Amber glass container for pharmaceuticals and method for manufacturing the same

Abstract

The present invention provides a colored amber glass container that has a function to block UV light so that the drug does not change due to light irradiation. [Solution] The present invention relates to a pharmaceutical amber glass container having a transmittance of 25% or less over the entire wavelength range of 290 nm to 450 nm when measured at a thickness of 1.0 mm, and a transmittance of 45% or more over the entire wavelength range of 590 nm to 610 nm when measured at a thickness of 1.0 mm, a method for manufacturing the pharmaceutical amber glass container, and the use of the pharmaceutical amber container for storing a pharmaceutical composition or cosmetic composition or a drug, preferably an antibody drug conjugate.

Description

[Technical Field]

[0001] The present invention relates to a pharmaceutical amber glass container having a transmittance of 25% or less across the entire wavelength range of 290 nm to 450 nm when measured at a thickness of 1.0 mm, and a transmittance of 45% or more across the entire wavelength range of 590 nm to 610 nm when measured at a thickness of 1.0 mm, a method for manufacturing the pharmaceutical amber glass container, and the use of the pharmaceutical amber container for storing pharmaceutical compositions, cosmetics, or drugs, preferably antibody drug conjugates.

[0002] Conventional technology Both pharmaceuticals and chemicals are often supplied in the form of solutions, suspensions, or emulsions and must be stored in containers. Orally administered drugs offer relatively greater flexibility in terms of storage and storage containers, but injectable drugs are often administered directly into the patient's bloodstream, and therefore the containers must be of significantly higher quality. In many cases, glass containers, especially borosilicate glass containers, are used and must meet specific properties in terms of physical and chemical resistance, as well as strength and glass composition requirements while also meeting specified limits.

[0003] Furthermore, in recent years, rapid advances in pharmacology have led to the creation of a wide variety of new drugs, and the number of extremely expensive drugs and substances that are highly unstable to UV light and require UV protection, such as anticancer drugs, has increased.

[0004] In many cases, colored glass containers, such as amber glass containers, that block UV light to prevent the drugs contained within from being altered by light exposure are used to store the above-mentioned substances. However, it is also important that the containers used for bottling and storage, as well as the compounds stored in the bottles, such as drugs, are at least partially transparent to visible light, allowing for visual inspection. These requirements are governed by different legal requirements in several countries. For example, in the United States and Europe, the requirements for containers are particularly governed by the United States Pharmacopeia (USP) <660> These requirements are set forth in the European Pharmacopoeia (EP3.2.1) and the European Pharmacopoeia. In Japan, these requirements are specified in "JP7.01". However, the requirements described in these documents are not consistent and sometimes conflict. Therefore, commercially available amber glass containers for pharmaceuticals are manufactured primarily in the European market, the US market, or the Japanese market.

[0005] Therefore, there is a sustained demand for improved amber glass containers for pharmaceuticals. In particular, it is desirable to provide pharmaceutical glass containers that have a predetermined transmittance in the visible region, while on the one hand blocking UV light, and on the other hand, allowing visual inspection of the container's empty and filled states. In particular, it is desirable that such containers meet the requirements for UV blocking and transmittance in the visible region according to the most important standards, especially those relevant to the United States, Europe, and Japan.

[0006] In this context, it is particularly desirable that already known glass types and colorant systems approved in the pharmaceutical field be used. Furthermore, it is desirable that these pharmaceutical glass containers meet additional requirements in terms of physical and chemical resistance and comply with relevant standards for such containers. Moreover, it is desirable that these containers can be manufactured using already known machinery without significant modifications or costly acquisitions.

[0007] Disclosure of the invention The above and other objects are achieved by the subject matter specified herein in each independent claim.

[0008] According to one aspect of the present invention, there is provided a method for producing an amber glass container for pharmaceuticals, the method comprising the following steps, that is, a) a step of providing an amber glass tube, and b) a step of hot forming the amber glass tube into an amber glass container, and c) a step of heating the amber glass container at a temperature of Tg+5°C to Tg+50°C, and d) a step of cooling the amber glass container heated in step c) to a temperature of Tg-60°C to Tg-10°C at a rate of 0.8°C / s to 4°C / s per 1.0 mm of wall thickness of the amber glass container, to obtain the amber glass container for pharmaceuticals There is provided a method for producing an amber glass container for pharmaceuticals, comprising the above steps.

[0009] In another aspect of the present invention, there is provided an amber glass container for pharmaceuticals, wherein the amber glass has a transmittance of 25% or less over the entire wavelength region of 290 nm to 450 nm when measured at a thickness of 1.0 mm, and has a transmittance of 45% or more over the entire wavelength region of 590 nm to 610 nm when measured at a thickness of 1.0 mm.

[0010] According to another aspect of the present invention, the amber glass container for pharmaceuticals according to the present invention is used for storing pharmaceutical compositions, cosmetic compositions or medicaments, preferably for storing antibody-drug conjugates.

[0011] According to another embodiment of the present invention, Fe₂O₃ and TiO₂ are used in borosilicate glass as a temperature-dependent colorant system, wherein the Fe₂O₃ and the TiO₂ are used in a ratio of 1:3.00 to 1:5.00, preferably 1:3.50 to 1:4.50, more preferably 1:3.80 to 1:4.00, based on the weight of the oxides.

[0012] The present inventors have surprisingly found that the method of the present invention makes it possible to produce an amber glass container for pharmaceuticals that satisfies the requirements for UV blocking properties and transmittance in the visible region according to the most important standards, namely USP <660>, E.P. 3.2.1, and JP7.01. More precisely, by the method of the present invention, it is possible to provide an amber glass container for pharmaceuticals that has a transmittance of 25% or less over the entire wavelength range of 290 nm to 450 nm when measured at a thickness of 1.0 mm to provide UV blocking properties, and has a transmittance of 45% or more over the entire wavelength range of 590 nm to 610 nm when measured at a thickness of 1.0 mm so as to be suitable for visual inspection. One of the advantages of the method of the present invention is that known amber glass tubes having a known colorant system, i.e., a colorant system of Fe₂O₃ and TiO₂, can be used. The present inventors have found in particular that Fe₂O₃ and TiO₂ can be used as a temperature-dependent colorant system, particularly in borosilicate glass in the above ratio. Accordingly, known glass types and known colorant systems, which are already approved in the pharmaceutical field, can be used in the method of the present invention for producing the pharmaceutical glass container of the present invention.

[0013] Furthermore, according to the method of the present invention, known amber glass tubes can be used, and there is no need to provide special machines or equipment, so that known and already available equipment can be used. Therefore, the present inventors have found that the above method is easy and economical, since existing apparatuses can be used on a large scale and only a small amount of conversion agent is required. Furthermore, the time required for preparing the pharmaceutical glass container of the present invention is practically not affected.

[0014] Furthermore, the inventors have surprisingly found that the method according to the present invention avoids negative effects on the physical and chemical resistance of the pharmaceutical glass containers according to the present invention, thereby ensuring that these containers meet relevant standards. In particular, the above method ensures that the most important standard, namely USP, is met. <660> This allows for the production of amber glass containers for pharmaceuticals that meet the requirements for UV blocking and transmission in the visible region according to EP.3.2.1 and JP7.01, and are sufficiently stable for use in the pharmaceutical field. In particular, the resulting amber glass containers for pharmaceuticals have a ring tension of 1 Friedel grade or less, making them suitable for use in the pharmaceutical field.

[0015] Advantageous embodiments of the present invention are provided in the corresponding dependent claims.

[0016] According to one embodiment, the heating step c) is carried out at a temperature of Tg+8°C to Tg+45°C, preferably Tg+10°C to Tg+35°C, and most preferably Tg+12°C to Tg+30°C.

[0017] According to another embodiment, the heating step c) is performed for 5 to 500 seconds, more preferably 10 to 300 seconds, and even more preferably 12 to 100 seconds.

[0018] According to another embodiment, cooling step d) is performed by cooling the amber glass container heated in step i) c) to a temperature of Tg-50°C to Tg-15°C, preferably Tg-40°C to Tg-20°C, and / or by cooling the amber glass container heated in step c) at a rate of 0.9°C / s to 3°C / s per 1.0 mm wall thickness of the amber glass container, preferably 1.0°C / s to 2.5°C / s, most preferably 1.0°C / s to 2.0°C / s.

[0019] According to another embodiment, the amber glass tube prepared in step a) has a transmittance of 15.0% or less, preferably 14.5% or less, over the entire wavelength range of 290 nm to 450 nm when measured at a thickness of 1.0 mm, and a transmittance of 50.0% or more, preferably 52.5% or more, over the entire wavelength range of 590 nm to 610 nm when measured at a thickness of 1 mm.

[0020] According to another embodiment, the amber glass tube prepared in step a) is a borosilicate glass tube, preferably an amber borosilicate glass tube containing Fe2O3 and TiO2 in the glass composition, most preferably the amber glass tube contains 60-85% by weight of SiO2, 5-20% by weight of B2O3, 1-10% by weight of Al2O3, 0.25-2% by weight of Fe2O3, 0.5-10% by weight of TiO2, 2-10% by weight of Na2O, 0-5% by weight of K2O, 0-2% by weight of BaO, and 0-2% by weight of CaO, based on all oxides present in the glass composition.

[0021] According to another embodiment, the amber glass container for pharmaceuticals according to the present invention is i) Hydrolysis resistance characterized by having an extractable Na2O equivalent in micrograms [μg / g] per gram of glass, determined according to ISO719:2020-09, of 62 μg / g or less, preferably 31 μg / g or less, and / or ii) A neck squeeze test load of at least 1100N, preferably at least 1500N, more preferably at least 2000N, and most preferably at least 3000N, and / or iii) Ring tension of less than 5 Friedel grades, preferably less than 4 Friedel grades, more preferably less than 3 Friedel grades, more preferably less than 2 Friedel grades, and / or less than 1 Friedel grade. iv) A burst pressure of 20-80 bar, preferably 30-70 bar, most preferably 40-60 bar, and / or v) Axial load pressure of 1500~6000N, preferably 2000~5000N, most preferably 2500~4000N, It holds.

[0022] According to another embodiment, the glass of the amber glass container for pharmaceuticals has a glass composition comprising, based on all oxides present in the glass composition, 60-85% by weight of SiO2, 5-20% by weight of B2O3, 1-10% by weight of Al2O3, 0.25-2% by weight of Fe2O3, 0.5-10% by weight of TiO2, 2-10% by weight of Na2O, 0-5% by weight of K2O, 0-2% by weight of BaO, and 0-2% by weight of CaO.

[0023] In another embodiment, the amber glass container for pharmaceuticals is a vial, preferably a 2R, 4R, 6R, 10R, 15R, or 20R vial according to ISO 8362-1:2018, or preferably a 0.5 ml, 1.1 ml, 2 ml, 2.25 ml, 3 ml, or 5 ml syringe according to ISO 11040-4:2024, or a cartridge according to ISO 13926-1:22, having the same dimensions as those specified in ISO 13926-1:2020-02 except for its length and diameter, and of 5 ml, 7.3 ml, 10 ml, or 20 ml.

[0024] In another embodiment, the amber glass container for pharmaceuticals is i) A 2R or 4R vial in accordance with ISO8362-1:2018, which has a transmittance of 15% or less across the entire wavelength range of 290nm to 450nm when measured at a thickness of 1.0mm, and a transmittance of 45% or more across the entire wavelength range of 590nm to 610nm when measured at a thickness of 1.0mm, or ii) A 6R or 8R vial in accordance with ISO8362-1:2018, which has a transmittance of 13% or less across the entire wavelength range of 290nm to 450nm when measured at a thickness of 1.0mm, and a transmittance of 45% or more across the entire wavelength range of 590nm to 610nm when measured at a thickness of 1.0mm, or iii) A 10R or 15R vial in accordance with ISO8362-1:2018, which has a transmittance of 12% or less across the entire wavelength range of 290nm to 450nm when measured at a thickness of 1.0mm, and a transmittance of 45% or more across the entire wavelength range of 590nm to 610nm when measured at a thickness of 1.0mm, or iv) A 20R vial in accordance with ISO8362-1:2018, wherein, except when the wall thickness s1 of the vial is 1.0 mm, it has a transmittance of 10% or less over the entire wavelength range of 290 nm to 450 nm when measured at a thickness of 1.0 mm, and a transmittance of 45% or more over the entire wavelength range of 590 nm to 610 nm when measured at a thickness of 1.0 mm. It holds.

[0025] According to another embodiment, the amber glass container for pharmaceuticals includes a coating on at least a portion of the surface of the container, preferably on the inner surface of the container, and preferably the coating has as an important component: i) A compound comprising the elements Si, C, O, and H, and further elements, wherein the further elements are present in a content of less than 10 atomic percent, The compound is composed of SiO x -C y H z Including, here, x is in the range of 0.6 to 0.9. y is in the range of 1.2 to 3.3, and z is in the range of 0.0 to 6.0, or ii) SiO2 It is a hydrophobic coating containing [a specific substance].

[0026] For the purposes of this invention, the following terms should be understood to have the following meanings.

[0027] In the context of this invention, "amber glass container for pharmaceuticals" refers to a glass container for pharmaceuticals having an amber color. In the context of this invention, amber color generally refers to a color spectrum found in the range of yellow-orange-brown-red. The color here can be defined by the CIE 1931 color space, which represents a color impression based on a combination of three values: x, y, and z (chromaticity coordinates). According to this invention, the color is determined similarly to DIN 5033, using a light source "C" at 6770K for a CIE standard observer within a 2° arc of the fovea (a 2° standard observer in CIE 1931). In short, the standard spectral values ​​of X, Y, and Z are obtained from a table of the CIE 1931 color space system, and each tristimulus value is obtained by multiplying these values ​​by the measured transmittance value. The color coordinates x, y, and z that define the color position in the color space are obtained by normalizing the sum x + y + z to equal 1. Therefore, the x, y, and z values ​​are positive, and their sum is x + y + z = 1. The CIE 1931 color space chromaticity diagram represents the color space, where the x-axis points to x values ​​and the y-axis points to y values. The z value can be inferred from any given pair of x and y values ​​by calculating z = 1 - xy. The point x = y = z = 1 / 3 represents the so-called "white point" that defines the color "white". High x values ​​represent reddish colors. High y values ​​represent greenish colors. High z values ​​represent bluish colors. Each chromaticity is expressed as a specific color position in the color space. Additive color mixing has color positions on a straight line connecting each component. To accurately characterize the specification of a color stimulus, the tristimulus value Y is used as a luminance reference value (DIN 5033, Part 1) by dividing the sum of all y values ​​by the ratio (= 21.293658). The resulting value is then normalized to a maximum value of 100. These values ​​indicate whether the glass is brighter or darker to the human eye compared to a comparison probe. The x, y, and z values ​​are positive values, and their sum is x + y + z = 1. The CIE1931 color space chromaticity diagram represents the color space, where the x-axis points to x values ​​and the y-axis points to y values. The z value can be inferred from any given pair of x and y values ​​by calculating z = 1 - xy. The point x = y = z = 1 / 3 represents the so-called "white point," which defines the color "white." Higher x values ​​represent reddish colors.A high y value represents a greenish color. A high z value represents a bluish color. According to the present invention, amber refers to x values ​​of 0.4140 to 0.4240 and y values ​​of 0.4065 to 0.4120 in the CIE1931 color space for a sample thickness of 1 mm.

[0028] In the sense of the present invention, "pharmaceutical glass container" means a glass container that can be used to bottle and store pharmaceuticals and cosmetic substances, preferably liquids such as solutions, suspensions, and emulsions. According to a preferred embodiment of the present invention, the pharmaceutical glass container is a vial, syringe, or cartridge.

[0029] In the sense of the present invention, a vial is a closable container that can be closed or sealed, for example, by crimping. In the sense of the present invention, a cartridge is a closable container that can be closed or sealed at two ends, for example, by crimping one end and inserting a piston or valve into the other end. In the sense of the present invention, a syringe is a tube having a nozzle that can be used with a piston or valve to draw in and dispense liquid, and may be fitted with a hollow needle for injecting or withdrawing liquid.

[0030] If the disclosure refers to the length of any element, the width of any element, or the height of any element, for example, the length l of a glass tube a , the inner diameter d of the glass tube i and outer diameter d o Furthermore, when referring to the wall thickness WT of a glass tube, it should be understood that, in terms of Cartesian coordinates, length always refers to the maximum extension in the x-direction, width always refers to the maximum extension in the y-direction, and height always refers to the maximum extension in the z-direction, where the x, y, and z directions are oriented orthogonally to each other. Measurements of length, width, or height can be made, for example, by a microscope or lightbox containing a linear scale with a calibrated size scale.

[0031] The "thickness" or "wall thickness" of an amber glass container or pharmaceutical amber glass container refers to the thickness of the glass of the amber glass container or pharmaceutical amber glass container as measured on the body of the container, for example, the body of the vial, syringe, or cartridge. Specifically, the thickness refers to the value s1 specified in ISO 8362-1:2018 or ISO 11040-4:2024 (for vials or syringes) or the value (d1-d2) / 2 specified in ISO 13926-1:2020-02 (for cartridges).

[0032] The term "ultraviolet radiation" or "UV light" is often abbreviated as "UV" or "UV light," and is known as electromagnetic radiation that is shorter than visible light and longer than X-rays. UV radiation is present in natural sunlight and accounts for about 10% of the total electromagnetic radiation emitted from the sun. Typically, the UV spectrum refers to various wavelength regions such as UV-A, UV-B, UV-C, or NUV, MUV, and FUV. When the UV spectrum is referred to below, unless otherwise specified, it refers to the wavelength region of 290 nm to 450 nm.

[0033] In the context of this invention, "transmittance" refers to the transmittance in the wavelength regions of 290-450 nm and 590-610 nm, which can be measured using a spectrophotometer.

[0034] In the context of this invention, the term "coating" refers to a material layer applied at least partially to the surface of a pharmaceutical amber glass container. This material layer can be applied in various forms, such as liquid, gas, or solid, and can be used for multiple purposes, such as protection, decoration, or functional enhancement, such as improving scratch resistance, reducing friction, or improving chemical and physical stability.

[0035] In the context of this invention, "liquid" refers to a substance that is a fluid at room temperature and can flow freely. In the context of this invention, "solid" refers to a substance that is neither a liquid nor a substrate at room temperature and has a defined shape and volume. Room temperature is defined as a temperature of 20°C under atmospheric pressure of 101325 Pa (1013.25 hPa).

[0036] In the context of this invention, the term "normal conditions" refers to room temperature of 20°C (293.15K, 68°F) and absolute atmospheric pressure of 1 atm (14.696 psi, 101.325 kPa).

[0037] Where the term “comprising” is used in this specification and in the claims, it does not exclude other elements. With respect to the object of the present invention, the term “consisting of” should be understood as a preferred embodiment of the term “comprising of.” Hereinafter, where a group is defined as comprising at least a certain number of embodiments, it should be understood that a group comprising only those embodiments is also disclosed.

[0038] When an indefinite or definite article is used with a singular noun, such as "a," "an," or "the," it also includes the plural form of that noun unless otherwise specified.

[0039] Terms such as “obtainable” or “definable” and terms such as “obtained” or “definable” are used interchangeably. This does not mean, for example, that the term “obtained” must be obtained by a series of steps described by the term “obtained,” unless the context clearly indicates otherwise; however, such a limited understanding is always included in the terms “obtained” or “definable” as a preferred embodiment.

[0040] Detailed explanation The present invention provides a method for manufacturing amber glass containers for pharmaceuticals. This method comprises the following steps: a) The process of preparing an amber glass tube, b) A process of hot-forming an amber glass tube into an amber glass container, c) A step of heating the amber glass container to a temperature of Tg+5°C to Tg+50°C, d) The amber glass container heated in step c) is cooled to a temperature of Tg-60°C to Tg-10°C at a rate of 0.8°C / s to 4°C / s per 1.0 mm of wall thickness of the amber glass container, thereby obtaining a pharmaceutical amber glass container. This includes the following. Details of the method and preferred embodiments of the present invention are described in more detail below. It should be understood that these technical details and embodiments also apply to the pharmaceutical amber glass container according to the present invention, and to the use of the pharmaceutical amber glass container according to the present invention for storing pharmaceutical or cosmetic compositions or medicines. Furthermore, these technical details and embodiments also apply to the use of Fe2O3 and TiO2 in borosilicate glass as temperature-dependent colorant systems according to the present invention.

[0041] Preferred embodiments of the present invention are illustrated and described in more detail below. Here, the same reference numerals indicate the same or similar components or elements. [Brief explanation of the drawing]

[0042] [Figure 1] This is a schematic diagram showing a vial with a wall thickness s1. [Figure 2] This is a schematic diagram showing a syringe with a wall thickness s1. [Figure 3] This is a schematic diagram showing a cartridge having a wall thickness defined by an outer diameter d1 and an inner diameter d2.

[0043] Method for manufacturing amber glass containers for pharmaceuticals According to one aspect of the present invention, there is provided a method for producing an amber glass container for pharmaceuticals, the method comprising the following steps, that is, a) a step of providing an amber glass tube, and b) a step of hot forming the amber glass tube into an amber glass container, and c) a step of heating the amber glass container at a temperature of Tg+5°C to Tg+50°C, and d) a step of cooling the amber glass container heated in step c) to a temperature of Tg-60°C to Tg-10°C at a rate of 0.8°C / s to 4°C / s per 1.0 mm of wall thickness of the amber glass container, to obtain the amber glass container for pharmaceuticals There is provided a method including the above steps.

[0044] Method Step a) According to method step a), an amber glass tube is provided. The amber glass tube is a tube made of glass having an amber color. The amber glass tube needs to be suitable for the pharmaceutical field, and therefore needs to have sufficiently high quality, particularly with respect to composition, dimensions, and appearance of defects. Such glass tubes are often produced by the Danner tube process or the Vello drawing process. A person skilled in the art is well aware of how to select such glass tubes according to the pharmaceutical containers to be produced by the method of the present invention. Such amber glass tubes are known to those skilled in the art, and are commercially available, for example, from SCHOTT under the trade name FIOLAX (registered trademark) amber.

[0045] The amber glass tube provided in step a) may be characterized by an inner diameter d i , an outer diameter d o , a wall thickness WT, and a length l along its longitudinal axis a .

[0046] According to one embodiment, the glass tube may have an outer diameter of 5 mm to 55 mm, preferably 8 mm to 40 mm, more preferably 9 mm to 35 mm, even more preferably 10 mm to 30 mm, most preferably 11 mm to 25 mm, for example, the glass tube may have an outer diameter d of 16 mm, 22 mm, or 24 mmo It may have.

[0047] Additionally or alternatively, the glass tube has an inner diameter d of 3mm to 53mm, preferably 6mm to 38mm, more preferably 7mm to 33mm, even more preferably 8mm to 28mm, and most preferably 9mm to 23mm. i It may have an inner diameter of 14 mm, 20 mm, or 22 mm, for example, the glass tube i It may have.

[0048] Additionally or alternatively, the glass tube may have a wall thickness WT of 0.4 mm to 2.5 mm, preferably 0.8 mm to 2.0 mm, more preferably 0.9 mm to 1.5 mm, and most preferably 1.0 mm.

[0049] Additionally or alternatively, the glass tube may have a length of 500-3500 mm, preferably 800-3000 mm, most preferably 1200-2000 mm. a It may have.

[0050] According to a preferred embodiment of the present invention, the glass tube has an outer diameter of 5 mm to 55 mm, an inner diameter of 3 mm to 53 mm, and a length of 500 mm to 3500 mm. a It may have an outer diameter of 5 mm to 55 mm, an inner diameter of 3 mm to 53 mm, and a length of 500 mm to 3500 mm. a The wall thickness WT can be 0.4 mm to 2.5 mm, most preferably 1.0 mm.

[0051] According to an exemplary embodiment, the glass tube has an outer diameter d of 16 mm to 30 mm. o , inner diameter d 14mm~28mm i , 1500mm in length a It may also have a wall thickness WT of 1.0 mm.

[0052] Those skilled in the art are familiar with how to measure the outer diameter, inner diameter, wall thickness, and length of glass tubes, and select the appropriate measuring device depending on the type and size of the object to be measured, and further depending on the object and the precision to which the tolerance must be determined. Such measuring devices are commercially available and include, for example, micrometers, calipers or two-point probe heads, or optical measuring devices, such as digital measuring projectors. Digital measuring projectors are available from companies such as Keyence.

[0053] Additionally or alternatively, the amber glass tube prepared in step a) has a transmittance of 18.0% or less, preferably 15.0% or less, and most preferably 14.5% or less, over the entire wavelength range of 290 nm to 450 nm when measured at a thickness of 1.0 mm. Additionally or alternatively, the amber glass tube prepared in step a) has a transmittance of at least 10.0%, preferably at least 12.0%, and most preferably at least 13.0%, over the entire wavelength range of 290 nm to 450 nm when measured at a thickness of 1.0 mm. According to a preferred embodiment, the amber glass tube prepared in step a) has a transmittance of 10.0% to 18.0% over the entire wavelength range of 290 nm to 450 nm when measured at a thickness of 1.0 mm, preferably 12.0% to 15.0%, and most preferably 13.0% to 14.5%.

[0054] Additionally or alternatively, the amber glass tube prepared in step a) has a transmittance of 45.0% or more, preferably 50.0% or more, and most preferably 52.5% or more, across the entire wavelength range of 590 nm to 610 nm when measured at a thickness of 1 mm. Additionally or alternatively, the amber glass tube prepared in step a) has a transmittance of less than 65.0%, preferably less than 60.0%, and most preferably less than 55.0%, across the entire wavelength range of 590 nm to 610 nm when measured at a thickness of 1 mm. According to a preferred embodiment, the amber glass tube prepared in step a) has a transmittance of 45.0% to 65.0%, preferably 50.0% to 60.0%, and most preferably 52.5% to 55.0%, across the entire wavelength range of 590 nm to 610 nm when measured at a thickness of 1.0 mm.

[0055] According to a preferred embodiment of the present invention, the amber glass tube prepared in step a) has a transmittance of 10.0% to 18.0%, preferably 12.0% to 15.0%, and most preferably 13.0% to 14.5%, over the entire wavelength range of 290 nm to 450 nm when measured at a thickness of 1.0 mm, and a transmittance of 45.0% to 65.0%, preferably 50.0% to 60.0%, and most preferably 52.5% to 55.0%, over the entire wavelength range of 590 nm to 610 nm when measured at a thickness of 1.0 mm.

[0056] According to another preferred embodiment of the present invention, the amber glass tube prepared in step a) has a temperature of 3.0 to 8.0 * 10 when measured in the range of 20°C to 300°C (CTE). -6 K -1 , or 3.5~7.0*10 -6 K -1 Or 4.0~6.0*10 -6 K -1 It has an average linear thermal expansion coefficient of . According to a preferred embodiment, the CTE is 5.2*10 -6 K -1 ~5.6*10 -6 K -1It is beneficial for amber glass tubes to have a CTE within the above range, because such glass tends to experience less stress during hot forming, resulting in a more uniform product. CTE can be measured according to DIN ISO 7991:1987.

[0057] According to another preferred embodiment of the present invention, the amber glass tube prepared in step a) has a Tg of 300 to 750°C, preferably 400 to 700°C, more preferably 500 to 600°C, and most preferably 520 to 570°C. In the sense of the present invention, Tg is also known as the transition temperature of glass and is defined in ISO 7884-8:1987.

[0058] Additionally or alternatively, the amber glass tube prepared in step a) is an amber borosilicate glass tube, an amber-colored aluminoborosilicate glass tube, an amber-colored aluminosilicate glass tube, or an amber-colored lithium aluminosilicate (LAS) glass tube. According to a preferred embodiment, the amber glass tube prepared in step a) is an amber-colored borosilicate glass tube.

[0059] Preferably, the amber glass tube has a glass composition containing the following components: [Table 1]

[0060] Where "glass composition" is mentioned, it should be understood as the composition of glass oxides obtained after melting a batch of glass raw materials and allowing the molten material to solidify to obtain glass tubes. This means that volatile components are in a gaseous state, and metals and metalloids are present in the glass composition as oxides and / or fluorides and / or chlorides. In other words, "glass composition" is the combination of oxides and / or fluorides and / or chlorides that can be obtained by melting glass tubes. Where "weight %" is mentioned in this context, it should be understood as a weight percentage based on the total weight of the glass composition, unless otherwise specified.

[0061] In this specification, when referring to a glass composition that is substantially free of components, or a glass composition that does not contain a particular component, or a glass composition in which such particular component is theoretically 0% by weight, it should be understood that the component may be present at most as an impurity. This means that it is not added in a significant amount, and is not added intentionally. The term "component" refers not only to elemental species but also to any molecule containing an element. A non-substantial amount should be understood as an amount less than 100 ppm, preferably less than 50 ppm, and most preferably less than 10 ppm, based on the weight percentage of all intentionally added components.

[0062] When "ppm" is mentioned in the context of solids or liquids, it should be understood as "weight / weight (w / w)". When "ppm" is mentioned in the context of gases, it should be understood as "vol / vol (vol / vol)".

[0063] SiO2 is a relevant network-forming agent that can be used in the glass composition. The glass may contain at least 60% by weight of SiO2. More preferably, the glass contains at least 62% by weight, at least 65% by weight, at least 68% by weight, more than 70% by weight, or even more than 75% by weight of SiO2. However, the SiO2 content in the glass should not be extremely high, as this may impair its meltability. The amount of SiO2 in the glass can be limited to a maximum of 85% by weight, or a maximum of 82% by weight. In embodiments, the SiO2 content in the glass is from 60% by weight to 85% by weight, or more than 65% by weight and 75% by weight or less.

[0064] B2O3 can be used to enhance the network by increasing the cross-linking oxides in the glass via the [BO4] tetrahedral morphology. B2O3 also helps improve the glass's damage resistance. However, B2O3 should not be used in large quantities in glass because it can reduce ion exchange performance. Furthermore, the addition of B2O3 can significantly reduce Young's modulus. Glass may contain 0-20% by weight, preferably 2.0-15% by weight, and more preferably 5.0-10% by weight of B2O3.

[0065] P2O5 can be used in the glass of the present invention to help reduce the melt viscosity by forming [PO4] tetrahedra, thereby significantly lowering the melting point without sacrificing anticrystallization properties. Limited amounts of P2O5 do not significantly increase geometric variation, but can significantly improve the melting, moldability, and ion exchange (chemical strengthening) properties of the glass. However, if large amounts of P2O5 are used, the degree of geometric expansion during chemical strengthening can increase significantly. Therefore, the glass may contain 0-4% by weight of P2O5 or 0-2% by weight of P2O5. In some embodiments, the glass does not contain P2O5.

[0066] Al2O3 is thought to readily form tetrahedral coordination when the alkali oxide content is greater than or equal to the Al2O3 content. [AlO4]tetrahedral coordination, along with [SiO4]tetrahedra, can help construct a more compact network, resulting in less geometric variation in the glass. [AlO4]tetrahedra can also dramatically improve the ion exchange process during chemical strengthening. Therefore, Al2O3 is preferably included in the glass in an amount of at least 0 wt%, more preferably more than 1 wt%, and more preferably more than 4 wt%. However, it is desirable that the amount of Al2O3 not be too large, as a large amount of Al2O3 can result in very high viscosity and impaired meltability. Therefore, the Al2O3 content in the glass is preferably a maximum of 20 wt%, a maximum of 12 wt%, or a maximum of 10 wt%. In preferred embodiments, the Al2O3 content in the glass is 0-20 wt%, 1-12 wt%, or 4-10 wt%.

[0067] TiO2 and Fe2O3 are used as coloring agents in amber glass tubes. However, since TiO2 can also form [TiO4], it can help in the construction of the glass network and may also be beneficial in improving the acid resistance of the glass. However, the amount of TiO2 in the glass should not be excessively high. High concentrations of TiO2 can act as a nucleating agent, which can lead to crystallization during manufacturing. Preferably, the TiO2 content in the glass is 0.5 to 10.0% by weight, more preferably 1.0 to 8.0% by weight, even more preferably 3.0 to 6.0% by weight, and most preferably 4.0 to 5.0% by weight.

[0068] In addition to TiO2, Fe2O3 is used as a coloring agent in amber glass tubes. According to a preferred embodiment of the present invention, the glass contains iron in an amount of 0.1 to 10.0% by weight, more preferably 0.5 to 5.0% by weight, even more preferably 0.7 to 2.0% by weight, and most preferably 1.0 to 1.5% by weight, calculated as Fe2O3.

[0069] According to a preferred embodiment of the present invention, the amber glass tube prepared in step a) contains Fe2O3 and TiO2 in the glass composition in a ratio of 1:3.00 to 1:5.00, preferably 1:3.50 to 1:4.50, and most preferably 1:3.80 to 1:4.00, based on the weight of the oxides.

[0070] In addition to the above-mentioned colorant system, the glass may contain further color-enhancing components. According to a preferred embodiment of the present invention, the glass contains MnO2 as a color-enhancing component in an amount preferably 0.001 to 0.1% by weight, preferably 0.005 to 0.05% by weight, and most preferably 0.008 to 0.015% by weight.

[0071] According to a preferred embodiment, the glass tube prepared in step a) does not contain any further colorants or color-enhancing components, and preferably does not contain Nd2O3, CoO, NiO, V2O5, CuO, CeO2, or Cr2O3.

[0072] ZrO2 has the function of lowering the CTE of glass and improving alkali resistance. ZrO2 can increase melt viscosity, but this can be suppressed by using P2O5. Similar to alkali metals, Zr 4+ It is also a network modifier. Furthermore, ZrO2 is an important contributing factor for improving Young's modulus. Preferably, the ZrO2 content in the glass is 0 to 5% by weight, preferably 0 to 2% by weight. According to a preferred embodiment, the glass does not contain ZrO2.

[0073] To supply sufficient oxygen anions to form a glass network, alkali metal oxides R2O (Li2O + Na2O + K2O + Cs2O) can be used as network modifiers. Preferably, the R2O content in the glass is more than 4% by weight, preferably more than 6% by weight. However, it is desirable that the R2O content in the glass not be too high, as a high R2O content may impair chemical stability and chemical strengthening. Preferably, the glass contains a maximum of 30% by weight, a maximum of 25% by weight, or a maximum of 20% by weight of R2O. Other embodiments do not contain alkali metal oxides, or at least Na2O, K2O, Cs2O, and / or Li2O.

[0074] Li2O can help improve the Young's modulus of glass and reduce its CTE. Li2O also has a significant impact on ion exchange. Surprisingly, the geometric variation of Li-containing glass has been found to be relatively small. However, it is desirable that the amount of Li2O not be too high, as high content can impair chemical stability and chemical strengthening. Therefore, the Li2O content in the glass can be 0-10% by weight or more preferably 0-5% by weight. According to a preferred embodiment, the glass does not contain Li2O.

[0075] Na2O can also be used as a network structure modifier. However, the Na2O content should not be excessively high, because this may impair chemical stability and chemical strengthening. Preferably, the Na2O content in the glass is 0 to 15% by weight, preferably 2 to 15% by weight. In preferred embodiments, the Na2O content in the glass is at least 5% by weight, at least 8% by weight, or at least 10% by weight.

[0076] K2O can be used as a network structure modifier. However, the K2O content should not be excessively high, as this may impair chemical stability and chemical strengthening. Preferably, the K2O content in the glass is between 0% and 15% by weight, or between 0.5% and 7% by weight. The glass does not need to contain K2O.

[0077] Preferably, the glass contains more Na2O than K2O. Therefore, preferably, the molar ratio Na2O / (Na2O+K2O) is greater than 0.5 and 1.0 or less, greater than 0.6 and 1.0 or less, greater than 0.7 and 1.0 or less, or greater than 0.8 and 1.0 or less.

[0078] The total content of Li2O and Na2O in the glass should preferably not be too high. Preferably, the total content of Li2O and Na2O in the glass should be at most 25% by weight, or at most 20% by weight.

[0079] The glass may also contain alkaline earth metal oxides and ZnO (collectively referred to herein as "RO"). The alkaline earth metals and Zn can act as network modifiers. Preferably, the glass contains 0 to 20% by weight, preferably 0 to 15% by weight of RO. In some embodiments, the glass preferably contains at least 0.5% by weight, more preferably at least 1% by weight, and more preferably at least 2% by weight of RO. Preferred alkaline earth metal oxides are selected from the group consisting of MgO, CaO, SrO, and BaO. More preferably, the alkaline earth metal is selected from the group consisting of BaO and CaO. More preferably, the alkaline earth metal is MgO. Preferably, the glass contains 0 to 10% by weight of MgO. Preferably, the glass does not contain MgO. Preferably, the glass contains CaO in an amount of 0 to 16% by weight, preferably 0 to 13% by weight, and more preferably 0 to 10% by weight. In some embodiments, the glass contains at least 0.5% by weight, and at least 1% by weight. Preferably, the glass contains BaO in an amount of 0 to 12% by weight, preferably 0 to 10% by weight. In some embodiments, the glass contains at least 0.5% by weight, at least 1% by weight of BaO.

[0080] Preferably, the glass contains 0 to 5% by weight of ZnO. In some embodiments, the glass contains at least 0.5% by weight, at least 1% by weight, or at least 2% by weight of ZnO. In other embodiments, the glass does not contain ZnO. Preferably, the total content of MgO and ZnO in the glass is 0 to 10% by weight. In other embodiments, the glass does not contain ZnO or MgO.

[0081] Ultimately, when forming glass by mixing different types of oxides, it should be understood that the combined effect results in a glass with a relatively low degree of expansion, supported by a high densification of the glass network. In other words, polyhedra such as the [BO4], [AlO4], and [PO4] tetrahedra, in addition to the [SiO4] tetrahedron, are expected to help bond [SiO4] more effectively than other types of polyhedra. In other words, for example, the [BO3] trihedron and the [AlO6] octahedron are undesirable. That is, it is preferable to provide sufficient oxygen anions by adding appropriate amounts of metal oxides, such as R2O and RO.

[0082] Preferably, the SnO2 content in the glass is 0-3% by weight. More preferably, the glass does not contain SnO2. Preferably, the Sb2O3 content in the glass is 0-3% by weight. More preferably, the glass does not contain Sb2O3. Preferably, the CeO2 content in the glass is 0-3% by weight. A high CeO2 content is undesirable because CeO2 has a coloring effect, and therefore has an unfavorable effect on the Fe2O3 and TiO2 coloring agent system. Therefore, more preferably, the glass does not contain CeO2.

[0083] The glass described herein is described as having a different composition of components. This means that the glass contains these components without excluding further components not mentioned herein. However, in a preferred embodiment, the glass consists of the components mentioned herein to the extent of at least 95% by weight, more preferably at least 97% by weight, and most preferably at least 99% by weight. In the most preferred embodiment, the glass consists substantially of the components mentioned herein.

[0084] The glass composition may contain one or more fining agents. The fining agents can be selected from polyvalent metal oxides, halides, sulfates, and combinations thereof. In one embodiment, the fining agent is selected from the list of arsenic oxide, antimony oxide, tin oxide, cerium oxide, chlorides, fluorides, sulfates, and combinations thereof. The total amount of the fining agent may be 0 to 5% by weight, preferably 0 to 2% by weight. In another embodiment, the glass composition contains a fining agent selected from the list of arsenic oxide, antimony oxide, tin oxide, or cerium oxide. The total amount of these fining agents may be 0.03 to 1.5% by weight. According to a preferred embodiment of the present invention, the amount of As2O3 and / or Sb2O3 and / or SnO2 and / or Ce2O3 in the glass composition is less than 1000 ppm, preferably less than 500 ppm, and most preferably less than 200 ppm. According to another preferred embodiment of the present invention, the glass composition does not contain As2O3 and / or Sb2O3 and / or SnO2 and / or Ce2O3.

[0085] In one embodiment, the glass composition comprises a fining agent selected from a list of chlorides, sulfates, and combinations thereof. The total amount of the fining agent may be 0.03 to 1.5% by weight. According to a preferred embodiment of the present invention, the glass composition of the present invention is a glass composition refined with a halide, preferably a glass composition refined with a chloride or fluoride, and most preferably a glass composition refined with a chloride. Such fining agents improve conductivity and reduce resistivity in the glass molten material.

[0086] According to one embodiment, the glass composition does not need to contain heavy metals.

[0087] In the embodiment, the glass used in the glass tube element has the following composition by weight: [Table 2]

[0088] Preferably, the amber glass tube has a glass composition that, based on all oxides present in the glass composition, contains 60-85% by weight of SiO2, 5-20% by weight of B2O3, 1-10% by weight of Al2O3, 0.25-2% by weight of Fe2O3, 0.5-10% by weight of TiO2, 2-10% by weight of Na2O, 0-5% by weight of K2O, 0-2% by weight of BaO, and 0-2% by weight of CaO.

[0089] According to another preferred embodiment of the present invention, the amber glass tube has a glass composition comprising or consisting of 65-75% by weight of SiO2, 5-10% by weight of B2O3, 2-8% by weight of Al2O3, 2-10% by weight of Na2O, 0.5-5% by weight of K2O, 0-1% by weight of MgO, 0-2% by weight of CaO, 0-1% by weight of SrO, 0-3% by weight of BaO, 0.25-2% by weight of Fe2O3, and 0.5-10% by weight of TiO2, based on all oxides present in the glass composition. According to another preferred embodiment of the present invention, the amber glass tube has a glass composition comprising or consisting of 65-75% by weight of SiO2, 5-10% by weight of B2O3, 2-8% by weight of Al2O3, 2-10% by weight of Na2O, 0.5-5% by weight of K2O, 0-1% by weight of MgO, 0-2% by weight of CaO, 0-1% by weight of SrO, 0-3% by weight of BaO, 0.25-2% by weight of Fe2O3, and 0.5-10% by weight of TiO2, where Fe2O3 and TiO2 in the glass composition are present in a ratio of 1:3.00-1:5.00, preferably 1:3.50-1:4.50, and most preferably 1:3.80-1:4.00, based on the weight of the oxides. According to another preferred embodiment of the present invention, the amber glass tube contains, based on all oxides present in the glass composition, 65-75% by weight of SiO2, 5-10% by weight of B2O3, 2-8% by weight of Al2O3, 2-10% by weight of Na2O, 0.5-5% by weight of K2O, 0.01-0.05% by weight of MgO, 0.1-1% by weight of CaO, 0.01-0.5% by weight of SrO, and 1-3% by weight of B The glass composition contains or comprises aO, 0.01 to 0.5 wt% MnO, 1.0 to 1.5 wt% Fe2O3, and 2 to 8 wt% TiO2, wherein the Fe2O3 and TiO2 in the glass composition are present in a ratio of 1:3.00 to 1:5.00, preferably 1:3.50 to 1:4.50, and most preferably 1:3.80 to 1:4.00, based on the weight of the oxides.According to another preferred embodiment of the present invention, the amber glass tube contains, based on all oxides present in the glass composition, 65-75% by weight of SiO2, 5-10% by weight of B2O3, 2-8% by weight of Al2O3, 2-10% by weight of Na2O, 0.5-5% by weight of K2O, 0.01-0.05% by weight of MgO, 0.1-1% by weight of CaO, 0.01-0.5% by weight of SrO, 1-3% by weight of BaO, and 0.01-0 The glass composition contains or comprises 0.5 wt% MnO, 1.0 to 1.5 wt% Fe2O3, and 2 to 8 wt% TiO2, wherein the Fe2O3 and TiO2 in the glass composition are present in a ratio of 1:3.00 to 1:5.00, preferably 1:3.50 to 1:4.50, and most preferably 3.80 to 1:4.00, based on the weight of the oxides, and in this case, the glass composition does not contain Li2O.

[0090] Method step b) According to step b) of the method, the amber glass tube prepared in step a) is hot-formed into an amber glass container.

[0091] Hot forming in the sense of the present invention is a process in which an amber glass tube is transformed / reshaped into an amber glass container of a defined shape by using hot forming tools. More precisely, the amber glass tube is reshaped at one or more forming stations using various hot forming tools, such as forming rollers and forming mandrels, to form an amber glass container, which can then be further processed to form a primary packaging means for pharmaceuticals, i.e., an amber glass container for pharmaceuticals. For example, the amber glass tube can be reshaped by heating the glass tube to a forming temperature using a gas burner at an upstream heating station. The heated glass tube can then be supplied to the forming station via a rotating chuck, with the longitudinal axis of the glass tube aligned with the rotational axis. In the forming system, the glass is formed by forming rollers and a forming mandrel, with the forming roller positioned outside the resulting container and the forming mandrel positioned inside the container. For reshaping, the forming rollers perform radial motion relative to the rotational or longitudinal axis of the container or tube section. The mandrel helps to ensure the internal shape of the product. To reduce friction between the glass and the forming tool, thereby preventing surface defects, lubricants are applied to the rollers and mandrel midway through the forming stroke. Oil can be used in such processes or in air coolers, which provides a cooling effect to the forming tool and prevents the glass from sticking to the tool.

[0092] A method for hot-forming an amber glass tube into an amber glass container, and the necessary tools, are known to those skilled in the art. For example, such a method and tools are described in European Patent Publication No. 3652120, German Patent Publication No. 102020114886, and European Patent Publication No. 3677554. Those skilled in the art will select and adapt the method according to the available apparatus and the amber glass container to be formed.

[0093] According to one embodiment of the present invention, the amber glass tube prepared in step a) is hot-formed into an amber glass container in the form of a vial, syringe, or cartridge.

[0094] According to one embodiment of the present invention, the amber glass tube prepared in step a) is hot-formed to form an amber glass container in the form of a vial. A vial in the sense of the present invention is a closure container that can be closed or sealed, for example, by crimping. According to a preferred embodiment of the present invention, the hot-formed vial is a 2R, 4R, 6R, 10R, 15R, or 20R vial according to ISO 8362-1:2018. According to another preferred embodiment of the present invention, the hot-formed vial is a 2R, 4R, 6R, 10R, 15R, or 20R vial having all the dimensions described in ISO 8362-1:2018, except that the wall thickness s1 of the vial is 1.0 mm. The wall thickness s1 of the vial can be seen in detail from Figure 1.

[0095] According to another embodiment of the present invention, the amber glass tube prepared in step a) is hot-formed into an amber glass container in the form of a syringe. A syringe in the sense of the present invention is a tube having a nozzle, which, together with a piston or valve, can be used for drawing in and discharging liquids, and which can be fitted with a hollow needle for injecting or withdrawing liquids. According to a preferred embodiment of the present invention, the hot-formed syringe is a 0.5 ml, 1.1 ml, 1.5 ml, 2 ml, 2.25 ml, 3 ml, 5 ml, 10 ml, or 20 ml syringe according to ISO 11040-4:2024. According to another preferred embodiment of the present invention, the hot-formed syringe is a 0.5 ml, 1.1 ml, 1.5 ml, 2 ml, 2.25 ml, 3 ml, 5 ml, 10 ml, or 20 ml syringe having any dimensions described in ISO 11040-4:2024, except that the syringe wall thickness s1 is 1.0 mm. The wall thickness s1 of the syringe can be seen in detail in Figure 2.

[0096] According to one embodiment of the present invention, the amber glass tube prepared in step a) is hot-formed into an amber glass container in the form of a cartridge. A cartridge in the sense of the present invention is a closure container that can be closed or sealed, for example, by crimping. According to a preferred embodiment of the present invention, the hot-formed cartridge is a 1.5 ml or 3 ml cartridge in accordance with ISO 13926-1:2020-02. According to another preferred embodiment of the present invention, the hot-formed cartridge is a 1.5 ml or 3 ml cartridge having all the dimensions described in ISO 13926-1:2020-02, except that the cartridge wall thickness (d1-d2) / 2 is 1.0 mm. The wall thickness calculated from the cartridge values ​​d1 and d2 can be seen in detail in Figure 3. According to another preferred embodiment, the hot-formed cartridge is a 5 ml, 7.3 ml, 10 ml, or 20 ml cartridge having the same dimensions as specified in ISO 13926-1:2020-02, except that the cartridge length and diameter. According to another preferred embodiment of the present invention, the hot-formed cartridge is a 5 ml, 7.3 ml, 10 ml, or 20 ml cartridge having the same dimensions as those specified in ISO 13926-1:2020-02, except that the length and diameter of the cartridge and the wall thickness (d1-d2) / 2 of the cartridge are 1.0 mm.

[0097] Those skilled in the art are well aware of how to measure the wall thickness of glass tubes, and select the appropriate measuring device depending on the type and size of the object to be measured, and further on the precision required for determining the tolerance. Such measuring devices are commercially available and include, for example, micrometers, calipers or two-point probe heads, or optical measuring devices, such as digital measuring projectors. Digital measuring projectors are available from companies such as Keyence.

[0098] During the hot forming process b), at least a portion of the amber glass tube is heated to a temperature near the forming temperature of the glass being used, and then formed / reformed by contact with a forming tool. According to a preferred embodiment of the present invention, only the reformed / formed portion of the amber glass tube, such as the bottom and shoulder and rounded rim of a vial or nozzle, and a portion of the finger grip of a syringe, is heated. The remaining portion of the amber glass tube that forms the body or barrel portion of the container is not actively heated, at least below or above the Tg of the amber glass tube.

[0099] According to one embodiment of the present invention, a method for manufacturing an amber glass container for pharmaceuticals, wherein during the hot forming step b), an amber glass tube is formed into an amber glass container, and here, i) During the hot forming process b), the body and / or barrel of the amber glass container are held below Tg, and / or ii) The portion of the amber glass tube to be reshaped is heated above Tg for 1 sec to 500 sec, preferably 2 sec to 200 sec, most preferably 3 sec to 100 sec.

[0100] According to one embodiment of the present invention, a method is provided for manufacturing an amber glass container for pharmaceuticals, wherein during a hot forming step b), an amber glass tube is formed into an amber glass container, and during the hot forming step b), the body and / or barrel of the amber glass container is held below Tg, preferably at least 90%, more preferably at least 70%, of the body and / or barrel of the amber glass container.

[0101] Method step c) According to step c) of the method, the amber glass container is heated to a temperature of Tg+5°C to Tg+50°C.

[0102] In the context of this invention, Tg is also known as the transition temperature of glass and is defined in ISO 7884-8:1987. This temperature corresponds to the intersection of two tangents drawn from the low-temperature and high-temperature branches of the dilatometer curve. This is 10 13.3 This corresponds to a dynamic viscosity on the order of dPa·s. Those skilled in the art will be familiar with the Tg value and how to measure the Tg value as described in the ISO standard above.

[0103] According to a preferred embodiment of the present invention, heating step c) is carried out at a temperature of Tg+8°C to Tg+45°C, preferably Tg+10°C to Tg+35°C, and most preferably Tg+12°C to Tg+30°C. According to one illustrated embodiment, heating step c) is carried out at a temperature of Tg+15°C ± 1°C.

[0104] The heating step c) can be carried out using any heating device suitable for heating the amber glass container to the required temperature, such as an oven, annealing oven, heating chamber, hot blower, or heating plate. Such heating devices are known to those skilled in the art and are commercially available, and those skilled in the art should be able to select a suitable heating device depending on the required temperature, further processing equipment, and the amount of body of the amber glass container to be heated. According to a preferred embodiment, the heating device is an oven through which the amber glass container is conveyed by a conveyor belt.

[0105] It is important to note that the given temperature is the temperature of the amber glass container, not the temperature of the heat source. The temperature of the heat source can be higher. Those skilled in the art will know how to adjust the temperature of the heat source, such as an oven, to achieve the desired temperature in the amber glass container.

[0106] The temperature does not need to remain constant throughout the entire duration of step c). For example, the amber glass container may be located within the specified low temperature range at the start of heating step c) and then within the specified high temperature range at the end of heating step c). According to a preferred embodiment of the present invention, the temperature remains constant throughout step c).

[0107] According to another preferred embodiment of the present invention, heating step c) is performed for 1 to 600 seconds, preferably 5 to 500 seconds, more preferably 10 to 300 seconds, and even more preferably 12 to 100 seconds. According to the illustrated embodiment, heating step c) is performed over 15 seconds ± 1 second.

[0108] According to another embodiment of the present invention, the heating step c) is performed at a temperature of Tg+5°C to Tg+50°C, preferably Tg+8°C to Tg+45°C, more preferably Tg+10°C to Tg+35°C, most preferably Tg+12°C to Tg+30°C, for 1 to 60 seconds, preferably 5 to 50 seconds, more preferably 10 to 300 seconds, and even more preferably 12 to 100 seconds.

[0109] According to an exemplary embodiment of the present invention, heating step c) is performed at a temperature of Tg + 15°C ± 1°C for a period of 15 sec ± 1 sec.

[0110] The heating step c) can be carried out in air or under a protective atmosphere, such as a nitrogen atmosphere. According to a preferred embodiment of the present invention, the heating step c) is carried out in air.

[0111] The heating step c) can be carried out under atmospheric pressure or reduced pressure. According to a preferred embodiment of the present invention, the heating step c) is carried out under atmospheric pressure.

[0112] According to step c) of the method, the amber glass container is directly heated to a temperature of Tg+5°C to Tg+50°C without any additional heating. According to another embodiment of the present invention, the amber glass container is heated to a temperature of Tg+5°C to Tg+50°C over a predetermined time period by a temperature gradient. The temperature may rise steadily in the temperature gradient, in a stepwise profile, or exponentially. However, a steady increase is preferred. According to a preferred embodiment of the present invention, the heating is carried out for 1 sec to 20 min, preferably 3 min to 18 min, more preferably 5 to 15 min, and even more preferably 8 to 12 min. According to an exemplary embodiment, the heating is carried out for 10 min ± 1 min.

[0113] Heating can be performed at a rate of 0.8°C / sec to 10°C / sec, preferably 1.0°C / sec to 8°C / sec, per 1.0 mm wall thickness of the amber glass container, most preferably at a rate of 1.5°C / sec to 5°C / sec per 1.0 mm wall thickness of the amber glass container.

[0114] Heating can be carried out in air or under a protective atmosphere, such as a nitrogen atmosphere. According to a preferred embodiment of the present invention, heating is carried out in air.

[0115] The heating can be carried out under normal pressure or reduced pressure. According to a preferred embodiment of the present invention, preheating is usually performed under pressure.

[0116] Method step d) During step d) of the method, the heated amber glass container from step c) is cooled to a temperature of Tg-60°C to Tg-10°C at a rate of 0.8°C / s to 4°C / s per 1.0 mm of wall thickness of the amber glass container.

[0117] According to a preferred embodiment of the present invention, the heated amber glass container in step c) is cooled to a temperature of Tg-50°C to Tg-15°C, preferably Tg-40°C to Tg-20°C, during step d). According to an exemplary embodiment of the present invention, the heated amber glass container in step c) is cooled to a temperature of Tg-30°C ± 1°C during step d).

[0118] According to another preferred embodiment of the present invention, the amber glass container heated in step c) is cooled during step d) at a rate of 0.9°C / sec to 3°C / sec, preferably 1.0°C / sec to 2.5°C / sec, and most preferably 1.0°C / sec to 2.0°C / sec, per 1.0 mm wall thickness of the amber glass container.

[0119] According to a preferred embodiment of the present invention, the heated amber glass container in step c) is cooled during step d) to a temperature of Tg-60°C to Tg-10°C, preferably Tg-50°C to Tg-15°C, most preferably Tg-40°C to Tg-20°C, at a rate of 0.8°C / sec to 4°C / sec, 0.9°C / sec to 3°C / sec, preferably 1.0°C / sec to 2.5°C / sec, most preferably 1.0°C / sec to 2.0°C / sec per 1.0 mm wall thickness of the amber glass container.

[0120] The cooling step d) can be carried out by any cooling device suitable for cooling the amber glass container to the required temperature, such as a cooling fan, cooling chamber, freezing chamber, or Peltier element. Alternatively, the amber glass container can be cooled by not actively heating it. In this case, the amber glass container will be cooled to room temperature. Such cooling devices and options are known to those skilled in the art and are commercially available, and those skilled in the art should be able to select an appropriate cooling device depending on the required temperature, further processing equipment, and the amount of amber glass container to be cooled. According to a preferred embodiment, the amber glass container obtained in step c) is transported out of the oven by a conveyor belt. Depending on the temperature outside the oven and the movement of the conveyor belt, the desired temperature and cooling rate can be obtained.

[0121] It is important to note that the given temperature is the temperature of the amber glass container, not the temperature of the cooling device. The temperature of the cooling device can be lower. Those skilled in the art will know how to adjust the temperature in the cooling device to achieve the required temperature and cooling rate in the amber glass container.

[0122] The cooling does not need to remain constant throughout the entire duration of step d). For example, the amber glass container may be cooled at the higher cooling rate specified above at the beginning of cooling step d), and then at the lower cooling rate specified above at the end of cooling step d).

[0123] According to another preferred embodiment of the present invention, the cooling step d) is performed for 1 to 600 seconds, preferably 5 to 500 seconds, more preferably 10 to 300 seconds, and even more preferably 12 to 100 seconds. According to the exemplary embodiment, the cooling step d) is performed over 15 seconds ± 1 second.

[0124] The cooling step d) can be carried out in air or under a protective atmosphere, for example, under a nitrogen atmosphere. According to a preferred embodiment of the present invention, the cooling step d) is carried out in air.

[0125] The cooling step d) can be carried out under normal pressure or reduced pressure. According to a preferred embodiment of the present invention, the cooling step d) is carried out under normal pressure.

[0126] After step d), an amber glass container for pharmaceuticals according to the present invention is obtained.

[0127] Surprisingly, the inventors of the present invention have found that the most important standard, namely USP, can be applied by the method of the present invention. <660> We have found that pharmaceutical amber glass containers that meet the requirements for UV blocking and transmittance in the visible region as stipulated in EP3.2.1 and JP7.01 can be manufactured. More precisely, the method of the present invention makes it possible to provide pharmaceutical amber glass containers that have a transmittance of 25% or less across the entire wavelength range of 290 nm to 450 nm when measured at a thickness of 1.0 mm to provide UV blocking properties, and a transmittance of 45% or more across the entire wavelength range of 590 nm to 610 nm when measured at a thickness of 1.0 mm to be suitable for visual inspection.

[0128] In this regard, the inventors have surprisingly found that the method of the present invention allows the use of known amber glass tubes having known colorant systems, namely Fe2O3 and TiO2 colorant systems.

[0129] Colorant systems based on Fe2O3 and TiO2 in glass compositions are known to those skilled in the art and have been used for decades to provide amber coloring in glass. However, one advantage of these colorant systems is that they are approved in the pharmaceutical sector. Surprisingly, the inventors have found that the above-mentioned colorant systems are advantageous in the method of the present invention for producing pharmaceutical amber glass containers according to the present invention. More precisely, the inventors have found that the combination of Fe2O3 and TiO2 can be used in borosilicate glass as a temperature-dependent colorant system. More precisely, the inventors have found that when Fe2O3 and TiO2 are used preferably in the above ratio, not only the UV transmittance but also the transmittance in the visible region can be controlled. In particular, the inventors have found that, surprisingly, customized properties can be achieved in the resulting pharmaceutical amber glass containers by controlling the target temperature during the post-treatment described above. In particular, the method of the present invention, namely heating the amber glass container heated in step c) to a temperature of Tg+5°C to Tg+50°C, and then cooling the amber glass container heated in step c) to a temperature of Tg-60°C to Tg-10°C at a rate of 0.8°C / s to 4°C / s per 1.0 mm of wall thickness of the amber glass container, makes it possible to form a pharmaceutical amber glass container that, when measured at a thickness of 1.0 mm suitable for visual inspection, has a transmittance of less than 25% across the entire wavelength range of 250 nm to 450 nm and a transmittance of 45% or more across the entire wavelength range of 590 nm to 610 nm. The manufacture of such a pharmaceutical amber glass container has been impossible until now. According to general knowledge, the two transmittance values ​​(in the UV region and the visible region) operate in opposite directions to each other. More precisely, the darker the color of the glass, the lower the transmittance in the visible region, as the legal requirements in the UV region are met. Conversely, the brighter the glass color in the visible region, and therefore the more the legal requirements for the visible region are met, the higher the transmittance in the UV region.

[0130] Furthermore, the inventors have found that the above heating step c) and cooling step d) can yield pharmaceutical amber glass containers with good chemical and physical stability, and in particular good physical stability. Physical stability also depends, among other parameters, on the heat treatment after hot forming. Therefore, such processing steps, particularly heating to a specified temperature and subsequent cooling, are usually not modified to provide a stable process. More precisely, it is advantageous to heat the body of the amber glass container to a high temperature, especially to a temperature well above Tg. This is because it is generally known that the physical stability of pharmaceutical amber glass containers increases with increasing heating temperature and decreases with decreasing heating temperature. Those skilled in the art usually do not select heating temperatures below Tg + 50°C. This is because below this temperature, the physical stability of the resulting pharmaceutical amber glass container decreases, and in particular, the ring tension, which can be measured by the de Senarmont method and the Friedel method, decreases and becomes measurable on the Friedel scale.

[0131] The inventors have surprisingly found that the method of the present invention makes it possible to manufacture pharmaceutical amber glass containers that meet ISO standards in terms of the required size and satisfy the required transmittance values ​​in the ranges of 290 nm to 450 nm and 590 nm to 610 nm. In addition, the manufactured pharmaceutical amber containers are physically stable and have an annular tension of 1 Friedel grade or less. The inventors have surprisingly found that the method of the present invention makes it possible to manufacture the pharmaceutical amber glass containers of the present invention on a large scale. Furthermore, the inventors have found that the above method is easy to handle and economical because existing equipment can be used on a large scale and only small conversion amounts are required. Moreover, it does not actually affect the time required to manufacture the pharmaceutical glass containers of the present invention. In addition, since there is no need to set up special machinery or equipment, known amber glass tubes and known available equipment that are already on the market can be used.

[0132] Further optional method steps The method of the present invention may include further additional process steps.

[0133] According to one embodiment of the present invention, the amber glass container for pharmaceuticals obtained after step d) can be further cooled to room temperature in step e).

[0134] For example, the cooling step e) is carried out for 1 sec to 24 hours, preferably 1 minute to 1 hour, more preferably 5 minutes to 30 minutes. According to one exemplary embodiment, the cooling step e) is carried out over 15 minutes ± 2 minutes.

[0135] According to another preferred embodiment of the present invention, during step e), the amber glass container for pharmaceuticals obtained in step d) is cooled at a rate of 0.8°C / sec to 20°C / sec, most preferably 2.0°C / sec to 10°C / sec, per 1.0 mm wall thickness of the amber glass container.

[0136] The cooling step e) can be carried out using any cooling device suitable for cooling the amber glass container to the required temperature. A suitable cooling device has already been prepared in step d).

[0137] The cooling step e) can be carried out in air or under a protective atmosphere, such as a nitrogen atmosphere. According to a preferred embodiment of the present invention, the cooling step e) is carried out in air. The cooling step e) can be carried out under normal pressure or under reduced pressure. According to a preferred embodiment of the present invention, the cooling step e) is carried out under normal pressure.

[0138] According to one embodiment of the present invention, the amber glass container for pharmaceuticals obtained after step d) or step e) can be further washed and optionally dried in step f). Those skilled in the art will be familiar with such methods and will be able to select appropriate parameters and apparatus for any washing and / or drying step f).

[0139] According to another embodiment of the present invention, the amber glass containers for pharmaceuticals obtained after step d), step e), or step f) can be further sterilized in step g). Those skilled in the art will be familiar with such sterilization processes and should be able to select appropriate parameters and apparatus for any sterilization step g). Sterilization may be, for example, steam sterilization or ethylene oxide sterilization.

[0140] According to another embodiment of the present invention, the amber glass container for pharmaceuticals obtained after step d), or step e), or step f), or step g) can be further coated in step h). Those skilled in the art will be familiar with such coating processes and will be able to select appropriate parameters and equipment as well as appropriate coatings for any coating step h).

[0141] For example, the coating composition can be coated by conventional coating means commonly used in the art. Suitable coating methods include, for example, air knife coating, electrostatic coating, metering size press, film coating, spray coating, winding rod coating, slot coating, slide hopper coating, gravure, curtain coating, high-speed coating, and PICVD (plasma impulse chemical vapor deposition). Some of these methods allow for the simultaneous coating of two or more layers. However, any other coating method suitable for forming the coating layer can also be used. The coating layer can then be dried. Drying can be carried out by any method known in the art, and those skilled in the art should be able to adapt the drying conditions, such as temperature, according to the process equipment. For example, the coating layer can be dried by infrared drying and / or convection drying. The drying process can be carried out at room temperature or other temperatures. In one embodiment, the coating is carried out at a surface temperature of 25-150°C on a pharmaceutical amber glass container.

[0142] According to a preferred embodiment of the present invention, the coating is applied by PICVD (plasma-assisted chemical vapor deposition). Such applications are advantageous because they form covalent bonds, thus avoiding, for example, the liberation of silicone within the pharmaceutical amber glass container. Such plasma coating methods are known, for example, from U.S. Patent No. 8592015. According to a preferred embodiment of the present invention, step h) is performed by depositing a coating on the inner surface of the pharmaceutical amber glass container by plasma-assisted chemical vapor deposition, in which a process gas having a silicon-containing gas component and carbon and oxygen as further gas components is introduced into a reaction chamber defined at least partially by the substrate, and a plasma is arced by pulsed irradiation of electromagnetic energy to form reaction products in the plasma.

[0143] Amber glass container for pharmaceuticals According to the present invention, an amber glass container for pharmaceuticals is provided, wherein the amber glass has a transmittance of 25% or less across the entire wavelength range of 290 nm to 450 nm when measured at a thickness of 1.0 mm, and a transmittance of 45% or more across the wavelength range of 590 nm to 610 nm when measured at a thickness of 1.0 mm.

[0144] According to a preferred embodiment of the present invention, the amber glass container for pharmaceuticals is a vial, syringe, or cartridge.

[0145] As already described in step b) of the method, the vial is a 2R, 4R, 6R, 10R, 15R, or 20R vial according to ISO 8362-1:2018. According to a preferred embodiment of the present invention, the vial is a 2R, 4R, 6R, 10R, 15R, or 20R vial having all the dimensions described in ISO 8362-1:2018, except that the wall thickness s1 of the vial is 1.0 mm. Alternatively, the vial is a 10R or 20R vial having all the dimensions described in ISO 8362-1:2018, except that the wall thickness s1 of the vial is 1.0 mm and the nominal volume is 10 ml or 20 ml. Alternatively, according to a preferred embodiment of the present invention, the amber glass container for pharmaceuticals is a 2R, 4R, 6R, 10R, or 15R vial according to ISO 8362-1:2018. According to the most preferred embodiment of the present invention, the amber glass container for pharmaceuticals is a 2R or 4R vial according to ISO 8362-1:2018.

[0146] As already described in step b) of the method, the syringe is a 0.5 ml, 1.1 ml, 1.5 ml, 2 ml, 2.25 ml, 3 ml, 5 ml, 10 ml, or 20 ml syringe according to ISO 11040-4:2024. According to a preferred embodiment of the present invention, the syringe is a 0.5 ml, 1.1 ml, 1.5 ml, 2 ml, 2.25 ml, 3 ml, 5 ml, 10 ml, or 20 ml syringe having all the dimensions described in ISO 11040-4:2024, except that the syringe wall thickness s1 is 1.0 mm. According to a preferred embodiment of the present invention, the syringe is a 0.5 ml, 1.1 ml, 1.5 ml, 2 ml, 2.25 ml, or 3 ml syringe according to ISO 11040-4:2024, where the syringe wall thickness s1 is 1.0 mm. According to a preferred embodiment of the present invention, the syringe is a 1.1 ml, 1.5 ml, or 2 ml syringe according to ISO 11040-4:2024, where the syringe wall thickness s1 is 1.0 mm.

[0147] As already described in step b) of the method, the cartridge is a 1.5 ml or 3 ml cartridge conforming to ISO 13926-1:2020-02. According to another preferred embodiment of the present invention, the cartridge is a 1.5 ml or 3 ml cartridge having all the dimensions described in ISO 13926-1:2020-02 except that the cartridge wall thickness (d1-d2) / 2 is 1.0 mm. According to another preferred embodiment, the cartridge is a 5 ml, 7.3 ml, 10 ml, or 20 ml cartridge having the same dimensions as specified in ISO 13926-1:2020-02 except that the cartridge length and diameter. According to another preferred embodiment of the present invention, the cartridge is a 5 ml, 7.3 ml, 10 ml, or 20 ml cartridge having the same dimensions as specified in ISO 13926-1:2020-02 except that the cartridge length and diameter, with a cartridge wall thickness (d1-d2) / 2 of 1.0 mm.

[0148] According to the present invention, a pharmaceutical amber glass container is provided, which, when measured at a thickness of 1.0 mm, has a transmittance of 1.0 mm, preferably 20% or less, more preferably 15% or less, even more preferably 13% or less, even more preferably 12% or less, and most preferably 10% or less, across the entire wavelength region of 290 nm to 450 nm. Additionally or alternatively, the amber glass has a transmittance of at least 5%, preferably at least 8%, preferably at least 10%, preferably at least 12%, preferably at least 15%, and preferably at least 20% across the entire wavelength region of 290 nm to 450 nm. For example, the amber glass has a transmittance of 5% to 10%, or 8% to 12%, or 10% to 13%, or 12% to 15%, or 15% to 20%, or 20% to 25% across the entire wavelength region of 290 nm to 450 nm.

[0149] The present invention provides an amber glass container for pharmaceuticals, wherein the amber glass has a transmittance of 45% or more, preferably 50% or more, and most preferably 52.5% or more, over the entire wavelength range of 590 nm to 610 nm when measured at a thickness of 1 mm. Additionally or alternatively, the amber glass has a transmittance of less than 65%, preferably less than 60%, and most preferably less than 55%, over the entire wavelength range of 590 nm to 610 nm when measured at a thickness of 1 mm. For example, the amber glass has a transmittance of 45% to 65.0%, or 50.0% to 60.0%, or 52.5% to 55.0%, over the entire wavelength range of 590 nm to 610 nm when measured at a thickness of 1.0 mm.

[0150] According to a preferred embodiment of the present invention, the amber glass container for pharmaceuticals of the present invention is a 2R or 4R vial according to ISO 8362-1:2018, having a transmittance of 15% or less over the wavelength range of 290 nm to 450 nm when measured at a thickness of 1.0 mm, and having a transmittance of 45% or more over the wavelength range of 590 nm to 610 nm when measured at a thickness of 1.0 mm.

[0151] According to another preferred embodiment of the present invention, the amber glass container for pharmaceuticals of the present invention is a 6R or 8R vial according to ISO 8362-1:2018, having a transmittance of 13% or less over the wavelength range of 290 nm to 450 nm when measured at a thickness of 1.0 mm, and a transmittance of 45% or more over the wavelength range of 590 nm to 610 nm when measured at a thickness of 1.0 mm.

[0152] According to another preferred embodiment of the present invention, the amber glass container for pharmaceuticals of the present invention is a 10R or 15R vial according to ISO 8362-1:2018, having a transmittance of 12% or less over the wavelength range of 290 nm to 450 nm when measured at a thickness of 1.0 mm, and having a transmittance of 45% or more over the wavelength range of 590 nm to 610 nm when measured at a thickness of 1.0 mm.

[0153] According to another preferred embodiment of the present invention, the pharmaceutical amber glass container of the present invention is a 10R vial according to ISO8362-1:2018, except that its nominal volume is 10 ml, and has a transmittance of 13% or less over the wavelength range of 290 nm to 450 nm when measured at a thickness of 1.0 mm, and a transmittance of 45% or more over the wavelength range of 590 nm to 6610 nm when measured at a thickness of 1.0 mm.

[0154] According to another preferred embodiment of the present invention, the pharmaceutical amber glass container of the present invention is a 20R vial according to ISO 8362-1:2018, having a transmittance of 10% or less over the wavelength range of 290 nm to 450 nm when measured at a thickness of 1.2 mm, and a transmittance of 45% or more over the wavelength range of 590 nm to 610 nm when measured at a thickness of 1.2 mm.

[0155] According to another preferred embodiment of the present invention, the amber glass container for pharmaceuticals of the present invention is a 20R vial according to ISO 8362-1:2018, except that the vial wall thickness s1 is 1.0 mm and the nominal volume is 20 ml, and has a transmittance of 10% or less over the entire wavelength range of 290 nm to 450 nm when measured at a thickness of 1.0 mm, and a transmittance of 45% or more over the entire wavelength range of 590 nm to 610 nm when measured at a thickness of 1.0 mm.

[0156] According to another preferred embodiment of the present invention, the amber glass container for pharmaceuticals of the present invention is a 20R vial according to ISO 8362-1:2018, except that the wall thickness s1 of the vial is 1.0 mm, it has a transmittance of 10% or less over the wavelength range of 290 nm to 450 nm when measured at a thickness of 1.0 mm, and a transmittance of 45% or more over the wavelength range of 590 nm to 610 nm when measured at a thickness of 1.0 mm.

[0157] Note that in ISO 8362-1:2018, each vial size relates to the full volume. More precisely, 2R refers to a volume of 4 ml, 4R to a volume of 6 ml, 6R to a volume of 10 ml, 8R to a volume of 11.5 ml, 10R to a volume of 13.5 ml, 15R to a volume of 19 ml, and 20R to a volume of 26 ml. United States Pharmacopeia (USP) <660> The European Pharmacopoeia (EP3.2.1) and the Japanese Pharmacopoeia (JP7.01) specify nominal volume rather than full volume. However, these values ​​are mutually convertible. A full volume of 4 ml corresponds to a nominal volume of 3.4 ml, a full volume of 6 ml corresponds to a nominal volume of 4.8 ml, a full volume of 10 ml corresponds to a nominal volume of 8.3 ml, a full volume of 11.5 ml corresponds to a nominal volume of 9.8 ml, a full volume of 13.5 ml corresponds to a nominal volume of 17.3 ml, and a full volume of 26 ml corresponds to a nominal volume of 21.7 ml.

[0158] According to one embodiment of the present invention, the amber glass container for pharmaceuticals is an amber-colored pharmaceutical borosilicate glass container, an amber-colored pharmaceutical aluminoborosilicate glass container, an amber-colored pharmaceutical aluminosilicate glass, or an amber-colored pharmaceutical lithium aluminosilicate (LAS) glass container. According to a preferred embodiment, the amber glass container for pharmaceuticals is an amber-colored pharmaceutical borosilicate glass container.

[0159] According to a preferred embodiment of the present invention, the amber glass container for pharmaceuticals according to the present invention has the glass composition already described above in step a) of the method. According to a preferred embodiment of the present invention, the amber glass container for pharmaceuticals has a glass composition comprising, based on all oxides present in the glass composition, 60 to 85% by weight of SiO2, 5 to 20% by weight of B2O3, 1 to 10% by weight of Al2O3, 0.25 to 2% by weight of Fe2O3, 0.5 to 10% by weight of TiO2, 2 to 10% by weight of Na2O, 0 to 5% by weight of K2O, 0 to 2% by weight of BaO, and 0 to 2% by weight of CaO.

[0160] According to a preferred embodiment of the present invention, the amber glass container for pharmaceuticals has a glass composition comprising, based on all oxides present in the glass composition, 65-75% by weight of SiO2, 5-10% by weight of B2O3, 2-8% by weight of Al2O3, 2-10% by weight of Na2O, 0.5-5% by weight of K2O, 0-1% by weight of MgO, 0-2% by weight of CaO, 0-1% by weight of SrO, 0-3% by weight of BaO, 0.25-2% by weight of Fe2O3, and 0.5-10% by weight of TiO2, or a glass composition comprising these.

[0161] According to another preferred embodiment of the present invention, the amber glass container for pharmaceuticals has a glass composition comprising or containing 65-75% by weight of SiO2, 5-10% by weight of B2O3, 2-8% by weight of Al2O3, 2-10% by weight of Na2O, 0.5-5% by weight of K2O, 0-1% by weight of MgO, 0-2% by weight of CaO, 0-1% by weight of SrO, 0-3% by weight of BaO, 0.25-2% by weight of Fe2O3, and 0.5-10% by weight of TiO2, where Fe2O3 and TiO2 in the glass composition are present in a ratio of 1:3.00-1:5.00, preferably 1:3.50-1:4.50, and most preferably 1:3.80-1:4.00, based on the weight of the oxides.

[0162] According to another preferred embodiment of the present invention, the amber glass container for pharmaceuticals contains, based on all oxides present in the glass composition, 65-75% by weight of SiO2, 5-10% by weight of B2O3, 2-8% by weight of Al2O3, 2-10% by weight of Na2O, 0.5-5% by weight of K2O, 0.01-0.05% by weight of MgO, 0.1-1% by weight of CaO, 0.01-0.5% by weight of SrO, and 1-3% by weight of The glass composition contains or comprises BaO, 0.01 to 0.5 wt% MnO, 1.0 to 1.5 wt% Fe2O3, and 2 to 8 wt% TiO2, wherein the Fe2O3 and TiO2 in the glass composition are present in a ratio of 1:3.00 to 1:5.00, preferably 1:3.50 to 1:4.50, and more preferably 1:3.80 to 1:4.00, based on the weight of the oxides.

[0163] According to another preferred embodiment of the present invention, the amber glass container for pharmaceuticals contains, based on all oxides present in the glass composition, 65-75% by weight of SiO2, 5-10% by weight of B2O3, 2-8% by weight of Al2O3, 2-10% by weight of Na2O, 0.5-5% by weight of K2O, 0.01-0.05% by weight of MgO, 0.1-1% by weight of CaO, 0.01-0.5% by weight of SrO, 1-3% by weight of BaO, 0 The glass composition contains or comprises 0.01 to 0.5 wt% MnO, 1.0 to 1.5 wt% Fe2O3, and 2 to 8 wt% TiO2, wherein the Fe2O3 and TiO2 in the glass composition are present in a ratio of 1:3.00 to 1:5.00, preferably 1:3.50 to 1:4.50, or 1:3.80 to 1:4.00, based on the weight of the oxides, and the glass composition does not contain Li2O.

[0164] According to another preferred embodiment of the present invention, the amber glass container for pharmaceuticals has a temperature of 3.0 to 8.0 * 10 when measured in the range of 20°C to 300°C (CTE). -6 K -1 , or 3.5~7.0*10 -6 K -1 , or 4.0~6.0*10 -6 K -1 , most preferably 5.2*10 -6 K -1 It has an average linear thermal expansion coefficient.

[0165] According to another preferred embodiment of the present invention, the amber glass container for pharmaceuticals has a Tg of 300 to 750°C, preferably 400 to 700°C, more preferably 500 to 600°C, and most preferably 520 to 570°C. In the sense of the present invention, Tg is also known as the transition temperature of glass and is defined in ISO 7884-8:1987.

[0166] According to another embodiment of the present invention, the amber glass container for pharmaceuticals according to the present invention has an annular tension of less than 5 Friedel grades, preferably less than 4 Friedel grades, more preferably less than 3 Friedel grades, even more preferably less than 2 Friedel grades, and most preferably less than 1 Friedel grade.

[0167] In another embodiment of the present invention, the amber glass container for pharmaceuticals of the present invention has an axial load of at least 1100 N, preferably at least 1500 N, more preferably at least 2000 N, and most preferably at least 3000 N.

[0168] According to another embodiment of the present invention, the amber glass container for pharmaceuticals of the present invention has a burst pressure of 20 to 80 bar, preferably 30 to 70 bar, and most preferably 40 to 60 bar.

[0169] In another embodiment of the present invention, the amber glass container for pharmaceuticals of the present invention has an axial load pressure of 1500 to 6000 N, preferably 2000 to 5000 N, and most preferably 2500 to 4000 N.

[0170] According to another embodiment of the present invention, the amber glass container for pharmaceuticals according to the present invention has good chemical durability. In the sense of the present invention, the term “chemical durability” refers to the ability of the amber glass container for pharmaceuticals according to the present invention and the manufactured glass composition to resist degradation when exposed to specific chemical conditions. Preferably, the chemical durability of the glass composition described herein was evaluated according to an established material testing standard, namely, “Glass-Hydrolytic resistance of glass grain at 121℃.-Method of test and classification” or ISO 720:1985 entitled “Glass-Hydrolytic resistance of glass grain at 98℃”. The ISO 719 standard is similar to the ISO 720 standard.

[0171] According to one embodiment of the present invention, a pharmaceutical amber glass container is characterized by hydrolysis resistance characterized by an extractable Na2O equivalent in micrograms [μg / g] per gram of glass, as determined by ISO 719:2020-09, being 62 μg / g or less, preferably 31 μg / g or less. The ISO 719 standard is a measure of the degradation resistance of glass in pure water that does not contain CO. Details regarding the measurement are specified in the Experiments section.

[0172] According to another embodiment of the present invention, a pharmaceutical amber glass container is characterized by hydrolysis resistance characterized by an extractable Na2O equivalent in micrograms [μg / g] per gram of glass, as determined by ISO 720:2020, being 527 μg / g or less, preferably 62 μg / g or less. The ISO 720 standard is a measure of the degradation resistance of glass in pure water that does not contain CO. Details regarding the measurement are specified in the Experiments section.

[0173] In another embodiment of the present invention, a pharmaceutical amber container includes a coating on at least a portion of the surface of the container. The coating may be present on the outer surface, the inner surface, or both the outer and inner surfaces of the container.

[0174] For example, the coating may include silicone, silane, or a mixture thereof, wherein the silicone or silane may or may not be crosslinked. Silanes and silicones suitable for treating the surface of the container are disclosed, for example, in U.S. Patent Publication No. 2011 / 0006028, U.S. Patent Publication No. 4420578, or International Publication No. 2014 / 105350. Additionally or alternatively, the coating may include a coupling agent layer containing a coupling agent disposed on the outer surface of the container, and a polymer layer containing a polymer chemical composition disposed above the coupling agent layer. For example, the coating is the coating described in U.S. Patent Publication No. 2013 / 171456.

[0175] According to a preferred embodiment of the present invention, the coating is present on the inner surface of the container. According to another embodiment of the present invention, the coating is a hydrophobic coating present on the inner surface of the container. For example, the coating is the coating described in U.S. Patent No. 8,592,015.

[0176] According to a preferred embodiment of the present invention, a pharmaceutical amber glass container comprises a hydrophobic coating on at least a portion of the inner surface of the container and contains a compound comprising the elements Si, C, O, and H as significant components, wherein the further elements are present in a content of less than 10 atomic percent, and the compound is composed of SiO x -C y H z This includes, where x is in the range of 0.6 to 0.9, y is in the range of 1.2 to 3.3, and z is in the range of 0.0 to 6.0. According to a preferred embodiment, the hydrophobic coating comprises, as significant components, a compound containing the elements Si, C, O, and H, as well as further elements, wherein the further elements are present in a content of less than 5 atomic percent, and the compound has the composition SiO x -C y H z The coating includes a cross-linked polymer, where x is in the range of 0.7 to 0.8, y is in the range of 1.5 to 2.5, and z is in the range of 0.0 to 6.0. Such coatings are known to those skilled in the art, for example, under the trade name SCHOTT TopLyo®.

[0177] In another preferred embodiment of the present invention, the amber glass container for pharmaceuticals includes a coating on at least a portion of the inner surface of the container that contains a significant component SiO2.

[0178] The inventors have surprisingly found that the method of the present invention can produce pharmaceutical amber glass containers that meet the most important standards, namely the visible-range UV blocking and transmission requirements of the USP, Ph.Eu., and JP requirements. More precisely, the method of the present invention can provide pharmaceutical amber glass containers that have a transmittance of 25% or less across the entire wavelength range of 290 nm to 450 nm when measured at a thickness of 1.0 mm to provide UV blocking, and a transmittance of 45% or more across the entire wavelength range of 590 nm to 610 nm when measured at a thickness of 1.0 mm to make them suitable for visual inspection. In addition, the manufactured pharmaceutical amber containers are physically stable and preferably have an annular tension of 1 Friedel grade or less. Therefore, the containers are sufficiently stable for use in the pharmaceutical field.

[0179] This is particularly advantageous because the pharmaceutical container can be used for bottling and storing UV-critical substances, such as ADCs, while still retaining transparency in the visible region, allowing for inspection of the container before and after filling with such UV-critical substances. Furthermore, the amber glass pharmaceutical container of the present invention is USP <660> It meets the standards specified in EP3.2.1 and JP7.01. Only one type of glass container can be used in different countries, such as the United States, Europe, and Japan. This means that only one type of glass container and one manufacturing method are needed, resulting in significant cost savings. This makes it possible to manufacture containers more economically in large quantities. Furthermore, if necessary, already bottled drugs can be divided among multiple countries. In particular, surplus volume in one country, such as the United States or Europe, can be used in another country where demand has increased, such as Japan (or conversely, surplus volume in Japan can be used in the United States or Europe).

[0180] Furthermore, the inventors have surprisingly found that the amber glass container for pharmaceuticals of the present invention exhibits excellent physical and chemical resistance.

[0181] Use of amber glass containers for pharmaceuticals According to one aspect of the present invention, the amber glass container for pharmaceuticals according to the present invention is used to store pharmaceutical compositions, cosmetic compositions, or drugs. More precisely, the amber glass container for pharmaceuticals is used to store pharmaceutical compositions, cosmetic compositions, or drugs, wherein the amber glass has a transmittance of 25% or less across the entire wavelength range of 290 nm to 450 nm when measured at a thickness of 1.0 mm, and a transmittance of 45% or more across the entire wavelength range of 590 nm to 610 nm when measured at a thickness of 1.0 mm.

[0182] According to another embodiment of the present invention, a pharmaceutical amber glass container obtained according to the method of the present invention is used to store a pharmaceutical composition or cosmetic composition or drug. More precisely, each of the following steps of the method, namely, a) The process of preparing an amber glass tube, b) A process of hot-forming an amber glass tube into an amber glass container, c) A step of heating the amber glass container to a temperature of Tg+5°C to Tg+50°C, d) A step to obtain a pharmaceutical amber glass container by cooling the amber glass container heated in step c) to a temperature of Tg-60°C to Tg-10°C at a rate of 0.8°C / s to 4°C / s per 1.0 mm of wall thickness of the amber glass container. A pharmaceutical amber glass container obtained by a method including the above is used to store pharmaceutical compositions, cosmetic compositions, or medicines.

[0183] According to a preferred embodiment of the present invention, the amber glass container for pharmaceuticals according to the present invention is used to store pharmaceutical compositions and more preferably compositions comprising ADCs. ADC is an abbreviation for antibody-drug-conjugate or anything-drug-conjugate. ADCs are a class of biopsy drugs designed as molecular targeted therapies for cancer treatment. Unlike chemotherapy, ADCs are intended to target and kill tumor cells while preserving healthy cells. An ADC is a complex molecule consisting of a biologically active cytotoxic (anti-cancer) payload or antibody conjugated to a drug. An ADC mainly consists of three components: an antibody that targets the surface of cancer cells to induce a therapeutic response, a payload that induces the desired therapeutic response, and a linker that is circulating and stable, only binding the payload to the antibody and releasing the payload at the desired target. Several ADCs exist that are approved and commercially available by the FDA.

[0184] According to one embodiment of the present invention, the amber glass container for pharmaceuticals according to the present invention is used to store pharmaceutical compositions comprising gemtuzumab ozogamicin, brentuximab vedotin, trastuzumab emtansine, inotuzumab ozogamicin, polatuzumab vedotin, enfortumab vedotin, trastuzumab deruxtecan, sacituzumab govitecan, beramba mahodotin, moxetumomab pasdotox, ronkastuximab tesirin, tisotumab vedotin, milbetuximab sorabtansine and / or datopotamab deruxtecan.

[0185] Gemtuzumab ozogamicin, known as Mylotarg®, targets CD33 and can be used to treat acute myeloid leukemia (AML). Brentuximab vedotin, known as Adcetris®, targets CD30 and can be used to treat Hodgkin lymphoma and anaplastic large cell lymphoma. Trastuzumab emtansine, known as Kadcyla®, targets HER2 and can be used to treat HER2-positive metastatic breast cancer (mBC). Inotuzumab ozogamicin, known as Besponsa®, targets CD22 and can be used to treat relapsed / refractory acute lymphoblastic leukemia. Polivy®, known as polatuzumab vedotin, targets CD79B and can be used to treat relapsed / refractory diffuse large B-cell lymphoma. Enfortumab vedotin, known by the trade name Padcev®, targets Nectin-4 and can be used for locally advanced or metastatic urothelial carcinoma. Trastuzumab deruxtecan, known by the trade name Enhertu®, targets HER2 and can be used for breast cancer, gastric cancer, and non-small cell lung cancer. Sacituzumab govitecan, known by the trade name Trodelvy® T, targets trop-2 and can be used for breast cancer and urothelial carcinoma. Roncustuximab tecilin, known by the trade name Zynlonta®, targets CD19 and can be used to treat large cell lymphoma and high-grade B-cell lymphoma. Belantamab mahodotin, known by the trade name Blenrep®, binds to BCMA on the surface of myeloma cells, causing cell cycle arrest, and can be used to treat relapsed and refractory multiple myeloma. Moxetumomab pasdotox, known by the trade name Lumoxiti®, targets CD22 and can be used to treat adults with relapsed or refractory hairy cell leukemia (HCL). Tisotumab vedotin, known by the trade name Tivdak®, can be used to treat cervical cancer.This is a combination of tisotumab, a monoclonal antibody against tissue factor, and monomethyl auristatin E (MMAE), a potent inhibitor of cell division. Milbetuximab sorabtansine, known under the trade name Elahere®, targets FOLR1 and can be used to treat epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. Milbetuximab sorabtansine, known under the trade name Datroway®, targets Trop-2 and can be used to treat breast cancer.

[0186] In addition to the pharmaceutical compounds mentioned above, the pharmaceutical composition may contain further compounds such as surfactants, stabilizers, buffers, penetrating agents, pH adjusters, freeze-drying protective agents, viscosity modifiers, antioxidants and chelating agents, and preservatives.

[0187] In another embodiment of the present invention, a pre-filled amber glass container for pharmaceuticals is provided, the amber glass having a transmittance of 25% or less over the entire wavelength range of 290 nm to 450 nm when measured at a thickness of 1.0 mm, and a transmittance of 45% or more over the entire wavelength range of 590 nm to 610 nm when measured at a thickness of 1.0 mm, and the container is pre-filled with an ADC, or more preferably an ADC comprising gentuzumab ozogamicin, brentuximab vedotin, trastuzumab emtansine, inotuzumab ozogamicin, polatuzumab vedotin, enfortumab vedotin, trastuzumab deruxtecan, sacituzumab govitecan, verantamab mahodotin, moxetumab pastutox, loncustuximab tecillin, tisotumab vedotin, milbetuximab sorabtansine and / or datopotamab deruxtecan.

[0188] Preferably, the pre-filled amber glass container for pharmaceuticals is a 2R or 10R vial and more preferably has physical stability in the form of a circumferential tension of 1 Friedel grade or less.

[0189] Although the present invention has been described with reference to preferred examples of embodiments, the present invention is not limited thereto and can be modified in various ways.

[0190] Examples Various amber glass containers for pharmaceuticals were manufactured according to the method of the present invention, and further according to the prior art shown in the following examples.

[0191] In the first step, a length of 1500 mm l a , outer diameter d of 24mm o Amber glass tubes with a wall thickness of 1.0 mm (WT) were prepared. The amber glass tubes are amber borosilicate glass tubes having a glass composition containing 60-85 wt% SiO2, 5-20 wt% B2O3, 1-10 wt% Al2O3, 0.25-2 wt% Fe2O3, 0.5-10 wt% TiO2, 2-10 wt% Na2O, 0-5 wt% K2O, 0-2 wt% BaO, and 0-2 wt% CaO, relative to all oxides present in the glass composition. These glass tubes are commercially available from SCHOTT under the trade name Fiolax® braun, and are 5.4*10 -6 K -1 It has a CTE and a Tg of 550°C. The glass tube contains Fe2O3 and TiO2 in a ratio of 1:3.80 to 1:4.00 based on the weight of the oxides.

[0192] The amber glass tube is hot-formed into an amber glass container in the form of a vial with a size of 10R, in accordance with ISO 8362-1:2018.

[0193] Subsequently, the amber glass containers were heated at the different temperatures shown in the following table, and then cooled to a temperature of 520°C at a rate of 1.5°C / s per 1.0 mm of wall thickness to obtain amber glass containers for pharmaceuticals. Several samples were prepared and measured according to the measurement methods described below. The transmittance at wavelengths of 450 nm and below 590 nm is the average value of the measured samples. The ring tension is the maximum ring tension of the measured samples.

[0194] [Table 3]

[0195] From the above measurements, it can be seen that when the prepared amber glass container is heated to a temperature below Tg and then cooled to a temperature of 520°C at a rate of 1.5°C / s per 1.0 mm of wall thickness, an amber glass container unsuitable for use in the pharmaceutical field is produced due to the high cyclic tension of the container. When the prepared amber glass container is heated to temperatures of Tg+10°C and Tg+20°C and then cooled to a temperature of 520°C at a rate of 1.5°C / s per 1.0 mm of wall thickness, a pharmaceutical-grade amber glass container usable in the pharmaceutical field is obtained due to the low cyclic tension of the container. Furthermore, these containers satisfy the requirements of having a transmittance of 12% or less across the entire wavelength range of 290 nm to 450 nm when measured at a thickness of 1.0 mm, and a transmittance of 45% or more across the entire wavelength range of 590 nm to 610 nm when measured at a thickness of 1.0 mm.

[0196] Measurement method Neck squeeze test The neck squeeze test load, also known as the mechanical resistance of the vial neck to diametrical compression, can be determined by a diametrical load strength test in accordance with DIN EN ISO 8113 ("Glass containers - Resistance to vertical loads - Test method"), in which a compressive force is applied diametrically (radially) at two opposing positions on the outer surface geometry of the vial neck. Using a universal testing machine, the compressive force is increased at a constant load rate of 2000 N / min until the container breaks (breakage can be detected as a sharp drop in the force-time graph F(t)). The diametrical load is applied by two opposing uniaxial steel concave surfaces, with the vial neck positioned between them parallel to the axis. One of the concave surfaces is configured to self-adjust to compensate for geometric irregularities. The radii of the two steel concave surfaces are 25% greater than the radius of the outer diameter of the neck, and the load is applied along two opposing lines. The width of the steel concave surfaces is selected to be slightly shorter than the height of the vial neck.

[0197] Transmittance Transmittance was measured using a spectrophotometer (PerkinElmer LAMBDA1050+, a two-beam instrument with a wavelength selector (monochromator) and a photodiode detector, with continuous data acquisition) on glass with a 1 mm thickness and a mirror-finished surface. Sample preparation was performed by cutting a pharmaceutical amber glass container with a circular saw fitted with a wet polishing wheel. A section representing the wall thickness was selected and trimmed and mounted in the spectrophotometer. Each specimen was carefully cleaned and dried to avoid surface damage. Before placing the specimen in the holder, it was wiped with lens tissue. The specimen was positioned in the spectrophotometer so that its cylindrical axis was parallel to the slit and the light beam was perpendicular to the surface of the cross-section to minimize loss due to reflection.

[0198] The measurement wavelength range was set to 200nm to 800nm, the slit width to 5nm, the scanning speed to medium, and the sampling pitch to 1nm. It was found that the wavelength of 450nm yielded the highest transmittance in the wavelength range of 290nm to 450nm. Therefore, Table 1 shows only the value for "Transmittance at 450nm (Wall thickness: 1mm) (%)". Furthermore, it was found that the wavelength of 590nm yielded the lowest transmittance in the wavelength range of 590nm to 610nm. Therefore, Table 1 shows only the value for "Transmittance at 590nm (Wall thickness: 1mm) (%)".

[0199] Chemical stability according to ISO719:2020-09 According to the ISO 719 standard protocol, crushed glass particles were placed in contact with CO-free pure water at 98°C and 1 atm for 30 minutes. The solution was then neutralized to a neutral pH by calorimetry with diluted HCl. The amount of HCl required for titration to the neutral solution is converted to the equivalent amount of Na2O extracted from the glass and reported as Na2O in micrograms [mg / g] per unit weight of glass, with a smaller value indicating higher durability. The ISO 719 standard is classified into individual types. Type HGB1 is indicated as having a maximum extracted Na2O equivalent of 31 μg, Type HGB2 as having a maximum extracted Na2O equivalent of 62 μg, and Type HGB3 as having a maximum extracted Na2O equivalent of 62 μg and a maximum of 264 μg. Type HGB4 is indicated as having an extracted Na2O equivalent greater than 264 μg and less than or equal to 620 μg, and Type HGB5 is indicated as having an extracted Na2O equivalent greater than 620 μg and less than or equal to 1085 μg.

[0200] Chemical stability compliant with ISO 720:2020 According to the ISO 720 standard, crushed glass particles were placed in contact with CO-free pure water for 30 minutes under autoclave conditions (121°C, 2 atm). The solution was then neutralized to a neutral pH by calorimetry with diluted HCl. The amount of HCl required for titration to the neutral solution is converted to an equivalent amount of Na2O extracted from the glass, reported as Na2O in micrograms per unit weight of glass, with a smaller value indicating higher durability. The ISO 720 standard is classified into individual types. Type HGA1 indicates a maximum extracted equivalent of 62 μg of Na2O per gram of tested glass, Type HGA2 indicates an extracted equivalent of more than 62 μg and less than or equal to 527 μg of Na2O per gram of tested glass, and Type HGA3 indicates an extracted equivalent of more than 527 μg and less than or equal to 930 μg of Na2O per gram of tested glass.

[0201] Physical stability by de Senarmont and Friedel A pharmaceutical amber glass container was placed at room temperature between a polarizer (Strainoptics PS-100-BS polarimeter) and a quarter-wave plate. An analyzer (Strainoptics A-100A analyzer) was placed behind the quarter-wave plate. Light with a wavelength of 565 nm was used. The analyzer was oriented to coincide with the direction of the polarizer. The pharmaceutical amber glass container was oriented so that the angle between the polarization direction and the principal stress direction was 45°. Regions where the stress is parallel to the direction of the polarizer or analyzer appear dark (so-called isoclinic). The analyzer was rotated until the isoclinic disappeared, and the degree of rotation was measured.

[0202] Burst pressure The mechanical resistance to the internal pressure of a vial, also known as the bursting pressure, is determined by a bursting strength test according to DINEN ISO 7458:2004 ("Glass containers - resistance to internal pressure - test methods"), in which a liquid pressure is applied from the inside of the vial, increasing at a constant load ratio of 5.8 bar / sec until the container breaks.

[0203] The internal hydraulic pressure p was created by applying a force F to a water-filled piston-cylinder system (diameter D=10mm) and transmitted to a pharmaceutical amber glass container via a high-pressure hose.

[0204] After fracture, the macroscopic fracture pattern of each amber glass container for pharmaceuticals is visually inspected using fractography to determine the axial position of the fracture origin. The reference position is set at y=0mm at the top of the amber glass container for pharmaceuticals.

[0205] Axial load pressure The mechanical resistance of the vial to axial compression, also known as axial load pressure, was determined by a vertical load strength test according to DINEN ISO 8113:2004 ("Glass containers - Resistance to vertical loads - Test methods"), in which the compressive force was applied axially, increasing at a constant load ratio of 500 N / min until the container broke. [Explanation of Symbols]

[0206] 101 Vial sidewall 102 vial neck area 103 Bottom of the vial 201 Side wall of a syringe 202 Syringe neck area 203 Open bottom of syringe 204 Syringe plunger 301 Cartridge side wall 302 Cartridge neck area 303 Open bottom of the cartridge s1 wall thickness d1 outer diameter d2 inner diameter

Claims

1. A method for manufacturing amber glass containers for pharmaceuticals, The method involves the following steps, namely, a) The process of preparing an amber glass tube, b) A step of hot-forming the amber glass tube into an amber glass container, c) A step of heating the amber glass container at a temperature of Tg + 5°C to Tg + 50°C, d) A step to obtain a pharmaceutical amber glass container by cooling the amber glass container heated in step c) to a temperature of Tg-60°C to Tg-10°C at a rate of 0.8°C / s to 4°C / s per 1.0 mm of wall thickness of the amber glass container. A method for manufacturing amber glass containers for pharmaceutical use, including [the specified ingredient].

2. A method for producing a pharmaceutical amber glass container according to claim 1, wherein the heating step c) is performed at a temperature of Tg + 8°C to Tg + 45°C, preferably Tg + 10°C to Tg + 35°C, and most preferably Tg + 12°C to Tg + 30°C.

3. A method for producing a pharmaceutical amber glass container according to claim 1 or 2, wherein the heating step c) is performed for 5 to 500 seconds, more preferably 10 to 300 seconds, and even more preferably 12 to 100 seconds.

4. The aforementioned cooling step d) i) Cooling the amber glass container heated in step c) to a temperature of Tg-50°C to Tg-15°C, preferably Tg-40°C to Tg-20°C, and / or ii) Cool the amber glass container heated in step c) at a rate of 0.9°C / s to 3°C / s per 1.0 mm wall thickness of the amber glass container, preferably at a rate of 1.0°C / s to 2.5°C / s, most preferably at a rate of 1.0°C / s to 2.0°C / s, A method for manufacturing a pharmaceutical amber glass container according to any one of claims 1 to 3.

5. The amber glass tube prepared in step a) above is When measured at a thickness of 1.0 mm, it has a transmittance of 15.0% or less, preferably 14.5% or less, across the entire wavelength range of 290 nm to 450 nm, and furthermore, When measured at a thickness of 1 mm, it has a transmittance of 50.0% or more, preferably 52.5% or more, across the entire wavelength range of 590 nm to 610 nm. A method for manufacturing a pharmaceutical amber glass container according to any one of claims 1 to 4.

6. The amber glass tube prepared in the aforementioned step a) is an amber borosilicate glass tube, preferably Fe in the glass composition ２ O ３ and TiO ２ amber borosilicate glass tube, and most preferably, the amber glass tube has 60 to 85 wt% of SiO based on all oxides present in the glass composition ２ , 5 to 20 wt% of B ２ O ３ , 1 to 10 wt% of Al ２ O ３ , 0.25 to 2 wt% of Fe ２ O ３ , 0.5 to 10 wt% of TiO ２ , 2 to 10 wt% of Na ２ O, 0 to 5 wt% of K ２ O, 0 to 2 wt% BaO, and 0 to 2 wt% CaO A method for manufacturing a pharmaceutical amber glass container according to any one of claims 1 to 5.

7. A pharmaceutical amber glass container, wherein the amber glass is When measured with a thickness of 1.0 mm, the transmittance is 25% or less across the entire wavelength range from 290 nm to 450 nm. When measured at a thickness of 1.0 mm, the transmittance is 45% or more across the entire wavelength range of 590 nm to 610 nm. A pharmaceutical amber glass container having the following features.

8. The aforementioned amber glass container for pharmaceuticals, i) Na extracted in micrograms per gram of glass [μg / g] as determined in accordance with ISO 719:2020-09. ２ Hydrolysis resistance characterized by an O equivalent of 62 μg / g or less, preferably 31 μg / g or less, and / or ii) A neck squeeze test load of at least 1100 N, preferably at least 1500 N, more preferably at least 2000 N, most preferably at least 3000 N, and / or iii) Ring tension of less than 5 Friedel grade, preferably less than 4 Friedel grade, even more preferably less than 3 Friedel grade, even more preferably less than 2 Friedel grade, most preferably 1 Friedel grade or less, and / or iv) A burst pressure of 20 to 80 bar, preferably 30 to 70 bar, most preferably 40 to 60 bar, and / or v) Axial load pressure of 1500 to 6000 N, preferably 2000 to 5000 N, most preferably 2500 to 4000 N, The amber glass container for pharmaceuticals according to claim 7, having the following features.

9. The amber glass of the aforementioned pharmaceutical amber glass container contains 60 to 85% by weight of SiO2 based on all oxides present in the glass composition. ２ , 5-20% by weight of B ２ O ３ , 1-10% by weight of Al ２ O ３ , 0.25 to 2% by weight of Fe ２ O ３ , 0.5 to 10% by weight of TiO ２ , 2-10% by weight of Na ２ O, 0-5% by weight of K ２ The glass composition contains O, 0-2% by weight of BaO, and 0-2% by weight of CaO. The amber glass container for pharmaceuticals according to claim 7 or 8.

10. The amber glass container for pharmaceuticals according to any one of claims 7 to 9, wherein the pharmaceutical container is a vial, preferably a 2R, 4R, 6R, 10R, 15R, or 20R vial in accordance with ISO 8362-1:2018, or a syringe, preferably a 0.5 ml, 1.1 ml, 1.5 ml, 2 ml, 2.25 ml, 3 ml, or 5 ml syringe in accordance with ISO 11040-4:2024.

11. The aforementioned drug container, i) A 2R or 4R vial in accordance with ISO 8362-1:2018, which has a transmittance of 15% or less across the entire wavelength range of 290 nm to 450 nm when measured at a thickness of 1.0 mm, and a transmittance of 45% or more across the entire wavelength range of 590 nm to 610 nm when measured at a thickness of 1.0 mm, or ii) A 6R or 8R vial in accordance with ISO 8362-1:2018, which has a transmittance of 13% or less across the entire wavelength range of 290 nm to 450 nm when measured at a thickness of 1.0 mm, and a transmittance of 45% or more across the entire wavelength range of 590 nm to 610 nm when measured at a thickness of 1.0 mm, or iii) A 10R or 15R vial in accordance with ISO 8362-1:2018, having a transmittance of 12% or less across the entire wavelength range of 290 nm to 450 nm when measured at a thickness of 1.0 mm, and having a transmittance of 45% or more across the entire wavelength range of 590 nm to 610 nm when measured at a thickness of 1.0 mm, or iv) A 20R vial in accordance with ISO 8362-1:2018, wherein the wall thickness of the vial is s １ Except when the thickness is 1.0 mm, a 20R vial has a transmittance of 10% or less across the entire wavelength range of 290 nm to 450 nm when measured at a thickness of 1.0 mm, and a transmittance of 45% or more across the entire wavelength range of 590 nm to 610 nm when measured at a thickness of 1.0 mm. Having, A pharmaceutical amber glass container according to any one of claims 7 to 10.

12. The aforementioned amber container for pharmaceuticals includes a coating on at least a portion of the surface of the container, preferably on the inner surface of the container, and preferably the coating contains an important component. i) A hydrophobic coating comprising a compound containing the elements Si, C, O, and H, and further elements (provided that the further elements are present in an amount of less than 10 atomic percent), The compound is composition SiO ｘ -C ｙ H ｚ Including, here, x is in the range of 0.6 to 0.

9. y is in the range of 1.2 to 3.3, and z is in the range of 0.0 to 6.

0. It is a hydrophobic coating, or ii) SiO ２ It is a hydrophobic coating that includes The amber glass container for pharmaceuticals according to any one of claims 7 to 11.

13. Use of a pharmaceutical amber glass container according to any one of claims 7 to 12 for storing a pharmaceutical composition or cosmetic composition or a drug, preferably for storing an antibody drug conjugate.

14. Fe in borosilicate glass as a temperature-dependent coloring agent system ２ O ３ and TiO ２ In use, The Fe ２ O ３ and the TiO ２ It is used in a ratio of 1:3.00 to 1:5.00 based on the weight of the oxide, preferably 1:3.50 to 1:4.50, and preferably 1:3.80 to 1:4.

00. use.

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