Glass containers with increased bottom thickness

Abstract

The present application is directed to glass containers with increased bottom thickness. The glass containers disclosed herein have a bottom with an increased thickness compared to conventional glass containers. Due to the thermal insulating properties of glass, the greater thickness of the bottom of the glass vials slows down the heat transfer rate through the bottom so that the heat transfer rate through the bottom of the glass vial is the same as or less than the heat transfer rate through the sidewalls of the glass vial. This in turn provides for more even cooling of the contents of the glass vial, which results in formation of smaller crystals during crystallization and reduces concentration gradients throughout the composition.

Description

GLASS CONTAINERS WITH INCREASED BOTTOM THICKNESSCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority under 35 U.S.C. §119 of U.S. Provisional Application Serial No. 63 / 554,596 filed on February 16, 2024, the content of which are relied upon and incorporated herein by reference in their entirety.FIELD

[0002] The present specification generally relates to containers and, more particularly, to vials with an increased bottom thickness for pharmaceutical purposes.TECHNICAL BACKGROUND

[0003] Historically, glass has been used to produce a variety of articles. In particular, because of its hermeticity, optical clarity, and excellent chemical durability relative to other materials, glass has been a preferred material for pharmaceutical applications, including, without limitation, vials, syringes, ampoules, cartridges, jars, and other glass articles. Production of these articles from glass starts with providing glass tubing that may subsequently be formed and separated into a plurality of the glass articles. Specifically, the glass used in pharmaceutical packaging must have adequate mechanical and chemical durability so as to not affect the stability of the pharmaceutical formulations contained therein. Glasses having suitable chemical durability include those glass compositions within the ASTM standard ‘Type IA’ and ‘Type IB’ glass compositions which have a proven history of chemical durability

[0004] Wall thickness of glass pharmaceutical containers has evolved over time. For instance, pharmaceutical vials were initially formed through blow molding techniques. This method produces variable wall thicknesses due to inherent asymmetries of heat removal during forming. Preserving mechanical strength for these vials was done by managing the minimum wall thickness rather than average thickness. Tubular vials added advantages for optical inspections during filling operations due to the increased thickness uniformity and reduced optical distortions. The uniform wall thickness of tubes enabledbetter targeting of thickness values, with minimum molded vial wall thickness as a reference, leading to today’s range of thickness values.SUMMARY

[0005] Accordingly, an ongoing need exists for vials having alternative geometries and methods of manufacturing the same may be desired.

[0006] According to one or more aspects of the present disclosure, a glass container comprises: a body having at least a sidewall and a bottom portion; the sidewall having a sidewall thickness ts extending between an outer surface and an inner surface of the sidewall; and the bottom having a bottom thickness tn extending between an outer bottom surface and an inner bottom surface, wherein tn is greater than or equal to 1.2 times greater than ts.

[0007] A second aspect may include the previous aspect, wherein the glass container has a center of mass, wherein the center of mass is from 15 mm to 25 mm from the outer bottom surface in a direction parallel to a center axis of the glass container.

[0008] A third aspect may include either one of the previous aspects, wherein t B is from 0.25 mm to 1.25 mm.

[0009] A fourth aspect may include any one of the previous aspects, wherein a ratio of the bottom thickness tn to the sidewall thickness ts is from 1.2 to 20.

[0010] A fifth aspect may include any one of the previous aspects, wherein the body further comprises: a shoulder; a neck extending from the shoulder; and a flange extending from the neck, the flange comprising: an underside surface extending from the neck; an external surface extending from the underside surface, the external surface defining an outer diameter of the flange.

[0011] According to one or more aspects disclosed herein, a pharmaceutical product may include any of the previous aspects, the pharmaceutical product comprising a pharmaceutical composition contained with the glass container, and a closure coupled to the glass container, wherein the closure seals the pharmaceutical composition within the glass container.

[0012] According to one or more aspects, a method for storing a pharmaceutical composition at low temperature may comprise filling the pharmaceutical composition into the glass container of any previous aspect; sealing the glass container comprising the pharmaceutical composition; and reducing the temperature of an environment of the glass container.

[0013] Additional features and advantages of the container profiles with increased bottom thicknesses 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.

[0014] 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 subj ect 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 DRAWINGS

[0015] FIG. 1 schematically depicts a cross-section of a pharmaceutical container having an increased bottom thickness, according to one or more embodiments shown and described herein;

[0016] FIG. 2 schematically depicts a lyophilization process having a Freezing Stage, a Primary Drying Stage, and a Secondary Drying Stage, according to one or more embodiments shown and described herein;

[0017] FIG. 3 schematically depicts a cross-section of a pharmaceutical container having a standard bottom thickness, according to the prior art;

[0018] FIG. 4 schematically depicts a cross-section of a crystallization front within a pharmaceutical container having a standard bottom thickness, according to the prior art;

[0019] FIG. 5 schematically depicts a cross section of a crystallization front within a pharmaceutical container having an increased bottom thickness, according to one or more embodiments shown and described herein; and

[0020] FIG. 6 graphically depicts a center of mass elevation (y-axis) as a function of wall thickness (x-axis) for glass pharmaceutical vials, according to one or more embodiments shown and described herein.DETAILED DESCRIPTION

[0021] Reference will now be made in detail to exemplary embodiments which are illustrated in the accompanying drawings. Whenever possible, the same reference numerals will be used throughout the drawings to refer to the same or like parts. Now referring to FIG. 1, a glass vial 300 of the present disclosure is schematically depicted in cross section. The glass vial 300 generally comprises a sidewall 303 having an outer surface 301 and an inner surface 308. The inner surface may enclose an internal volume 304. In the embodiment shown in FIG. 1, the glass vial 300 also comprises a bottom portion 302 that comprises an inner bottom surface 307 and an outer bottom surface 306. The glass vial 300 also generally has a sidewall thickness, ts, and a bottom thickness, tu. The sidewall thickness extends between the outer surface 301 and the inner surface 308 of the sidewall 303. The bottom thickness extends between the inner bottom surface 307 and the outer bottom surface 306. The sidewall 303 transitions into the bottom portion 302 through a heel portion 309.

[0022] Glass containers 300 disclosed herein may comprise a body having at least a sidewall 303 and a bottom portion 302; the sidewall 303 having a sidewall thickness ts extending between an outer surface 301 and an inner surface 308 of the sidewall 303; and the bottom portion 302 having a bottom thickness tn extending between an outer bottom surface 306 and an inner bottom surface 307, wherein tn is at least greater than or equal to 1.2 times greater than ts.

[0023] Glass containers disclosed herein may be coupled to a closure to seal the contents within. In embodiments, glass containers may also comprise a shoulder 320 and a neck321 extending from the shoulder 320. The glass containers may further comprise a flange322 extending from the neck 321. The flange 322 may comprise an underside surface 323extending from the neck 321 and an external surface 324 extending from the underside surface 323, the external surface 324 defining an outer diameter d0of the flange 322. It should be understood that the thickness of the sidewall ts refers to the thickness of the sidewall 303 and not the thickness of the shoulder 320, neck 321, or flange 322.

[0024] The components in the drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the exemplary embodiments. The disclosure should not be construed as limited to the embodiments set forth herein. Rather, these embodiments are provided so that this disclosure will be thorough and complete, and will fully convey the subject matter to those skilled in the art.

[0025] Additionally, any examples set forth in this specification are illustrative, but not limiting, and merely set forth embodiments of the subjected matter described herein. Other suitable modifications and adaptions of the variety of conditions and parameters normally encountered in the field, and which would be apparent to those skilled in the art, are within the spirit and scope of this disclosure.

[0026] 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. The terminology used in the disclosure herein is for describing particular embodiments only and is not intended to be limiting.

[0027] Ranges can be expressed herein as from “about” one particular value, and / or to “about” another particular value. When such a range is expressed, another embodiment includes from the one particular value and / or to the other particular value. Similarly, when values are expressed as approximations, by use of the antecedent “about,” it will be understood that the particular value forms another embodiment. It will be further understood that the endpoints of each of the ranges are significant both in relation to the other endpoint, and independently of the other endpoint.

[0028] Directional terms as used herein - for example up, down, right, left, front, back, top, bottom - are made only with reference to the figures as drawn and are not intended to imply absolute orientation.

[0029] The term “and / or” shall also be interpreted to be inclusive (e.g., “x and / or y” means one or both x or y). In situations where “and / or” or “or” are used as a conjunctionfor a group of three or more items, the group should be interpreted to include one item alone, all the items together, or any combination or number of the items. Moreover, terms used in the specification and claims such as have, having, include, and including should be construed to be synonymous with the terms comprise and comprising.

[0030] 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.

[0031] As used herein, the singular forms “a,” “an” and “the” include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to “a” component includes aspects having two or more such components, unless the context clearly indicates otherwise.

[0032] As used herein, the term “semi-stoppered” refers to a vial where a stopper is inserted into the top opening but not so far that gases are unable to escape from the container during the primary drying stage and secondary drying stage of lyophilization.

[0033] As used herein, the term “standard bottom thickness” refers to the minimum thickness according to International Organization for Standardization (ISO) 8362-1.

[0034] Because of its hermeticity, optical clarity, and excellent chemical durability relative to other materials, glass has been a preferred material for pharmaceutical applications, including, without limitation, vials, syringes, ampoules, cartridges, jars, and other glass articles. These pharmaceutical glass containers, as well as other types of glass articles, can be produced through a process of converting a length of glass tube to one or more of the glass articles through a plurality of heating and forming operations. Glass vialsare widely used in pharmaceutical applications to maintain the integrity of the pharmaceutical products stored therein. Containers for pharmaceutical contents are chosen based on their container closure integrity, which is a measure of how well a container protects the contents from contamination with a variety of factors, including moisture intrusion, oxygen intrusion, chemical contamination, or combinations of these. Glass vials provide an effective oxygen or moisture barrier. As a result, glass vials are the packaging of choice for most biologies, including vaccines.

[0035] With the advent of the SARS-CoV-2 pandemic in 2020, new mRNA vaccines were developed to aid in efforts to prevent the spread of the disease. The Centers for Disease Control (CDC) recommended that the vaccines be stored long-term at ultralow temperatures. For example, the Pfizer-BioNTech vaccines were to be stored in an ultralow- temperature freezer between negative 80 degrees and negative 60 degrees Celsius (° C) (negative 112 degrees and negative 76 degrees Fahrenheit (° F)). This requirement ensures the ingredients’ stability and ensures the vaccines’ viability because, regardless of how effective a vaccine may be in the laboratory, unless the suspension can be stabilized for storage and distribution, its commercial potential will be limited.

[0036] Pharmaceutical compositions such as vaccines and biological-products have similar requirements for storage at ultralow temperatures. In some cases, the pharmaceutical industry has been able to satisfy these storage requirements with the use of freeze-drying processes. Freeze-drying enables a product to be stored as a powder at room temperature, and then reconstituted when it is ready to be used. One such technique is known as lyophilization. Lyophilization is a well-established technique used in the pharmaceutical industry for stabilizing high-cost, labile bio-products, such as vaccines. During a lyophilization cycle, solvent is removed from the liquid product in manufacturing steps that include but are not limited to freezing, primary drying (sublimation), and secondary drying (desorption).

[0037] Referring now to FIG. 2, a lyophilization method 100 is schematically depicted. The lyophilization method 100 includes a Freezing Stage, a Primary Drying Stage, and a Secondary Drying Stage. During Step A of the Freezing Stage, a glass container, such as but not limited to a pharmaceutical glass vial, is semi-stoppered with a biological product disposed therein at atmospheric pressure while on a metal shelf in a freezer. The biological product in the glass container may be dissolved in a suitable solvent. At Step B, thetemperature of the environment containing the glass container (e.g., the freezer) is reduced until the temperature of the biological product is about -40° C and maintained at this temperature for the duration of Step B. During this freezing step, ice crystals form in the biological product disposed within the vial. FIG. 2 shows the temperature 101 of the metal shelf (y-axis) and the temperature 102 of the biological product in the glass vial (y-axis) as a function of time during the lyophilization method 100.

[0038] Following Step B of the Freezing Stage, the metal shelf temperature 101 is increased by increasing the freezer temperature to allow for the Primary Drying Stage to begin. At the beginning of the Primary Drying Stage, the metal shelf temperature 101 may be increased to a temperature of greater than -40 °C and less than 0 °C. The freezer temperature and metal shelf temperature 101 may be maintained constant throughout the Primary Drying Stage. As shown in FIG. 2, during the Primary Drying Stage, the biological product temperature 102 remains relatively constant and increases only slightly due to the heat transfer from the metal shelf and sublimation of ice crystals during the Primary Drying Stage.

[0039] Referring again to FIG. 2, at Step C, the Primary Drying Stage commences. During the Primary Drying Stage, the semi-stoppered glass container is subjected to a vacuum and the temperature of the freezer is increased and held steady through Step C and Step D. As shown in FIG. 2, during the Primary Drying Stage, the temperature of the metal shelf increases to this second temperature and is maintained at this temperature throughout steps C and D of the Primary Drying Stage. The greater temperature of the shelf during Step D allows the ice crystals to begin to sublime and escape the semi-stoppered glass container. However, voids may be created during this process, as depicted in Step D. These voids can occur as part of an uneven cooling rate due to the design of the glass container. Once the ice crystals have sublimed, as depicted in Step E, voids may be present throughout the remaining solids of the biological product. In the last part of the Primary Drying Stage, the temperature of the freezer and the metal shelf may be increased while maintaining the vacuum, and the voids remain, even through the Secondary Drying Stage, as depicted in Step F.

[0040] During the Secondary Drying Stage, desorption of water from the solids in the glass container occurs. Although the biological product appears to be dry, there may be remaining moisture content of absorbed water in the solids. The Secondary Drying isnormally continued at a high vacuum and at an elevated temperature greater than ambient temperature but compatible with the temperature sensitivity of the product (e.g., less than a temperature at which one or more constituents of the biological product degrades). In embodiments, the freezer may be operated to maintain the temperature of the biological product at less than or equal to -25° C. In embodiments, the temperature of the biological product may be maintained at less than or equal to -25 °C, less than -40 °C, or even less than -80 °C. Once the desorption of water is complete, the biological product may be returned to atmospheric pressure and the glass container may be fully stoppered, as depicted in Step G. However, as depicted in FIG. 2, the voids created during the dehydration of the biological product remain.

[0041] As shown in FIG. 2, the voids in the solid biological products may be a result of non-homogeneous crystallization during the uneven cooling process. To illustrate one aspect of this problem, a conventional glass vial will be examined and its crystallization pattern depicted.

[0042] Referring now to FIG. 3, a pharmaceutical container is schematically depicted in cross-section. The pharmaceutical container may be a glass vial 200. The glass vial 200 comprises a sidewall 203 having an inner surface 208 and an outer surface 201. The inner surface may enclose an internal volume 204. In the embodiment shown in FIG. 3, the glass vial 200 also comprises a bottom portion 202 that comprises an inner bottom surface 207 and an outer bottom surface 206. The glass vial 200 also generally has a sidewall thickness, ts, and a bottom thickness, tn. The sidewall thickness extends between the outer surface 201 and the inner surface 208 of the sidewall 203. The bottom thickness extends between the inner bottom surface 207 and the outer bottom surface 206. In a conventional glass vial, such as the glass vial 200 depicted in FIG. 3, the sidewall thickness ts and the bottom thicknesses tn may be very similar or equal, such as within 10% or even 5% of each other. In other conventional glass vials, the bottom thickness may be 60% to 70% of the thickness of the sidewall, depending upon the size of the glass vial. The sidewall 203 transitions into the bottom portion 202 through a heel portion 209. While FIG. 3 depicts a pharmaceutical glass container that is glass vial 200, it should be understood that the pharmaceutical glass container may have other form factors, including, without limitation, vacutainers, cartridges, syringes, syringe barrels, ampoules, bottles, flasks, phials, tubes, beakers, or the like.

[0043] Now referring to FIG. 4, a crystallization pattern 219 of the conventional glass vial 200 is schematically depicted in cross-section. When the freezing stage Steps A and B of lyophilization method 100 depicted in FIG. 2 occur in conventional glass vials, such as the glass vial 200, the uneven cooling rate created by the overall design of the glass vial 200 creates concentration gradients within the vial contents. Because bottom thickness is similar or equal to the thickness of the sidewalls, as mentioned hereinabove, the cooling rate from the bottom is more rapid due to conduction from the metal supporting shelf through the bottom of the vial. This creates a bias towards the nucleation and crystallization starting from the bottom and moving vertically upward (e.g., in the +Z direction of the coordinate axis in FIG. 4).

[0044] For instance, line 210 represents the first moment in time during the freezing stage of Step A to Step B. Line 210 represents the first bio-product crystallization pattern, which continues to move upward to line 211, and line 212. As time continues to progress, the crystallization pattern 219 continues to move upward to line 213. At this point in time, a concentration gradient is forming unevenly within the glass vial 200. Gradients in the composition contained within the glass vial 200 along with the associated buildup of mechanical forces within the sidewalls of the glass vial can result in failures. For example, the crystallization pattern 219 creates larger crystals at the bottom, which exhibit greater expansion during freezing, which then exerts greater stress on the sidewall of the glass vial 200. By the time the crystallization reaches lines 214, 215, and 216, the stresses on the sidewall of the glass vial 200 caused by the greater expansion during freezing may be enough to cause breakage of the glass vial 200.

[0045] Accordingly, a need exists for pharmaceutical vials that provide more consistent and even heat transfer through the sidewalls and bottom of the pharmaceutical vials. Glass vials having thicker bottoms may provide thermal management during biological storage processes, such as but not limited to freezing or the lyophilization process previously discussed herein. The increased thickness may provide an increased barrier to thermal conduction at the bottom, which may create a bias toward nucleation and crystallization from the sidewalls of the glass vials instead of from the bottom. The increased thickness of the bottom of the glass vial may also lower the center of mass of the vial, among other features.

[0046] The present application is directed to glass vials having a bottom with an increased thickness compared to conventional glass vials. Due to the thermal insulating properties of glass, the greater thickness of the bottom of the glass vials slows down the heat transfer rate through the bottom so that the heat transfer rate through the bottom of the glass vial is the same as or less than the heat transfer rate through the sidewalls of the glass vial. This in turn provides for more even cooling of the contents of the glass vial, which results in formation of smaller crystals during crystallization and reduces concentration gradients throughout the composition.

[0047] The glass vials 300 disclosed herein may be formed from a variety of different glass compositions. The specific glass composition of the glass vials 300 may be selected according to the specific application such that the glass has a desired set of physical properties. In embodiments, the glass of the glass vial 300 may be a glass composition that is known to exhibit chemical durability and low thermal expansion, such as but not limited to alkali borosilicate glasses. In embodiments, the glass composition of the glass vial 300 may be a silicate glass, an aluminosilicate glass, an alkali aluminosilicate glass, an ion- exchanged aluminosilicate glass, an ion-exchanged alkali aluminosilicate glass, a borosilicate glass, an ion-exchanged borosilicate glass, a soda lime glass, or combinations of these. In embodiments, the glass vial 300 may comprise a glass composition that meets the criteria for pharmaceutical glasses described in United States Pharmacopoeia (USP) <600> or European Pharmacopoeia 7. According to embodiments, the glass vial 300 may be formed from a Type I, Class B glass, which is defined according to ASTM Standard E438-92.

[0048] In one particularly exemplary embodiment, the glass vials 300 may be formed from an ion-exchangeable glass composition described in U.S. Patent No. 8,980,777, granted on March 17, 2015, and entitled “Glass Compositions with Improved Chemical and Mechanical Durability,” which is assigned to Coming, Incorporated. However, it should be understood that the glass vials 300 described herein may be formed from other glass compositions including, without limitation, ion-exchangeable glass compositions and non-ion exchangeable glass compositions. For example, in embodiments, the glass vials 300 may be formed from a borosilicate glass. In embodiments, the glass vials 300 may be formed from Type IB glass compositions such as, for example, Schott Type IB borosilicate glass. In embodiments, the glass vial 300 may be formed from ion-exchangeable borosilicate glass composition, such as those described in co-pending U.S. Application No. 16 / 533,954, filed August 7, 2019 and entitled “Ion Exchangeable Borosilicate Glass Compositions and Glass Articles Formed from the Same,” which is assigned to Coming Incorporated.

[0049] In embodiments described herein, the glass vials 300 may be formed from a glass composition which meets the criteria for pharmaceutical glasses described by regulatory agencies such as the USP (United States Pharmacopoeia), the EP (European Pharmacopeia), and / or the JP (Japanese Pharmacopeia) based on their hydrolytic resistance. Per USP <660> and EP 7, borosilicate glasses meet the Type I criteria and are routinely used for parenteral packaging. Examples of borosilicate glass include, but are not limited to, Coming® Pyrex® 7740, 7800 and Wheaton 180, 200, and 400, Schott Duran, Schott Fiolax, KIMAX® N-51A, Gerrescheimer GX®-51, Flint, and others. Soda-lime glass meets the Type III criteria and is acceptable in packaging of dry powders which are subsequently dissolved to make solutions or buffers. Type III glasses are also suitable for packaging liquid formulations that prove to be insensitive to alkali. Examples of Type III soda lime glass include Wheaton 800 and 900. De-alkalized soda-lime glasses have higher levels of sodium hydroxide and calcium oxide and meet the Type II criteria. These glasses are less resistant to leaching than Type I glasses but more resistant than Type III glasses. Type II glasses can be used for products that remain below a pH of 7 for their shelf life. Examples include ammonium sulfate treated soda lime glasses.

[0050] The glass containers of the present disclosure, such as but not limited to the glass vial 300 in FIG. 1, have the bottom portion 302 that has a bottom thickness tn that is greater than the bottom thickness tn of conventional glass vials, such as the glass vials 200 of FIG. 3. The bottom thickness tn of the glass containers may be sufficient to reduce the heat transfer rate through the bottom of the glass containers so that the heat transfer rate through the bottom portion 302 is similar to the heat transfer rate through the sidewall 303. In embodiments, the glass containers may comprise a bottom thickness (tn) that is greater than or equal to 1.2 times the sidewall thickness (ts). This ratio results in a thicker vial bottom having an increased barrier to thermal conduction, thereby changing the thermal management during processes such as lyophilization and freezing. Specifically, the crystallization fronts may proceed from the vial inside surfaces toward the center of the vial contents.

[0051] In embodiments, the sidewall thickness ts may be from about 0.20 mm to about 1.6 mm. In embodiments, the sidewall thickness ts may be greaterthan or equal to 0.2 mm, greater than or equal to 0.3 mm, greater than or equal to 0.4 mm, greater than or equal to 0.5 mm, or even greater than or equal to 0.6 mm. In embodiments, the sidewall thickness ts may be less than or equal to 1.60 mm, less than or equal to 1.50 mm, less than or equal to 1.40 mm, or even less than or equal to 1.30 mm. In embodiments, the sidewall thickness ts may be greater than or equal to 0.2 mm and less than or equal to 1 .60 mm, greater than or equal to 0.2 mm and less than or equal to 1.50 mm, greater than or equal to 0.2 mm and less than or equal to 1.40 mm, greater than or equal to 0.2 mm and less than or equal to 1.30 mm, greater than or equal to 0.3 mm and less than or equal to 1.60 mm, greater than or equal to 0.3 mm and less than or equal to 1.50 mm, greater than or equal to 0.3 mm and less than or equal to 1.40 mm, greater than or equal to 0.3 mm and less than or equal to 1.30 mm, greater than or equal to 0.40 mm and less than or equal to 1.60 mm, greater than or equal to 0.40 mm and less than or equal to 1.50 mm, greater than or equal to 0.40 mm and less than or equal to 1.40 mm, greater than or equal to 0.40 mm and less than or equal to 1.30 mm, greater than or equal to 0.50 mm and less than or equal to 1.60 mm, greater than or equal to 0.50 mm and less than or equal to 150 mm, greater than or equal to 0.50 mm and less than or equal to 1.40 mm, greater than or equal to 0.50 mm and less than or equal to 1.30 mm, greater than or equal to 0.60 mm and less than or equal to 1.60 mm, greater than or equal to 0.60 mm and less than or equal to 1 .50 mm, greater than or equal to 0.60 mm and less than or equal to 1.40 mm, greater than or equal to 0.60 mm and less than or equal to 1.30 mm, or any and all end points formed by these sub ranges.

[0052] In embodiments, the ratio of the bottom thickness (tn) to the sidewall thickness (ts) (i.e., tn / ts) may be greater than or equal to 1.2, greater than or equal to 1.3, greater than or equal to 1 .4, or even greater than or equal to 1.5. In embodiments, the ratio of the bottom thickness (tn) to the sidewall thickness (ts) may be less than or equal to 20, less than or equal to 15, less than or equal 10, or even less than or equal to 5. In embodiments, the ratio of the bottom thickness (tn) to the sidewall thickness (ts) may be from greater than or equal to 1.2 to less than or equal to 20, from greater than or equal to 1.3 to less than or equal to 20, from greater than or equal to 1.5 to less than or equal to 20, from greater than or equal to 2.0 to less than or equal to 20, from greater than or equal to 1 .2 to less than or equal to 15, from greater than or equal to 1.3 to less than or equal to 15, from greater than or equal to 1 .5 to less than or equal to 15, from greater than or equal to 2.0 toless than or equal to 15, from greater than or equal to 1.2 to less than or equal to 10, from greater than or equal to 1.3 to less than or equal to 10, from greater than or equal to 1.5 to less than or equal to 10, from greater than or equal to 2.0 to less than or equal to 10, from greater than or equal to 1.2 to less than or equal to 5, from greater than or equal to 1.3 to less than or equal to 5, from greater than or equal to 1.5 to less than or equal to 5, from greater than or equal to 2.0 to less than or equal to 5, or any and all end points formed by these sub ranges.

[0053] In embodiments, the glass vial may have a concave bottom surface such that the air or other gas between the bottom and the metal shelf can slow down the heat transfer rate even further during lyophilization.

[0054] The thicker bottom of the glass vials 300 may be formed during the converting process for producing the glass vials 300 from glass tubes. The settings on the converting machine may be modified to increase the volume of glass forming the bottom of the glass vial, thereby increasing the thickness of the bottom of the glass vials 300.

[0055] Referring now to FIG. 5, a crystallization pattern 319 of the glass vial 300 is schematically depicted in cross-section. When the lyophilization method 100 depicted in FIG. 2 occurs in a glass containers such as the glass vial 300, a preferential freezing is observed in the crystallization pattern 319. As used herein, the term “preferential freezing” means that the crystallization pattern 319 of the biological product occurs in a uniform manner, allowing crystals to form at a similar rate. Thus, instead of starting from the bottom, as in FIG. 4, the freezing begins on the sidewalls, such as with line 310, and moves inward instead of upward. For example, after freezing along line 310, the crystallization will occur further inward at lines 311, 312, 313, 314, 315, and all the way to the fill-line, 316. As a result of the preferential freezing, the forces exhibited through the freezing process result in reduced stresses on the walls and bottom of the glass vial, yielding a glass vial with more integrity and less chance for breakage.

[0056] Additionally, the increased bottom thickness may lower the elevation of the center of mass of the glass container as compared to a glass container of standard bottom thickness. The elevation of the center of mass of the glass container refers to the distance between the center of mass and the bottom most surface of the glass container in a direction parallel to a center axis of the glass container (i.e., in a direction parallel to the + / -Zdirection of the coordinate axis in FIG. 1). In embodiments, glass containers with increased bottom thickness may have a center of mass closer to the outer bottom surface 306 of the glass container 300 of FIG. 1 compared to glass containers with standard bottom thickness. In embodiments, glass containers with increased bottom thickness may have a center of mass from 15 mm to 25 mm from the outer bottom surface. The center of mass may decrease in elevation in a direction parallel to a center axis of the glass container (e.g., move the center of mass of the glass vial 300 downward in the -Z direction of the coordinate axis in FIG. 1), thereby reducing the potential for vial tip-overs during filling operations.

[0057] The lowered center of mass may be particularly beneficial for thin wall vials which may have a generally higher elevation of the center of mass due to the decrease in the amount of glass in the sidewall with the same volume of glass in the flange. In embodiments, the glass vials 300 may have an elevation of the center of mass that is less than 95% of the elevation of the center of mass of a glass vial with a standard bottom thickness. In embodiments, the glass vials 300 may have an elevation of the center of mass that is less than 95%, less than 94%, less than 92%, less than 90%, less than 88%, less than 86%, less than 84%, less than 82%, or even less than 80% of the elevation of the center of mass of a vial with a standard bottom thickness. It should be understood that the center of mass of a glass vial as described herein is a glass vial that is not filled and has no contents.

[0058] The thickened bottom of the glass vials 300 may increase a tipping angle of the glass vials 300. The glass vials 300 may have a tipping angle sufficient to reduce the probability of the glass vial 300 falling over in response to application of a force to the flange or sidewall. In embodiments, the glass vials 300 having a thickened bottom may have a tipping angle greater than a vial with a standard bottom thickness. In embodiments, the glass vials 300 having a thickened bottom may have a tipping angle that is at least 5 %, at least 10%, or even at least 15% greater than the tipping angle of a glass vial having a standard bottom thickness.EXAMPLES

[0059] The embodiments described herein 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.

[0060] Comparative Example 1: Glass vials with standard bottom thickness

[0061] Comparative Example 1 was a conventional glass vial having a standard bottom thickness. The conventional glass vial of Comparative Example 1 was a 3 mL vial having a nominal diameter of 16.75 mm. The elevation of the center of mass of the conventional glass vial of Comparative Example 1 is provided in Table 1 and in FIG. 6.

[0062] Examples 2 and 3: Glass vials with thickened bottom portions

[0063] Example 2 was a glass vial having a larger bottom thickness than the conventional glass vial of Comparative Example 1. The glass vial of comparative Example 2 was a 3 mL vial having a diameter of 16.75 mm with an additional 0.5 mm added to the bottom thickness. The elevation of the center of mass of the glass vial of Example 2 is provided in Table 1 and in FIG. 6.

[0064] Example 3 was also a glass vial having a larger bottom thickness than the conventional glass vial of Comparative Example 1. The glass vial of comparative Example 3 was a 3 mL vial having a diameter of 16.75 mm with an additional 1 mm added to the bottom thickness. The elevation of the center of mass of the glass vial of Example 3 is provided in Table 1 and in FIG. 6.

[0065] Table 1: Center of Mass Elevation for Comparative Example 1 and Examples 2 and 3Center of Mass Elevation (mm)2521 20 18.52019

[0066] Table 1 illustrates Comparative Example 1 (CE1) with Examples #2 and #3 (E2 and E3), which show the center of mass elevation change for various example vials as a function of wall thickness. CE1 represents a 3 ml, 16.75 mm vial. E2 has 0.5 mm added to the bottom thickness of CE1, and E3 has 1.0 mm added to the bottom thickness of CE1.E2 and E3 illustrate the effect of increased bottom thickness on decreasing the center of mass elevation. FIG. 6 represents a graphical depiction of Table 1. FIG. 6 shows the center of mass elevation (y-axis) as a function of wall thickness.

[0067] It will be apparent to those skilled in the art that various modifications and variations can be made without departing from the spirit or scope of the claimed subject matter. Accordingly, the claimed subject matter is not to be restricted except in light of the attached claims and their equivalents.

Claims

CLAIMSWhat is claimed is:

1. A glass container comprising: a body having at least a sidewall and a bottom portion; the sidewall having a sidewall thickness ts extending between an outer surface and an inner surface of the sidewall; and the bottom having a bottom thickness tu extending between an outer bottom surface and an inner bottom surface, wherein tu is at least greater than or equal to 1.2 times greater than ts.

2. The glass container of claim 1 , wherein the glass container has a center of mass, wherein the center of mass is from 15 mm to 25 mm from the outer bottom surface in a direction parallel to a center axis of the glass container.

3. The glass container of claim 1, wherein tn is from 0.25 mm to 1.25 mm.

4. The glass container of claim 1, wherein a ratio of the bottom thickness tn to the sidewall thickness ts is from 1.2 to 20.

5. The glass container of claim 1, wherein the body further comprises: a shoulder; a neck extending from the shoulder; and a flange extending from the neck, the flange comprising: an underside surface extending from the neck; an external surface extending from the underside surface, the external surface defining an outer diameter of the flange.

6. A pharmaceutical product comprising the glass container of claim 1, a pharmaceutical composition contained with the glass container, and a closure coupled to the glass container, wherein the closure seals the pharmaceutical composition within the glass container.

7. A method for storing a pharmaceutical composition at low temperature, the method comprising: filling the pharmaceutical composition into the glass container of claim 1; sealing the glass container comprising the pharmaceutical composition; and reducing the temperature of an environment of the glass container.

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