Detection system and method for simulating capsule dissolution process

Abstract

The invention relates to the field of detection for simulating the capsule dissolution process, in particular to a detection system and method for simulating the capsule dissolution process, and the system comprises an environment simulation module which is used for simulating the internal environment of the stomach of a human body, comprising a reaction cup used for containing simulated gastric juice and a temperature control unit connected with the reaction cup and used for adjusting the temperature in the reaction cup. The stirring module is connected with the environment simulation module and used for simulating the flowing environment in the stomach of the human body; the detection module is connected with the environment simulation module and used for collecting dissolution characteristic data in the capsule dissolution process; and the control module is used for judging whether the accuracy of capsule dissolving capacity detection meets the requirement or not according to the variance of the dissolving ratio of the capsule in the simulated gastric juice under the same environment, and determining the processing mode of the dissolving degree according to the judgment result of the capsule dissolving capacity. According to the invention, the real-time detection of the dissolution process of the capsule in gastric acid is realized through a simulation experiment.

Description

Technical Field

[0001] The present invention relates to the field of detection of a simulated capsule dissolution process, and in particular to a detection system and method for a simulated capsule dissolution process. Background Art

[0002] With the continuous advancement of medical technology, capsules, as a common drug dosage form, are widely used in the packaging and delivery of various drugs. In order to ensure the safety and effectiveness of capsule drugs, it is necessary to have a deep understanding of the dissolution process of capsules in the body. However, there are many limitations to conducting research directly in the human body, such as large individual differences and difficulty in accurately controlling experimental conditions. Therefore, establishing a detection system that simulates the capsule dissolution process has become an important requirement for drug development and quality control. At present, the commonly used capsule dissolution test methods mainly use the dissolution determination methods specified in the pharmacopoeia, such as the basket method and the paddle method. Although these methods can reflect the dissolution characteristics of capsules to a certain extent, they have problems such as complex operation, long time consumption, and difficulty in real-time detection. The environment of the human stomach is complex, including temperature, pH, enzyme content, mechanical stirring and other factors. Existing simulation methods often find it difficult to accurately reproduce these conditions, resulting in deviations between the simulation results and the actual situation. Existing detection methods mainly rely on regular sampling and analysis, and cannot achieve continuous and real-time detection. This makes it difficult to capture transient changes and key events in the capsule dissolution process.

[0003] Chinese patent publication number CN101639471A discloses a device for evaluating the dissolution / absorption process of a solid drug preparation. The present invention provides a device for evaluating the dissolution / absorption process of a solid drug preparation, which is mainly composed of a drug dissolution chamber, a pH adjustment chamber and a diffusion cell, wherein a magnetic stirrer is arranged at the bottom of the drug dissolution chamber, the diffusion cell is composed of a supply chamber, a receiving chamber and a Caco-2 monolayer cell membrane or an isolated intestinal tube of an animal (such as a rat) embedded therebetween, the chambers are connected by a silicone tube with an inner diameter of 1.0 mm-2.0 mm, a drug carrier is also arranged in the drug dissolution chamber, and a distance is left between the drug carrier and the magnetic stirrer at the bottom of the drug dissolution chamber; a stainless steel screen can also be arranged at the top of the pH adjustment chamber, and a microporous filter is added in the silicone tube between the pH adjustment chamber and the supply chamber. The device can be applied to a wider range of solid preparations such as tablets, soft capsules, and hard capsules; and solves the blockage problem caused by drug excipients; and truly simulates the influence of gastrointestinal pH changes on the release law of solid drug preparations under human physiological conditions. It can be seen that the device for evaluating the dissolution / absorption process of a solid pharmaceutical preparation of the present invention has the problem that it is unable to continuously and in real time detect the dissolution process of the capsule in gastric acid, and thus is unable to determine the dissolution time of the capsule and the factors affecting the dissolution. Summary of the invention

[0004] To this end, the present invention provides a detection system and method for simulating the capsule dissolution process, so as to overcome the problem in the prior art that the capsule dissolution process in gastric acid cannot be continuously and in real time detected, and thus the dissolution time of the capsule and the factors affecting the dissolution cannot be determined.

[0005] To achieve the above object, the present invention provides a detection system for simulating the capsule dissolution process, comprising: An environmental simulation module, used to simulate the internal environment of the human stomach, including a reaction cup for containing simulated gastric juice and a temperature control unit connected to the reaction cup for adjusting the temperature inside the reaction cup; A stirring module, which is connected to the environment simulation module and is used to simulate the flow environment inside the human stomach; A detection module, connected to the environmental simulation module, for detecting dissolution characteristic data during capsule dissolution; A control module, which is connected to the environment simulation module, the stirring module and the detection module respectively, and is used to determine whether the accuracy of the capsule dissolution performance test meets the requirements according to the variance of the dissolution ratio of the capsule in the simulated gastric fluid under the same environment, and determine the processing method of the dissolution degree according to the determination result of the accuracy of the capsule dissolution performance test, including: adjusting the angle between the reaction cup and the light source, or determining the loss degree of the stirring structure according to the ratio of the stirring speed to the flow rate of the simulated gastric fluid, and adjusting the single change amount of the stirring rate, And, the single change amount of the stirring rate is quadratically adjusted according to the linear fit between the stirring time and the capsule dissolution time.

[0006] Furthermore, the environment simulation module also includes a basket for fixing the position of the capsule.

[0007] Furthermore, the dissolution characteristic data includes the dissolution ratio of the test capsule in the simulated gastric fluid, the stirring rate and the flow rate of the simulated gastric fluid.

[0008] Furthermore, the detection module also includes a thermometer arranged in the reaction cup for detecting the temperature of the simulated gastric fluid.

[0009] Furthermore, the stirring module comprises: A stirring bar, which is placed at the bottom of the reaction cup and is used to stir the simulated gastric juice; The electromagnet is located below the constant temperature water bath and is used to rotate the stirring bar through magnetic force.

[0010] Furthermore, if the variance of the dissolution ratio of the capsule in the simulated gastric fluid is greater than the preset second variance, it is determined that the accuracy of the capsule dissolution ability detection does not meet the requirements, and the angle between the reaction cup and the light source is reduced.

[0011] Furthermore, if the variance of the dissolution ratio of the capsule in the simulated gastric fluid is greater than the preset first variance and less than or equal to the preset second variance, a secondary judgment is made on the accuracy of the capsule dissolution ability detection based on the ratio of the stirring speed to the flow rate. If the ratio of the stirring speed to the flow rate is greater than the preset ratio, the single change in the stirring rate is increased.

[0012] Furthermore, if the linear fit between the stirring time and the capsule dissolution time is less than a preset fit, the single change amount of the stirring rate is reduced.

[0013] Furthermore, the angle between the reaction cup and the light source is the angle formed by the light emitted from a point of the light source after being refracted by the convex lens and the central axis of the reaction cup.

[0014] The present invention also provides a detection method for simulating the capsule dissolution process, comprising: Prepare simulated gastric fluid in a reaction cup and adjust the temperature to a preset temperature; The experimental capsules were placed in a mesh basket and completely immersed in simulated gastric fluid; Adjust the electromagnet to the preset stirring speed; After the reaction is completed, the dissolution ratio of the capsule in the simulated gastric fluid is tested; If the variance of the dissolution ratio of the capsule in the simulated gastric fluid is greater than the preset second variance, it is determined that the accuracy of the capsule dissolution ability test does not meet the requirements; If the variance of the dissolution ratio of the capsule in the simulated gastric fluid is greater than the preset first variance and less than or equal to the preset second variance, a secondary determination is made on the accuracy of the capsule dissolution ability detection according to the ratio of the stirring speed to the flow rate, and the single change amount of the stirring speed is adjusted; If the linear fit between the stirring time and the capsule dissolution time is less than a preset fit, a secondary adjustment is performed on the single change in the stirring rate.

[0015] Compared with the prior art, the beneficial effects of the present invention are that, by setting an environmental simulation module, a stirring module, a detection module and a control module, the present invention quantifies the phenomena in the capsule dissolution process by setting dissolution characteristic data, thereby realizing real-time detection of the dissolution process; by adjusting the component proportion of the simulated gastric juice solution by the capsule dissolution speed and the content of pepsin, the similarity between the simulated gastric juice and the human gastric juice components is improved, making the experimental results more accurate; by adjusting the time to start stirring by the difference in the degree of drug concentration after dissolution, the stirring process is optimized, which helps to improve the stability and controllability of dissolution.

[0016] Furthermore, the present invention sets a preset first variance and a preset second variance, and adjusts the angle between the reaction cup and the light source according to the dissolution ratio of the capsule in the simulated gastric fluid, thereby overcoming the problem of uneven propagation of light in the liquid in the reaction cup due to an inappropriate angle between the light source and the reaction cup, thereby affecting the accurate measurement of the capsule dissolution ratio, and helps to locate the reason why the dissolution degree does not meet the requirements.

[0017] Furthermore, the present invention sets a preset ratio and reduces the single change in the stirring rate, thereby overcoming the problem of uneven expansion of the capsule shell due to repeated absorption of water by the capsule shell due to uneven impact force of the solution on the capsule gelatin shell during stirring, thereby causing uneven breakage of the capsule gelatin shell and affecting the drug release concentration, thereby improving the consistency of drug release.

[0018] Furthermore, the present invention sets a linear fit between the stirring time and the capsule dissolution time, and overcomes the problem that the detection time is prolonged due to the single change of the stirring rate being too low, thereby causing a large difference between the stirring effect and the actual decomposition situation in the stomach, such as the degree of capsule particle crushing far exceeds the actual situation, by quadratically adjusting the single change of the stirring rate. This helps to improve the accuracy of simulated dissolution. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 Schematic diagram of the overall structure of a detection system for simulating capsule dissolution process according to an embodiment of the present invention; Figure 2 The overall structural block diagram of the detection system for simulating the capsule dissolution process according to an embodiment of the present invention; Figure 3 It is a structural block diagram of an environmental simulation module of a detection system for simulating a capsule dissolution process according to an embodiment of the present invention; Figure 4 A method step diagram of a detection system for simulating a capsule dissolution process according to an embodiment of the present invention; The accompanying drawings are marked as follows: 1-constant temperature water bath, 2-reaction cup, 3-thermometer, 4-electromagnet, 5-stirring bar, 6-net basket, 7-base, 8-electric adjustment rod, 9-convex lens. DETAILED DESCRIPTION

[0020] In order to make the objects and advantages of the present invention more clearly understood, the present invention is further described below in conjunction with embodiments; it should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention.

[0021] The preferred embodiments of the present invention are described below with reference to the accompanying drawings. It should be understood by those skilled in the art that these embodiments are only used to explain the technical principles of the present invention and are not intended to limit the protection scope of the present invention.

[0022] It will be understood by those skilled in the art that, unless otherwise stated, the singular forms "a", "an" and "the" used herein may also include plural forms. It should be further understood that the term "comprising" used in this specification refers to the presence of features, integers, steps, operations, elements / components, but does not exclude the presence or addition of one or more other features, integers, steps, operations, elements / components. It should be understood that when we refer to a module as being "connected" or "coupled" to another module, it may be directly connected or coupled to the other module, or there may be an intermediate unit. In addition, "connected" or "coupled" used herein may include wireless connection or wireless coupling.

[0023] See also Figure 1 , Figure 2 , Figure 3 as well as Figure 4 As shown, they are respectively an overall structural schematic diagram of a detection system for simulating capsule dissolution process according to an embodiment of the present invention, an overall structural block diagram, a structural block diagram of an environmental simulation module, and a step diagram of a method. A detection system for simulating capsule dissolution process according to an embodiment of the present invention comprises: An environmental simulation module, used to simulate the internal environment of the human stomach, including a reaction cup 2 for containing simulated gastric juice and a temperature control unit connected to the reaction cup 2 for adjusting the temperature inside the reaction cup 2; A stirring module, which is connected to the environment simulation module and is used to simulate the flow environment inside the human stomach; A detection module, connected to the environmental simulation module, for detecting dissolution characteristic data during capsule dissolution; The control module is connected to the environment simulation module, the stirring module and the detection module respectively, and is used to determine whether the accuracy of the capsule dissolution performance test meets the requirements according to the variance of the dissolution ratio of the capsule in the simulated gastric fluid under the same environment, and determine the processing method of the dissolution degree according to the determination result of the accuracy of the capsule dissolution performance test, including: adjusting the angle between the reaction cup 2 and the light source, or determining the loss degree of the stirring structure according to the ratio of the stirring speed to the flow rate of the simulated gastric fluid, and adjusting the single change amount of the stirring rate, And, the single change amount of the stirring rate is quadratically adjusted according to the linear fit between the stirring time and the capsule dissolution time.

[0024] In implementation, the present invention sets an environmental simulation module, a stirring module, a detection module and a control module, sets dissolution characteristic data, quantifies the phenomena in the capsule dissolution process, and realizes real-time detection of the dissolution process; adjusts the component ratio of the simulated gastric juice solution by the capsule dissolution speed and the content of pepsin, thereby improving the similarity between the simulated gastric juice and the human gastric juice components and making the experimental results more accurate; adjusts the time to start stirring by the difference in the degree of drug concentration after dissolution, optimizes the stirring process, and helps to improve the stability and controllability of dissolution.

[0025] Specifically, the capsule dissolution ratios at n sampling points in the simulated gastric fluid after the capsule is dissolved are detected, and the variance of the dissolution ratios at the n sampling points is calculated; the dissolution ratio of the capsule in the simulated gastric fluid is calculated by high performance liquid chromatography, and the method for calculating the variance of the dissolution ratio of the capsule in the simulated gastric fluid is a conventional technical means well known to those skilled in the art, and the calculation process of the variance of the dissolution ratio of the capsule in the simulated gastric fluid will not be repeated here.

[0026] Specifically, the environment simulation module is used to fix the basket 6 of the capsule position.

[0027] Specifically, the dissolution characteristic data include the dissolution ratio of the test capsule in the simulated gastric fluid, the stirring rate and the flow rate of the simulated gastric fluid.

[0028] Specifically, the temperature control unit is a constant temperature water bath 1 .

[0029] Specifically, the detection module further includes a thermometer 3 disposed in the reaction cup 2 for detecting the temperature of the simulated gastric fluid.

[0030] Specifically, the stirring module includes: A stirring bar 5, which is placed at the bottom of the reaction cup 2 and is used to stir the simulated gastric juice; An electromagnet 4, which is located below the constant temperature water bath and is used to rotate the stirrer 5 through magnetic force; A control knob is arranged on the housing of the electromagnet 4 to control the stirring speed.

[0031] Specifically, if the variance of the dissolution ratio of the capsule in the simulated gastric fluid is greater than the preset second variance, it is determined that the accuracy of the capsule dissolution ability detection does not meet the requirements, and the angle between the reaction cup 2 and the light source is reduced; The angle between the reaction cup 2 and the light source is adjusted by changing the angle of the convex lens 9 .

[0032] In implementation, the present invention adjusts the angle between the reaction cup 2 and the light source by setting a preset first variance and a preset second variance according to the dissolution ratio of the capsule in the simulated gastric fluid, thereby overcoming the problem of uneven propagation of light in the liquid in the reaction cup 2 caused by an inappropriate angle between the light source and the reaction cup 2, thereby affecting the accurate measurement of the capsule dissolution ratio, and helps to locate the reason why the dissolution degree does not meet the requirements.

[0033] Optionally, the preset second variance may be in the range of [5%, 7%]; Preferably, the preferred embodiment of the preset second variance is 6%; In a specific embodiment, the variance of the dissolution ratio of the capsule in the simulated gastric fluid is 8%, which is greater than the preset second variance; for every 0.5% by which the variance of the dissolution ratio of the capsule in the simulated gastric fluid is greater than the preset second variance, the angle between the reaction cup 2 and the light source is reduced by 1° compared with the current angle between the reaction cup 2 and the light source. The current angle between the reaction cup 2 and the light source is 90°, and the reduced angle between the reaction cup 2 and the light source is 90-[(8-6) / 0.5]×=86°.

[0034] Specifically, if the variance of the dissolution ratio of the capsule in the simulated gastric fluid is greater than the preset first variance and less than or equal to the preset second variance, a secondary judgment is made on the accuracy of the capsule dissolution ability detection based on the ratio of the stirring speed to the flow rate. If the ratio of the stirring speed to the flow rate is greater than the preset ratio, the single change in the stirring rate is increased.

[0035] In practice, the present invention overcomes the problem of uneven breakage of the gelatin shell of the capsule, which affects the drug release concentration, due to uneven impact force of the solution on the gelatin shell of the capsule during stirring, and thus affects the consistency of drug release, by setting a preset ratio and reducing the single change in the stirring rate.

[0036] Optionally, the value range of the preset first variance may be [3%, 5%], and the value range of the preset ratio may be [2r / min·v, 3r / min·v]; Preferably, the preferred embodiment of the preset first variance is 4%, and the preferred embodiment of the preset ratio is 2.5 r / min·v; In a specific embodiment, the variance of the dissolution ratio of the capsule in simulated gastric fluid is 5%, which is greater than the preset first variance and less than the preset second variance, and the ratio of the stirring speed to the flow rate is 2.75r / min·v; for every 0.25r / min·v that the ratio of the stirring speed to the flow rate is less than the preset ratio, the single change in the stirring rate increases by 2r / min compared with the current single change in the stirring rate. The current single change in the stirring rate is 50r / min, and the increased single change in the stirring rate is 50+[(2.75-2.5) / 0.25]×2=52r / min.

[0037] Specifically, if the linear fit between the stirring time and the capsule dissolution time is less than a preset fit, the single change amount of the stirring rate is reduced; The linear fitting degree is the influence of stirring time on capsule dissolution time.

[0038] Optionally, the preset fitness value range may be [1.5, 2]; Preferably, the preferred embodiment of the preset fit degree is 1.5; In one or more specific embodiments, the linear fit between the stirring time and the capsule dissolution time is 1.2. When the linear fit is less than the preset fit by 0.1, the single change in the stirring rate is reduced by 1 r / min compared with the single change in the current stirring rate. The current single change in the stirring rate is 56 r / min, and the reduced single change in the stirring rate is 56-[(1.5-1.2) / 0.1]=53 r / min.

[0039] Specifically, the angle between the reaction cup 2 and the light source is the angle formed by the light emitted from a point of the light source after being refracted by the convex lens 9 and the central axis of the reaction cup 2 .

[0040] In implementation, the present invention further sets a linear fit between the stirring time and the capsule dissolution time, and overcomes the problem that the detection time is lengthened due to the single change of the stirring rate being too low, thereby causing a large difference between the stirring effect and the actual decomposition situation in the stomach, such as the degree of capsule particle crushing far exceeds the actual situation, by adjusting the single change of the stirring rate for a second time. This helps to improve the accuracy of simulated dissolution.

[0041] Specifically, a detection method for simulating the capsule dissolution process includes: Step S1, preparing simulated gastric fluid in reaction cup 2 and adjusting the temperature to 37° C.; Step S2, placing the test capsule in the basket 6 and completely immersing it in the simulated gastric fluid; Step S3, adjusting the electromagnet 4 to 60 revolutions / minute; Step S4, after the reaction is completed, detecting the dissolution ratio of the capsule in the simulated gastric fluid; Step S5, if the variance of the dissolution ratio of the capsule in the simulated gastric fluid is greater than the preset second variance, it is determined that the accuracy of the capsule dissolution ability test does not meet the requirements; Step S6, if the variance of the dissolution ratio of the capsule in the simulated gastric fluid is greater than the preset first variance and less than or equal to the preset second variance, a secondary determination is made on the accuracy of the capsule dissolution ability detection according to the ratio of the stirring speed to the flow rate, and the single change amount of the stirring speed is adjusted; Step S7, if the linear fit between the stirring time and the capsule dissolution time is less than a preset fit, a secondary adjustment is made to the single change in the stirring rate; The composition of the simulated gastric fluid is 36% analytical pure hydrochloric acid: distilled water = 0.0083:1000; the content of pepsin in the gastric acid solution is 2 g / L.

[0042] So far, the technical solutions of the present invention have been described in conjunction with the preferred embodiments shown in the accompanying drawings. However, it is easy for those skilled in the art to understand that the protection scope of the present invention is obviously not limited to these specific embodiments. Without departing from the principle of the present invention, those skilled in the art can make equivalent changes or substitutions to the relevant technical features, and the technical solutions after these changes or substitutions will fall within the protection scope of the present invention.

Claims

1. A detection system for simulating capsule dissolution process, characterized in that: include: An environmental simulation module, used to simulate the internal environment of the human stomach, including a reaction cup for containing simulated gastric juice and a temperature control unit connected to the reaction cup for adjusting the temperature inside the reaction cup; A stirring module, which is connected to the environment simulation module and is used to simulate the flow environment inside the human stomach; A detection module, connected to the environmental simulation module, for detecting dissolution characteristic data during capsule dissolution; A control module, which is connected to the environment simulation module, the stirring module and the detection module respectively, and is used to determine whether the accuracy of the capsule dissolution performance test meets the requirements according to the variance of the dissolution ratio of the capsule in the simulated gastric fluid under the same environment, and determine the processing method of the dissolution degree according to the determination result of the accuracy of the capsule dissolution performance test, including: adjusting the angle between the reaction cup and the light source, or determining the loss degree of the stirring structure according to the ratio of the stirring speed to the flow rate of the simulated gastric fluid, and adjusting the single change amount of the stirring rate, And, the single change amount of the stirring rate is quadratically adjusted according to the linear fit between the stirring time and the capsule dissolution time.

2. The detection system for simulating capsule dissolution process according to claim 1, characterized in that: The environment simulation module also includes a basket for fixing the position of the capsule.

3. The detection system for simulating capsule dissolution process according to claim 2, characterized in that: The dissolution characteristic data include the dissolution ratio of the test capsule in the simulated gastric fluid, the stirring rate and the flow rate of the simulated gastric fluid.

4. The detection system for simulating capsule dissolution process according to claim 3, characterized in that: The detection module includes a thermometer arranged in the reaction cup for detecting the temperature of the simulated gastric fluid.

5. The detection system for simulating capsule dissolution process according to claim 4, characterized in that: The stirring module comprises: A stirring bar, which is placed at the bottom of the reaction cup and is used to stir the simulated gastric juice; The electromagnet is located below the constant temperature water bath and is used to rotate the stirring bar through magnetic force.

6. The detection system for simulating capsule dissolution process according to claim 5, characterized in that: If the variance of the dissolution ratio of the capsule in the simulated gastric fluid is greater than the preset second variance, it is determined that the accuracy of the capsule dissolution ability detection does not meet the requirements, and the angle between the reaction cup and the light source is reduced.

7. The detection system for simulating capsule dissolution process according to claim 6, characterized in that: If the variance of the dissolution ratio of the capsule in the simulated gastric fluid is greater than the preset first variance and less than or equal to the preset second variance, a secondary judgment is made on the accuracy of the capsule dissolution ability detection based on the ratio of the stirring speed to the flow rate. If the ratio of the stirring speed to the flow rate is greater than the preset ratio, the single change of the stirring rate is increased.

8. The detection system for simulating capsule dissolution process according to claim 7, characterized in that: If the linear fit between the stirring time and the capsule dissolution time is less than a preset fit, the single change amount of the stirring rate is reduced.

9. The detection system for simulating capsule dissolution process according to claim 8, characterized in that: The angle between the reaction cup and the light source is the angle formed by the light emitted from a point of the light source after being refracted by the convex lens and the central axis of the reaction cup.

10. A detection method applied to the detection system for simulating capsule dissolution process according to any one of claims 1 to 9, characterized in that: include: Prepare simulated gastric fluid in a reaction cup and adjust the temperature to a preset temperature; The experimental capsules were placed in a mesh basket and completely immersed in simulated gastric fluid; Adjust the electromagnet to the preset stirring speed; After the reaction is completed, the dissolution ratio of the capsule in the simulated gastric fluid is tested; If the variance of the dissolution ratio of the capsule in the simulated gastric fluid is greater than the preset second variance, it is determined that the accuracy of the capsule dissolution ability test does not meet the requirements; If the variance of the dissolution ratio of the capsule in the simulated gastric fluid is greater than the preset first variance and less than or equal to the preset second variance, a secondary determination is made on the accuracy of the capsule dissolution ability detection according to the ratio of the stirring speed to the flow rate, and the single change amount of the stirring speed is adjusted; If the linear fit between the stirring time and the capsule dissolution time is less than a preset fit, a secondary adjustment is performed on the single change in the stirring rate.

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