Glass tube for pharmaceutical container, and process for the production of glass tube

Abstract

To provide a glass tube for a pharmaceutical container, having low cost and high throughput and enabling in-process control of the quality of a manufactured glass tube, and a process for the production of the glass tube.SOLUTION: A glass tube has an inner surface and an outer surface and further has an inner diameter, an outer diameter, a first end portion, a second end portion, and a first position. The first position is 400 mm distant from the first end portion. The glass tube has a first intermediate position, which is 15 mm distant from the first end portion. The first end portion is formed at a first closed end portion and preferably the second end portion is also formed at a second closed end portion. A vent hole is arranged in a first neighborhood of the first closed end portion. The first neighborhood is located between the first intermediate position and the first position. A ToF-SIMS signal including a Na2F+ signal and a 30Si+ signal can be measured on the inner surface of the first neighborhood.SELECTED DRAWING: Figure 2

Description

[Technical Field]

[0001] This invention relates to glass tubes for pharmaceutical containers and to a method for manufacturing glass tubes. [Background technology]

[0002] Glass tubes for pharmaceutical containers are well-known and widely found in hospitals and clinics. The requirements for these glass tubes are constantly increasing to ensure the quality and integrity of the pharmaceuticals they contain.

[0003] Glass tubing for pharmaceutical containers is typically manufactured by drawing molten glass into a glass tube. During subsequent stages, the drawn glass tube is cut into sections, which are then further processed into, for example, glass vials, glass ampoules, glass cartridges, or glass syringes. Some glass tubes are fitted with vents.

[0004] In this technical field, several problems are known that affect the performance and suitability of glass tubes for use as pharmaceutical containers.

[0005] Glass tubes for pharmaceutical containers are mass-produced. Despite their expected simplicity and low cost, they are subject to high quality requirements that must be guaranteed during and after manufacturing, and therefore undergo quality control before sale. Contamination is particularly unacceptable, as even extremely small amounts of contamination can adversely affect the quality of pharmaceuticals.

[0006] Glass tubes for pharmaceutical containers are manufactured from glass compositions that melt at high temperatures. This is because excellent hydrolysis resistance, one of the fundamental requirements for glass containers, is based on glass components with very high melting points, such as SiO2 and Al2O3. Therefore, during manufacturing, high melting temperatures are sometimes required to reach sufficient melt viscosity for homogenization and removal of bubbles from the molten material. However, high melting temperatures also impose high demands on the materials of the melting furnace and clarification tank. For example, the leaching of materials from the melting and / or clarification furnace into the molten glass must be avoided at all costs.

[0007] Current manufacturing methods already provide good quality standards. Nevertheless, contamination of glass tubes is still reported to occur rarely, so its prevention remains a constant focus and issue for manufacturers of pharmaceutical containers. [Overview of the Initiative] [Problems that the invention aims to solve]

[0008] To ensure the desired high quality requirements, it remains necessary to provide sufficient and consistent product monitoring. Therefore, there are related and independent requirements that enable low cost, high throughput, and in-process control of the quality of the manufactured glass tubes. [Means for solving the problem]

[0009] These issues are resolved by the scope of the claims and by the scope described below.

[0010] Summary of the Invention In a first embodiment, the present invention relates to a glass tube for a pharmaceutical container, wherein the glass tube has an inner surface and an outer surface, and the glass tube has an inner diameter d i and outer diameter d ohas, the glass tube has a first end and a second end, the glass tube has a first position, the first position is at a distance of 400 mm from the first end, the glass tube has a first intermediate position, the first intermediate position is at a distance of 15 mm from the first end, the first end is formed into a first closed end, preferably the second end is also formed into a second closed end, a vent hole is arranged in a first vicinity of the first closed end, the first vicinity is between the first intermediate position and the first position, Na2F + signal and 30 Si + The signal of ToF - SIMS including the signal of can be measured on the inner surface of the first vicinity, and the integrated Na2F + signal of, the integrated 30 Si + The area on the inner surface in the first vicinity where the ratio of the signal to the signal of is at least 0.10 is 36 mm 2 or less, and the Na2F + signal and the 30 Si + signal are integrated over a depth of 100 nm, regarding the glass tube.

[0011] In a second aspect and / or related aspects, the present invention is a glass tube for a pharmaceutical container, the glass tube has an inner surface and an outer surface, the glass tube has an inner diameter d i and an outer diameter d o has, the glass tube has a first end and a second end, the glass tube has a first position, the first position is at a distance of 400 mm from the first end, the glass tube has a first intermediate position, the first intermediate position is at a distance of 15 mm from the first end, the first end is formed into a first closed end, preferably the second end is also formed into a second closed end, a vent hole is arranged in a first vicinity of the first closed end, the first vicinity is between the first intermediate position and the first position, the glass tube has a length l along its longitudinal axis aThe glass tube further has a central section, the central section is 0.5 l along the longitudinal axis a 5d with the position as the center. i The glass tube extends over a distance of , wherein the ratio between the fluorescence emission specified in the first vicinity and the fluorescence emission specified in the central region is at least 0.6.

[0012] Accordingly, the present invention provides a glass tube for pharmaceutical containers having a vent, enabling high-throughput in-process screening via fluorescence analysis. The glass tube of this disclosure has an improved fluorescence level compared to conventional glass tubes. The inventors believe that this improved fluorescence level is due to a reduced level of deposited material on the internal surface of the first periphery of the glass tube. The reduced contamination level is thought to increase the length of the travel path of the excitation wavelength light within the glass tube wall, because an increased portion of the excitation light is reflected by the internal surface of the glass tube. This reflected portion of the excitation light incident on the glass tube via the external surface enters the glass tube wall and is reflected by the internal surface, so that the light passes through the glass tube wall twice to achieve stronger excitation of the fluorescent species. It has been found that a certain level of contamination on the internal surface within the first periphery reduces the amount of light reflected by the internal surface, thereby reducing the emission of fluorescence from the fluorescent compound in the glass tube. The glass tube of this disclosure has reduced contamination on the internal surface within the first periphery, thereby increasing the fluorescence signal, or in other words, reducing the adverse effect of contamination on the fluorescence signal intensity. A stronger signal in fluorescence analysis means that a smaller amount of fluorescent component can be detected. This also means that a higher signal-to-noise ratio is achieved, which enables higher reliability in high-throughput analysis. Therefore, the glass tube of this invention enables high-throughput in-process screening via fluorescence analysis. The glass tube of this invention exhibits residual fluorescence caused by fluorescent components intentionally present in the glass composition, such as Fe2O3, TiO2, ZrO2, CeO2, As2O3, and K2O.

[0013] ToF-SIMS (Time-of-Flight Secondary-Ion-Mass-Spectrometry) is a sensitive method for characterizing glass surfaces and is therefore useful for evaluating the internal surface of glass tubes. The inventors have established conditions to provide a glass tube for pharmaceutical containers with vents in which manufacturing-induced deposition material is minimized compared to glass tubes known in the prior art. 30 Si + The integrated Na2F for the signal + The signal serves as a fingerprint and / or indicator of the deposited material on the internal surface, which is characteristic of glass tubes for pharmaceutical containers. The glass tube according to the present invention advantageously minimizes the area near the first vent where the characteristic signal can be detected, and consequently increases the fluorescence signal in the first vicinity.

[0014] Fluorescent impurities from molten glass, such as ZrO2 which may originate from the molten bath during the melting of glass raw material batches, exhibit fluorescence that can be detected in the resulting glass tubes. The following phenomenon is thought to explain why minimizing deposited material on the inner surface of the glass tube improves fluorescence detection: The excitation light beam can be directed at the outer surface of the glass tube, refracted into the glass, and totally reflected at the glass-air interface toward the inner part of the glass tube. Along its optical path inside the glass tube, (residual) fluorescent components are excited, and their fluorescence can be detected perpendicular to the excitation beam. If the inner surface of the glass tube is affected by deposited material resulting from manufacturing, the total reflection of the excitation light beam is blocked, which leads to a loss of excitation light and / or a reduction in excitation light intensity at the glass-air interface. This loss in excitation light (intensity) directly correlates with a loss in fluorescence emission, which is readily detectable by a fluorescence detector. A suitable fluorescence detector can be incorporated into the manufacturing equipment and serves as a direct means of integrated product control. The absence of deposited material in the first periphery can be confirmed by ToF-SIMS measurement and / or by comparing the residual fluorescence of the central region of the glass tube with that of the first periphery. If the first periphery exhibits deposited material, for example, due to the introduction of vents, the fluorescence intensity in the first periphery will be lower than that in the central region. Even in glass tubes without residual fluorescence, the absence of deposited material can be confirmed using the ToF-SIMS signal.

[0015] In a third aspect, the present invention relates to a method for manufacturing a glass tube for pharmaceutical containers, comprising the following steps: • A step of preparing a glass melt containing volatile components, such as borates, preferably a step of melting a batch of raw materials that will result in oxides being contained in the glass melt. The step of shaping the molten glass into a glass tube, for example, by drawing. - The step of forming the glass tube into a glass tube having a first end and a second end, • The step of forming the first end into a first closed end, • In the step of introducing a vent hole into the glass tube, • During at least part of the introduction step, and / or immediately after the introduction step, a step using suction, Optionally, the step of forming and / or sealing the second end into a second closed end. The method includes the foregoing.

[0016] Accordingly, the present inventors have established a method for manufacturing glass tubes for pharmaceutical containers that enables high-throughput in-process screening via fluorescence analysis.

[0017] The present invention provides a glass tube for pharmaceutical containers, in which one of the open ends is formed into a closed end, wherein a vent is introduced into the glass tube and suction is used for at least part of the introduction step and / or immediately after the introduction step to ensure improvement in the internal surface conditions. It has been observed that due to the high temperature required to introduce the vent into the glass tube, a portion of the glass composition may evaporate and subsequently condense on the internal surface of the glass tube, particularly near the closed end. In rare and extreme cases, even visible deposits, such as micron-sized water stains, have been observed. Therefore, the present invention provides an effective countermeasure against material deposits on the internal surface of the glass tube. [Brief explanation of the drawing]

[0018] [Figure 1] Figure 1A shows a glass tube manufactured by a prior art method, showing water stains on the inner surface. Figure 1B shows a glass tube manufactured by a prior art method, showing borate deposits on the inner glass surface. Figure 1C shows a glass tube manufactured by the method of the present invention. [Figure 2] Figure 2 shows a three-dimensional ToF-SIMS mapping analysis obtained on the affected internal surface region of the glass tube shown in Figure 1A. The analysis is based on the cation species detected by ToF-SIMS. [Figure 3]Figure 3 shows the analysis of ToF-SIMS data obtained from five locations on the inner surface of the glass tube: Data for "Reference" and "Reference 2" indicate the absence of deposited material, data indicated as "Relatively Weak" and "Weak" indicate signals originating from detectable stains, and data indicated as "Strong" indicate signals originating from severe stains. The monitored ToF-SIMS signals are based on the ratio of the integrated Na2F+ signal to the integrated 30Si+ signal, where the Na2F+ and 30Si+ signals are integrated over a depth of 100 nm. [Figure 4] Figures 4A–E show recordings of underlying ToF-SIMS data at depths greater than 100 nm using the analysis and sputtering parameters described in the Methods section. The aforementioned recordings relate to the data shown in Figure 3, where Figure 4A is "Reference 2", Figure 4B is "Reference", Figure 4C is "Relatively Weak", Figure 4D is "Weak", and Figure 4E is "Strong", and relate to the signals shown in Figure 3. [Figure 5] Figure 5A illustrates the principle of high-throughput fluorescence analysis for monitoring the quality of glass tubes. Excitation light from a xenon lamp is spectrally filtered by a monochromator and irradiated onto the glass tube, penetrating the glass wall. Inside the glass wall, the excitation light beam undergoes total internal reflection. Fluorescence emission is collected perpendicular to the excitation light beam and spectrally filtered by the monochromator. Figure 5B shows fluorescence spectra obtained from six locations on the inner surface of the glass tube. Reference locations 1 and 2 are free of deposited materials on the inner surface, such as water stains, and exhibit the highest fluorescence intensity. In comparison, glass tubes with deposited materials are classified as "weak 1," "weak 2," and "strong," consistent with the ToF-SIMS data in Figures 3 and 4A-E, and exhibit significantly reduced fluorescence emission. [Modes for carrying out the invention]

[0019] Detailed explanation In a first embodiment, the present invention relates to a glass tube for a pharmaceutical container, wherein the glass tube has an inner surface and an outer surface, and the glass tube has an inner diameter d iand outer diameter d o The glass tube has a first end and a second end, the glass tube has a first position, the first position is 400 mm away from the first end, the glass tube has a first intermediate position, the first intermediate position is 15 mm away from the first end, the first end is formed into a first closed end, preferably the second end is also formed into a second closed end, a vent hole is located in the first vicinity of the first closed end, the first vicinity is located between the first intermediate position and the first position, and Na2F + The signal and 30 Si + The ToF-SIMS signal, which includes the signal of Na2F, can be measured on the internal surface of the first neighborhood, and the integrated Na2F + The integrated signal 30 Si + The area on the internal surface of the first neighborhood is 36 mm², where the ratio to the signal is at least 0.10. 2 The following is the Na2F + The signal and the 30 Si + The signal is integrated over a depth of 100 nm, relating to the glass tube.

[0020] ToF-SIMS (Time-of-Flight Secondary Ion Mass Spectrometry) is a sensitive method for evaluating glass surfaces and is therefore useful for evaluating the internal surfaces of glass tubes. The inventors have established conditions to provide a glass tube for pharmaceutical containers with vents in which manufacturing-induced deposition material is minimized compared to glass tubes known in the prior art. 30 Si + Integrated Na2F for the signal + The signal serves as a fingerprint and / or indicator of the deposited material on the internal surface, which is characteristic of glass tubes used for pharmaceutical containers.

[0021] To ensure a rigorous and thorough evaluation of the inner surface of the glass tube, Na2F + The signal is integrated over a depth of 100 nm, and in the same depth range 30The signal was normalized for Si. 30 Si isotopes are 28 This was chosen to avoid detector saturation of the Si signal. Three-dimensional (3D) ToF-SIMS analysis allows for the measurement of a map on the internal glass surface. The area resolution of 3D ToF-SIMS analysis is approximately 4 × 4 μm, or 16 μm. 2 This was the estimated cost (see Figure 2).

[0022] In one embodiment of the glass tube, the first neighborhood is characterized by the ToF-SIMS signal and the integrated Na2F + The integrated signal 30 Si + The area where the ratio to the signal is at least 0.10 is 36 mm². 2 Below, 25mm 2 Below, 20mm 2 Below, 16mm 2 Below, 10mm 2 Below, 5mm 2 Below, 3mm 2 The following, or 1 mm 2 The following is the case, where the Na2F + The signal and the 30 Si + The signal is integrated over a depth of 100 nm. Advantageously, the glass tube is used to store the integrated Na2F + The integrated signal 30 Si + This allows us to show only small areas of the deposited material that exceed a detection threshold of at least 0.10 for the signal.

[0023] In one embodiment of the glass tube, the first neighborhood is characterized by the ToF-SIMS signal and the integrated Na2F + The integrated signal 30 Si + The area where the ratio to the signal is at least 0.10 and 0.50 is 36 mm². 2 Below, 25mm 2 Below, 20mm 2 Below, 16mm 2 Below, 10mm 2 Below, 5mm2 Hereinafter, 3 mm 2 or less, or 1 mm 2 or less, and here the signal of the Na2F + and the 30 Si + signal are integrated over a depth of 100 nm. In one embodiment of the glass tube, the first vicinity is characterized by the signal of ToF-SIMS, and the integrated Na2F + signal, of the integrated 30 Si + signal, the area where the ratio is at least 0.10 and 0.50 or less is 36 mm 2 ~0.0001 mm 2 10 mm 2 ~0.001 mm 2 or less, 3 mm 2 ~0.01 mm 2 or 1 mm 2 ~0.1 mm 2 or less, and here the signal of the Na2F + and the 30 Si + signal are integrated over a depth of 100 nm.

[0024] In one embodiment of the glass tube, the first vicinity is characterized by the signal of ToF-SIMS, and the integrated NaF + signal, of the integrated 30 Si + signal, the area where the ratio is at least 0.10 is 0 mm 2 or less, and here the signal of the Na2F + and the 30 Si + signal are integrated over a depth of 100 nm. In one embodiment of the glass tube, the first vicinity is characterized by the signal of ToF-SIMS, and the integrated Na2F + signal, of the integrated 30 Si + signal, the area where the ratio is at least 0.10 and 0.50 or less is 0 mm 2 or less, and here the signal of the Na2F + and the 30 Si+ The signal is integrated over a depth of 100 nm.

[0025] Advantageously, the glass tube contains the accumulated Na2F + The integrated signal 30 Si + There may be no deposited material at all that exceeds the detection threshold of at least 0.10 for the signal.

[0026] In one embodiment, the ToF-SIMS signal is obtained using Ga at 25 keV as the primary ion source. + Using a primary ion current of 1 pA, preferably with a mass resolution Δm / m at a mass of 65 (mass 65) greater than 5000, and analyzing an area of ​​50 × 50 μm 2 , as sputter ions, O2 at 1 keV + Using a sputter ion current of 300 nA and a sputter area of ​​300 × 300 μm 2 Then, optionally, an electron flood gun is used to generate it for charge compensation.

[0027] In one embodiment, the ToF-SIMS signal is used to identify the detected ion species, for example, Na2F + The count is set to 1 by definition. 30 Si + The sputtering depth was determined by normalizing to the ion count and measuring the depth of the depression using a white light microscope, and the Na2F within 100 nm outside the inner surface was identified. + The cumulative strength and 30 Si + It is determined by calculating the quotient between the integrated intensity and the Na2F within 100 nm outside the inner surface. + The cumulative strength and 30 Si + The quotient between the cumulative intensity and the ΣNa2F + / Σ 30 Si + It can be expressed as follows.

[0028] In a second embodiment, the present invention relates to a glass tube for a pharmaceutical container, wherein the glass tube has an inner surface and an outer surface, and the glass tube has an inner diameter d i and outer diameter d o The glass tube has a first end and a second end, the glass tube has a first position which is 400 mm away from the first end, the glass tube has a first intermediate position which is 15 mm away from the first end, the first end is formed into a first closed end, preferably the second end is also formed into a second closed end, a vent hole is located in the first vicinity of the first closed end, the first vicinity is located between the first intermediate position and the first position, and the glass tube has a length l along its longitudinal axis. a The glass tube further has a central section, the central section is 0.5 l along the longitudinal axis a 5d with the position as the center. i The glass tube extends over a distance of , wherein the ratio between the fluorescence emission specified in the first vicinity and the fluorescence emission specified in the central region is at least 0.6.

[0029] The inventors have established that fluorescent components intentionally present in the glass composition, such as Fe2O3, TiO2, ZrO2, CeO2, As2O3, and K2O, contribute to the fluorescence of the resulting glass tube. One of these fluorescent oxide components, such as ZrO2, may originate from the melting bath during the melting of batches of glass raw materials. The present invention provides a glass tube for pharmaceutical containers having vents, wherein the deposition of material on the glass surface inside the glass tube is minimized and / or avoided compared to glass tubes known in the prior art, thereby enabling high-throughput in-process screening via fluorescence analysis.

[0030] The following phenomenon has been observed and is applied in industry: The excitation light beam can be directed at the outer surface of the glass tube, refracted into the glass tube, and totally reflected at the glass-air interface on the inside of the glass tube. Along its optical path inside the glass tube, a fluorescent component is excited, and its fluorescence can be detected perpendicular to the excitation beam. If the inner surface of the glass tube has deposited material, for example, from manufacturing, the total reflection of the excitation light beam is blocked, which leads to a loss of excitation light and / or a reduction in excitation light intensity at the glass-air interface. This loss in excitation light (intensity) directly correlates with a loss in fluorescence emission, which is easily detectable by a fluorescence detector. A suitable fluorescence detector can be incorporated into the manufacturing equipment and serves as a direct means of integrated product control.

[0031] In one embodiment, fluorescence emission is measured at an excitation wavelength of 290 nm and an emission wavelength of 370 nm, where the slit width for excitation is 10 nm and the slit width for emission is 10 nm, and the integration is optionally 100 ms, and the glass tube is positioned such that the angle between the incident excitation light beam and the reflected excitation light beam is approximately 90°, and fluorescence emission is detected at an angle of approximately 90°.

[0032] In one embodiment, a glass tube for a pharmaceutical container, wherein the glass tube has an inner surface and an outer surface, and the glass tube has an inner diameter d i and outer diameter d o The glass tube has a first end and a second end, the glass tube has a first position which is 400 mm away from the first end, the glass tube has a first intermediate position which is 15 mm away from the first end, the first end is formed into a first closed end, preferably the second end is also formed into a second closed end, a vent hole is located in the first vicinity of the first closed end, the first vicinity is located between the first intermediate position and the first position, and the glass tube has a length l along its longitudinal axis. aThe glass tube further has a central section, the central section is 0.5 l along the longitudinal axis a 5d with the position as the center. i A glass tube is provided, extending over a distance of , wherein the ratio between the fluorescence emission identified in the first vicinity and the fluorescence emission identified in the central region is at least 0.6, the fluorescence emission is measured at an excitation wavelength of 290 nm and an emission wavelength of 370 nm, the slit width for excitation is 10 nm and the slit width for emission is 10 nm, the integration is optionally 100 ms, the glass tube is positioned such that the angle between the incident excitation light beam and the reflected excitation light beam is approximately 90°, and the fluorescence emission is detected at an angle of approximately 90°.

[0033] In one embodiment, the glass tube has a ratio between the fluorescence emission specified in the first vicinity and the fluorescence emission specified in the central region of at least 0.6, at least 0.7, at least 0.8, at least 0.9, or at least 0.95. In one embodiment, the glass tube has a ratio between the fluorescence emission specified in the first vicinity and the fluorescence emission specified in the central region of 1.0 or less, 0.99 or less, 0.98 or less, 0.97 or less, or 0.96 or less. In one embodiment, the glass tube has a ratio between the fluorescence emission specified in the first vicinity and the fluorescence emission specified in the central region of 0.6 to 1.0, 0.7 to 0.99, 0.8 to 0.98, 0.9 to 0.97, or 0.95 to 0.96.

[0034] Advantageously, the glass tube has an internal surface in the first periphery that is similar to the internal surface of the central region. In other words, the glass tube can exhibit similar surface properties in both the first periphery and the central region, which reflects a reduction and / or complete removal of deposited material that may be found on the internal surface of the first periphery.

[0035] In one embodiment of the glass tube, the inner surface includes a deposit located in the first vicinity, the deposit having an area of ​​deposit extending parallel to the inner surface of the glass tube, and the area of ​​the deposit is 0.01 mm².2 ~36mm 2 Furthermore, the sediment is composed of accumulated Na2F + The integrated signal 30 Si + The ratio to the signal is 0.0002 to less than 0.10, and the Na2F + The signal and the 30 Si + The signal is integrated over a depth of 100 nm.

[0036] In one embodiment, the deposit located in the first vicinity of the inner surface extends parallel to the inner surface of the glass tube and is 0.01 mm thick. 2 ~36mm 2 The area of ​​the sediment has the cumulative Na2F + The integrated signal 30 Si + Identifiable and / or detectable by a ratio of 0.0002 to less than 0.10 to the signal, and the Na2F + The signal and the 30 Si + The signal is integrated over a depth of 100 nm.

[0037] In one embodiment, the deposits are due to condensates and / or sublimations, such as sodium salts, such as NaCl and / or NaF, and / or borates, such as sodium borate, which may occur through evaporation from the glass while a vent is introduced into the glass tube.

[0038] In one embodiment of the glass tube, the area of ​​the deposit is 0.01 mm². 2 ~1mm 2 Furthermore, the sediment is composed of accumulated Na2F + The integrated signal 30 Si + The ratio of the signal to the deposit is less than 0.0002 to 0.025, or the area of ​​the deposit is 0.01 mm². 2 ~36mm 2 Furthermore, the sediment is composed of accumulated Na2F + The integrated signal 30 Si +The ratio to the signal is between 0.0002 and less than 0.025.

[0039] In one embodiment, the area of ​​the sediment is at least 0.01 mm². 2 at least 0.03 mm 2 at least 0.1 mm 2 at least 0.2 mm 2 at least 0.3 mm 2 , or at least 0.5 mm 2 In one embodiment, the area of ​​the deposit is 36 mm². 2 Below, 25mm 2 Below, 20mm 2 Below, 16mm 2 Below, 10mm 2 Below, 5mm 2 Below, 3mm 2 The following, or 1 mm 2 The following applies: In one embodiment, the area of ​​the deposit is 36 mm². 2 ~0.01mm 2 , 25mm 2 ~0.03mm 2 , 20mm 2 ~0.05mm 2 , 16mm 2 ~0.07mm 2 , 10mm 2 ~0.1mm 2 , 5mm 2 ~0.2mm 2 , 3mm 2 ~0.3mm 2 , or 1mm 2 ~0.5mm 2 That is the case.

[0040] In one embodiment, the sediment is composed of accumulated Na2F + The integrated signal 30 Si + The ratio of the signal to the is at least 0.0002, at least 0.0005, at least 0.001, at least 0.002, at least 0.005, or at least 0.01. In one embodiment, the sediment is the accumulated Na2F + The integrated signal 30Si + The ratio to the signal is 0.2 or less, 0.1 or less, 0.08 or less, 0.06 or less, 0.05 or less, 0.04 or less, or 0.025 or less. In one embodiment, the sediment is the accumulated Na2F + The integrated signal 30 Si + The ratio of the signal to the signal is 0.0002-0.2, 0.0005-0.1, 0.001-0.08, 0.002-0.06, 0.005-0.04, or 0.01-0.025.

[0041] In one embodiment of the glass tube, the area of ​​the deposit is 0.01 mm². 2 ~1mm 2 Furthermore, the sediment is composed of accumulated Na2F + The integrated signal 30 Si + The ratio of the signal to the signal is 0.0002-0.2, 0.0005-0.1, 0.001-0.08, 0.002-0.06, 0.005-0.04, or 0.01-0.025.

[0042] In one embodiment of the glass tube, the sediment is accumulated Na2F + The integrated signal 30 Si + The ratio to the signal is less than 0.0002 to 0.025, and the area of ​​the deposit is 36 mm². 2 ~0.01mm 2 , 25mm 2 ~0.03mm 2 , 20mm 2 ~0.05mm 2 , 16mm 2 ~0.07mm 2 , 10mm 2 ~0.1mm 2 , 5mm 2 ~0.2mm 2 , 3mm 2 ~0.3mm 2 , or 1mm 2 ~0.5mm 2 That is the case.

[0043] In one embodiment of the glass tube, at least 90%, at least 99%, at least 99.9%, or at least 99.99% of the internal surface of the first vicinity is composed of accumulated Na2F + The integrated signal 30 Si + Characterized by a ratio of 0.0002 to less than 0.025 to the signal, the Na2F + The signal and the 30 Si + The signal is integrated over a depth of 100 nm.

[0044] In one embodiment of the glass tube, at least 99% of the internal surface of the first vicinity is made up of accumulated Na2F + The integrated signal 30 Si + Characterized by a ratio of 0.0002-0.2, 0.0005-0.1, 0.001-0.08, 0.002-0.06, 0.005-0.04, or 0.01-0.025 to the signal, the Na2F + The signal and the 30 Si + The signal is integrated over a depth of 100 nm.

[0045] In one embodiment of the glass tube, at least 99.99% of the internal surface of the first vicinity is made up of accumulated Na2F + The integrated signal 30 Si + Characterized by a ratio of 0.0002-0.2, 0.0005-0.1, 0.001-0.08, 0.002-0.06, 0.005-0.04, or 0.01-0.025 to the signal, the Na2F + The signal and the 30 Si + The signal is integrated over a depth of 100 nm.

[0046] In one embodiment, the glass tube has "hydrolysis resistance," defined as alkali leaching in the central region of its inner surface and specified as the Na2O equivalent in an eluate prepared in accordance with ISO 4802-2:2010, wherein the hydrolysis resistance is 0.5 μg cm³. -2 Less than 0.4 μg cm⁻¹ -2 Less than 0.3 μg cm -2 Less than 0.2 μg cm⁻¹ -2 Less than 0.1 μg cm³ -2 It is less than.

[0047] In one embodiment, the glass tube contains at least 0.01 μg cm³ -2 at least 0.02 μg cm³ -2 at least 0.03 μg cm⁻¹ -2 at least 0.04 μg cm³ -2 , or at least 0.05 μg cm³ -2 It has hydrolysis resistance.

[0048] In one embodiment, the glass tube contains 0.01 to 0.5 μg cm³ -2 , 0.02~0.4 μg cm -2 , 0.03~0.3 μg cm -2 , 0.04~0.2 μg cm -2 , or 0.05~0.1 μg cm³ -2 It has hydrolysis resistance.

[0049] glass composition In one embodiment of a glass tube for pharmaceutical containers, the glass tube comprises a glass composition selected from a list of soda-lime glass, borosilicate glass, aluminosilicate glass, and glass containing 5 to 20 mol% B2O3 based on all oxides present in the glass composition.

[0050] The glass composition may, in particular, include oxide species that inherently exhibit at least some fluorescence when excited by UV light, i.e., in the range of 100 to 380 nm, such as Fe2O3, TiO2, ZrO2, CeO2, As2O3, and / or K2O.

[0051] In one embodiment of a glass tube for pharmaceutical containers, the glass tube comprises a glass composition containing 5-20 mol% B2O3 and / or 2-10 mol% Na2O. Optionally, the glass composition comprises 60-85 mol% SiO2, 5-20 mol% B2O3, 2-10 mol% Al2O3, 0-2 mol% Fe2O3, 2-10 mol% Na2O, 0-5 mol% K2O, 0-2 mol% BaO, 0-2 mol% CaO, and / or 0-10 mol% TiO2, based on all oxides present in the glass composition.

[0052] In one embodiment, the glass composition contains at least 60 mol% SiO2, at least 62 mol% SiO2, at least 64 mol% SiO2, at least 66 mol% SiO2, or at least 68 mol% SiO2 based on all oxides present in the glass composition. In one embodiment, the glass composition contains 85 mol% or less SiO2, 83 mol% or less SiO2, 81 mol% or less SiO2, 79 mol% or less SiO2, or 77 mol% or less SiO2 based on all oxides present in the glass composition. In one embodiment, the glass composition contains 60-85 mol% SiO2, 62-83 mol% SiO2, 64-81 mol% SiO2, 66-79 mol% SiO2, or 68-77 mol% SiO2 based on all oxides present in the glass composition.

[0053] In one embodiment, the glass composition contains at least 5.0 mol% B2O3, at least 5.5 mol% B2O3, at least 6.0 mol% B2O3, at least 6.5 mol% B2O3, or at least 7.0 mol% B2O3 based on all oxides present in the glass composition. In one embodiment, the glass composition contains 20.0 mol% or less B2O3, 18.0 mol% or less B2O3, 16.0 mol% or less B2O3, 14.0 mol% or less B2O3, or 12.0 mol% or less B2O3 based on all oxides present in the glass composition. In one embodiment, the glass composition contains 5.0 to 20.0 mol% of B2O3, 5.5 to 18.0 mol% of B2O3, 6.0 to 16.0 mol% of B2O3, 6.5 to 14.0 mol% of B2O3, or 7.0 to 12.0 mol% of B2O3, based on all oxides present in the glass composition.

[0054] In one embodiment, the glass composition contains at least 2.0 mol% Al2O3, at least 3.0 mol% Al2O3, at least 4.0 mol% Al2O3, or at least 5.0 mol% Al2O3 based on all oxides present in the glass composition. In one embodiment, the glass composition contains 10.0 mol% or less Al2O3, 9.0 mol% or less Al2O3, 8.0 mol% or less Al2O3, or 7.0 mol% or less Al2O3 based on all oxides present in the glass composition. In one embodiment, the glass composition contains 2.0 to 10.0 mol% Al2O3, 3.0 to 9.0 mol% Al2O3, 4.0 to 8.0 mol% Al2O3, or 5.0 to 7.0 mol% Al2O3 based on all oxides present in the glass composition.

[0055] In one embodiment, the glass composition contains at least 0 mol% Fe2O3, at least 0.2 mol% Fe2O3, or at least 0.5 mol% Fe2O3 based on all oxides present in the glass composition. In one embodiment, the glass composition contains 2.0 mol% or less Fe2O3, 1.5 mol% or less Fe2O3, or 1.2 mol% or less Fe2O3 based on all oxides present in the glass composition. In one embodiment, the glass composition contains 0 to 2.0 mol% Fe2O3, 0.2 to 1.5 mol% Fe2O3, or 0.5 to 1.2 mol% Fe2O3 based on all oxides present in the glass composition.

[0056] In one embodiment, the glass composition contains at least 2 mol% Na2O, at least 4 mol% Na2O, or at least 6 mol% Na2O based on all oxides present in the glass composition. In one embodiment, the glass composition contains 10 mol% or less Na2O, 9 mol% or less Na2O, or 8 mol% or less Na2O based on all oxides present in the glass composition. In one embodiment, the glass composition contains 2 to 10 mol% Na2O, 4 to 9 mol% Na2O, or 6 to 8 mol% Na2O based on all oxides present in the glass composition.

[0057] In one embodiment, the glass composition contains at least 0.0 mol% K2O, at least 0.2 mol% K2O, or at least 0.5 mol% K2O based on all oxides present in the glass composition. In one embodiment, the glass composition contains 5.0 mol% or less K2O, 3.5 mol% or less K2O, 2.5 mol% or less K2O, 2.0 mol% or less K2O, or 1.5 mol% or less K2O based on all oxides present in the glass composition. In one embodiment, the glass composition contains 0.0 to 5.0 mol% K2O, 0.2 to 3.5 mol% K2O, or 0.5 to 2.5 mol% K2O based on all oxides present in the glass composition.

[0058] In one embodiment, the glass composition contains at least 0.0 mol% BaO, at least 0.2 mol% BaO, or at least 0.5 mol% BaO based on all oxides present in the glass composition. In one embodiment, the glass composition contains 3.0 mol% or less BaO, 2.5 mol% or less BaO, or 2.0 mol% or less BaO based on all oxides present in the glass composition. In one embodiment, the glass composition contains 0.0 to 3.0 mol% BaO, 0.2 to 2.5 mol% BaO, or 0.5 to 2.0 mol% BaO based on all oxides present in the glass composition.

[0059] In one embodiment, the glass composition contains at least 0.0 mol% CaO, at least 0.2 mol% CaO, or at least 0.5 mol% CaO based on all oxides present in the glass composition. In one embodiment, the glass composition contains 3.0 mol% or less CaO, 2.5 mol% or less CaO, or 2.0 mol% or less CaO based on all oxides present in the glass composition. In one embodiment, the glass composition contains 0.0 to 3.0 mol% CaO, 0.2 to 2.5 mol% CaO, or 0.5 to 2.0 mol% CaO based on all oxides present in the glass composition.

[0060] In one embodiment, the glass composition contains at least 0.0 mol% TiO2, at least 1.0 mol% TiO2, at least 2.0 mol% TiO2, at least 3.0 mol% TiO2, or at least 4.0 mol% TiO2 based on all oxides present in the glass composition. In one embodiment, the glass composition contains 10.0 mol% or less TiO2, 9.0 mol% or less TiO2, 8.0 mol% or less TiO2, 7.0 mol% or less TiO2, or 6.0 mol% or less TiO2 based on all oxides present in the glass composition. In one embodiment, the glass composition contains 0.0 to 10.0 mol% TiO2, 1.0 to 9.0 mol% TiO2, 2.0 to 8.0 mol% TiO2, 3.0 to 7.0 mol% TiO2, or 4.0 to 6.0 mol% TiO2 based on all oxides present in the glass composition.

[0061] In one embodiment of a glass tube for pharmaceutical containers, the glass tube comprises a glass composition comprising one or more clarifying agents, selected from a list of arsenic oxide, antimony oxide, tin oxide, cerium oxide, chlorides, sulfates, and combinations thereof.

[0062] It is advantageous to use a clarifying agent in the glass composition to enable the formation of bubbles and their release from the molten glass during the manufacturing process of glass tubes for pharmaceutical containers.

[0063] In one embodiment of a glass tube for pharmaceutical containers, the glass composition comprises a clarifying agent selected from the list of arsenic oxide, antimony oxide, and tin oxide.

[0064] In one embodiment of a glass tube for pharmaceutical containers, the glass composition comprises a clarifying agent selected from a list of chlorides, sulfates, and combinations thereof.

[0065] In one embodiment, the glass composition is heated at a temperature above 1580°C for 10 2It has a viscosity of dPas.

[0066] Glass tube dimensions and glass tube sets In one embodiment, the glass tube has an inner diameter of 5.0 to 49.0 mm, preferably 9.0 to 26 mm, and / or an outer diameter of 6.0 to 50 mm, preferably 8.0 to 30 mm, and / or a glass wall thickness of 0.5 to 2.0 mm, preferably 0.6 to 1.5 mm, and / or a length of 1100 to 5000 mm, preferably 1500 to 2000 mm.

[0067] In one embodiment of a glass tube for pharmaceutical containers, the glass tube has an inner diameter of 5.0 to 49.0 mm, 6.0 to 45.0 mm, 7.0 to 40.0 mm, 8.0 to 35.0 mm, or 9.0 to 26 mm.

[0068] In one embodiment of a glass tube for pharmaceutical containers, the glass tube has an outer diameter of 6.0 to 50.0 mm, 7.0 to 40.0 mm, or 8.0 to 30 mm.

[0069] In one embodiment of a glass tube for pharmaceutical containers, the glass tube has a glass wall thickness of 0.5 to 2.0 mm, 0.6 to 1.5 mm, 0.7 to 1.3 mm, or 0.8 to 1.2 mm.

[0070] In one embodiment of a glass tube for pharmaceutical containers, the glass tube has a length of 1100-5000 mm, 1200-3000 mm, or 1500-2000 mm.

[0071] In one embodiment, a set is provided that includes at least 50 glass tubes, at least 100 glass tubes, or at least 200 glass tubes. In one embodiment, a set is provided that includes 1000 or fewer glass tubes, 700 or fewer glass tubes, or 500 or fewer glass tubes.

[0072] Method for manufacturing glass tubes In a third aspect, the present invention relates to a method for manufacturing a glass tube for pharmaceutical containers, comprising the following steps: • A step of preparing a glass melt containing volatile components, such as borates, preferably a step of melting a batch of raw materials that will result in oxides being contained in the glass melt. The step of shaping the molten glass into a glass tube, for example, by drawing. - The step of forming the glass tube into a glass tube having a first end and a second end, • The step of forming the first end into a first closed end, • In the step of introducing a vent hole into the glass tube, • During at least part of the introduction step, and / or immediately after the introduction step, a step using suction, Optionally, the step of forming and / or sealing the second end into a second closed end. The method includes the foregoing.

[0073] Accordingly, the present inventors have established a method for manufacturing glass tubes for pharmaceutical containers that avoids problems known in the prior art and thereby provides glass tubes in which there is no or at least minimal deposit material that may be observed on the internal surface.

[0074] The present invention provides a glass tube for pharmaceutical containers, in which one of the open ends is formed to a closed end, wherein a vent is introduced into the glass tube and improved internal surface conditions are ensured by using suction during at least part of the introduction step and / or immediately after the introduction step. It has been observed that during the high temperature required to introduce the vent into the glass tube, a portion of the glass composition may evaporate and subsequently condense on the internal surface of the glass tube, particularly near the closed end. In rare and extreme cases, visible deposits, such as micron-sized water stains, have even been observed. Therefore, the present invention provides an effective countermeasure against the deterioration of glass tubes during the manufacture of glass vials, glass ampoules, glass cartridges or glass syringes, and ensures high-quality glass tubes by removing undesirable chemicals and seeds as part of the process.

[0075] In one embodiment of the above method, the glass tube has an inner surface and an outer surface, and an inner diameter d i and outer diameter d o , the length l along the longitudinal axis of the glass tube a The glass tube has a first end and a second end, a first position, the first position being 400 mm from the first end, the glass tube has a first intermediate position, the first intermediate position being 15 mm from the first end, the first neighborhood is defined as the inner surface of the glass tube between the first intermediate position and the first position, and a vent is introduced into the glass tube in the first neighborhood of the glass tube.

[0076] Placing or introducing vents in the first vicinity of the glass tube offers numerous practical advantages in the final product. For example, the portion of the glass tube with vents can be easily removed by cutting or burning without any essential loss of glass material. Introducing vents in or near the first vicinity during the manufacturing method of the glass tube is also advantageous from a mechanical design perspective. That is, it is not necessary to introduce mechanical components provided for suction very deep into the glass tube.

[0077] In one embodiment of the method, the use of suction during the introduction phase is accompanied by heating the glass tube to a temperature of at least 100°C, at least 150°C, or at least 200°C in the first vicinity of the glass tube. In one embodiment of the method, the use of suction during the introduction phase is accompanied by heating the glass tube to a temperature of 400°C or less, 350°C or less, or 300°C or less in the first vicinity of the glass tube. In one embodiment of the method, the use of suction during the introduction phase is accompanied by heating the glass tube to a temperature of 100°C to 400°C, 150°C to 350°C, or 200°C to 300°C in the first vicinity of the glass tube.

[0078] Advantageously, the combination of heating the glass tube in the first vicinity and using suction provides efficient removal of condensing and / or sublimating species, such as sodium salts, e.g., NaCl and / or NaF, and / or borates, e.g., sodium borate, which may occur through evaporation from the glass while introducing a vent into the glass tube.

[0079] In one embodiment of the above method, the use of suction under static conditions is performed with an average airflow rate of 5-50 m / s inside the glass tube. -1 Preferably 15-25 m s -1 This results in the following: Advantageously, a suitable airflow rate can further facilitate the efficient removal of condensing and / or sublimating species, such as sodium salts, e.g., NaCl and / or NaF, and / or borates, e.g., sodium borate, which may occur through evaporation from the glass while introducing vents into the glass tube.

[0080] Those skilled in the art recognize that sodium salts, such as NaCl and / or NaF, and / or borates, such as sodium borate, are typical components for pharmaceutical container glass, and that their chemical properties result in sublimation and / or condensation during the high temperatures used for the manufacture of glass tubes, particularly during the introduction of vents.

[0081] In one embodiment of the above method, the introduction of the vents begins at time t0 and ends at time t2, and the use of suction begins at time t1 and ends at time t3, where t1 is between t0 and t2 and t3 is after t2.

[0082] Advantageously, the timing between the introduction of the vents and the use of suction is optimized to enable and result in the efficient removal of species that tend to condense and / or sublimate, such as sodium salts, e.g., NaCl and / or NaF, and / or borates, e.g., sodium borate, within the time range in which they would typically occur through evaporation from the glass during the aforementioned method. [Examples]

[0083] Examples and Methods Fluorescence spectroscopy I used a Horiba FLUOROLOG 3 (PE-4-0503) fluorescence spectrometer.

[0084] The sample was positioned so that the excitation beam and emission beam were perpendicular, and measurements were taken at a 45° angle. The sample was placed in the sample chamber so that the UV light beam entered the glass tube and was reflected by total internal reflection inside the glass tube wall. As the UV light passed through the glass wall, it excited fluorescent species present in the glass composition, such as Fe2O3, TiO2, ZrO2, CeO2, As2O3, and K2O, and the emission was detected perpendicular to the excitation beam. If the glass tube shows anomalies on its internal surface, such as deposits, physical changes affecting surface roughness, or precipitation of volatile components (e.g., borates and halides), total internal reflection is blocked, which leads to at least a partial loss of excitation light. This loss in excitation light intensity results in lower fluorescence emission, which serves as a sensitive reading of anomalies or heterogeneity on the internal surface of the glass tube.

[0085] The following spectrometer settings were used: a slit width of 10 nm for excitation and emission, an integration time of 0.1 seconds for measurements in a stable state, and a wavelength sampling of 1 nm. The measurement uncertainty (k=2) for the analysis was estimated to be ±2.0% for fluorescence intensity and ±1 nm for wavelength.

[0086] The samples were first evaluated under a 254 nm excitation lamp to visually assess fluorescence and homogeneity, identify areas that appeared heterogeneous, and prepare them for testing. The fluorescence emission of six samples was identified, and the intrinsic fluorescence of the glass was measured.

[0087] An excitation wavelength of 290 nm, which has been proven to provide effective excitation for the glass composition used as part of the present invention, was used (Figure 5B). The difference between the measured intensities between individual samples was greater than the relative measurement uncertainty of ±3% between the initial fluorescence measurements.

[0088] ToF-SIMS (time-of-flight secondary ion mass spectrometry) ToF-SIMS technology is based on surface erosion by a sputtered ion beam. Secondary ions generated by the primary ion beam are extracted from the surface and detected by mass separation. The resulting depth profile provides qualitative surface composition information for various ion species.

[0089] Using the TOF-SIMS IV (ION-TOF GmbH) instrument, Ga is used as the primary ion source at 25 keV. + Using a primary ion current of 1 pA, with a mass resolution Δm / m at a mass of 65 greater than 5000, and an analysis area of ​​50 × 50 μm, 2 Furthermore, as a sputter ion, O2 at 1 keV + Using a sputter ion current of 300 nA and a sputter area of ​​300 × 300 μm 2 So, an electron flood gun was used for charge compensation.

[0090] To evaluate the data, all ion counts are set to 1 by definition. 30 Si + Normalized with respect to ions.

[0091] The sputtering depth was determined by further measuring the depth of the depressions using a white light microscope. Na2F within 100 nm of the outer surface. + The cumulative strength and 30 Si + The quotient between the cumulative intensity and ΣNa2F + / Σ 30 Si + I calculated it.

[0092] ToF-SIMS data was acquired and interpreted using ASTM standards E 1829-14 (2014; Standard Guide for Handling Specimens Prior to Surface Analysis) and E 2695-09 (2009; Standard Guide for Interpretation of Mass Spectral Data Acquired with Time-of-Flight Secondary Ion Mass Spectroscopy). Specifically, samples were kept clean and handled in a manner that avoided the introduction of contaminants. The sampled glass tubes were opened and broken, and glass fragments were removed by blowing air / N2 before data acquisition.

[0093] Hydrolysis resistance Hydrolysis resistance is defined as alkali leaching in the central region of the internal surface. Alkali leaching on the internal surface is identified as the Na2O equivalent in the eluate prepared according to ISO 4802-2:2010. This measured parameter is then associated with the internal surface in contact with the eluate during the ISO 4802-2:2010 method.

[0094] To conduct the test, the glass tube is cut into sections corresponding to the central area, each section having a length of at least 25 mm, although selective lengths of 50 mm and 60 mm are also possible.

[0095] Referring to point 8.3 of ISO 4802-2:2010, cap each glass tube section with a silicone rubber stopper at one open end, which by definition is referred to as the bottom end. After filling with test water, cap the glass tube section at the other open end with aluminum foil. Before first use, clean the silicone rubber stopper and ensure that there is no alkali leaching from the silicone rubber stopper. Clean the silicone rubber stopper after each use. The filling volume with distilled water is determined according to point 7.2.1 or point 7.2.2 of ISO 4802-2:2010, with respect to the inner diameter (or lumen diameter) of the glass tube section, i.e., d i ≤20mm or d i It is determined by the 20mm size.

Claims

1. A glass tube for a pharmaceutical container, the glass tube having an inner surface and an outer surface, the glass tube having an inner diameter d i and outer diameter d o the glass tube has a first end and a second end, the glass tube has a first position, the first position being 400 mm from the first end, the glass tube has a first intermediate position, the first intermediate position being 15 mm from the first end; the first end is molded to a first closed end, and preferably the second end is also molded to a second closed end; a vent hole disposed within a first vicinity of the first closed end, the first vicinity being between the first intermediate position and the first position; Na 2 F + Signals and 30 Si + ToF-SIMS signals including a signal of Na 2 F + The integrated signal 30 Si + the area on the inner surface of the first vicinity where the ratio of the signal to the signal is at least 0.10 is 36 mm 2 The Na 2 F + and the signal 30 Si + The signal is integrated over a depth of 100 nm.

2. The area is 25 mm 2 Below, 16mm 2 Below, 1mm 2 Less than or equal to, and preferably 0 mm 2 2. The glass tube according to claim 1, wherein

3. A glass tube for a pharmaceutical container, the glass tube having an inner surface and an outer surface, the glass tube having an inner diameter d i and outer diameter d o the glass tube has a first end and a second end, the glass tube has a first position, the first position being 400 mm from the first end, the glass tube has a first intermediate position, the first intermediate position being 15 mm from the first end; the first end is molded to a first closed end, and preferably the second end is also molded to a second closed end; a vent hole disposed within a first vicinity of the first closed end, the first vicinity being between the first intermediate position and the first position; The glass tube has a length l along its longitudinal axis. a the glass tube further having a central section, the central section extending along the longitudinal axis by 0.5 l. a 5d centered on the position i extends for a distance of The glass tube has a ratio between the fluorescent emission determined in the first vicinity and the fluorescent emission determined in the central region of at least 0.

6.

4. The inner surface includes a deposit located in the first vicinity, the deposit having an area of ​​the deposit extending parallel to the inner surface of the glass tube, the area of ​​the deposit being 0.01 mm 2 ~36mm 2 and the deposit has a measurable Na concentration on the interior surface in the first vicinity. 2 F + Signals and 30 Si + The ToF-SIMS signal includes a signal of 2 F + The integrated signal 30 Si + a ratio of 0.0002 to less than 0.10 for the signal of Na 2 F + and the signal 30 Si + 4. The glass tube according to claim 1, wherein the signal is integrated over a depth of 100 nm.

5. The area of ​​the deposit is 0.01 mm 2 ~1mm 2 and the deposit is an integrated Na 2 F + The integrated signal 30 Si + or the area of ​​the deposit is less than 0.01 mm 2 ~36mm 2 and the deposit is an integrated Na 2 F + The integrated signal 30 Si + 5. The glass tube of claim 4, wherein the ratio of the signal to the signal is from 0.0002 to less than 0.

025.

6. At least 90%, preferably at least 99%, of the inner surface of the first vicinity is 2 F + The integrated signal 30 Si + a ratio of 0.0002 to less than 0.025 of the Na 2 F + and the signal 30 Si + 4. The glass tube according to claim 1, wherein the signal is integrated over a depth of 100 nm.

7. The glass tube is alkali leachable in the central area of ​​the inner surface, defined as Na in the leachate prepared in accordance with ISO 4802-2:2010. 2 O equivalent, and the hydrolysis resistance is 0.5 μg cm -2 Less than 0.4 μg cm -2 Less than 0.3 μg cm -2 Less than 0.2 μg cm -2 Less than, or 0.1 μg cm -2 The glass tube according to claim 1 or 3, wherein the thickness is less than 1 / 2 mm.

8. Soda lime glass, borosilicate glass, aluminosilicate glass, 5 mol% to 20 mol% B based on all oxides present in the glass composition 2 O 3 4. The glass tube of claim 1, comprising a glass composition selected from the list of glasses comprising:

9. 60-85 mol % SiO based on all oxides present in the glass composition 2 , 5 to 20 mol% B 2 O 3 , 2 to 10 mol% Al 2 O 3 , 0 to 2 mol% Fe 2 O 3 , 2 to 10 mol% Na 2 O, 0 to 5 mol% K 2 O, 0 to 2 mol% BaO, 0 to 2 mol% CaO, 0 to 10 mol% TiO 2 4. The glass tube of claim 1 or 3, comprising a glass composition comprising:

10. The glass tube is Inner diameter d i 5.0 to 49.0 mm, preferably 9.0 to 26 mm, and / or ・Outer diameter d o 6.0 to 50 mm, preferably 8.0 to 30 mm, and / or a glass wall thickness WT of 0.5 to 2.0 mm, preferably 0.6 to 1.5 mm, and / or Length l a 1100 to 5000 mm, preferably 1200 to 3000 mm, more preferably 1500 to 2000 mm The glass tube according to claim 1 or 3, wherein

11. A set of glass tubes comprising at least 50, preferably 100, glass tubes according to claim 1 or 3.

12. 1. A method for manufacturing a glass tube for a pharmaceutical container, comprising the steps of: preparing a glass melt containing volatile components, e.g. borates, preferably by melting a batch of raw materials that will result in the oxides contained in the glass melt; forming the glass melt into a glass tube, for example by drawing; forming the glass tube into a glass tube having a first end and a second end; forming the first end into a first closed end; - introducing a vent into the glass tube; using suction during at least a portion of the introducing step and / or immediately after the introducing step; and Optionally, molding and / or sealing said second end into a second closed end. The method comprising:

13. The glass tube has an inner surface and an outer surface, and the glass tube has an inner diameter d i and outer diameter d o and the glass tube has a length l along its longitudinal axis. a wherein the glass tube has a first end and a second end, the glass tube has a first position, the first position being 400 mm from the first end, the glass tube has a first intermediate position, the first intermediate position being 15 mm from the first end, and a first vicinity is defined as an inner surface of the glass tube between the first intermediate position and the first position; 13. The method of claim 12, wherein a vent is introduced into the glass tube at the first vicinity of the glass tube.

14. 14. The method of claim 12 or 13, wherein the use of suction during the introducing step involves heating the glass tube to a temperature of at least 100°C in a first vicinity of the glass tube.

15. The use of said suction under static conditions results in an average air flow rate of 5-50 m s inside the glass tube. -1 , preferably 15 to 25 m s -1 and / or The introduction of the vent hole 0 Starts at time t 2 and the use of suction ends at time t 1 Starts at time t 3 It ends at time t 1 is 0 and 2 Between t and t 3 is 2 and / or a further step of screening said glass tube, said screening being carried out by measuring fluorescence emission.

14. The method of claim 12 or 13.

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