % to about 14 mol. %, on an oxide basis.

[0047] The alkaline earth oxide in the alkali aluminosilicate glass composition may include MgO, CaO, SrO, BaO or combinations thereof. For example, in the embodiments described herein the alkaline earth oxide may include MgO. In some embodiments, MgO may be present in the alkali aluminosilicate glass composition in an amount which is greater than or equal to about 2 mol. % and less than or equal to about 7 mol. %, on an oxide basis, or even greater than or equal to about 3 mol. % and less than or equal to about 5 mol. %, on an oxide basis.

[0048] In some embodiments, the alkaline earth oxide in the alkali aluminosilicate glass composition may also include CaO. In these embodiments, CaO may be present in the alkali aluminosilicate glass composition in an amount from about 0.01 mol. % to less than or equal to 2 mol., on an oxide basis. In some embodiments, CaO is present in the alkali aluminosilicate glass composition in an amount from about 0.01 mol. % to less than or equal to 1 mol. %, on an oxide basis. In some of these embodiments, CaO may be present in the alkali aluminosilicate glass composition in an amount greater than or equal to about 0.01 mol. % and less than or equal to about 0.2 mol. %. [0049] In some embodiments described herein, the alkaline earth oxide further comprises at least one of SrO or BaO. The inclusion of SrO reduces the liquids temperature of the glass composition and, as a result, improves the formability of the glass composition. In some embodiments the alkali aluminosilicate glass composition may include SrO in an amount greater than 0 mol. % and less than or equal to about 6.0 mol. %. In some other embodiments, the alkali aluminosilicate glass composition may include SrO in an amount greater than about 0 mol. % and less than or equal to about 5 mol. %. In some of these embodiments, the alkali aluminosilicate glass composition may include greater than or equal to about 2 mol. % and less than or equal to about 4 mol. % SrO, such as when CaO is substituted for MgO in the alkaline earth oxide to decrease the liquids temperature and increase the liquids viscosity. In some other embodiments, the glass composition may include from about 1 mol. % to about 2 mol. % SrO. In still other embodiments, SrO may be present in the glass composition in an amount greater than or equal to about 3 mol. % and less than or equal to about 6 mol. %, such as when SrO is substituted for MgO in the alkaline earth oxide to decrease the liquids temperature and increase the liquids viscosity.

[0050] In embodiments where the alkali aluminosilicate glass composition includes BaO, the BaO may be present in an amount greater than about 0 mol. % and less than about 2 mol. %. In some of these embodiments, BaO may be present in the alkali aluminosilicate glass composition in an amount less than or equal to about 1.5 mol. % or even less than or equal to about 0.5 mol. %. However, in some other embodiments, the alkali aluminosilicate glass composition is substantially free from barium and compounds of barium.

[0051] In the embodiments of the alkali aluminosilicate glass compositions described herein, the alkali aluminosilicate glass compositions generally contain less than about 10 mol. % of boron or oxides of boron, such as B2O3. For example, in some embodiments the alkali aluminosilicate glass compositions may comprise greater than or equal to about 0 mol. % B2O3 and less than or equal to 1 mol. % B2O3. In some other embodiments, the alkali aluminosilicate glass compositions may comprise greater than or equal to about 0 mol. % B2O3 and less than or equal to 0.6 mol. % B2O3. In still other embodiments, the alkali aluminosilicate glass compositions are substantially free from boron and compounds of boron such as B2O3. Specifically, it has been determined that forming the glass composition with a relatively low amount of boron or compounds of boron (i.e., less than or equal to 1 mol. %) or without boron or compounds of boron significantly increases the chemical durability of the glass composition. In addition, it has also been determined that forming the glass composition with a relatively low amount of boron or compounds of boron or without boron or compounds of boron improves the ion exchangeability of the glass compositions by reducing the process time and/or temperature required to achieve a specific value of compressive stress and/or depth of layer.

[0052] In some embodiments of the alkali aluminosilicate glass compositions described herein, the glass compositions are substantially free from phosphorous and compounds containing phosphorous including, without limitation, P2O5. Specifically, it has been determined that formulating the glass composition without phosphorous or compounds of phosphorous increases the chemical durability of the glass composition.

[0053] In addition to the SiCh, AI2O3, alkali oxides and alkaline earth oxides, the alkali aluminosilicate glass compositions described herein may optionally further comprise one or more fining agents such as, for example, Sb20s, SnCf. AS2O3, F" (from fluorine salts or oxides or the like), and/or Cl" (from NaCl or the like). When a fining agent is present in the glass composition, the fining agent may be present in an amount less than or equal to about 1 mol. % or even less than or equal to about 0.5 mol. %. For example, in some embodiments the alkali aluminosilicate glass composition may include SnCh as a fining agent. In these embodiments SnCh may be present in the glass composition in an amount greater than about 0 mol. % and less than or equal to about 0.30 mol. %.

[0054] Moreover, the alkali aluminosilicate glass compositions described herein may comprise one or more additional metal oxides to further improve the chemical durability of the glass composition. For example, the alkali aluminosilicate glass composition may further include ZnO or ZrCh. each of which further improves the resistance of the glass composition to chemical attack. In these embodiments, the additional metal oxide may be present in an amount which is greater than or equal to about 0 mol. % and less than or equal to about 2.0 mol. %. For example, when the additional metal oxide is ZrC>2, the ZrCh may be present in an amount less than or equal to about 1.5 mol. %. Alternatively or additionally, the additional metal oxide may include ZnO in an amount less than or equal to about 2.0 mol. %. In some embodiments, ZnO may be included as a substitute for one or more of the alkaline earth oxides. For example, in embodiments where the alkali aluminosilicate glass composition includes the alkaline earth oxides MgO, CaO and SrO, the amount of MgO may be reduced to decrease the liquids temperature and increase the liquids viscosity, as described above. In these embodiments, ZnO may be added to the alkali aluminosilicate glass composition as a partial substitute for MgO, in addition to or in place of at least one of CaO or SrO.

[0055] Based on the foregoing, it should be understood that, in one embodiment, the alkali aluminosilicate glass composition may include from about 65 mol. %to about 75 mol. % SiCh; from about 6 mol. % to about 12.5 mol. % AI2O3; and from about 5 mol. % to about 12 mol. % alkali oxide, wherein the alkali oxide comprises Na2O and K2O. The K2O may be present in an amount less than or equal to 0.5 mol. %. The alkali aluminosilicate glass composition may also include from about 8.0 mol. % to about 15 mol. % of alkaline earth oxide. The alkali aluminosilicate glass composition may be susceptible to strengthening by ion exchange.

[0056] In another embodiment of the alkali aluminosilicate glass composition, the alkali aluminosilicate glass composition includes from about 67 mol. % to about 75 mol. % SiCh; from about 6 mol. % to about 10 mol. % AI2O3; from about 5 mol. % to about 12 mol. % alkali oxide; and from about 9 mol. % to about 15 mol. % of alkaline earth oxide. The alkali oxide comprises at least Na2O and K2O. The glass composition is free from boron and compounds of boron and is susceptible to ion exchange thereby facilitating chemically strengthening the glass to improve the mechanical durability.

[0057] In yet another embodiment of the alkali aluminosilicate glass composition, the alkali aluminosilicate glass composition may include from about 67 mol. %to about 75 mol. % SiCh; from about 6 mol. % to about 10 mol. % AI2O3; from about 5 mol. % to about 12 mol. % alkali oxide; and from about 9 mol. % to about 15 mol. % of alkaline earth oxide. The alkaline earth oxide comprises at least one of SrO and BaO. The glass composition is free from boron and compounds of boron and is susceptible to ion exchange thereby facilitating chemically strengthening the glass to improve the mechanical durability. 58 Referring now to some other embodiments of the alkali aluminosilicate glass, the alkali aluminosilicate glass may include from about 70 mol. % to about 80 mol. % SiCh; from about 3 mol. % to about 13 mol. % alkaline earth oxide; X mol. % AI2O3; and ¥ mol. % alkali oxide. Tire alkali oxide may include Na2O in an amount greater than about 8 mol. %. A ratio of Y:X may be greater than 1 and the alkali aluminosilicate glass may be free of boron and compounds of boron. In some embodiments, the alkali aluminosilicate glass may also be free of phosphorous and compounds of phosphorous. 0059] In embodiments, the alkali aluminosilicate glass described herein may generally comprise silica (SiCh), alumina (AI2O3), alkaline earth oxides (such as MgO and/or CaO), and alkali oxides (such as Na2O and/or K2O) in amounts which impart chemical durability to the glass composition. In some embodiments, the glass compositions may be free from boron and compounds containing boron. 0060] In some embodiments of the alkali aluminosilicate glass, SiCh is the largest constituent of the composition and, as such, is the primary constituent of the resulting glass network. In embodiments, the alkali aluminosilicate glass may comprise SiCh in an amount greater than or equal to 67 mol.% and less than or equal to about 80 mol. % or even less than or equal to 78 mol.%. In some embodiments, the amount of SiCh in the alkali aluminosilicate glass may be greater than about 68 mol.%, greater than about 69 mol.% or even greater than about 70 mol.%. In some other embodiments, the amount of SiCh in them may be greater than 72 mol.%, greater than 73 mol.% or even greater than 74 mol.%. For example, in some embodiments, the alkali aluminosilicate glass may include from about 68 mol.% to about 80 mol.% or even to about 78 mol.% SiCh. In some other embodiments the alkali aluminosilicate glass may include from about 69 mol.% to about 80 mol.% or even to about 78 mol.% SiCh. In some other embodiments the alkali aluminosilicate glass may include from about 70 mol.% to about 80 mol.% or even to about 78 mol.% SiC>2. In still other embodiments, the alkali aluminosilicate glass comprises SiCh in an amount greater than or equal to 70 mol.% and less than or equal to 78 mol.%. In some embodiments, SiCh may be present in the alkali aluminosilicate glass in an amount from about 72 mol.% to about 78 mol.%. In some other embodiments, SiCh may be present in the alkali aluminosilicate glass in an amount from about 73 mol.% to about 78 mol.%. In other embodiments, SiCh may be present in the alkali aluminosilicate glass in an amount from about 74 mol.% to about 78 mol.%. In still other embodiments, SiCh may be present in the alkali aluminosilicate glass in an amount from about 70 mol.% to about 76 mol.%.

[0061] In embodiments, the alkali aluminosilicate glass may further include AI2O3. In some embodiments, AI2O3 is present in the alkali aluminosilicate glass in X mol.% while the alkali oxides are present in the alkali aluminosilicate glass in Y mol.%. The ratio Y:X in the alkali aluminosilicate glass described herein may be greater than 1 in order to facilitate ion exchange strengthening. Specifically, the diffusion coefficient or diffusivity D of the alkali aluminosilicate glass relates to the rate at which alkali ions penetrate into the glass surface during ion exchange. Glasses which have a ratio Y:X greater than about 0.9 or even greater than about 1 have a greater diffusivity than glasses which have a ratio Y:X less than 0.9. Glasses in which the alkali ions have a greater diffusivity can obtain a greater depth of layer for a given ion exchange time and ion exchange temperature than glasses in which the alkali ions have a lower diffusivity. Moreover, as the ratio of Y:X increases, the strain point, anneal point, and softening point of the glass decrease, such that the glass may be more readily formable. In addition, for a given ion exchange time and ion exchange temperature, it has been found that compressive stresses induced in glasses which have a ratio Y:X greater than about 0.9 and less than or equal to 2 are generally greater than those generated in glasses in which the ratio Y :X may be less than 0.9 or greater than 2. Accordingly, in some embodiments, the ratio of Y :X may be greater than 0.9 or even greater than 1. In some embodiments, the ratio of Y:X may be greater than 0.9, or even greater than 1, and less than or equal to about 2. In still other embodiments, the ratio of Y:X may be greater than or equal to about 1.3 and less than or equal to about 2.0 in order to maximize the amount of compressive stress induced in the glass for a specified ion exchange time and a specified ion exchange temperature.

[00621 However, if the amount of AI2O3 in the alkali aluminosilicate glass is too high, the resistance of the alkali aluminosilicate glass to acid attack is diminished. Accordingly, the alkali aluminosilicate glass may include AI2O3 in an amount greater than or equal to about 2 mol.% and less than or equal to about 10 mol.%. In some embodiments, the amount of AI2O3 in the alkali aluminosilicate glass may be greater than or equal to about 4 mol.% and less than or equal to about 8 mol.%. In some other embodiments, the amount of AI2O3 in the alkali aluminosilicate glass may be greater than or equal to about 5 mol.% to less than or equal to about 7 mol.%. In some other embodiments, the amount of AI2O3 in the alkali aluminosilicate glass may be greater than or equal to about 6 mol.% to less than or equal to about 8 mol.%. In still other embodiments, the amount of AI2O3 in the alkali aluminosilicate glass may be greater than or equal to about 5 mol.% to less than or equal to about 6 mol.%.

[00631 The alkali aluminosilicate glass may also include one or more alkali oxides such as Na2O and/or K2O. The alkali oxides facilitate the ion exchangeability of the alkali aluminosilicate glass and, as such, facilitate chemically strengthening the glass. The alkali oxide may include one or more of Na2O and K2O. The alkali oxides are generally present in the alkali aluminosilicate glass in a total concentration of Y mol.%. In some embodiments described herein, Y may be greater than about 2 mol.% and less than or equal to about 18 mol.%. In some other embodiments, Y may be greater than about 8 mol.%, greater than about 9 mol.%, greater than about 10 mol.% or even greater than about 11 mol.%. For example, in some embodiments described herein Y may be greater than or equal to about 8 mol.% and less than or equal to about 18 mol.%. In still other embodiments, Y may be greater than or equal to about 9 mol.% and less than or equal to about 14 mol.%. 64 The ion exchangeability of the alkali aluminosilicate glass is primarily imparted to the alkali aluminosilicate glass by the amount of the alkali oxide Na2O initially present in the alkali aluminosilicate glass prior to ion exchange. Accordingly, the alkali aluminosilicate glass may include at least Na2O. Specifically, in order to achieve the desired compressive strength and depth of layer in the alkali aluminosilicate glass upon ion exchange strengthening, the alkali aluminosilicate glass include Na2O in an amount from about 2 mol.% to about 15 mol.% based on the molecular weight of the alkali aluminosilicate glass. In some embodiments the alkali aluminosilicate glass includes at least about 8 mol.% of Na2O based on the molecular weight of the alkali aluminosilicate glass. For example, the concentration of Na2O may be greater than 9 mol.%, greater than 10 mol.% or even greater than 11 mol.%. In some embodiments, the concentration ofNa2O may be greater than or equal to 9 mol.% or even greater than or equal to 10 mol.%. For example, in some embodiments the alkali aluminosilicate glass may include Na2O in an amount greater than or equal to about 9 mol.% and less than or equal to about 15 mol.% or even greater than or equal to about 9 mol.% and less than or equal to 13 mol.%.

[01)65] As noted above, the alkali oxide in the alkali aluminosilicate glass may further include K2O. The amount of K2O present in the alkali aluminosilicate glass also relates to the ion exchangeability of the alkali aluminosilicate glass. Specifically, as the amount of K2O present in the alkali aluminosilicate glass increases, the compressive stress obtainable through ion exchange decreases as a result of the exchange of potassium and sodium ions. Accordingly, it is often desirable to limit the amount of K2O present in the alkali aluminosilicate glass. In some embodiments, the amount of K2O is greater than or equal to 0 mol.% and less than or equal to 3 mol.%. In some embodiments, the amount of K2O may be less or equal to 2 mol.% or even less than or equal to 1.0 mol.%. In embodiments where the alkali aluminosilicate glass includes K2O, the K2O may be present in a concentration greater than or equal to about 0.01 mol.% and less than or equal to about 3.0 mol.% or even greater than or equal to about 0.01 mol.% and less than or equal to about 2.0 mol.%. In some embodiments, the amount of K2O present in the alkali aluminosilicate glass may be greater than or equal to about 0.01 mol.% and less than or equal to about 1.0 mol.%. Accordingly, it should be understood that K2O need not be present in the alkali aluminosilicate glass. However, when K2O may be included in the alkali aluminosilicate glass, the amount of K2O may be generally less than about 3 mol.% based on the molecular weight of the alkali aluminosilicate glass.

|0066| Alkaline earth oxides may be present in the composition to improve the meltability of the glass batch materials and increase the chemical durability of the alkali aluminosilicate glass. In embodiments, the total mol.% of alkaline earth oxides present in the alkali aluminosilicate glass may be generally less than the total mol.% of alkali oxides present in the alkali aluminosilicate glass in order to improve the ion exchangeability of the alkali aluminosilicate glass. In embodiments, the alkali aluminosilicate glass may include from about 3 mol.% to about 13 mol.% of alkaline earth oxide. In some of these embodiments, the amount of alkaline earth oxide in the alkali aluminosilicate glass may be from about 4 mol.% to about 8 mol.% or even from about 4 mol.% to about 7 mol.%. 0067 The alkaline earth oxide in the alkali aluminosilicate glass may include MgO, CaO, SrO, BaO or combinations thereof. In some embodiments, the alkaline earth oxide includes MgO, CaO or combinations thereof. For example, in embodiments the alkaline earth oxide includes MgO. MgO may be present in the alkali aluminosilicate glass in an amount which is greater than or equal to about 3 mol.% and less than or equal to about 8 mol.% MgO. In some embodiments, MgO may be present in the alkali aluminosilicate glass in an amount which is greater than or equal to about 3 mol.% and less than or equal to about 7 mol.% or even greater than or equal to 4 mol.% and less than or equal to about 7 mol.% by molecular weight of the alkali aluminosilicate glass.

[6668] In some embodiments, the alkaline earth oxide may further include CaO. In these embodiments CaO may be present in the alkali aluminosilicate glass in an amount from about 0 mol.% to less than or equal to 6 mol.% by molecular weight of the alkali aluminosilicate glass. For example, the amount of CaO present in the alkali aluminosilicate glass may be less than or equal to 5 mol.%, less than or equal to 4 mol.%, less than or equal to 3 mol.%, or even less than or equal to 2 mol.%. In some of these embodiments, CaO may be present in the alkali aluminosilicate glass in an amount greater than or equal to about 0.1 mol.% and less than or equal to about 1.0 mol.%. For example, CaO may be present in the alkali aluminosilicate glass in an amount greater than or equal to about 0.2 mol.% and less than or equal to about 0.7 mol.% or even in an amount greater than or equal to about 0.3 mol.% and less than or equal to about 0.6 mol.%. 0069 In embodiments, the alkali aluminosilicate glass may be rich in MgO, (i.e., the concentration of MgO in the alkali aluminosilicate glass is greater than the concentration of the other alkaline earth oxides in the alkali aluminosilicate glass including, without limitation, CaO). Forming the alkali aluminosilicate glass such that the alkali aluminosilicate glass is MgO-rich improves the hydrolytic resistance of the resultant glass, particularly following ion exchange strengthening. Moreover, alkali aluminosilicate glasses which are MgO-rich generally exhibit improved ion exchange performance relative to glass compositions which are rich in other alkaline earth oxides. Specifically, glasses formed from MgO-rich alkali aluminosilicate glass generally have a greater diffusivity than glass compositions which are rich in other alkaline earth oxides, such as CaO. The greater diffusivity enables the formation of a deeper depth of layer in the glass. MgO-rich glass compositions also enable a higher compressive stress to be achieved in the surface of the glass compared to glass compositions which are rich in other alkaline earth oxides such as CaO. In addition, it is generally understood that as the ion exchange process proceeds and alkali ions penetrate more deeply into the glass, the maximum compressive stress achieved at the surface of the glass may decrease with time. However, glasses formed from glass compositions which are MgO-rich exhibit a lower reduction in compressive stress than glasses formed from glass compositions that are CaO-rich or rich in other alkaline earth oxides (i.e., glasses which are MgO-poor). Thus, MgO-rich glass compositions enable glasses which have higher compressive stress at the surface and greater depths of layer than glasses which are rich in other alkaline earth oxides.

[0070 In order to fully realize the benefits of MgO in the alkali aluminosilicate glass described herein, it has been determined that the ratio of the concentration of CaO to the sum of the concentration of CaO and the concentration of MgO in mol. % (i.e., (CaO/(CaO+MgO)) should be minimized. Specifically, it has been determined that (CaO/(CaO+MgO)) should be less than or equal to 0.5. In some embodiments (CaO/(CaO+MgO)) may be less than or equal to 0.3 or even less than or equal to 0.2. In some other embodiments (CaO/(CaO+MgO)) may even be less than or equal to 0.1.

[00711 Boron oxide (B2O3) is a flux which may be added to alkali aluminosilicate glass to reduce the viscosity at a given temperature (e.g., the strain, anneal and softening temperatures) thereby improving the formability of the glass. However, it has been found that additions of boron adversely impacts the boron leachability of the resultant glass. Accordingly, in some embodiments described herein, the amount of boron added to the alkali aluminosilicate glass is minimized.

[0072] In embodiments, the concentration of B2O3 in the alkali aluminosilicate glass is generally less than or equal to about 4 mol.%, less than or equal to about 3 mol.%, less than or equal to about 2 mol.%, or even less than or equal to 1 mol.%. For example, in embodiments where B2O3 is present in the alkali aluminosilicate glass, the concentration of B2O3 may be greater than about 0.01 mol.% and less than or equal to 4 mol.%. In some of these embodiments, the concentration of B2O3 may be greater than about 0.01 mol.% and less than or equal to 3 mol.% In some embodiments, the B2O3 may be present in an amount greater than or equal to about 0.01 mol.% and less than or equal to 2 mol.%, or even less than or equal to 1.5 mol.%. Alternatively, the B2O3 may be present in an amount greater than or equal to about 1 mol.% and less than or equal to 4 mol.%, greater than or equal to about 1 mol.% and less than or equal to 3 mol.% or even greater than or equal to about 1 mol.% and less than or equal to 2 mol.%. In some of these embodiments, the concentration of B2O3 may be greater than or equal to about 0.1 mol.% and less than or equal to 1.0 mol.%. 0073] While in some embodiments the concentration of B2O3 in the glass composition is minimized to improve the forming properties of the glass without detracting from the ion exchange performance of the glass, in some other embodiments the glass compositions are free from boron and compounds of boron such as B2O3. Specifically, it has been determined that forming the alkali aluminosilicate glass without boron or compounds of boron improves the boron leachability properties of the alkali aluminosilicate glass. 0074 In some embodiments of the alkali aluminosilicate glass described herein, the alkali aluminosilicate glass are free from phosphorous and compounds containing phosphorous including, without limitation, P2O5. Specifically, it has been determined that formulating the alkali aluminosilicate glass without phosphorous or compounds of phosphorous increases the chemical durability of the alkali aluminosilicate glass.

[0075] In addition to the SiCh, AI2O3, alkali oxides and alkaline earth oxides, the alkali aluminosilicate glass described herein may optionally further comprise one or more fining agents such as, for example, SnCh, AS2O3, and/or Cl" (from NaCl or the like). When a fining agent is present in the alkali aluminosilicate glass, the fining agent may be present in an amount less than or equal to about 1 mol.% or even less than or equal to about 0.4 mol.%. For example, in some embodiments the alkali aluminosilicate glass may include SnO2 as a fining agent. In these embodiments SnC may be present in the alkali aluminosilicate glass in an amount greater than about 0 mol.% and less than or equal to about 1 mol.% or even an amount greater than or equal to about 0.01 mol.% and less than or equal to about 0.30 mol.%.

[0076 Moreover, the alkali aluminosilicate glass may comprise one or more additional metal oxides to further improve the chemical durability of the alkali aluminosilicate glass. For example, the alkali aluminosilicate glass may further include ZnO, TiCh, or ZrCh, each of which further improves the resistance of the alkali aluminosilicate glass to chemical attack. In these embodiments, the additional metal oxide may be present in an amount which is greater than or equal to about 0 mol.% and less than or equal to about 2 mol.%. For example, when the additional metal oxide is ZnO, the ZnO may be present in an amount greater than or equal to 1 mol.% and less than or equal to about 2 mol.%. When the additional metal oxide is ZrO2 or TiO2, the ZrO2 or TiO2 may be present in an amount less than or equal to about 1 mol.%.

[0077] In embodiments, the alkali aluminosilicate glass may be VALOR™ glass manufactured and marketed by Coming Incorporated.

[0078] Referring now to the borosilicate glass compositions, the borosilicate glass compositions may generally comprise one or more of silica (SiCh), alkali oxides (Na2O and K2O), alkaline-earth oxides (MgO, CaO, BaO, and SrO), alumina (AI2O3), and boron oxide B2O3.

[0079] In some embodiments of the borosilicate glass compositions, SiC>2 is the largest constituent of the composition and, as such, is the primary constituent of the resulting glass network. In embodiments, the borosilicate glass may comprise SiC>2 in an amount greater than or equal to 74 mol.% and less than or equal to 82 mol. %. In embodiments, the borosilicate glass may comprise SiC>2 in an amount greater than or equal to 74 mol.% and less than or equal to 80 mol. %, such as less than or equal to 78 mol. %, or less than or equal to 76 mol. %. the borosilicate glass may comprise SiC>2 in an amount less than or equal to 82 mol. % and greater than or equal to 76 mol.%, such as greater than or equal to 78 mol. % or greater than or equal to 80 mol. %.

[0080] In some embodiments, the borosilicate glass compositions may include one or more alkaline-earth oxides, such as MgO, CaO, BaO, and/or SrO. The borosilicate glass compositions may comprise from 0 mol. % to 5 mol. % of the one or more alkaline-earth oxides. In embodiments, the borosilicate glass compositions may comprise from 0 mol. % to 4 mol. %, from 0 mol. % to 3 mol. %, from 0 mol. % to 2 mol. %, from 0 mol. % to 1 mol. %, from 0.1 mol. %to 5 mol. %, from 0.1 mol. %to 4 mol. %, from 0.1 mol. %to 3 mol. %, from 0.1 mol. % to 2 mol. %, from 0. 1 mol. % to 1 mol. %, from 1 mol. % to 5 mol. %, from 1 mol. % to 4 mol. %, from 1 mol. % to 3 mol. %, from 1 mol. % to 2 mol. %, from 2 mol. % to 5 mol. %, from 3 mol. % to 5 mol. %, from 4 mol. % to 5 mol. %, or any subset thereof of the one or more alkaline-earth oxides. In other embodiments, the borosilicate glass compositions may be free of alkaline-earth oxides, such as comprising less than 1 mol. %, less than 0.5 mol. %, less than 0. 1 mol. % or even less than 0.01 mol. % of the alkaline earth oxides.

[0081] The borosilicate glass compositions may include one or more alkali oxides, such as Na2O and/or K2O. The alkali oxides are generally present in the borosilicate glass compositions in a total concentration of at least 2 mol. %. In some embodiments described herein, the concentration of the alkali oxides may be at least 3 mol. %, such as at least 4 mol. %, from 2 mol. % to 10 mol. %, from 3 mol. % to 10 mol. %, from 4 mol. % to 10 mol. %, from 5 mol. % to 10 mol. %, from 2 mol. % to 9 mol. %, from 2 mol. % to 8 mol. %, from 2 mol. % to 7 mol. %, from 3 mol. % to 9 mol. %, from 4 mol. % to 8 mol. %, from 3 mol. % to 5 mol. %, or any subset thereof. In certain embodiments the borosilicate glass compositions may be free of alkaline-earth oxides and may comprise from 3 mol. % to 5 mol. % of the alkali oxides. In certain embodiments, the borosilicate glass compositions may include alkaline earth oxides and may comprise from 4 mol. % to 8 mol. % of the alkali oxides.

[0082] The borosilicate glass compositions may include alumina (AI2O3). The alumina is generally present in the borosilicate glass compositions in an amount from 1 mol. % to 8 mol. %. In embodiments, the alumina may be present in the borosilicate glass compositions in an amount from 1 mol. % to 7 mol. %, from 1 mol. % t to 6 mol. %, from 1 mol. % to 5 mol. %, from 1 mol. % to 4 mol. % from 1 mol. % to 3 mol. %, from 2 mol. % to 7 mol . %, from 2 mol. % to 4 mol. % , from 2 mol. %to 3 mol. %, from 3 mol. % to 8 mol. % , from 3 mol. % to 7 mol. %, from 4 mol. % to 8 mol. %, from 4 mol. % to 7 mol. %, or any subset thereof, thereof. In certain embodiments the borosilicate glass compositions may be free of alkaline-earth oxides and may comprise from 2 mol. % to 3 mol. % of the alumina. In certain embodiments, the borosilicate glass compositions may include alkaline earth oxides and may comprise from 2 mol. % to 7 mol. % of the alumina.

[0083] The borosilicate glass compositions may comprise boron oxide B2O3. The B2O3 is generally present in the borosilicate glass compositions in an amount greater than 8 mol. %. In embodiments, the B2O3 may be present in the borosilicate glass compositions in an amount greater than 10 mol. %, greater than 12 mol. %, from 8 mol. %to 14 mol. %, from 8 mol. % to 13 mol. %, from 8 mol. % to 12 mol. %, from 9 mol. % to 13 mol. %, from 10 mol. % to 13 mol. %, from 11 mol. % to 13 mol. %, from 12 mol. % to 13 mol. %, or any subset thereof. In certain embodiments the borosilicate glass compositions may be free of alkaline-earth oxides and may comprise from 12 mol. % tol 3 mol. % of the B2O3. In certain embodiments, the borosilicate glass compositions may include alkaline earth oxides and may comprise from 8 mol. % to 12 mol. % of the B2O3.

[0084] The borosilicate glass compositions may be free of lead oxide (PbO). In embodiments, the borosilicate glass may comprise less than 1 mol. %, less than 0.5 mol. %, less than 0.1 mol. %, less than 0.01 mol. %, or even less than 0.001 mol. % of lead oxide.

[0085] Referring now to FIG. 3 and FIG. 4, the first layer 312 may extend through a thickness 314 of the sidewall 304, such as through the entirety of a thickness 314 of the sidewall 304. The first layer 312 may be a glass layer integral to the sidewall 304. The glass layer (i.e. the first layer 312) may be coterminous with the sidewall 304.

[0086] Embodiments where the first layer 312 extends through a thickness 314 of the sidewall 304, such as through the entirety of a thickness 314 of the sidewall 304 may be particularly suitable in embodiments where the glass body 302 (and by extension the sidewall 304) comprises minimal amounts of boron. In embodiments, the glass body 302, including the sidewall 304 and the first layer 312, may comprise less than 10 mol. %, such as less than 8 mol. %, less than 6 mol. %, less than 4 mol. %, less than 2 mol. %, less than 1 mol. %, less than 0.5 mol. %, less than 0.1 mol. %, less than 0.01 mol. % boron and compounds of boron, on an oxide basis. In embodiments, the first layer 312 may be free of boron and compounds of boron or substantially free boron and compounds of boron.

[0087] In embodiments, the glass body 302 may be formed from an alkali-aluminosilicate glass. Similarly, each of the sidewall 304 and the first layer 312 may be formed from the alkali aluminosilicate glass.

[0088] Referring again to FIG. 1 and FIG. 2, the first layer 112 may be disposed on the sidewall 104, or may refer to a glass layer integral to the sidewall 104. In such embodiments, the sidewall 104 and the glass body 102 may comprise a borosilicate glass composition or an alkali aluminosilicate glass composition. In some embodiments, the first layer 112 may be a glass layer integral to the sidewall 104 which has been leached of boron and compounds of boron or the first layer 112 may be a barrier coating applied to the sidewall 104. In embodiments where the first layer 112 is a glass layer integral to the sidewall 104 which has been leached of boron and compounds of boron, the boundary between the first layer 112 and the sidewall 104 may be sharp (defined as occurring over a depth of less than 50 nm), may be intermediate (defined as occurring over a depth of from 50 nm to 100 nm), or may be diffuse (defined as occurring over a depth of from 100 nm to 2000 nm).

[0089] In embodiments, the first layer 112 may be a glass layer integral to the sidewall 104 which was formed on the inner surface 108 of the sidewall 104 by treating the inner surface 108 to remove boron and compounds of boron, prior to the introduction of the pharmaceutical composition 110. In such embodiments, the glass body 102 may be formed from a borosilicate glass, as described herein. The glass layer integral to the sidewall 104 may have been formed by etching the inner surface 108 to remove boron and compounds of boron with an acidic solution.

[0090] In one embodiment, etching may be accomplished by exposing the inner surface of the glass container to an acid solution, or a combination of acid solutions. The acid solutions may include, without limitation, mineral acids (such as sulfuric acid, nitric acid, hydrochloric acid, hydrofluoric acid, hydrobromic acid, and phosphoric acid) organic acids (such as citric acid, silicic acid, and acetic acid), or combinations thereof. For example, the acid solution may include mineral acids and combinations thereof. These acid solutions may effectively remove boron from an inner surface 108 of the glass container 100, thereby leaving a depleted “leach layer” on the inner surface 108 of the glass container. In embodiments, the acid solution may have a pH of less than or equal to 4, such as less than or equal to 2, less than or equal to 1, less than or equal to 0, from -1 to 4, from -1 to 2, from -1 to 1, from -1 to 0, from 0 to 4, from 0 to 2, from 0 to 1, or any subset thereof. The etching may occur at an elevated temperature to reduce reaction times. The elevated temperature may be at least 30 °C, such as at least 40 °C, at least 50 °C, at least 60 °C, from 30 °C to 100 °C, from 30 °C to 90 °C, from 30 °C to 70 °C, from 50 °C to 100 °C, from 50 °C to 90 °C, from 50 °C to 70 °C, or any subset thereof. The etching may occur over a time of from 15 seconds to 24 hours, such as from 15 seconds to 12 hours, from 15 seconds to 6 hours, from 15 seconds to 3 hours, from 15 seconds to 1.5 hours, from 15 seconds to 45 minutes, from 15 seconds to 20 minutes, from 15 seconds to 5 minutes, from 1 minute to 24 hours, from 2 minutes to 24 hours, from 20 minutes to 24 hours, from 1 hour to 24 hours, or any subset thereof. In embodiments, the etching may occur after converting a tube to the vial shape but before annealing the vial. Without being limited by theory, it is believed that etching before annealing may improve the kinetics of the etching and increase the solubility of the boron in the etching solution, further speeding the etching process,

[0091] Alternatively, the boron content in the first layer 112 may be accomplished by exposing the inner surface of the glass container to a base solution or a combination of base solutions. Suitable base solutions include, for example, sodium hydroxide, potassium hydroxide, ammonium hydroxide, or combinations thereof. The basic solution may have a pH of at least 10, such as at least 11, at least 12, or even at least 13.

[0092] In yet further embodiments, boron reduction in the first layer 112 may be accomplished by sequentially exposing the first layer 112 to acid solutions followed by base solutions or vice-versa.

[0093] Still referring to FIG. 1 and FIG. 2, in some embodiments, the first layer 112 may be a barrier coating disposed on the sidewall 104. In embodiments, the barrier coating may be an inorganic coating, an organic coating, or combinations thereof.

[0094] In embodiments where the barrier coating is an inorganic coating, the inorganic coating may comprise metals such as in oxide or nitride form. In embodiments, the inorganic coating may comprise Al, Si, Ti, Zn, Zr, oxides of Al, Zn, Si, Ti or Zr, nitrides of Al, Zn, Si, Ti, or Zr, or combinations of these. In these embodiments, the inorganic coating may be deposited using a variety of deposition techniques including, without limitation, atomic layer deposition, chemical vapor deposition, physical vapor deposition, and the like. Alternatively, the inorganic coating may be applied with one or more liquid application techniques such as dip coating or spray coating. As yet another alternative, the inorganic coating may be applied by plasma coating. Spray coating techniques may include high volume low pressure (HVLP) and low volume low pressure (LVLP) spray coating, electrostatic spray coating, airless spray coating, ultrasonic atomization with airless spray coating, aerosol jet coating, and ink jet coating. Plasma coating techniques may include standard primary and secondary plasma coating, microwave assisted plasma coating, atmospheric plasma coating and the like.

[0095] In embodiments, the barrier coating may an organic coating, such as a polymeric coating. For example, in embodiments where the barrier coating is an organic coating, the organic coating may comprise ethylene-vinyl acetate, polybenzimidazoles, polybisoxazoles, polybisthiazoles, polyetherimides, polyquinolines, polythiophenes, phenylene sulfides, polysulfones, polycyanurates, parylenes, fluorinated polyolefins including polytetrafluorethylenes and other fluoro-substituted polyolefins, perfluoroalkoxy polymers, polyether ether ketones (PEEK), polyamides, polyphenolics, polyurethane acrylates, cyclic olefin copolymer and cyclic olefin polymers, polyolefins including polyethylenes, oxidized polyethylenes, polypropylenes, polyethylene/propylene copolymers, polyethylene/vinyl acetate copolymers, polyvinylchloride, polyacrylates, polymethacrylates, polystyrenes, polyterpenes, polyanhydrides, polyacetals and copolymers of polyacetals, polysiloxanes of dimethyl or diphenyl or methyl/phenyl mixtures, perfluorinated siloxanes and other substituted siloxanes, polyimides, polycarbonates, polyesters, parafins and waxes, or various combinations thereof. In some embodiments, the organic coating used as a first layer 112 may include ethylene-vinyl acetate.

[0096] In some embodiments, the first layer 112 may be formed from a layered structure comprising one or more of the aforementioned inorganic coatings and/or one or more of the aforementioned polymers/copolymers. In embodiments, the first layer 112 may further comprise a coupling agent, such as a silane-coupling agent, to adhere the first layer 112 to the sidewall 104. The coupling agent may be present with the organic or inorganic coating in separate layers or the coupling agent may be mixed with the organic or inorganic coating.

[0097] Still referring to FIG. 1 and FIG. 2, in embodiments where the glass body 102 is formed from a borosilicate glass composition, a concentration of boron and compounds of boron at a midpoint of a thickness 114 of the sidewall 104 may be greater than a concentration boron and compounds of boron in the first layer 112. In embodiments, the concentration of boron and compounds of boron at the midpoint 118 of a thickness 114 of the sidewall 104 may be at least 100 %, at least 300 %, at least 500 %, at least 800 %, at least 1000 %, at least 1500 %, or even at least 2000 % greater than the concentration of boron and compounds of boron in the first layer 112. As depicted in FIG. 2, for the purposes of taking the midpoint 118 of the thickness 114 of the sidewall 104, the first layer 112 should be considered as part of the thickness 114 of the sidewall 104. The concentration of boron and compounds of boron in the first layer 112 may be taken as the average concentration of boron and compounds of boron throughout the first layer 112. The concentration of boron and compounds of boron may be determined by standard spectroscopy techniques such as x-ray photoelectron spectroscopy (XPS) or dynamic secondary ion mass spectrometry (DSIMS).

[0098] In embodiments where the first layer 112 is not coterminous with the sidewall 104, the first layer 112, whether leached or barrier coating, may have a thickness of from 10 nm to 1 mm. Without being limited by theory, it is believed that if the first layer 112 is too thin, such as less than 10 nm, it may not stop the diffusion of sufficient quantities of boron from the sidewall 104 to the pharmaceutical composition 110. The thickness of the first layer 112 may be relevant when the glass body 102 is formed from a glass composition comprising boron and compounds of boron. It is further believed that if the first layer 112 is too thick, such as thicker than 1 mm, it may add unnecessary cost and/or reduce the strength of the glass body 102. In embodiments, the first layer 112 may have a thickness of at least at least 10 nm, at least 50 nm, at least 100 nm, at least 250 nm, at least 500 nm, at least 750 nm, at least 1 pm, at least 10 pm, at least 20 pm, at least 50 pm, at least 100 pm, at least 300 pm, at least 400 pm, at least 600 pm, at least 800 pm, at least 1000 nm, from 50 nm to 1 mm, from 100 nm to 1 mm, from 250 nm to 1 mm, from 500 nm to 1 mm, from 750 nm to 1 mm, from 1 pm to 1 mm, from 10 pm to 1 mm, from 50 pm to 1 mm, from 100 pm to 1 mm, from 250 pm to 1 mm, from 500 pm to 1 mm, from 10 nm to 0.5 mm, from 50 nm to 0.5 mm, from 100 nm to 0.5 mm, from 250 nm to 0.5 mm, from 500 nm to 0.5 mm, from 750 nm to 0.5 mm, from 1 pm to 0.5 mm, from 10 pm to 0.5 mm, from 50 pm to 0.5 mm, from 100 pm to 0.5 mm, from 250 pm to 0.5 mm, from 500 pm to 0.5 mm, from 10 nm to 0. 1 mm, from 50 nm to 0.1 mm, from 100 nm to 0.1 mm, from 250 nm to 0. 1 mm, from 500 nm to 0.1 mm, from 750 nm to 0.1 mm, from 1 pm to 1 mm, from 10 pm to 1 mm, from 50 pm to 1 mm, from 100 pm to 1 mm, from 250 pm to 1 mm, from 500 pm to 1 mm, or any subset thereof. Where a thickness of the first layer 112 is not uniform, the thickness of the first layer 112 is determined as the minimum thickness of the first layer 112 in the portion of the glass container 100 which is in contact with the pharmaceutical composition 110. The thickness of the first layer may be measured by, for example, scanning electron microscopy (SEM).

[0099] The distinct first layer 112, such as when the first layer is a leached first layer or the first layer is a barrier coating, may be utilized in conjunction with glass containers 100 formed from any glass composition, such as alkali aluminosilicate glass or borosilicate glass. However, the distinct first layer 112 is particularly well suited for use with glass containers 100 formed from glass compositions which comprise boron, such as borosilicate glass compositions. Such glass compositions may include, without limitation, those glass compositions designated as Type I Class A and Type I Class B glass compositions according to ASTM Standard E438-92 (2018) entitled “Standard Specification for Glasses in Laboratory Apparatus.” Such glass compositions may have the requisite chemical durability under the ASTM Standard, but do not necessarily exhibit the low leach rates of boron and compounds of boron. As such, distinct first layers 112 as described herein may be used on at least the inner surfaces of glass containers 100 formed from these compositions such that the container has a boron leach rate as described previously.

[0100] Referring now to the pharmaceutical composition 110, 310 itself, the pharmaceutical composition 310, 110 may comprise a molecule which reacts with boron and compounds of boron. In embodiments, the molecule may react with boron and compounds of boron to form a chelate compound or a chelate complex. Similar to typical chelate compounds formed between ligands and metal ions which have two or more separate coordinate bonds between a ligand and a single central metal atom, boronic acids can react with bidentate ligands, such as 1,2-diols including catechols and sugars, to form complexes.

[0101] In embodiments, the molecule that reacts with boron and compounds of boron may comprise at least two OH groups. The two OH groups may be arranged on the molecule such that the molecule comprises a 1,2-diol-containing ligand. It should be understood that the 1,2- diol-containing-ligand may comprise additional substituents, including additional OH groups.

[0102] In embodiments, the molecule may comprise at least one ring structure and the at least two OH groups may be bonded to the ring structure. The at least two OH groups may be bonded to the ring structure such that the ring structure forms at least a portion of a 1 ,2-diol-containing- ligand. The 1, 2-diol-containing-ligand may comprise a pyranose, a furanose, a catechol, or combinations of these. In embodiments, the 1, 2-diol-containing-ligand comprises a saponin, a saccharide, or both. In some embodiments, a molecule may have two or more 1,2-diol- containing-ligands, such as a saponin conjugated to a catechol.

[0103] The molecule may serve in the pharmaceutical composition as one or more of an excipient, a surfactant, or an active pharmaceutical ingredient (API). In embodiments, molecule may be a catechol. For example, the API may comprise masoprocol, methocarbamol, guaifenesin, carbidopa, alprazolam, dipivefrin, methyldopa, isoprenaline, levodopa, fluorodopa ( 18F), guaiacol, curcumin, amphetamine, norepinephrine, epinephrine, orciprenaline, dobutamine, dopamine, arbutamine, fenoterol, 4-vinylguaiacol, 6-hydroxydopa quinone, droxidopa, etilevodopa, levonordefrin, protokylol, zucapsaicin, racepinephrine, nonivamide, terameprocol, dopexamine, dichloroisoproterenol, reproterol, theodrenaline, melevodopa, ibopamine, adrenalone, potassium guaiacolsulfonate, deoxy epinephrine, dhydrocapsiate, zingerone, dopastatin, and N-oleoyldopamine. In embodiments, the molecule may be a saponin. For example, the molecule may comprise smilagenin, ginsenoside C, ginsenoside Rbl, ginsenoside B2, escin, beta-escin, saponin QS-21 , Matrix M-adjuvant (which contains saponin extracts from the bark of the Soapbark tree). In another embodiment, the molecule is a carbohydrate. For example, the molecule may comprise monosaccharides, oligosaccharides, polysaccharides, ribose, starches, lactose, heparin, hyaluronic acid, chitosan, glucose, mannose, pullulan, carbohydrate, glycosides (e.g., digoxin, gemcitabine, framy cetin, vitamin C, or any compound that contains a constituent sugar), glycans, and large molecules (including biologies, glycoproteins such as Varicella zoster vaccine (recombinant), hyaluronidase (ovine), Ebola Zaire vaccine (live, attenuated), drotrecogin alfa, and Imiglucerase).

[0104] An initial concentration of the molecule in the pharmaceutical composition (i.e., the concentration when the pharmaceutical composition is first introduced in the glass container) may be from 0.1 micro molar to 100 mill molar. In embodiments, an initial concentration of the molecule may be from 0.1 micro molar (pM) to 75 mill molar (mM), from 0.1 pM to 50 mM, from 0.1 pM to 25 mM, from 0.1 pM to 45 mM, from 0. 1 pM to 45 mM, from 0. 1 pM to 30 mM, from 0.1 pM to 15 mM, from 0.1 pM to 1000 pM, from 0. 1 pM to 750 pM, from 0. 1 pM to 500 pM, from 0.1 pM to 250 pM, or any subset thereof. [0105] In embodiments, multiple molecules which react with boron and compounds of boron may be present in the pharmaceutical composition. In such cases, the concentration of the molecule which may react with boron should be taken as the concentration of the single molecule with the highest affinity for boron and compounds of boron. However, if two or more molecules have about the same affinity for boron and compounds of boron, the concentration of the molecule with the lower concentration should be used. Without being limited by theory, it is believed that some pharmaceutical compositions 110, 310 may comprise a molecule which may bind to multiple boron atoms. However, it is believed that the affinity of the molecule for the second boron atom will be sufficiently lower than the affinity for the first boron atom, such that all or nearly all of the molecules will react with their first boron atom before a significant quantity of the molecules will react with a second boron atom. Affinity may be calculated as 1/kd, where kd is the equilibrium disassociation constant.

[0106] In embodiments, the pharmaceutical composition may be in a liquid form or a gel form.

[0107] Referring again to FIG. 1 and FIG. 3, the sidewall 104, 104, including the first layer 112, 312 may have a thickness 114, 314 of from 0.4 mm to 3.0 mm, such as from 0.4 mm to 2.5 mm, from 0.4 mm to 2.0 mm, from 0.4 mm to 1.5 mm, from 0.4 mm to 1.0 mm, from 0.5 mm to 3.0 mm, from 1.0 mm to 3.0 mm, from 1.5 mm to 3.0 mm, from 2.0 mm to 3.0 mm, from 2.5 mm to 3.0 mm, from 0.5 mm to 2.5 mm, from 1.0 mm to 2.0 mm, or any subset thereof.

[0108] The interior volume 106, 306 may be from 0.5 cm³ to 1000 cm³, from 0.5 cm³ to 750 cm³, from 0.5 cm³ to 500 cm³, from 0.5 cm³ to 250 cm³, from 0.5 cm³ to 100 cm³, from 0.5 cm³ to 50 cm³, from 0.5 cm³ to 10 cm³, from 0.5 cm³ to 5 cm³, from 1 cm³ to 1000 cm³, from 5 cm³ to 1000 cm³, from 10 cm³ to 1000 cm³, from 50 cm³ to 1000 cm³, from 100 cm³ to 1000 cm³, from 250 cm³ to 1000 cm³, from 500 cm³ to 1000 cm³, from 750 cm³ to 1000 cm³, from 1 cm³ to 100 cm³, from 1 cm³ to 10 cm³, or any subset thereof.

[0109] The inner surface 108, 308 may have a surface area of from 3 cm² to 1000 cm², such as from 3 cm² to 300 cm², from 3 cm² to 200 cm², from 3 cm² to 100 cm², from 3 cm² to 50 cm², from 3 cm² to 10 cm², from 5 cm² to 300 cm², from 10 cm² to 300 cm², from 50 cm² to 300 cm², from 100 cm² to 300 cm², from 10 cm² to 200 cm², from 10 cm² to 100 cm², or any subset thereof. [0110] The pharmaceutical composition 110, 310 may be in contact with from 2 cm² to 800 cm² of the inner surface 108, 308, such as from 3 cm² to 300 cm², from 3 cm² to 200 cm², from 3 cm² to 100 cm², from 3 cm² to 50 cm², from 3 cm² to 10 cm², from 5 cm² to 300 cm², from 10 cm² to 300 cm², from 50 cm² to 300 cm², from 100 cm² to 300 cm², from 10 cm² to 200 cm², from 10 cm² to 100 cm², or any subset thereof.

[oni] A method of using a glass container may comprise storing a pharmaceutical composition that comprises a molecule that reacts with boron and compounds of boron inside of the glass container for a storage time. As the pharmaceutical composition is stored in the glass container, at least a portion of boron and compounds of boron in the glass composition of the glass container may leach out of the glass composition of the glass container and into the pharmaceutical composition, resulting in a final concentration of boron in the pharmaceutical composition. As noted herein, the glass containers described herein reduce or even mitigate the leaching of boron and compounds of boron in the pharmaceutical composition 110, 310 contained therein. As such, after an extended period of leaching at room temperature, the concentration of boron in the pharmaceutical composition 110, 310 may be less than 100 %, less than 75 %, less than 50 %, less than 25 %, less than 20 %, less than 15 %, less than 10 %, less than 5 %, less than 2.5 %, less than 2 %, less than 1.50 %, less than 1.00 %, less than less than 0.50 %, less than 0.25 %, or even less than 0.1 % of a concentration of the molecule in the pharmaceutical composition, on a molar basis.

[0112] The method may comprise storing the glass container comprising a pharmaceutical composition that comprises a molecule that reacts with boron and compounds of boron for a storage time and at a storage temperature, such that boron (if present in the glass composition of the glass container) leaches out of the glass container into the pharmaceutical composition to yield a final concentration of boron. The storage time may be from 6 months to 10 years, such as from 1 year to 10 years, from 1.5 years to 10 years, from 3 years to 10 years, from 1.5 years to 5 years, from 1.5 years to 4 years, from 1.5 years to 3 years, or any subset thereof. The storage temperature may be any temperature range at which the pharmaceutical composition is a liquid, such as at least 0 °C, at least 2 °C, at least 4 °C, from 2 °C to 75 °C, from 2 °C to 50 °C, from 2 °C to 30 °C, from 2 °C to 25 °C, from 2 °C to 20 °C, from 2 °C to 15 °C, from 2 °C to 10 °C, from 2 °C to 8 °C, at least 15 °C, at least 20 °C, from 15 °C to 40 °C, from 15 °C to 35 °C, from 15 °C to 30 °C, from 15 °C to 25 °C, or any subset thereof). It should be understood that if no boron is present in the glass, no boron will leach into the pharmaceutical composition and this feature will be satisfied.

[0113] As noted herein, the final concentration of boron in the pharmaceutical comprising the molecule that reacts with boron and compounds of boron may be less than 100 mol. % of a concentration of the molecule, such as less than 75 mol. %, less than 50 mol. %, less than 25 mol. %, less than 15 mol. %, less than 10 mol. %, less than 5 mol. %, less than 2.5 mol. %, less than 1 mol. %, less than 0.5 mol. %, or even less than 0. 1 mol. %.

[0114] According to a first aspect, a glass container may comprise a glass body may comprise a sidewall enclosing an interior volume, the sidewall of the glass body may comprise a first layer and the first layer may comprise an inner surface; and a pharmaceutical composition disposed in the interior volume, wherein: the glass body meets Type 1 criteria according to USP <660>, Class HGA 1 hydrolytic resistance when tested according to the ISO 720-1985 testing standard, or both; the pharmaceutical composition may be in contact with the inner surface; and the pharmaceutical composition may comprise a molecule that reacts with boron and compounds of boron.

[0115] According to a second aspect, a glass container may comprise: a glass body may comprise a sidewall enclosing an interior volume, the sidewall of the glass body may comprise a first layer and the first layer may comprise an inner surface; and a pharmaceutical composition disposed in the interior volume, wherein: the first layer may comprise less than 1 mol. % of boron and compounds of boron; the pharmaceutical composition may be in contact with the first layer of the inner surface; and the pharmaceutical composition may comprise a molecule that reacts with boron and compounds of boron.

[0116] According to a third aspect, in conjunction with either of the first or second aspects the glass container may have an accelerated boron leaching score of less than 1.5 pg/ mb.

[0117] According to a fourth aspect, in conjunction with any one of aspects 1-3, the pharmaceutical composition may leach boron out of the glass body and into the pharmaceutical composition such that the pharmaceutical composition has a dissolved boron concentration; and after one year of leaching at room temperature, the dissolved boron concentration may be less than 100 mol. % of a concentration of the molecule. [0118] According to a fifth aspect, in conjunction with any one of aspects 1-4, the pharmaceutical composition may leach boron out of the glass body and into the pharmaceutical composition such that the pharmaceutical composition has a dissolved boron concentration; and after one year of leaching at room temperature, the dissolved boron concentration may be less than 10 mol. % of a concentration of the molecule.

[0119] According to a sixth aspect, in conjunction with any one of aspects 1-3, the glass body may be formed from an alkali-aluminosilicate glass that is free from boron; and the first layer may extend through a thickness of the sidewall.

[0120] According to a seventh aspect, in conjunction with any one of aspects 1-6, the first layer may be a glass layer integral with the glass body.

[0121] According to an eighth aspect, in conjunction with any one of aspects 1-7, a concentration of boron and compounds of boron at a midpoint of a thickness of the sidewall may be greater than a concentration of boron and compounds of boron in the first layer.

[0122] According to a ninth aspect, in conjunction with any one of aspects 1-8, the first layer may extend from the inner surface into the glass body to a depth of from 10 nm to 1 mm from the inner surface.

[0123] According to a tenth aspect, in conjunction with any one of aspects 1-5 and 7-9, the glass body may be formed from a boron-containing glass; and the glass body may comprise an inner surface and the inner surface has been treated to remove boron and compounds of boron prior to introduction of the pharmaceutical into the interior volume.

[0124] According to an eleventh aspect, in conjunction with any aspect 10, the inner surface of the glass body may have been treated in an acidic solution.

[0125] According to a twelfth aspect, in conjunction with any one of aspects 1-2, the first layer may be a coating disposed on the glass body.

[0126] According to athirteenth aspect, in conjunction with aspect 12, the first layer may be an inorganic coating.

[0127] According to a fourteenth aspect, in conjunction with either of aspects 12-13, wherein the inorganic coating may comprise Al, Zn, Si, Ti, Zr, oxides of Al, Zn, Si, Ti or Zr, nitrides of Al, Zn, Si, Ti, or Zr, or combinations of these.

[0128] According to a fifteenth aspect, in conjunction with aspects 12, the first layer may be an organic coating. [0129] According to a sixteenth aspect, in conjunction with aspect 15, the organic coating may comprise a polymeric coating.

[0130] According to a seventeenth aspect, in conjunction with aspects 16, the polymeric coating may comprise ethylene -vinyl acetate (EVA).

[0131] According to an eighteenth aspect, in conjunction with any one of aspects 12-17, the coating may have a thickness of at least 10 nm.

[0132] According to a nineteenth aspect, in conjunction with any one of aspects 1-18, the first layer may comprise from 0 mol. % to 0.1 mol. % of boron and compounds of boron. [0133] According to a twentieth aspect, in conjunction with any one of aspects 1-19, the first layer may be free of boron and compounds of boron.

[0134] According to a twenty-first aspect, in conjunction with any one of aspects 1-20, the pharmaceutical composition may leach boron out of the glass body and into the pharmaceutical composition such that the pharmaceutical composition has a dissolved boron concentration; and after one year of leaching at room temperature, the dissolved boron concentration may be less than 10 pg/ mL.

[0135] According to a twenty-second aspect, in conjunction with any one of aspects 1- 21, the pharmaceutical composition may leach boron out of the glass body and into the pharmaceutical composition such that the pharmaceutical composition has a dissolved boron concentration; and after one year of leaching at room temperature, the dissolved boron concentration may be less than 1 pg/ mL.

[0136] According to a twenty-third aspect, in conjunction with any one of aspects 1-22, the pharmaceutical composition may leach boron out of the glass body and into the pharmaceutical composition such that the pharmaceutical composition has a dissolved boron concentration, and after one year of leaching at room temperature, the dissolved boron concentration may be less than 0.1 pg/ mL.

[0137] According to a twenty-fourth aspect, in conjunction with any one of aspects 1-3, 7, and 9-20, the glass body may be free of boron and compounds of boron.

[0138] According to a twenty -fifth aspect, in conjunction with any one of aspects 1-24, the molecule may comprise at least two OH groups.

[0139] According to a twenty-sixth aspect, in conjunction with any one of aspects 1-25, the molecule may comprise a 1,2-diol-containing ligand. [0140] According to a twenty-seventh aspect, in conjunction aspect 26, the 1,2-diol- containing-ligand may comprise at least one ring structure and the at least two OH groups are each bonded to the ring structure.

[0141] According to a twenty -eighth aspect, in conjunction with any one of aspects 26-

27, the 1,2-diol-containing-ligand may comprise a pyranose, a furanose, a catechol, or combinations of these.

[0142] According to a twenty-ninth aspect, in conjunction with any one of aspects 26-

28, the 1,2-diol-containing-ligand may be a saponin or a saccharide.

[0143] According to a thirtieth aspect, in conjunction with any one of aspects 1-29, the molecule may be one or more of an excipient, a surfactant, or an active pharmaceutical ingredient (API).

[0144] According to a thirty-first aspect, in conjunction with any one of aspects 1-30, the pharmaceutical composition may be a liquid or a gel.

[0145] According to a thirty-second aspect, in conjunction with any one of aspects 1-31, the molecule that reacts with boron and compounds of boron, may react with boron and compounds of boron to form a chelate compound or complex forming compound.

[0146] According to a thirty-third aspect, a method of using a glass container, the glass container may comprise : a glass body may comprise a sidewall enclosing an interior volume, the sidewall of the glass body may comprise an inner surface; and a pharmaceutical composition disposed in the interior volume, wherein: the pharmaceutical composition may comprise a molecule that reacts with boron and compounds of boron; and the method may comprise: storing the pharmaceutical container for from 18 months to 10 years, thereby leaching boron out of the glass container into the pharmaceutical composition to yield a final concentration of boron; and the final concentration of boron in the pharmaceutical composition may be less than 100 % of a concentration of the molecule.

EXAMPLES

[0147] The various aspects of the present disclosure will be further clarified by the following examples. The examples are illustrative in nature and should not be understood to limit the subject matter of the present disclosure.

[0148] Example 1 [0149] To confirm the effectiveness of the accelerated boron-leaching test described above, a series of glass vials were washed with deionized water. The vials were then filled to target volumes (~0.5 to ~6mL, depending on vial size) with an aqueous phosphate buffer solution containing a boron-sensitive molecule and stored for 24 months at 5 °C or 6 months at 22 °C. Identical vials were filled to 90 % with purified water and subjected to the accelerated boron- leaching test. Specifically, they were heated to 100 °C and then heated from 100 °C to 121 °C at a ramp rate of 1 °C /min at a pressure of 2 atmospheres. The glass containers and solutions were held at this temperature for 60 minutes, then cooled to 95°C at a rate of 0.5 °C /min before being cooled to room temperature. The results of this testing are shown in Table 1 below. The concentrations of each atom are shown in pg (of the atom) per gram of solution. Ci is the peak boron concentration after 24 months of storage at 5 °C and C2 is the peak boron concentration after 6 months of storage at 22 °C. B is the boron concentration after the accelerated boron- leaching test.

[0150] Samples EX-A and EX-B were chemically strengthened alkali aluminosilicate glasses with from 72 wt. % to 75 wt. % of SiO2, 0 wt. % of B2O3, 9 wt. % to 12 wt. % of AI2O3, from 10 wt. % to 13 wt. % of Na2O and K2O, from 3 wt. % to 5 wt. % of CaO and MgO, from 0. 1 wt. % to 1 wt. % of SnCh, and less than 400 ppm of Fe2C>3. Samples EX-A and EX-B meet HGB1 hydrolytic resistance according to ISO 719 and Type 1 criteria according to USP <660>.

Table 1

[0151] In Table 1, some boxes are labelled N/A. Such a label indicates that the test was not performed. Fill volume is given in units of mb. All other units are in pg B/g solution.

[0152] As can be seen from Table 1, the concentration of boron after the accelerated boron leaching test correlates well with the concentration of boron after 6 months of storage at room temperature.

[0153] The above experimental testing was performed using a solution which lacked the molecule which reacts with boron or compounds of boron. However, it is anticipated that a solution which included the molecule which reacts with boron or compounds of boron would have reacted with any boron leached/extracted from the glass body.

Claims

CLAIMS What is claimed is:

1. A glass container comprising: a glass body comprising a sidewall enclosing an interior volume, the sidewall of the glass body comprising a first layer and the first layer comprising an inner surface; and a pharmaceutical composition disposed in the interior volume, wherein: the glass body meets Type 1 criteria according to USP <660>, Class HGA 1 hydrolytic resistance when tested according to the ISO 720-1985 testing standard, or both; the pharmaceutical composition is in contact with the inner surface; and the pharmaceutical composition comprises a molecule that reacts with boron and compounds of boron.

2. A glass container comprising: a glass body comprising a sidewall enclosing an interior volume, the sidewall of the glass body comprising a first layer and the first layer comprising an inner surface; and a pharmaceutical composition disposed in the interior volume, wherein: the first layer comprises less than 1 mol. % of boron and compounds of boron; the pharmaceutical composition is in contact with the first layer of the inner surface; and the pharmaceutical composition comprises a molecule that reacts with boron and compounds of boron.

3. The glass container of claim 1 or 2, wherein the glass container has an accelerated boron leaching score of less than 1.5 pg/ mL.

4. The glass container of any one of claims 1 to 3, wherein: the pharmaceutical composition leaches boron out of the glass body and into the pharmaceutical composition such that the pharmaceutical composition has a dissolved boron concentration; and and after one year of leaching at room temperature, the dissolved boron concentration is less than 100 mol. % of a concentration of the molecule.

5. The glass container of any one of claims 1 to 4, wherein: the glass body is formed from an alkali-aluminosilicate glass that is free from boron; and the first layer extends through a thickness of the sidewall.

6. The glass container of any one of claims 1 to 5, wherein the first layer is a glass layer integral with the glass body.

7. The glass container of any one of claims 1 to 6, wherein a concentration of boron and compounds of boron at a midpoint of a thickness of the sidewall is greater than a concentration of boron and compounds of boron in the first layer.

8. The glass container of any one of claims 1 to 7, wherein the first layer extends from the inner surface into the glass body to a depth of from 10 nm to 1 mm from the inner surface.

9. The glass container of any one of claims 1 to 4 and 7-8, wherein: the glass body is formed from a boron-containing glass; and the glass body comprises an inner surface and the inner surface has been treated to remove boron and compounds of boron prior to introduction of the pharmaceutical into the interior volume.

10. The glass container of any one of claims 1-9, wherein the inner surface of the glass body has been treated in an acidic solution.

11. The glass container of any one of claims 1 -9, wherein the first layer is an inorganic coating.

12. The glass container of claim 11, wherein the inorganic coating comprises Al, Zn, Si, Ti, Zr, oxides of Al, Zn, Si, Ti or Zr, nitrides of Al, Zn, Si, Ti, or Zr, or combinations of these.

13. The glass container of any one of claims 9, wherein the first layer is an organic coating.

14. The glass container of any one of claims 1 to 13, wherein the first layer is free of boron and compounds of boron.

15. The glass container of any one of claims 1 to 14, wherein: the pharmaceutical composition leaches boron out of the glass body and into the pharmaceutical composition such that the pharmaceutical composition has a dissolved boron concentration; and after one year of leaching at room temperature, the dissolved boron concentration is less than 10 pg/ mL.

16. The glass container of any one of claims 1 to 15, wherein the glass body is free of boron and compounds of boron.

17. The glass container of any one of claims 1-16, wherein the molecule comprises a 1 ,2-diol- containing ligand.

18. The glass container of any one of claim 17, wherein the 1,2-diol-containing -ligand comprises a pyranose, a furanose, a catechol, or combinations of these.

19. The glass container of any one of claims 1 to 18, wherein the molecule is one or more of an excipient, a surfactant, or an active pharmaceutical ingredient (API).

20. A method of using a glass container, wherein the glass container comprises: a glass body comprising a sidewall enclosing an interior volume, the sidewall of the glass body comprising an inner surface; and a pharmaceutical composition disposed in the interior volume, wherein: the pharmaceutical composition comprises a molecule that reacts with boron and compounds of boron; and the method comprises: storing the pharmaceutical container for from 18 months to 10 years, thereby leaching boron out of the glass container into the pharmaceutical composition to yield a final concentration of boron; and the final concentration of boron in the pharmaceutical composition is less than 100 % of a concentration of the molecule.