The present specification generally relates to container closure systems, such as glass containers for storing pharmaceutical compositions.
Pharmaceutical containers, such as vials and syringes, are typically sealed via a stopper or other closure to preserve the integrity of the contained material. Closures are typically made of synthetic rubbers and other elastomers. Such materials beneficially have high permeation resistance and elasticity to facilitate insertion into the container to seal the container's interior. The elasticity of typically-used closure materials, however, may reduce at low temperatures. For example, synthetic rubbers currently in use as material closures may comprise transition temperatures that are greater than or equal to −70° C. and less than or equal to −30° C. Below the transition temperature, closures constructed of such synthetic rubbers may behave as a solid and be unable to expand elastically to compensate for the relatively large difference between coefficients of thermal expansion of the glass and a crimping cap used to secure the closure to the container. Given this, existing sealing assemblies for pharmaceutical containers may fail at temperatures less than or equal to −30° C.
Some biological materials (e.g., blood, serum, proteins, stem cells, and other perishable biological fluids) require storage at temperatures below the glass transition temperatures of conventional elastomers to remain useful. For example, certain RNA-based vaccines may require storage at dry-ice temperatures (e.g., approximately −80° C.) or liquid nitrogen temperatures (e.g., approximately −180° C.) to remain active. Such low temperatures may result in dimensional changes in the closure components (e.g., the glass or polymer container, the stopper, an aluminium cap), leading to issues in the integrity of the seal, and potential contamination of the material stored therein.
A first aspect of the present disclosure includes a sealed pharmaceutical container comprises a shoulder, a neck extending from the shoulder, and a flange extending from the neck. The flange comprises an underside surface extending from the neck, an outer surface extending from the underside surface, the outer surface defining an outer diameter of the flange, and a contact surface extending between the outer surface and an inner surface defining an opening in the sealed pharmaceutical container. The contact surface comprises an inner edge disposed proximate to the opening and an outer peripheral edge disposed proximate to the outer surface of the flange. The sealed pharmaceutical container comprises a sealing assembly comprising a stopper extending over the contact surface of the flange and covering the opening, and a cap securing the stopper to the flange. The stopper comprises a sealing surface that is secured in contact with the contact surface of the flange to form a seal between the flange and the stopper. An outer peripheral edge of the sealing surface is disposed at or radially inward of the outer peripheral edge of the contact surface of the flange.
A second aspect of the present disclosure includes the sealed pharmaceutical container of according to the first aspect, wherein the contact surface comprises a conical region of an upper surface of the flange.
A third aspect of the present disclosure includes the sealed pharmaceutical container of according to any of the first through the second aspects, wherein the contact surface comprises a surface roughness of less than or equal to 0.2 μm
A fourth aspect of the present disclosure includes the sealed pharmaceutical container of according to any of the first through the third aspects, wherein the contact surface is free of surface height variations greater than or equal to 5.0 μm.
A fifth aspect of the present disclosure includes the sealed pharmaceutical container of according to any of the first through the fourth aspects, wherein the flange further comprises a fillet extending between the contact surface and the outer surface.
A sixth aspect of the present disclosure includes the sealed pharmaceutical container of according to any of the first through the fifth aspects, wherein the fillet comprises a radius of curvature that is less than or equal to 21% of a length of the contact surface of the flange.
A seventh aspect of the present disclosure includes the sealed pharmaceutical container of according to any of the first through the sixth aspects, wherein the outer peripheral edge of the sealing surface is disposed radially inward of a transition between the upper sealing surface and the fillet.
A eighth aspect of the present disclosure includes the sealed pharmaceutical container of according to any of the first through the seventh aspects, wherein the flange further comprises a chamfer extending between the contact surface and the outer surface at an angle relative to the contact surface.
A ninth aspect of the present disclosure includes the sealed pharmaceutical container of according to any of the first through the eighth aspects, wherein the angle is less than or equal to 30°.
A tenth aspect of the present disclosure includes the sealed pharmaceutical container of according to any of the first through the ninth aspects, wherein the outer peripheral edge of the sealing surface is disposed radially inward of a transition between the upper sealing surface and the chamfer.
An eleventh aspect of the present disclosure includes the sealed pharmaceutical container of according to any of the first through the tenth aspects, wherein the upper sealing surface extends at a flange angle relative to a plane extending through an end of the opening.
A twelfth aspect of the present disclosure includes the sealed pharmaceutical container of according to any of the first through the eleventh aspects, wherein the flange angle is greater than or equal to 5°.
A thirteenth aspect of the present disclosure includes the sealed pharmaceutical container of according to any of the first through the twelfth aspects, wherein the flange angle is less than or equal to 30°.
A fourteenth aspect of the present disclosure includes the sealed pharmaceutical container of according to any of the first through the thirteenth aspects, wherein: the cap comprises a metallic portion crimped around the underside surface of the flange and a plastic portion retaining an upper portion the metallic portion on an upper surface of the stopper, and an inner edge of the metallic portion is inserted into the plastic portion such that the upper portion extends at a cap angle relative to the plane extending through the end of the opening.
A fifteenth aspect of the present disclosure includes the sealed pharmaceutical container of according to any of the first through the fourteenth aspects, wherein the flange angle is within one degree of the cap angle.
A sixteenth aspect of the present disclosure includes the sealed pharmaceutical container of according to any of the first through the fifteenth aspects, wherein the stopper is compressed by the cap to provide a residual nominal strain of less than or equal to 8%.
A seventeenth aspect of the present disclosure includes the sealed pharmaceutical container of according to any of the first through the sixteenth aspects, wherein the sealing assembly maintains the helium leakage rate of the sealed pharmaceutical container of less than or equal to 1.4×10−6 cm3/s as the sealed pharmaceutical container is cooled to a temperature of less than or equal to −80° C.
An eighteenth aspect of the present disclosure includes the sealed pharmaceutical container of according to any of the first through the seventeenth aspects, wherein the sealing surface maintains a contact area of greater than or equal to 10% of a total surface area of the contact surface as the sealed pharmaceutical container is cooled to a temperature of less than or equal to −80° C.
A nineteenth aspect of the present disclosure includes a sealed pharmaceutical container comprising a shoulder; a neck extending from the shoulder; and a flange extending from the neck, The flange comprises an underside surface extending from the neck; an outer surface extending from the underside surface, the outer surface defining an outer diameter of the flange; and an upper surface extending between the outer surface and an inner surface defining an opening in the sealed pharmaceutical container. The upper surface comprises a conical region extending between the opening and the outer surface, wherein the conical region is free of surface height deviations of greater than or equal to 5 μm; and a transition region extending between the conical region and the outer surface. The sealed pharmaceutical container comprises a sealing assembly comprising: a stopper covering the opening; and cap crimped to the underside surface of the flange so as to compress a sealing surface of the stopper against the conical region such that an outer peripheral edge of the sealing surface contacts the conical region.
A twentieth aspect of the present disclosure includes a sealed pharmaceutical container according to the nineteenth aspect, wherein the contact surface comprises a Ra value of less than or equal 5 nm.
A twenty first aspect of the present disclosure includes a sealed pharmaceutical container according to any of the nineteenth through the twentieth aspects, wherein the sealing surface maintains a contact area of greater than or equal to 10% of a total surface area of the upper surface as the sealed pharmaceutical container is cooled to a temperature of less than or equal to −80° C.
A twenty second aspect of the present disclosure includes a sealed pharmaceutical container according to any of the nineteenth through the twenty first aspects, wherein the transition region comprises a fillet having a radius of curvature that is less than or equal to 21% of a width of the conical section.
A twenty third aspect of the present disclosure includes a sealed pharmaceutical container according to any of the nineteenth through the twenty second aspects, wherein the radius of curvature is less than or equal to 0.5 mm.
A twenty fourth aspect of the present disclosure includes a sealed pharmaceutical container according to any of the nineteenth through the twenty third aspects, wherein the transition region comprises a chamfer extending at an angle relative to the conical region.
A twenty fifth aspect of the present disclosure includes a sealed pharmaceutical container according to any of the nineteenth through the twenty fourth aspects, wherein the angle is less than or equal to 30°.
A twenty sixth aspect of the present disclosure includes a sealed pharmaceutical container according to any of the nineteenth through the twenty fifth aspects, wherein the conical portion extends at a flange angle relative to a plane extending through an end of the opening that is greater than or equal to 5°.
A twenty seventh aspect of the present disclosure includes a sealed pharmaceutical container according to any of the nineteenth through the twenty sixth aspects, wherein the flange angle is less than or equal to 30°.
A twenty eighth aspect of the present disclosure includes a sealed pharmaceutical container according to any of the nineteenth through the twenty seventh aspects, wherein: the cap comprises a metallic portion crimped around the underside surface of the flange and a plastic portion retaining an upper portion the metallic portion on an upper surface of the stopper, and an inner edge of the metallic portion is inserted into the plastic portion such that the upper portion extends at a cap angle relative to the plane extending through the end of the opening.
A twenty ninth aspect of the present disclosure includes a sealed pharmaceutical container according to any of the nineteenth through the twenty eighth aspects, wherein the flange angle is within one degree of the cap angle.
A thirtieth aspect of the present disclosure includes a sealed pharmaceutical container according to any of the nineteenth through the twenty ninth aspects, wherein the stopper is compressed by the cap to provide a residual nominal strain of less than or equal to 8%.
A thirty first aspect of the present disclosure includes a sealed pharmaceutical container according to any of the nineteenth through the thirtieth aspects, wherein the sealing assembly maintains the helium leakage rate of the sealed pharmaceutical container of less than or equal to 1.4×10−6 cm3/s as the sealed pharmaceutical container is cooled to a temperature of less than or equal to −80° C.
A thirty second aspect of the present disclosure includes a sealed pharmaceutical container according to any of the nineteenth through the thirty first aspects, wherein the sealing surface maintains a contact area of greater than or equal to 20 mm2 with the contact surface as the sealed pharmaceutical container is cooled to a temperature of less than or equal to −80° C.
A thirty third aspect of the present disclosure includes a method of sealing a sealed pharmaceutical container, the method comprising the steps of: providing a sealed pharmaceutical container comprising 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 outer surface extending from the underside surface, the outer surface defining an outer diameter of the flange; and an upper surface extending between the outer surface to an inner surface of the sealed pharmaceutical container that defines an opening, the upper surface comprising a conical region; inserting a pharmaceutical composition into the sealed pharmaceutical container; providing a sealing assembly comprising a stopper extending over the upper surface of the flange and covering the opening; crimping a metal-containing cap over the stopper and against flange to thereby compress the stopper against the upper surface such that an outer peripheral edge of a sealing surface of the stopper contacts the conical region; and cooling the sealed pharmaceutical container to a temperature of less than or equal to −45° C., wherein, after the cooling of the sealed pharmaceutical container, the compression is maintained on the sealing surface such that a helium leakage rate of the sealed pharmaceutical container is less than or equal to 1.4×10−6 cm3/s at the temperature.
A thirty fourth aspect of the present disclosure includes a method according to the thirty third aspect, wherein the metal-containing cap is crimped such that the stopper is compressed against the upper surface to provide a residual nominal strain of less than or equal to 8%.
A thirty fifth aspect of the present disclosure includes a method according to any of the thirty third to the thirty fourth aspects, wherein a contact area between the sealing surface of the stopper and the upper surface of the flange is greater than or equal to 10% of a total surface area of the upper surface when the sealed pharmaceutical container is cooled to the temperature.
A thirty sixth aspect of the present disclosure includes a method according to any of the thirty third to the thirty fifth aspects, wherein the temperature is less than or equal to −80° C.
A thirty seventh aspect of the present disclosure includes a method according to any of the thirty third through the thirty sixth aspects, wherein the temperature is less than or equal to −180° C.
A thirty eighth aspect of the present disclosure includes a method according to any of the thirty third through the thirty seventh aspects, wherein: the upper surface further comprises a transition region extending between the conical region and the outer surface of the flange, and the outer peripheral edge of the sealing surface does not contact the transition region as a result of the compression of the stopper.
A thirty ninth aspect of the present disclosure includes a method according to any of the thirty third through the thirty eighth aspects, wherein the transition region comprises a fillet having a radius of curvature of less than 1.0 mm.
A fortieth aspect of the present disclosure includes a method according to any of the thirty third through the thirty ninth aspects, wherein the radius of curvature is less than or equal to 0.5 mm.
A forty first aspect of the present disclosure includes a method according to any of the thirty third through the fortieth aspects, wherein the transition region comprises a chamfer extending at an angle of less than or equal to 30° relative to the conical region.
A forty second aspect of the present disclosure includes a method according to any of the thirty third through the forty first aspects, wherein the conical region extends at a flange angle relative to a plane extending through an end of the opening that is greater than or equal to 5°.
A forty third aspect of the present disclosure includes a method according to any of the thirty third through the forty second aspects, wherein: the metal-containing cap comprises a metallic portion crimped around the underside surface of the flange and a plastic portion retaining an upper portion the metallic portion on an upper surface of the stopper, and an inner edge of the metallic portion is inserted into the plastic portion such that the upper portion extends at a cap angle relative to the plane extending through the end of the opening.
A forty fourth aspect of the present disclosure includes a method according to any of the thirty third through the forty third aspects, wherein the flange angle is within one degree of the cap angle.
A forty fifth aspect of the present disclosure includes a method according to any of the thirty third through the forty fourth aspects, wherein the sealed pharmaceutical container is cooled to the temperature at a rate of less than or equal to 3° C. per minute.
A forty sixth aspect of the present disclosure includes a glass container comprising: 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 outer surface extending from the underside surface, the outer surface defining an outer diameter of the flange; and an upper surface extending between the outer surface and an inner surface defining an opening in the glass container, wherein the upper surface comprises: a conical region extending between the opening and the outer surface, wherein the conical region is free of surface height deviations of greater than or equal to 5 μm; and a transition region extending between the conical region and the outer surface, wherein at least one of: the transition region comprises a chamfer extending at a chamfer angle relative to the upper surface that is less than or equal to 30° or a fillet comprising a fillet radius rf that is less than or equal to 0.8 mm, and the conical region extends at a flange angle relative to a plane extending through an end of the opening that is greater than or equal to 5°.
A forty seventh aspect includes the glass container according to the forty sixth aspect, wherein: the transition region comprises the chamfer, and the chamfer angle is less than or equal to 10°.
A forty eighth aspect of the present disclosure includes a glass container according to any of the forty sixth through the forty seventh aspects, wherein: the transition region comprises the fillet, and the fillet radius is less than or equal to 21% of a width of the conical section.
A forty ninth aspect of the present disclosure includes a glass container according to any of the forty sixth through the forty eighth aspects, wherein: the conical region extends at the flange angle relative to the plane, and the angle is greater than or equal to 5° and less than or equal to 20°.
The embodiments set forth in the drawings are illustrative and exemplary in nature and not intended to limit the subject matter defined by the claims. The following detailed description of the illustrative embodiments can be understood when read in conjunction with the following drawings, where like structure is indicated with like reference numerals and in which:
Reference will now be made in detail to embodiments of sealed pharmaceutical containers comprising sealing assemblies that maintain container closure integrity at relatively low storage temperatures (e.g., less than or equal to −30° C., less than or equal to −40° C., less than or equal to −50° C., less than or equal to −60° C., less than or equal to −70° C., less than or equal to −80° C., less than or equal to −100° C., less than or equal to −125° C., less than or equal to −150° C., less than or equal to −175° C., −180° C.). To facilitate maintenance of container closure integrity at such low storage temperatures, the sealed glass containers described herein may include a flange that is designed such that, when a crimping process is used to compress a sealing surface of a stopper against an upper surface of the flange, an outer peripheral edge of the sealing surface contacts the upper surface. The upper surface of the flange may comprise a relatively low surface roughness (e.g., comprise an Ra value of less than or equal to 5 nm) and be free of surface height variations and defects to facilitate seal formation with the stopper. In embodiments, the outer peripheral edge of the sealing surface may be disposed at or radially inward of an outer peripheral edge of the upper surface of the flange to ensure a continuous contact area between the stopper and the flange starting at the outer peripheral edge of the sealing surface. In embodiments, such positioning of the outer peripheral edge of the sealing surface in contact with the upper surface beneficially maintains a contact area between the stopper and upper surface at greater than or equal to 10% of a total surface area of the upper surface at such low storage temperatures, thereby lessening the probability of seal breakage as compared to existing glass containers. Without wishing to be bound by theory, it is believed that such placement of the outer peripheral edge of the sealing surface of the stopper facilitates more uniform compression of the stopper via capping by avoiding a concentration of compression at the outer diameter of the stopper.
Various structural modifications to existing pharmaceutical glass containers may be made to achieve the beneficial relative positioning between the outer peripheral edges of the stopper sealing surface and upper surface of the flange described herein. For example, when an outer diameter of the flange is fixed at a standard, commonly used diameter (e.g., 13 mm, 20 mm), such relative positioning may be achieved by fabricating glass containers such that a radial extent of a transition region between the upper surface of the flange and an outer surface of the flange is diminished as compared to existing pharmaceutical glass containers. In embodiments, the radial extent of the transition region is diminished by limiting a radius of curvature of a fillet extending between upper and outer surfaces of the flange to less than one-third (e.g., less than or equal to 21%) of a width of the upper surface (e.g., less than or equal to 0.8 mm, less than or equal to 0.7 mm, less than or equal to 0.6 mm, less than or equal to 0.5 mm, less than or equal to 0.4 mm, less than or equal to 0.3 mm, less than or equal to 0.2 mm). In embodiments, the radial extent of the transition region is diminished by maintaining a chamfer angle of a chamfer extending between the upper and outer surfaces to less than or equal to 30° (e.g., less than or equal to 25°, less than or equal to 20°, less than or equal to 15°, less than or equal 10°, less than or equal to 5°). In embodiments, when the outer dimeter of the flange is fixed at a standard, commonly used value, the relative positioning between the outer peripheral edges of the stopper sealing surface and the upper surface of the flange may be obtained by increasing a flange angle at which the upper surface extends relative to a plane extending through an end of an opening of the glass container over existing pharmaceutical glass containers. In embodiments, the upper surface of the flange may extend at a flange angle that is greater than or equal to 5° (e.g., 6°, 7°, 8°, 9°, 10°, 11°, 12, 13°, 14°, 15°, 16°, 17°, 18°, 19°, 20°, and any values lying between such flange angles). Such increased flange angles increase the surface area of the upper surface, thereby facilitating placement of the outer peripheral edge of the sealing surface of the stopper radially inward of the transition region between the upper surface and the outer surface.
The pharmaceutical glass containers described herein may further be beneficial over existing pharmaceutical glass containers in that they are capable of maintaining seals at low storage temperatures with lower amounts of stopper compression during crimping processes. Existing pharmaceutical containers may be sealed with crimping processes resulting in residual seal forces at the upper surfaces of the flange that are greater than 20 lbf (e.g., greater than or equal to 25 lbf, resulting in compression of the stopper that is greater than 10% and less than or equal to 20%). The improved seals provided by the pharmaceutical glass containers described herein may be capable of maintaining container closure integrity at lower residual forces (e.g., resulting in the stopper having a residual nominal strain of less than or equal to 8% after crimping). Such a reduction in residual seal force may facilitate use of more simple and efficient crimping processes, thereby lowering production costs.
As used herein, the term “surface roughness” refers to an Ra value or an Sa value. An Ra value is a measure of the arithmetic average value of a filtered roughness profile determined from deviations from a centerline of the filtered roughness. For example, an Ra value may be determined based on the relation:
where Hi is a surface height measurement of the surface and HCL corresponds to a centerline (e.g., the center between maximum and minimum surface height values) surface height measurement among the data points of the filtered profile. An Sa value may be determined through a real extrapolation of equation 1 herein. Filter values (e.g., cutoff wavelengths) for determining the Ra or Sa values described herein may be found in ISO ISO 25718 (2012). Surface height may be measured with a variety of tools, such as an optical interferometer, stylus-based profilometer, or laser confocal microscope. To assess the roughness of surfaces described herein (e.g., sealing surfaces or portions thereof), measurement regions should be used that are as large as is practical, to assess variability that may occur over large spatial scales.
As used herein, the term “container closure integrity” refers to maintenance of a seal at an interface between a glass container and a sealing assembly (e.g., between a sealing surface of a glass container and a stopper) that is free of gaps above a threshold size to maintain a probability of contaminant ingress or reduce the possibility of gas permeability below a predetermined threshold based on the material stored in a glass container. For example, in embodiments, a container closure integrity is maintained if a helium leakage rate during a helium leak test described in USP <1207> (2016) at less than or equal to 1.4×10−6 cm3/s.
As used herein, the term “about” means that amounts, sizes, formulations, parameters, and other quantities and characteristics are not and need not be exact, but may be approximate and/or larger or smaller, as desired, reflecting tolerances, conversion factors, rounding off, measurement error and the like, and other factors known to those of skill in the art. When the term “about” is used in describing a value or an end-point of a range, the specific value or end-point referred to is included. Whether or not a numerical value or end-point of a range in the specification recites “about,” two embodiments are described: one modified by “about,” and one not modified by “about.” 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.
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.
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.
Referring now to
In embodiments, the glass container 102 may be formed from Type I, Type II or Type III glass as defined in USP <660>, including borosilicate glass compositions such as Type 1B borosilicate glass compositions under USP <660>. Alternatively, the glass container 102 may be formed from alkali aluminosilicate glass compositions such as those disclosed in U.S. Pat. No. 8,551,898, hereby incorporated by reference in its entirety, or alkaline earth aluminosilicate glasses such as those described in U.S. Pat. No. 9,145,329, hereby incorporated by reference in its entirety. In embodiments, the glass container 102 may include a coating such as a heat tolerant coating disclosed in U.S. Pat. No. 10,0273,049, hereby incorporated by reference in its entirety. In embodiments, the glass container 102 may be constructed from a soda lime glass composition. In embodiments, the glass container 102 is constructed of a glass composition having a coefficient of thermal expansion that is greater than or equal to 0×10−7/K and less than or equal to 100×10−7/K (e.g., greater than or equal to 30×10−7/K and less than or equal to 70×10−7/K).
While the glass container 102 is depicted in
The wall thickness Tw of the glass container 102 may vary depending on the implementation. In embodiments, the wall thickness Tw of the glass container 102 may be from less than or equal to 6 millimetres (mm), such as less than or equal to 4 mm, less than or equal to 2 mm, less than or equal to 1.5 mm or less than or equal to 1 mm. In some embodiments, the wall thickness Tw may be greater than or equal to 0.1 mm and less than or equal to 6 mm, greater than or equal to 0.3 mm and less than or equal to 4 mm, greater than or equal to 0.5 mm and less than or equal to 4 mm, greater than or equal to 0.5 mm and less than or equal to 2 mm, or greater than or equal to 0.5 mm and less than or equal to 1.5 mm. In embodiments, the wall thickness Tw may be greater than or equal to 0.9 mm and less than or equal to 1.8 mm. The wall thickness Tw may vary depending on the axial location within the glass container 102.
As depicted in
In embodiments, the flange 126 further comprises a transition region 144 extending between the upper surface 138 and the outer surface 136. In embodiments, within the transition region 144, the outer surface 116 of the glass container 102 deviates from the conical surface followed by the upper surface 138 and a second surface (e.g., cylindrical surface) followed by the outer surface 136. The transition region 144 may take a variety of forms depending on the implementation. In embodiments, the transition region 144 comprises a corner such that the outer surface 116 directly transitions from the upper surface 138 to the outer surface 136. In embodiments, the transition region 144 comprises a chamfer extending at a chamfer angle from the upper surface 138. In embodiments, the transition region 144 comprises a fillet comprising a radius of curvature (rf). As will be described in greater detail herein, the relative positioning of the transition region 144 and a sealing surface of a stopper (e.g., the stopper 106 described herein) is an important factor to ensure that the sealed pharmaceutical container 100 maintains closure integrity at relatively low storage temperatures.
In embodiments, each cross-section of the upper surface 138 of the flange 126 extends at a flange angle α relative to a plane 146 extending through an end of the opening 105 of the glass container 102. In embodiments, the plane 146 contacts (e.g., lies on top of) a most distant portion of the glass container 102 from the floor portion 122 along the axis A. In embodiments, the most distant portion comprises the inner edge 140 of the upper surface 138 of the flange 126. In embodiments, the plane 146 extends perpendicular to the axis A. As described in greater detail herein, the greater the flange angle α, the greater the surface area of the upper surface 108, which renders the transition region 144 more distant from the inner edge 140 along the upper sealing surface 146. As described in greater detail herein, such distance between the transition region 144 and the inner edge 140 may beneficially ensure an outer peripheral edge of a sealing surface of a stopper is disposed radially inward of the transition region 144, which may ensure maintenance of container closure integrity at relatively low storage temperatures. In embodiments, the flange angle α may vary between −2° and 30° depending on the implementation.
Referring still to
The cap assembly 108 is depicted to include a metallic portion 148 and a plastic portion 150. The metallic portion 148 is crimped around the underside surface 132 of the flange 126 such that an underlying portion 152 thereof contacts the underside surface 132. In embodiments, the length of the underlying portion 152 of the metallic portion 148 that directly contacts the underside surface 132 of the flange 126 possesses a length (e.g., in the X-direction depicted in
In embodiments, during the crimping process, the stopper 106 is inserted into the opening 105 and a compression force is applied to the metallic portion 148 during crimping. Compression of the stopper 106 generates a residual sealing force within the flange 126 that maintains compression on the stopper 106 after the metallic portion 148 is crimped into place. In embodiments, the residual seal force may vary from 5 lbf to 25 lbf and result in nominal stopper strains between 5% and 19%.
In embodiments, various aspects of the glass container 102 and cap assembly 108 have been designed to maintain container closure integrity at relatively low storage temperatures. As depicted in
In embodiments, the glass container 102 is shaped such that, when the stopper 106 is compressed against the upper surface 138 of the flange 126 via the cap assembly 108, the outer peripheral edge 164 of the sealing surface 121 lies at or radially inward (e.g., with respect to the axis A) of the transition region 144 extending between the upper surface 138 and the outer surface 136 of the flange 126. That is, after the sealing portion 119 is compressed between the upper portion 158 and the upper surface 138, the outer peripheral edge 164 (e.g., the portion of the sealing surface 121 that is disposed most radially outward from the axis A) is disposed at or radially inward of the transition region 144. In embodiments, the glass container 102 is shaped such that, when the stopper 106 is compressed against the upper surface 138 of the flange 126 via the cap assembly 108, the outer peripheral edge 164 of the sealing surface is in contact with the upper surface 138 of the flange 126. In embodiments, no portion of the sealing surface 121 contacts the transition region 144. Without wishing to be bound by theory, it is believed that keeping the sealing surface 121 from contacting the transition region 144 prevents deformation of the sealing portion 119 that may reduce a contact area between the sealing surface 121 and the upper surface 138 of the flange 126.
While maintaining the outer peripheral edge 164 at or radially inward of the transition region 144 may be achieved by reducing the radial extent of the stopper 106 (e.g., making the stopper 106 smaller), such an alteration to the stopper 106 would detrimentally reduce a contact area between the upper surface 138 and the stopper 106, reducing the quality of the seal. As such, by eliminating the need to modify the shape of the stopper 106, the structures of the glass container 102 described herein beneficially maximize a contact area between the stopper 106 and the upper surface 138. Moreover, the glass containers described herein are compatible with existing capping processes, eliminating the need to alter existing production lines. Various structural aspects of the flange 126 will now be described in greater detail.
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In view of the foregoing description, it should be understood that sealed glass containers capable of maintaining container closure integrity at storage temperatures of less than or equal to −70° C. are disclosed. Improved seals may be achieved entirely through modification of the structure of flanges of the glass containers without adjusting current capping processes. Flange angles, fillet radii, and chamfer angles of glass pharmaceutical containers meeting the requirements described herein beneficially facilitate an outer peripheral edge of a sealing surface of a stopper associated with a standard capping process contacting upper surfaces of the flanges. Such upper surfaces may be free of surface defects to facilitate continuous contact with the sealing surface of the stopper and improved seal quality.
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.
It will be apparent to those skilled in the art that various modifications and variations can be made to the embodiments described herein without departing from the spirit and scope of the claimed subject matter. Thus, it is intended that the specification cover the modifications and variations of the various embodiments described herein provided such modification and variations come within the scope of the appended claims and their equivalents.
This application claims the benefit of priority under 35 U.S.C. § 119 of U.S. Provisional Application Ser. No. 63/179,719 filed on Apr. 26, 2021, the content of which is relied upon and incorporated herein by reference in its entirety.
Number | Date | Country | |
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63179719 | Apr 2021 | US |