Preparation system for penicillin bottles with different oxygen contents

Abstract

The utility model discloses a preparation system for penicillin bottles with different oxygen contents, which comprises a vacuum cavity, penicillin bottles are arranged in the vacuum cavity, one side of the vacuum cavity is communicated with a first pipeline, a first needle valve is arranged on the first pipeline, a three-way valve is arranged at the tail end of the first pipeline, and the first pipeline is respectively connected with oxygen standard gas and nitrogen standard gas through the three-way valve. A mass flow meter I is arranged on the front end pipeline of the oxygen standard gas, and a mass flow meter II is arranged on the front end pipeline of the nitrogen standard gas; the other side of the vacuum cavity is communicated with a second pipeline, the vacuum cavity is communicated with a vacuum pump through the second pipeline, and a second needle valve, a vacuum gauge and an oxygen sensor are arranged on the second pipeline. According to the utility model, the preparation of standard penicillin bottles with different pressures, different materials and different oxygen contents is realized through the self-developed preparation system for the penicillin bottles with different oxygen contents; the high-precision measurement of the oxygen concentration in the penicillin bottle is realized based on the TDLAS technology, and the prepared penicillin bottles with different oxygen contents are accurately obtained according to the comparison between the measurement result and the numerical value of the oxygen sensor.

Description

Technical Field

[0001] The utility model relates to a system for preparing vials with different oxygen contents. Background Art

[0002] In the pharmaceutical industry, vials, a common drug packaging material, enjoy enormous annual global demand. However, the integrity of vial seals can be easily compromised due to factors such as unstable stoppering and capping, as well as damage to the packaging itself, allowing oxygen to enter. Furthermore, limited vacuum and nitrogen filling processes can cause the oxygen content within vials to differ from expected levels. Oxygen content is a crucial factor affecting the shelf life of drugs. Exceeding industry standards can accelerate drug deterioration, posing a serious threat to drug production and medical safety. Therefore, quantitative oxygen testing within vials has become a crucial step in ensuring drug quality.

[0003] Vials are primarily made of soda-lime glass and borosilicate glass. They are used for packaging pharmaceuticals such as lyophilized powders, lyophilized aqueous solutions, vaccines, and biologics. To ensure the stability and sterility of the drug within the vial, vacuum evacuation or nitrogen filling is typically used to isolate the drug from the atmosphere. However, due to process limitations, it is not possible to ensure the expected residual oxygen level within the vial. The 2010 revised Good Manufacturing Practice (GMP) for Pharmaceuticals clearly stipulates that the seal of sterile pharmaceutical packaging containers must be verified to prevent product contamination. The 2015 GMP Inspection Guidelines for Sterile Pharmaceuticals stipulate that sealed pharmaceutical products must undergo regular oxygen content testing and trend analysis at 0, 6, 12, and 24 months within their expiration date. Therefore, there is a significant market demand for quantitative oxygen detection in vials. Currently, most pharmaceutical companies use offline, destructive sampling methods based on gas chromatography, electrochemistry, or magnetic oxygen analysis. However, these instruments suffer from rapid sensor aging, prone to false positives over extended testing periods, and lack high-speed online testing capabilities. With the continuous development of laser technology, tunable diode laser absorption spectroscopy (TDLAS) has gained increasing attention due to its high resolution, high sensitivity, high stability, excellent selectivity, real-time performance, and dynamics. It has been gradually applied to trace gas monitoring, becoming an effective method for detecting gas parameters such as temperature, concentration, and pressure. These advantages of TDLAS technology have given it great potential for oxygen concentration detection, making it ideal for real-time online oxygen concentration monitoring. During the detection process, since the test sample cannot be destroyed, standard oxygen vials of varying concentrations must be prepared as a reference set. However, due to the high oxygen content in air (approximately 21%), preparing vials with varying oxygen contents at atmospheric pressure is difficult. Currently, only a very small number of pharmaceutical companies use the water displacement method to prepare standard oxygen vials at atmospheric pressure. However, due to differences in packaging processes, vacuum-sealed vials are under negative pressure, while nitrogen-filled vials are under positive pressure. Simultaneously preparing vials at different pressures and oxygen concentrations is extremely difficult.

[0004] In summary, the existing technology has the following shortcomings:

[0005] 1. Currently, most pharmaceutical companies and testing institutions are unable to accurately prepare oxygen standard bottles and often use the drainage method. However, this method will introduce liquid water into the bottle. Liquid water is easy to condense or adsorb on the wall of the vial, hindering the laser from penetrating the vial, thereby affecting the measurement results.

[0006] 2. Since the air contains about 21% oxygen and the volume of the vial is small, it is impossible to accurately prepare an oxygen standard bottle with a certain concentration in an open environment.

[0007] 3. Since freeze-dried preparations use vacuum extraction to remove oxygen from the bottle, creating a negative pressure environment inside the bottle, accurate testing requires the preparation of a standard oxygen bottle with a determined concentration under negative pressure, which is difficult to achieve under conventional experimental conditions.

[0008] In order to solve the above problems, the present utility model is hereby proposed. Utility Model Content

[0009] The utility model aims to provide a system for dispensing vials with different oxygen contents.

[0010] The purpose of the utility model can be achieved through the following technical solutions:

[0011] A system for preparing vials with different oxygen contents comprises a vacuum chamber, wherein a vial is arranged inside the vacuum chamber, one side of the vacuum chamber is connected to a first pipeline, a first needle valve is arranged on the first pipeline, a three-way valve is arranged at the end of the first pipeline, the first pipeline is respectively connected to oxygen standard gas and nitrogen standard gas through the three-way valve, a first mass flow meter is arranged on the front end pipeline of the oxygen standard gas, and a second mass flow meter is arranged on the front end pipeline of the nitrogen standard gas; the other side of the vacuum chamber is connected to a second pipeline, the vacuum chamber is connected to a vacuum pump through the second pipeline, and the second pipeline is provided with a second needle valve, a vacuum gauge and an oxygen sensor.

[0012] Preferably, a vertical stepping motor is fixed above the vacuum chamber, the vertical stepping motor is connected to a retractable clamp, a rubber stopper is connected below the retractable clamp, and the retractable clamp is located above the vial.

[0013] Furthermore, it also includes a high-precision oxygen concentration measurement system based on TDLAS.

[0014] Preferably, the high-precision oxygen concentration measurement system based on TDLAS includes a laser collimator and a photodetector, the laser collimator and the photodetector are located in the vacuum chamber, the laser collimator and the photodetector are located on both sides of the vial, the straight line formed by the laser collimator and the photodetector passes through the vial, the laser collimator is connected to the laser, the laser is connected to the laser controller, and the laser controller is connected to the signal generator.

[0015] Furthermore, a base is provided in the vacuum chamber, and a vial is provided on the base.

[0016] Preferably, the base is provided with a buckle for fixing the vial.

[0017] Beneficial technical effects:

[0018] The utility model realizes the preparation of standard vials of different pressures, different materials, and different oxygen contents through a self-developed system for preparing vials with different oxygen contents; based on TDLAS technology, high-precision measurement of the oxygen concentration in the vials is achieved, and by comparing the measurement results with the values of the oxygen sensor, the configured vials with different oxygen contents are accurately obtained. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] The present invention will be further described below with reference to the accompanying drawings.

[0020] Figure 1 This is a block diagram of the system for preparing vials with different oxygen contents in the utility model.

[0021] 1. Oxygen standard gas; 2. Nitrogen standard gas; 3-1. Mass flow meter 1; 3-2. Mass flow meter 2; 4-1. Needle valve 1; 4-2. Needle valve 2; 5. Vertical stepping motor; 6. Retractable clamp; 7. Rubber stopper; 8. Base; 9. Vial; 10. Vacuum chamber; 11. Vacuum gauge; 12. Oxygen sensor; 13. Vacuum pump; 14. Signal generator; 15. Laser controller; 16. Laser; 17. Laser collimator; 18. Photodetector; 19. Data acquisition and processing system. DETAILED DESCRIPTION

[0022] The following will be combined with the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the embodiments described are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts shall fall within the scope of protection of the present invention.

[0023] This utility model establishes a laboratory-based system for dispensing vials with varying oxygen contents. A mass flowmeter is used to mix and distribute oxygen of varying concentrations into a vacuum chamber. The chamber contains a base for placing the vials, and a vertical stepper motor is built into the upper cover of the chamber. This automatically caps the vials when the oxygen concentration reaches the standard, preventing gas contamination within the vials. The chamber's cavity is connected to a pressure gauge and an oxygen sensor, enabling real-time monitoring of pressure and oxygen concentration changes within the chamber. By varying the pressure within the chamber, vials with varying oxygen concentrations can be dispensed under varying pressures. TDLAS technology is used to measure the oxygen concentration within the standard vials, and the resulting data is compared with the oxygen sensor's value to verify the accuracy of the method.

[0024] The principle of this utility model is as follows: Based on the research needs of a system for dispensing vials with different oxygen contents, a dispensing system for vials with different oxygen concentrations and a TDLAS synchronous measurement system were designed and constructed. To dispense vials with different oxygen concentrations, the front end of the oxygen concentration vial dispensing system uses a mass flow meter to mix and deliver oxygen of varying concentrations into a proprietary vacuum chamber. A solenoid valve is used to control the type and concentration of gas entering the vacuum chamber. The vacuum chamber houses a vial holder with an adjustable clip to secure vials of varying sizes, ensuring accurate placement and stability during the dispensing process. The upper cover of the vacuum chamber houses a vertical stepper motor with a retractable clamp mounted on it. The clamp contains a clip to secure the vial stopper. The stopper's position corresponds to the vial's position, ensuring alignment during capping. The other side of the vacuum chamber is connected to a pressure gauge, an oxygen sensor, and a vacuum pump. During the dispensing process, the vacuum pump draws air into the chamber, bringing it close to a vacuum. The residual oxygen level within the chamber can be determined based on the readings from the meter and the oxygen sensor. Nitrogen is then introduced into the vacuum chamber to purge the entire chamber, ensuring there is no residual oxygen, and then the chamber is evacuated again. After the vacuum pump is turned off, oxygen of varying concentrations is introduced into the chamber. When the oxygen concentration measured by the oxygen sensor matches the formulated concentration, the vertical motor is controlled to release the retractable clamp for capping. The entire preparation process is completed within the vacuum chamber, where the pressure and oxygen concentration are adjustable and controllable, eliminating interference from oxygen in the air and producing vials of varying pressures, materials, and oxygen concentrations.

[0025] Reference Figure 1 A system for preparing vials with different oxygen contents includes a vacuum chamber 10, a vial 9 is arranged inside the vacuum chamber 10, a vertical stepping motor 5 is fixed above the vacuum chamber 10, the vertical stepping motor 5 is connected to a retractable clamp 6, a rubber stopper 7 is connected below the retractable clamp 6, and the retractable clamp 6 is located above the vial 9. One side of the vacuum chamber 10 is connected with a pipeline 1, a needle valve 1 4-1 is provided on the pipeline 1, a three-way valve is provided at the end of the pipeline 1, and the pipeline 1 is respectively connected to an oxygen standard gas 1 and a nitrogen standard gas 2 through the three-way valve, a mass flow meter 1 3-1 is provided on the front end pipeline of the oxygen standard gas 1, and a mass flow meter 2 3-2 is provided on the front end pipeline of the nitrogen standard gas 2; the other side of the vacuum chamber 10 is connected with a pipeline 2, the vacuum chamber 10 is connected to a vacuum pump 13 through the pipeline 2, and a needle valve 2 4-2, a vacuum gauge 11 and an oxygen sensor 12 are provided on the pipeline 2.

[0026] The capping of the vial 9 by means of the vertical stepping motor 5 , the retractable clamp 6 and the rubber stopper 7 belongs to the prior art in this field and does not fall within the scope of protection of the present utility model.

[0027] A base 8 is provided in the vacuum chamber 10 , and a vial 9 is provided on the base 8 .

[0028] Vials 9 are compatible with a variety of sizes.

[0029] A buckle is provided on the base 8 for fixing the vial 9 .

[0030] A system for dispensing vials with different oxygen contents also includes a high-precision oxygen concentration measurement system based on TDLAS.

[0031] The high-precision oxygen concentration measurement system based on TDLAS includes a laser collimator 17 and a photodetector 18. The laser collimator 17 and the photodetector 18 are located in the vacuum chamber 10, and the laser collimator 17 and the photodetector 18 are located on both sides of the syringe bottle 9. The straight line formed by the laser collimator 17 and the photodetector 18 passes through the syringe bottle 9. The laser collimator 17 is connected to the laser 16, the laser 16 is connected to the laser controller 15, and the laser controller 15 is connected to the signal generator 14; the photodetector 18 is connected to the data acquisition and processing system 19.

[0032] The high-precision oxygen concentration measurement system based on TDLAS itself belongs to the prior art, especially the data acquisition and processing system 19 connected to the rain photoelectric detector 18 belongs to the prior art.

[0033] The following steps are required to prepare standard vials of different oxygen concentrations using the different oxygen content vial preparation system:

[0034] 1) Open the vacuum chamber 10, place the vial 9 into the base 8 in the vacuum chamber 10, the buckle in the base 8 will fix the vial 9, place the rubber stopper 7 into the retractable clamp 6 in the vacuum chamber 10, the buckle in the retractable clamp 6 will lock the rubber stopper 7, after placement is completed, check the correspondence between the rubber stopper 7 and the vial 9, and seal the vacuum chamber 10 after confirming that it is correct.

[0035] 2) Open needle valve 2 4-2 and close needle valve 1 4-1. At the same time, turn on the vacuum pump 13 to evacuate the vacuum chamber 10. The pressure and oxygen concentration in the vacuum chamber 10 can be monitored in real time by the vacuum gauge 11 and the oxygen sensor 12. When the values of the vacuum gauge 11 and the oxygen sensor 12 are observed to be stable over a period of time, close needle valve 2 4-2 and turn off the vacuum pump 13.

[0036] 3) Open needle valve 4-1, introduce nitrogen standard gas 2 into the vacuum chamber 13, observe the values of the vacuum gauge 11 and the oxygen sensor 12. When the vacuum gauge 11 shows a slightly positive pressure and the oxygen content measured by the oxygen sensor 12 is zero, close needle valve 4-1.

[0037] 4) Open the second needle valve 4-2. At the same time, turn on the vacuum pump 13 to evacuate the vacuum chamber 10 again. When the values of the vacuum gauge 11 and the oxygen sensor 12 stabilize, close the second needle valve 4-2 and turn off the vacuum pump 13.

[0038] 5) Oxygen standard gas 1 and nitrogen standard gas 2 are mixed and matched through mass flow meter 1 3-1 and mass flow meter 2 3-2 to obtain oxygen of different concentrations. Needle valve 1 4-1 is opened to deliver oxygen of different concentrations into vacuum chamber 10. When the pressure displayed by vacuum gauge 11 and the result displayed by oxygen sensor 12 are consistent with the expectation and remain stable for a period of time, needle valve 1 4-1 is closed and a command is sent to vertical motor 5 to release retractable clamp 6 to cap vial 9. After the capping is successful, retractable clamp 6 is retracted to obtain a standard vial.

[0039] The high-precision oxygen measurement system based on TDLAS uses a signal generator 14 to emit a high-frequency triangular wave superimposed on a low-frequency sine wave, which is coupled into a laser controller 15. The laser controller 15 then tunes the temperature and current to drive the laser 16 to output a laser beam. This laser beam is collimated by a laser collimator 17 and then injected into the vial under test. The emitted light enters a detector 18, generating a photoelectric signal that is then connected to a data processing system 19 for real-time analysis, enabling the measurement of the oxygen concentration within the vial. By measuring the oxygen concentration within vials of varying pressures, materials, and storage times, and comparing the measured results with the oxygen sensor's readings, the system accurately identifies the vials with varying oxygen contents.

[0040] The utility model does not need to introduce impurity molecules such as H2O into the standard vial, and the entire operation is carried out in an air-isolated environment, thereby avoiding the interference of oxygen in the air. By adjusting the pressure in the vacuum chamber with the assistance of a vacuum pump and a pressure gauge, the preparation of oxygen-containing standard vials under different pressures can be achieved, thereby being compatible with the measurement of low-pressure freeze-dried preparations.

[0041] In addition, it should be understood that although this specification is described in terms of implementation methods, not every implementation method contains only one independent technical solution. This narrative method of the specification is only for the sake of clarity. Those skilled in the art should regard the specification as a whole. The technical solutions in each embodiment can also be appropriately combined to form other implementation methods that can be understood by those skilled in the art.

Claims

1. A system for dispensing vials with different oxygen contents, characterized in that: It includes a vacuum chamber, a cillin bottle is arranged inside the vacuum chamber, one side of the vacuum chamber is connected to pipeline one, a needle valve one is arranged on pipeline one, a three-way valve is arranged at the end of pipeline one, pipeline one is connected to oxygen standard gas and nitrogen standard gas respectively through the three-way valve, a mass flow meter one is arranged on the front end pipeline of oxygen standard gas, and a mass flow meter two is arranged on the front end pipeline of nitrogen standard gas; the other side of the vacuum chamber is connected to pipeline two, the vacuum chamber is connected to a vacuum pump through pipeline two, and needle valve two, a vacuum gauge and an oxygen sensor are arranged on pipeline two.

2. The system for dispensing vials with different oxygen contents according to claim 1, characterized in that: A vertical stepping motor is fixed above the vacuum chamber, the vertical stepping motor is connected to a retractable clamp, a rubber stopper is connected below the retractable clamp, and the retractable clamp is located above the vial.

3. The system for dispensing vials with different oxygen contents according to claim 2, characterized in that: Also included is a high-precision oxygen concentration measurement system based on TDLAS.

4. The system for dispensing vials with different oxygen contents according to claim 3, characterized in that: The high-precision oxygen concentration measurement system based on TDLAS includes a laser collimator and a photodetector. The laser collimator and the photodetector are located in a vacuum chamber, and the laser collimator and the photodetector are located on both sides of a vial. A straight line formed by the laser collimator and the photodetector passes through the vial. The laser collimator is connected to a laser, the laser is connected to a laser controller, and the laser controller is connected to a signal generator.

5. The system for dispensing vials with different oxygen contents according to claim 2, characterized in that: A base is provided in the vacuum chamber, and a cillin bottle is provided on the base.

6. The system for dispensing vials with different oxygen contents according to claim 5, characterized in that: The base is provided with a buckle for fixing the vial.

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