Sample test system and apparatus for inhalation formulation delivery rate and total delivery amount

Abstract

The invention relates to the technical field of chromatographic testing, in particular to a sample testing system and device for the delivery rate and the total delivery amount of an inhalation preparation, and the testing system comprises a simulation inhalation and aerosol generation module which is used for simulating human respiratory dynamics conditions and generating aerosol to be tested; the time-resolved automatic sampling module is used for respectively capturing the flowing aerosol into independent collection containers according to a preset time sequence; the automatic sample pretreatment and transfer module is used for adding and uniformly mixing a solvent into the collection container and automatically transferring the treated sample sequence; the online chromatographic separation and detection module is used for carrying out automatic chromatographic analysis and detection on the transferred time sequence sample; the central control and data processing module is used for coordinating the operation of each module and generating a delivery rate-time curve and total delivery quantity data according to an analysis result and time information; according to the method, a comprehensive and reliable quantitative basis is provided for performance evaluation of the inhalation preparation.

Description

Technical Field

[0001] This invention relates to the field of chromatographic testing technology, specifically to a sample testing system and apparatus for the delivery rate and total amount of inhaled formulations. Background Technology

[0002] Procaterol hydrochloride, a highly selective β2-receptor agonist, effectively promotes bronchodilation, inhibits the release of inflammatory mediators, and enhances respiratory ciliary movement by activating adenylate cyclase in respiratory smooth muscle. It is widely used clinically to treat respiratory diseases such as bronchial asthma and chronic obstructive pulmonary disease. Its inhalation solution formulation allows for direct drug delivery to the lesion, featuring rapid onset of action and high bioavailability, making it a commonly used clinical dosage form. However, quality control methods for its inhalation solution formulations are still lacking in the pharmacopoeias of many countries, especially a systematic evaluation method for its delivery performance under simulated human inhalation conditions.

[0003] Currently, quality control analysis for inhaled formulations mainly focuses on static indicators such as related substances and content uniformity. Although these methods can effectively identify and quantify process impurities and degradation products, they all use isocratic elution mode, which has limited elution efficiency and insufficient ability to separate complex impurities. More importantly, these methods cannot reflect the dynamic delivery characteristics of the formulation during actual use.

[0004] The efficacy of inhaled formulations depends not only on the total amount of drug but also on the delivery rate and release behavior at different time points during inhalation. Current technology lacks automated equipment capable of time-resolved sampling and online coupling with chromatographic analysis systems under simulated human inhalation conditions, making it difficult to accurately assess the delivery kinetics of formulations. Furthermore, traditional manual sampling methods suffer from drawbacks such as cumbersome operation, inaccurate timing control, susceptibility to cross-contamination, and poor repeatability, failing to meet the need for refined and automated analysis of delivery rate and total amount. Summary of the Invention

[0005] The purpose of this invention is to provide a sample testing system and apparatus for the delivery rate and total amount of inhaled formulations, so as to provide a comprehensive and reliable quantitative basis for the performance evaluation of inhaled formulations and to solve the problems mentioned in the background art.

[0006] To achieve the above objectives, the present invention provides the following technical solution: a sample testing system for the delivery rate and total amount of inhaled formulations, comprising: The simulated inhalation and aerosol generation module is used to simulate human respiratory dynamics conditions and generate the aerosol to be tested; The time-resolved automatic sampling module is used to capture the flowing aerosols into separate collection containers according to a preset time sequence; The automatic sample pretreatment and transfer module is used to add and mix solvent into the collection container and automatically transfer the processed sample sequence. The online chromatographic separation and detection module is used for automated chromatographic analysis and detection of transferred time-series samples; The central control and data processing module coordinates the operation of each module and generates delivery rate-time curves and total delivery volume data based on analysis results and time information.

[0007] The test apparatus for a sample testing system for inhaled formulation delivery rate and total delivery volume includes: The base is installed in the liquid chromatograph; The sample preparation turntable is rotatably mounted on the base, and has a ring array of stations for accommodating collection containers to complete the initial mixing of aerosol samples and solvents. The sample loading turntable is rotatably mounted on the base, with a portion of its area overlapping the sample preparation turntable in the vertical direction, and is used to receive the collection container from the sample preparation turntable. The first solvent assembly, corresponding to the sample preparation turntable, is used to add a quantitative amount of solvent to the collection container; The sampling component, corresponding to the sample preparation turntable, is used to extract samples from the external aerosol flow path and inject them into the collection container; The second solvent assembly, corresponding to the sample dispensing turntable, is used to add solvent to the collection container that has been transferred to the sample dispensing turntable; The sample loading assembly, corresponding to the sample loading turntable, is used to extract the mixed sample from the collection container and inject it into the chromatographic system's injection interface; The sample preparation turntable and the sample dispensing turntable rotate in coordination under the control of the sample testing system, realizing the automatic transfer and sequential positioning of the collection container from the sample preparation station to the sample dispensing station.

[0008] The base is equipped with a drive mechanism, which includes a servo motor and a belt drive assembly installed in the base. The servo motor drives the sample preparation turntable and the sample application turntable to rotate at the same angular velocity via a belt drive assembly.

[0009] Among them, the projections of the sample preparation turntable and the sample addition turntable on the horizontal plane overlap and intersect; The sample preparation turntable is equipped with an electromagnetically controlled tray structure. When the overlapping and intersecting areas of the tray structure are opened, the collection container it carries falls into the corresponding position of the sample dispensing turntable under the action of gravity.

[0010] The sampling component is mounted in the control base via a rotating seat and is driven by a servo motor to switch between an inclined sampling position and a vertical sample application position. The sampling station is aligned with the sample box, which is then connected to the aerosol flow path of the simulated inhalation device via the sample channel.

[0011] The first solvent assembly and the second solvent assembly each include a vertically arranged solvent tube, an injection needle connected to the bottom of the solvent tube, a flow valve disposed on the solvent tube, and a vertical rail for driving the solvent tube and the injection needle to move up and down.

[0012] The sampling component and the sample dispensing component each include an outer slide rail, an inner slide rail driven and mounted on the outer slide rail, a syringe fixed on the inner slide rail, and a puller driven and mounted on the inner slide rail and connected to the piston of the syringe.

[0013] The bottom of the sample dispensing turntable is equipped with an arc-shaped air blowing box, the bottom of which is connected to an air supply pipe, and the top is equipped with air holes corresponding to the work positions on the sample dispensing turntable. The bottom of the sample loading turntable is equipped with a buffer support mechanism, which includes a counterweight, an elastic pad, and a conical base. The airflow generated by the air blowing box acts on the conical base, causing the buffer support mechanism to rise to catch the falling collection container.

[0014] The air blowing box is equipped with an oscillation mechanism, which includes a spring rod that can slide through the outer wall of the air blowing box. The end of the spring rod located inside the air blowing box is equipped with a stop for sealing the air hole, and the end located outside the air blowing box is equipped with a ball head. It also includes an arc-shaped rail installed outside the air blowing box. A round-headed slide is reciprocating in the arc-shaped rail, which periodically presses the ball head to make the spring rod move inward, thereby blocking the airflow and realizing the oscillation of the bearing seat.

[0015] Among them, gaps are opened between adjacent stations on the sample addition turntable; The sample dispensing turntable has a full-width rotation mode and a half-width rotation mode. In the full-width rotation mode, its rotation angle is the distance between adjacent stations. In the half-width rotation mode, its rotation angle is the distance between the station and the notch, so that the sample dispensing component can alternately align with the collection container and the injection seat located below the notch.

[0016] Compared with the prior art, the beneficial effects of the present invention are: 1. This invention, through its integrated mechanical structure and automated control process, achieves a fully integrated operation of the entire process of automatic time-series acquisition, online dilution and mixing, and high-performance liquid chromatography (HPLC) analysis of inhaled formulation aerosol samples. This effectively avoids errors and sample contamination introduced by traditional manual operation, and significantly improves the accuracy and repeatability of test results.

[0017] 2. The testing system of the present invention adopts a time-resolved sampling method, which can accurately capture the drug delivery rate at different time points, completely depict the delivery kinetic curve, and automatically calculate the total delivery amount by combining chromatographic analysis data, providing a comprehensive and reliable quantitative basis for the performance evaluation of inhaled formulations.

[0018] 3. This invention employs a unique rotary transfer and pneumatic buffer oscillation design, which not only achieves non-destructive transfer and efficient mixing of samples, but also significantly improves sample throughput and system integration, making the entire testing process efficient, stable, and automated, and greatly enhancing the efficiency and scientific rigor of inhaled formulation quality control analysis. Attached Figure Description

[0019] Figure 1 This is a first schematic diagram of the overall structure of the chromatograph of the present invention.

[0020] Figure 2 This is a second schematic diagram of the overall structure of the chromatograph of the present invention.

[0021] Figure 3 This is a first schematic diagram of the combined structure of the sample loading seat and control seat of the present invention.

[0022] Figure 4 This is a second schematic diagram of the combined structure of the sample loading seat and control seat of the present invention.

[0023] Figure 5 This is a schematic diagram of the sample preparation turntable and sample loading turntable structure of the present invention.

[0024] Figure 6 This is a schematic diagram of the sample preparation turntable structure of the present invention.

[0025] Figure 7 This is a schematic diagram of the sampling component structure of the present invention.

[0026] Figure 8 This is a schematic diagram of the sample loading turntable and sample loading component structure of the present invention.

[0027] Figure 9 This is a schematic diagram of the sample loading turntable structure of the present invention.

[0028] Figure 10 This is a schematic diagram of the sample loading component structure of the present invention.

[0029] Figure 11 This is a schematic diagram of the internal structure of the sample loading turntable of the present invention.

[0030] Figure 12 This is a schematic diagram of the sample loading turntable and air blowing box structure of the present invention.

[0031] Figure 13 This is a schematic diagram of the air-blowing box structure of the present invention.

[0032] In the diagram: 1. Sample dispensing seat; 2. Control seat; 3. Base; 4. Sample dispensing turntable; 5. Lifting seat; 6. Sample preparation turntable; 7. Cylinder seat; 8. First solvent assembly; 9. Sampling assembly; 10. Tube; 11. Solvent box; 12. Sample box; 13. Sample channel; 14. Second solvent assembly; 15. Sample dispensing assembly; 16. Injection seat; 17. Notch; 18. Counterweight seat; 19. Upper pad; 20. 201. Lower pad; 21. Slide rod; 22. Conical base; 23. Air blowing box; 24. Air supply pipe; 25. Air hole; 26. Spring rod; 27. Stop; 28. Ball head; 29. ​​Arc rail; 30. Round head slide; 101. Solvent tube; 102. Injection needle; 103. Flow valve; 104. Vertical rail; 201. Outer slide rail; 202. Inner slide rail; 203. Syringe; 204. Pulling component. Detailed Implementation

[0033] The present invention will now be further described with reference to the accompanying drawings and specific embodiments. It should be noted that, without conflict, the various embodiments or technical features described below can be arbitrarily combined to form new embodiments. It should be understood that the described embodiments are merely some embodiments of the present invention, and not all embodiments. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort are within the scope of protection of the present invention.

[0034] Please see Figures 1 to 13 The present invention provides a technical solution: a sample testing system for delivery rate and total delivery of inhaled formulations. This sample testing system can detect related substances in procaterol hydrochloride inhaled formulations during the inhalation process, simulate the human inhalation process, and test the delivery rate and total delivery at different time periods.

[0035] The sample testing system is an automated analysis platform based on high-performance liquid chromatography (HPLC). It achieves precise characterization of the dynamic delivery performance of inhaled formulations by coordinating the collaborative work of multiple functional modules. The system mainly consists of a simulated inhalation and aerosol generation module, a time-resolved automatic sampling module, an automatic sample pretreatment and transfer module, an online chromatographic separation and detection module, and a central control and data processing module. The simulated inhalation and aerosol generation model is responsible for simulating human respiratory dynamics and generating the aerosol to be tested. Its core includes a programmable airflow control system for generating an inhalation flow profile that meets pharmacopoeia specifications or specific clinical needs; a temperature and humidity control unit for simulating the human respiratory environment; and a standardized inhalation formulation interface for reliably activating and introducing the procaterol hydrochloride inhalation formulation to be tested.

[0036] The time-resolved automatic sampling module is responsible for discretizing the continuous inhalation process according to a time sequence. Under the precise timing command of the control system, it can automatically capture the aerosols flowing through different time windows into a series of independent collection containers, thereby providing basic samples for plotting the "delivery rate-time" curve.

[0037] The automated sample pretreatment and transfer module is responsible for the automated pretreatment of captured time-series samples. Its functions include: extracting aerosol samples from the pre-channel of the collection container; pre-filling or adding a quantitative amount of collection solvent; online diluting the sample to ensure its concentration falls within the linear range of HPLC detection; and promoting sample homogenization through physical methods. Simultaneously, this module is responsible for automatically and systematically transferring the processed sample sequence to the subsequent injection analysis location.

[0038] The online chromatographic separation and detection module consists of a high-performance liquid chromatography (HPLC) system, serving as the center for qualitative and quantitative analysis of samples. It separates and detects automatically fed time-series samples according to preset, validated chromatographic conditions, accurately outputting the chromatographic peak area or concentration data of the drug components in each sample.

[0039] The central control and data processing module is responsible for coordinating the operation of all modules and performing intelligent data analysis. On the one hand, it sends control commands to each hardware module to ensure the synchronization and accuracy of the entire testing process; on the other hand, it collects and correlates the HPLC analysis results of each sample with its corresponding collection time point, automatically plots the curve of drug delivery rate changing over time, calculates the total delivery amount through integration, and finally generates a complete test report.

[0040] Under the unified scheduling of the central control system, these five modules form a complete closed-loop testing system, realizing full automation of the entire process from inhalation simulation, time-series sampling, sample processing to data analysis. This provides an innovative evaluation method that surpasses traditional static testing and can accurately reflect the dynamic delivery characteristics of inhaled formulations.

[0041] like Figure 1 , Figure 2 As shown, the automatic sample pretreatment and transfer module mainly adopts the test device of the sample test system for the delivery rate and total delivery of inhaled preparations. The whole is a liquid chromatograph, which is equipped with a sample loading seat 1 and a control seat 2 located on top of the sample loading seat 1. The two are stacked and installed.

[0042] like Figure 3 , Figure 4As shown, a base 3 is installed at the bottom of the sample dispensing holder 1 by screws. A sample dispensing turntable 4 is installed on one side of the top of the base 3 by a rotating shaft. A lifting seat 5 is provided on the other side of the top of the base 3. A sample preparation turntable 6 is installed on the lifting seat 5 by a rotating shaft. The sample preparation turntable 6 is located above the sample dispensing turntable 4, and the sides of the sample preparation turntable 6 and the sample dispensing turntable 4 that are close to each other overlap and cross on the plane, so that the reagent bottle that has been prepared can fall from the sample preparation turntable 6 into the sample dispensing turntable 4 to complete the transfer.

[0043] like Figure 5 As shown, both the sample preparation turntable 6 and the sample dispensing turntable 4 are arranged in a circular array with identical cylindrical bases 7. The cylindrical bases 7 can be used to limit the placement of reagent bottles, so that the reagent bottles rotate synchronously with the sample preparation turntable 6 and the sample dispensing turntable 4. The base 3 is equipped with a servo motor and belt drive assembly, which can drive the sample preparation turntable 6 and the sample dispensing turntable 4 to rotate at the same angular velocity and switch the position of the reagent bottles.

[0044] like Figure 5 As shown, the sample preparation turntable 6, while rotating the reagent bottle, mainly completes the preliminary binding of the aerosol sample generated during the simulated inhalation of the procaterol hydrochloride inhalation formulation with the phosphate buffer solution. The reagent bottles are distributed and placed in the cylinder seat 7 of the sample preparation turntable 6. Both the cylinder seat 7 on the sample preparation turntable 6 and the sample dispensing turntable 4 are open at the top and bottom. The sample preparation turntable 6 is equipped with an electromagnetically controlled support plate structure. The support plate structure is located at the bottom of the cylinder seat 7 and can support the reagent bottle. When the sample preparation turntable 6 and the sample dispensing turntable 4 overlap and the reagent bottle needs to be transferred, the support plate structure opens, allowing the reagent bottle to fall into the cylinder seat 7 of the sample dispensing turntable 4.

[0045] like Figure 6 , Figure 7As shown, a first solvent assembly 8 and a sampling assembly 9 are installed in a staggered manner in the sample application base 1 and control base 2, respectively, to inject buffer solvent and inhalation preparation aerosol samples into the reagent bottle for preliminary fusion. The first solvent assembly 8 is movable and can be inserted into the reagent bottle to add buffer solution. Its top is connected to a solvent cartridge 11 via a flexible tube 10. The solvent cartridge 11 contains phosphate buffer solution. The sampling assembly 9 is rotatably mounted on a rotating seat within the control base 2. A servo motor is installed in the rotating seat to control the angle of the sampling assembly 9. The sampling assembly 9 is in a sample preparation rotation position. Downstream of the rotation direction of disk 6, aerosol samples are injected into the reagent bottle when buffer solution is present. Sampling component 9 is used for sampling when rotated to the tilted position and for sample addition when rotated to the vertical position. Sample box 12 is fixedly installed on the inner wall of sample addition seat 1 by screws. Sample box 12 is tilted and connected to sample channel 13. Sample channel 13 is externally connected to simulated inhalation device. Inhaled aerosol preparations pass through sample channel 13. Sample box 12 is provided with a self-closing rubber stopper structure, in which the needle of sampling component 9 can be inserted for sampling. Normally, it remains closed.

[0046] like Figure 8 , Figure 9 As shown, a second solvent assembly 14 and a sample loading assembly 15 are installed in a staggered manner in the sample loading seat 1 and the control seat 2. The second solvent assembly 14 has the same structure as the first solvent assembly 8, but is lower in height to accommodate the height of the sample loading turntable 4. The sample loading assembly 15 has the same overall structure as the sampling assembly 9, but is installed vertically, allowing it to descend to a lower position. It can not only take samples from the sample loading turntable 4, but also inject the samples into the injection seat 16. The injection seat 16 is assembled in the base 3 and can input the sample solution into the chromatographic column of the liquid chromatograph for detection. The second solvent assembly 14 is located upstream of the sample loading assembly 15. Here, upstream means on the rotation path of the sample loading turntable 4. The position of the second solvent assembly 14 is earlier than that of the sample loading assembly 15. It is also connected to the solvent cartridge 11 through the hose 10, which can inject the buffer solution into the reagent bottle again to further dilute the solution and ensure that it meets the detection requirements of the chromatograph.

[0047] like Figure 9As shown, the cylinder seats 7 on the sample dispensing turntable 4 are arranged in a circular array, and a notch 17 is provided between adjacent cylinder seats 7 so that the sample dispensing component 15 can be connected to the injection seat 16 from the notch 17 position. The injection seat 16 is located at the bottom of the sample dispensing turntable 4. The sample dispensing turntable 4 has two rotation modes. One is full-width rotation, and the angle of each rotation is the distance between adjacent cylinder seats 7. In this mode, it mainly docks with the sample preparation turntable 6 so that the reagent bottle on it can be transferred to the sample dispensing turntable 4. The other is half-width rotation, and the angle of each rotation is the distance between adjacent cylinder seats 7 and notch 17. In this mode, it mainly allows the sample dispensing component 15 to first be positioned above the reagent bottle to take a sample, and then allows the sample dispensing component 15 to be connected to the injection seat 16 from the notch 17 position to dispense the sample.

[0048] like Figure 11 As shown, the cylinder seat 7 on the sample transfer turntable 4 also has an open structure at the top and bottom. However, the bottom of the cylinder seat 7 is equipped with a buffer bearing mechanism, which can protect the reagent bottle when it falls into it, and at the same time can further play the role of uniform mixing.

[0049] The buffer support mechanism includes a counterweight 18 movably installed inside the cylinder base 7. An upper pad 19 is bonded to the top surface of the counterweight 18, and a lower pad 20 is bonded to the bottom surface. Both the upper pad 19 and the lower pad 20 are made of elastic rubber and can be combined to form a support with a buffering effect. At the same time, a sliding rod 21 is bonded to the bottom of the lower pad 20. The sliding rod 21 is vertically slidably installed inside the sample dispensing turntable 4, and a cylindrical cavity is provided in the sample dispensing turntable 4. The sliding rod 21 enters the cylindrical cavity, and a conical base 22 is fixedly installed at the bottom end of the sliding rod 21. Under sufficient air pressure, the conical base 22 can drive the sliding rod 21 and the support to float up, and the suspended support can support the reagent bottle to prevent damage. In addition, when air pressure is present, it can keep the reagent bottle in a high position.

[0050] like Figure 12 As shown, an arc-shaped air blowing box 23 is installed on the base 3 by screws. The air blowing box 23 is located at the bottom of the sample dispensing turntable 4. One end of the air blowing box 23 is located at the overlap of the sample dispensing turntable 4 and the sample preparation turntable 6, and the other end is located near the injection seat 16. It can generate air pressure to lift the reagent bottle falling into the sample dispensing turntable 4 until it enters the sample dispensing position.

[0051] like Figure 13 As shown, the bottom of the air blowing box 23 is connected to an air supply pipe 24 to deliver clean gas. The air supply pipe 24 is connected to an air pump. Air holes 25 are evenly spaced on the air blowing box 23. The air holes 25 can be aligned with the bottom end of the cylinder base 7. The air pressure generated by the air flow discharged through the air holes 25 lifts the conical base 22, causing the support seat to rise and providing better cushioning to support the reagent bottles falling on it.

[0052] Furthermore, by indirectly blocking the air pressure, the reagent bottle can fall with the carrier, generating an oscillation effect, which can promote the mixing of aerosol formulation and buffer solution. The mixing process takes place after the buffer solution for dilution is added to the second solvent component 14. A spring rod 26 is slidably installed through the outer wall of the air blowing box 23. The position of the spring rod 26 is set close to the air hole 25. A stop 27 is provided at one end of the spring rod 26 inside the air blowing box 23, and a ball head 28 is provided at the other end of the spring rod 26 outside the air blowing box 23. When the spring rod 26 moves inward, the stop 27 can close the air hole 25.

[0053] An arc-shaped rail 29 is installed on the outer ring of the air blowing box 23. A round-headed slide 30 is driven to be installed in the arc-shaped rail 29. The round-headed slide 30 can reciprocate in the arc-shaped rail 29. When the round-headed slide 30 moves to the position of the spring rod 26, it can compress the ball head 28 and push the spring rod 26 inward, so that the stop 27 closes the air hole 25 at that position, so that the air pressure at that position disappears, the support can fall, and the reagent bottle shakes to promote the fusion of aerosol and buffer solution.

[0054] like Figure 6 As shown, in one embodiment of the present invention, the first solvent assembly 8 and the second solvent assembly 14 have the same structure, both including a vertically arranged solvent tube 101. The bottom of the solvent tube 101 is connected to an injection needle 102, which is used to deliver the buffer solution into the reagent bottle. A flow valve 103 is provided on the solvent tube 101 near the injection needle 102 to monitor the delivery volume of the solvent assembly. Furthermore, the solvent tube 101 is mounted on a vertical rail 104, which adopts an electrically controlled linear track structure that can drive the solvent tube 101 to rise and fall for quantitative injection of the buffer solution.

[0055] like Figure 7 , Figure 10 As shown, in another embodiment of the present invention, the sampling component 9 and the sample dispensing component 15 have the same overall structure, both including a linear outer slide rail 201. An inner slide rail 202 is driven and installed in the outer slide rail 201. A syringe 203 is fixed on the inner slide rail 202 by a snap-fit. A pull member 204 is driven and installed on the inner slide rail 202. The pull member 204 can be connected to the piston of the syringe 203 to control the syringe 203 to perform sample extraction and injection. The sampling component 9 transfers the aerosol sample from the sample box 12 to the reagent bottle, while the sample dispensing component 15 transfers the fused sample from the reagent bottle to the injection seat 16.

[0056] In use, the present invention is as follows: First, the reagent bottle is placed in the cylinder seat 7 of the sample preparation turntable 6. The first solvent component 8 adds a quantitative amount of phosphate buffer solution to the bottle. After the simulated inhalation device is activated, procaterol hydrochloride aerosol is generated. The sampling component 9 extracts aerosol samples from the sample channel 13 according to a preset time sequence and injects them into the reagent bottle at the corresponding time point, achieving time-resolved sampling. After sampling, the reagent bottle rotates with the sample preparation turntable 6 to an overlap position with the sample dispensing turntable 4. The tray opens, and the reagent bottle falls into the corresponding cylinder seat 7 of the sample dispensing turntable 4. The air pressure provided by the air blowing box 23 lifts and buffers the bottle through the buffer support mechanism. The second solvent component 14 further dilutes the sample in the bottle. Then, the intermittent air cut-off of the air blowing box 23 causes the support seat to vibrate the reagent bottle, promoting sample mixing. The sample loading turntable 4 moves the reagent bottles sequentially below the sample loading assembly 15 in a half-amplitude rotation mode. After the sample loading assembly 15 extracts the sample, the turntable rotates half-amplitude again to align the sample loading assembly 15 with the injection seat 16, injecting the sample into the liquid chromatography system for analysis. The control system synchronously records the acquisition time and chromatographic analysis results of each sample, automatically generates a delivery rate-time curve, and calculates the total delivery volume, completing the fully automated test.

[0057] In the description of this disclosure, it should be noted that, unless otherwise expressly specified and limited, the terms "installation," "connection," and "linking" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection of two components. Those skilled in the art can understand the specific meaning of the above terms in this disclosure based on the specific circumstances. Although embodiments of the invention have been shown and described, those skilled in the art will understand that various changes, modifications, substitutions, and variations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A sample testing system for the delivery rate and total amount of inhaled formulations, characterized in that: include: The simulated inhalation and aerosol generation module is used to simulate human respiratory dynamics conditions and generate the aerosol to be tested; The time-resolved automatic sampling module is used to capture the flowing aerosols into separate collection containers according to a preset time sequence; The automatic sample pretreatment and transfer module is used to add and mix solvent into the collection container and automatically transfer the processed sample sequence. The online chromatographic separation and detection module is used for automated chromatographic analysis and detection of transferred time-series samples; The central control and data processing module coordinates the operation of each module and generates delivery rate-time curves and total delivery volume data based on analysis results and time information.

2. A testing apparatus for a sample testing system for the delivery rate and total amount of inhaled formulations as described in claim 1, characterized in that: include: The base is installed in the liquid chromatograph; A sample preparation turntable is rotatably mounted on the base, and a ring array of stations on it is provided for accommodating collection containers to complete the initial mixing of aerosol samples and solvents. A sample loading turntable is rotatably mounted on the base, with a portion of its area overlapping the sample preparation turntable in the vertical direction, for receiving a collection container from the sample preparation turntable; The first solvent assembly, corresponding to the sample preparation turntable, is used to add a quantitative amount of solvent to the collection container; A sampling component, corresponding to the sample preparation turntable, is used to extract samples from the external aerosol flow path and inject them into the collection container; The second solvent assembly, corresponding to the sample dispensing turntable, is used to add solvent to the collection container that has been transferred to the sample dispensing turntable; The sample loading assembly, corresponding to the sample loading turntable, is used to extract the mixed sample from the collection container and inject it into the injection interface of the chromatography system; The sample preparation turntable and the sample dispensing turntable rotate in coordination under the control of the sample testing system, so as to realize the automatic transfer and sequential positioning of the collection container from the sample preparation station to the sample dispensing station.

3. The testing apparatus for the sample testing system for the delivery rate and total amount of inhaled formulations according to claim 2, characterized in that: The base is provided with a drive mechanism, which includes a servo motor and a belt drive assembly disposed within the base; The servo motor drives the sample preparation turntable and the sample loading turntable to rotate at the same angular velocity via the belt drive assembly.

4. The testing apparatus of the sample testing system for the delivery rate and total amount of inhaled formulations according to claim 2, characterized in that: The projections of the sample preparation turntable and the sample dispensing turntable on the horizontal plane overlap and intersect; The sample preparation turntable is equipped with an electromagnetically controlled tray structure. When the tray structure is opened in the overlapping area, the collection container it carries falls into the corresponding position of the sample dispensing turntable under the action of gravity.

5. The testing apparatus for the sample testing system for the delivery rate and total amount of inhaled formulations according to claim 2, characterized in that: The sampling component is mounted in the control base via a rotating seat and is driven by a servo motor to switch between an inclined sampling position and a vertical sample application position. The sampling station is aligned with the sample box, which is connected to the aerosol flow path of the simulated inhalation device through the sample channel.

6. The testing apparatus for the sample testing system for the delivery rate and total amount of inhaled formulations according to claim 2, characterized in that: Both the first solvent assembly and the second solvent assembly include a vertically arranged solvent tube, an injection needle connected to the bottom of the solvent tube, a flow valve disposed on the solvent tube, and a vertical rail for driving the solvent tube and the injection needle to move up and down.

7. The testing apparatus for the sample testing system for the delivery rate and total amount of inhaled formulations according to claim 2, characterized in that: Both the sampling component and the sample dispensing component include an outer slide rail, an inner slide rail driven and mounted on the outer slide rail, a syringe fixed on the inner slide rail, and a pull member driven and mounted on the inner slide rail and connected to the piston of the syringe.

8. The testing apparatus for the sample testing system for the delivery rate and total amount of inhaled formulations according to claim 5, characterized in that: The bottom of the sample dispensing turntable is provided with an arc-shaped air blowing box, the bottom of which is connected to an air supply pipe, and the top is provided with air holes corresponding to the work positions on the sample dispensing turntable. The bottom of the sample loading turntable is equipped with a buffer support mechanism, which includes a counterweight, an elastic pad, and a conical base. The airflow generated by the air blowing box acts on the conical base, causing the buffer support mechanism to rise to catch the falling collection container.

9. The testing apparatus for the sample testing system for the delivery rate and total amount of inhaled formulations according to claim 8, characterized in that: The air blowing box is provided with an oscillation mechanism, which includes a spring rod that can slide through the outer wall of the air blowing box. The end of the spring rod located inside the air blowing box is provided with a stop for sealing the air hole, and the end located outside the air blowing box is provided with a ball head. It also includes an arc-shaped rail installed outside the air blowing box, in which a round-headed slide is reciprocating, periodically pressing the ball head to make the spring rod move inward, thereby blocking the airflow and realizing the oscillation of the bearing seat.

10. The testing apparatus for the sample testing system for the delivery rate and total amount of inhaled formulations according to claim 2, characterized in that: A notch is provided between adjacent stations on the sample dispensing turntable; The sample dispensing turntable has a full-width rotation mode and a half-width rotation mode. In the full-width rotation mode, its rotation angle is the distance between adjacent workstations. In the half-width rotation mode, its rotation angle is the distance between the workstation and the notch, so that the sample dispensing component can alternately align with the collection container and the injection seat located below the notch.

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