Disintegration testing device for quick release preparation

Abstract

The utility model discloses a disintegration testing device for a quick release preparation. The disintegration testing device mainly comprises a solvent injection part, a test sample accommodating cavity and a disintegration liquid outflow part, the upper end and the lower end of the test sample accommodating cavity are opened and are at least detachably connected with one of the solvent injection component and the disintegration liquid outflow component. The disintegration liquid outflow component comprises a disintegration liquid outflow pipeline and a sieve plate, and the sieve plate is arranged on the section of the disintegration liquid outflow pipeline. According to the utility model, by simulating oral administration, the disintegration effect of the quick-release preparation can be dynamically tested and is closer to the actual disintegration process of the quick-release preparation, and an important test means is provided for rapid research and development of novel oral medicines.

Description

Technical Field

[0001] The utility model belongs to the field of drug analysis instruments, and in particular relates to a disintegration test device for quick-release preparations. Background Art

[0002] Disintegration refers to the physical dissolution process of a drug preparation before absorption. Disintegration time refers to the time it takes for pills, tablets, and capsules to disintegrate into fragments under certain conditions. It was once considered the main factor affecting the bioavailability of oral drugs. The disintegration instrument used for drug testing is an instrument used to detect the disintegration time of drugs.

[0003] Since drugs typically disintegrate in the stomach, existing disintegration devices mostly simulate the disintegration of drugs in the stomach, resulting in complex structures and cumbersome operation. For example, patent publication number CN217007246U discloses a disintegration device for drug testing. Patent publication number CN215297337U discloses a drug disintegration device. Patent publication number CN214201415U discloses a disintegration device for drug testing.

[0004] However, existing drugs (such as freeze-dried tablets) begin to disintegrate in the mouth, and traditional disintegration instruments are not suitable for disintegration testing of rapid-release formulations. Therefore, developing a rapid-release formulation disintegration test device that simulates oral administration is of great significance for the development of new drugs. Utility Model Content

[0005] In order to meet the needs of new drug research and development and the disintegration test requirements for oral administration, the utility model provides a disintegration test device for immediate-release preparations. The specific technical solution is as follows:

[0006] A disintegration test device for a quick-release preparation comprises, from top to bottom, a solvent injection component, a test sample accommodating cavity, and a disintegrating liquid outflow component.

[0007] The test sample holding chamber is the disintegration site of the drug sample to be tested (such as a rapid-release preparation), has openings at the upper and lower ends, and is detachably connected to at least one of the solvent injection component and the disintegration liquid outflow component.

[0008] Preferably, the test sample holding chamber is arranged at an angle of 45-90 degrees to the horizontal plane in the vertical direction, for example: 45 degrees, 50 degrees, 55 degrees, 60 degrees, 65 degrees, 70 degrees, 75 degrees, 80 degrees, 85 degrees, 90 degrees.

[0009] Preferably, the test sample holding chamber is made of a transparent material, such as transparent plastic, glass, etc.

[0010] Preferably, a test sample adding port is provided on the test sample holding chamber to facilitate the addition of the drug sample to be tested (such as a rapid-release reagent).

[0011] The test sample holding chamber is provided with a test sample fixing device for fixing the drug sample to be tested (such as a rapid-release preparation).

[0012] Preferably, the sample fixing device is a sample clamp, which is provided on the cavity wall of the test sample holding cavity and is used to clamp the rapid-release preparation.

[0013] Preferably, the solvent injection component includes a solvent injection port, a solvent inflow pipe and a solvent outflow port.

[0014] Furthermore, the solvent outflow port is detachably connected to the inlet of the test sample holding chamber.

[0015] The disintegrating liquid outflow component comprises a disintegrating liquid outflow pipe and a sieve plate, and the sieve plate is arranged on the cross section of the disintegrating liquid outflow pipe.

[0016] The sieve plate is used to filter the mixed solution after the drug sample is disintegrated in the solvent, so as to observe whether there is residue after the drug disintegration and evaluate the degree of drug disintegration.

[0017] Preferably, the pore size of the sieve plate is 75-850 μm, for example: 75 μm, 100 μm, 200 μm, 300 μm, 400 μm, 500 μm, 600 μm, 700 μm, 710 μm, 800 μm, 850 μm.

[0018] Preferably, the solvent outflow port of the solvent injection component is porous, and the solvent flows out of the porous outflow port into the test sample holding chamber.

[0019] Preferably, the solvent injection component is used to drip solvent into the test sample holding chamber to cause the drug sample to disintegrate under the action of the solvent. The solvent injection component includes but is not limited to a syringe, a dropper, or a pipette. Any device capable of quantitatively adding liquid may be used.

[0020] Furthermore, the volume of the solvent injection component is ≥2 mL, for example: 2 mL, 3 mL, 4 mL, 5 mL, 6 mL, 7 mL, 8 mL.

[0021] Preferably, the disintegration test device further comprises a disintegration liquid collecting container, which is a storage place for the liquid after the drug sample is disintegrated and is arranged below the disintegration liquid outflow pipe.

[0022] Preferably, the disintegration test device further comprises a solvent storage container, a peristaltic pump and a catheter. The solvent storage container is used to place the disintegration solvent of the drug sample, and preferably the solvent is water.

[0023] Preferably, the conduit is fixed on the peristaltic pump. Furthermore, one end of the conduit is connected to the solvent storage container, and the other end passes through the peristaltic pump and is connected to the solvent injection port.

[0024] Preferably, the rotation speed of the peristaltic pump is 10 to 100 rpm, for example: 10 rpm, 20 rpm, 30 rpm, 40 rpm, 50 rpm, 60 rpm, 70 rpm, 80 rpm, 90 rpm, 100 rpm.

[0025] Preferably, the disintegration test device further comprises a bracket, which is used to fix the solvent injection component, the test sample receiving chamber and the disintegration liquid outflow component. The bracket ensures the stability of the entire disintegration test device.

[0026] Furthermore, the bracket includes a platform at the bottom and a fixed frame at the side.

[0027] Preferably, in order from top to bottom, the support is sequentially arranged with a solvent injection component, a test sample receiving cavity, a disintegrating liquid outflow component and a disintegrating liquid collecting container.

[0028] Preferably, the disintegration testing device further comprises a controller, the controller being electrically connected to the peristaltic pump and configured to control the peristaltic pump to pump the solvent in the solvent storage container into the solvent injection port.

[0029] The controller, which comprises a control panel and an integrated circuit board, is the automated mechanism for the entire disintegration tester. By regulating the speed and direction of the peristaltic pump, the controller can control the dripping rate and flow rate of the solvent injection component, thereby simulating the secretion of saliva in the human mouth and gradually dissolving the drug sample.

[0030] Preferably, the solvent dropping parameter of the disintegration test device is 0.01-0.2 mL / drop, for example: 0.01 mL / drop, 0.02 mL / drop, 0.05 mL / drop, 0.1 mL / drop, 0.12 mL / drop, 0.15 mL / drop, 0.18 mL / drop, 0.2 mL / drop.

[0031] Furthermore, the drop addition interval is 1 to 2 seconds, for example: 1 second, 1.2 seconds, 1.5 seconds, 1.8 seconds, and 2 seconds.

[0032] Preferably, the disintegration test device further comprises a cleaning liquid container and a waste liquid container. The cleaning liquid container is used to clean the liquid flow pipeline in the instrument to keep the disintegration test device clean. The waste liquid container is used to collect the cleaning waste liquid.

[0033] Beneficial effects of the utility model:

[0034] The utility model can dynamically test the disintegration effect of rapid-release preparations (such as lyophilized tablets and orally disintegrating films) by simulating oral administration, which is closer to the actual disintegration process of rapid-release preparations and provides an important testing method for the rapid development of new oral drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 Shown is a schematic structural diagram of a disintegration test device;

[0036] Figure 2 Shown is a cross-sectional view of the test site of a sample (tablet) in a disintegration test apparatus;

[0037] Figure 3 Shown is a cross-sectional view of the test site of the sample (film dosage form) in the disintegration test apparatus;

[0038] Figure 4 Shown is an enlarged view of the multi-well plate;

[0039] The reference numerals in the figures are as follows:

[0040] 1-injection component, 101-injection port, 102-porous plate, 103-outlet, 104-injection pipe, 2-sample holding chamber, 201-clamp, 3-outflow component, 301-sieve plate, 302-outflow pipe, 4-collection container, 5-storage container, 6-peristaltic pump, 7-catheter. DETAILED DESCRIPTION

[0041] The following is a clear and complete description of the technical solution of the present invention in conjunction with the embodiments and drawings. The embodiments described are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, other embodiments obtained by ordinary technicians in this field without making any creative efforts are within the scope of protection of the present invention.

[0042] Figure 1 A disintegration test apparatus for a rapid-release preparation is shown, comprising a solvent injection component 1, a test sample holding chamber 2, a disintegrating liquid outflow component 3, a disintegrating liquid collection container 4, a solvent storage container 5, a peristaltic pump 6, and a catheter 7. The solvent injection component 1, the test sample holding chamber 2, the disintegrating liquid outflow component 3, and the disintegrating liquid collection container 4 are arranged in order from top to bottom.

[0043] like Figure 1 and Figure 2As shown, the solvent injection component 1 is used to drip solvent into the test sample holding chamber 2 to cause the drug sample to disintegrate under the action of the solvent. The solvent injection component 1 includes but is not limited to a syringe, a dropper, and a pipette. As long as it can add liquid in a quantitative manner. The volume of the solvent injection component 1 is ≥2mL, such as 5.0mL. The solvent injection component 1 includes a solvent injection port 101, a solvent inflow pipe 104 and a solvent outflow port 103. The solvent outflow port 103 is porous, and the solvent flows out from the solvent outflow port 103 into the test sample holding chamber 2.

[0044] like Figure 1 and Figure 2 As shown, the test sample holding chamber 2 is the disintegration site of the drug sample to be tested (such as a rapid-release preparation), and its upper and lower ends are open, and are detachably connected to at least one of the solvent injection component 1 or the disintegration liquid outflow component 3. For example: the inlet of the test sample holding chamber 2 is detachably connected to the solvent outflow outlet 103. The test sample holding chamber 2 is arranged at 90 degrees to the horizontal line in the vertical direction. A test sample (such as a rapid-release preparation) addition port can also be provided on the test sample holding chamber 2 to facilitate the addition of the drug sample to be tested (such as a freeze-dried tablet). A test sample fixing device (such as a sample clamp 201) is provided on the cavity wall of the test sample holding chamber 2, and the clamp 201 can clamp the rapid-release preparation. The test sample holding chamber 2 is made of a transparent material, such as transparent plastic, glass, etc.

[0045] like Figure 1 and Figure 2 As shown, the disintegrating liquid outflow component 3 includes a disintegrating liquid outflow channel 302 and a sieve plate 301. The sieve plate 301 is disposed on the cross section of the disintegrating liquid outflow channel 302. The sieve plate 301 is used to filter the mixed solution after the drug sample is disintegrated in the solvent, so as to observe whether there is any residue after the drug disintegration and evaluate the degree of drug disintegration. The pore size of the sieve plate 301 is 75-850 μm.

[0046] like Figure 1 and Figure 2 As shown, the disintegration liquid collection container 4 is a storage place for the liquid after the drug sample is disintegrated, and is arranged below the disintegration liquid outflow pipe 302.

[0047] like Figure 1 As shown, the disintegration test apparatus further includes a solvent storage container 5, a peristaltic pump 6, and a conduit 7. The solvent storage container 5 is used to store the disintegration solvent (e.g., water) for the drug sample. The conduit 7 is fixed to the peristaltic pump 6, with one end of the conduit 7 connected to the solvent storage container 5 and the other end passing through the peristaltic pump 6 and connected to the solvent injection port 101.

[0048] The rotation speed of the peristaltic pump 6 is 10-100 rpm.

[0049] The disintegration test apparatus also includes a bracket (not shown) that secures the solvent injection component 1, the test sample holding chamber 2, and the disintegration fluid outflow component 3, thereby ensuring the stability of the entire disintegration test apparatus. The bracket includes a bottom platform and a side mounting frame. Arranged from top to bottom are the solvent injection component 1, the test sample holding chamber 2, the disintegration fluid outflow component 3, and the disintegration fluid collection container 4.

[0050] The disintegration test device also includes a controller, which is electrically connected to the peristaltic pump 6 and is used to control the peristaltic pump 6 to pump the solvent (e.g., water) from the solvent storage container 5 into the solvent injection port 101. The controller is the automated control mechanism for the entire disintegration test device and includes a control panel and an integrated circuit board. The controller regulates the speed and direction of the peristaltic pump 6 to control the dripping rate (e.g., a dripping interval of 1 to 2 seconds) and flow rate (e.g., 0.01 to 0.2 mL / drop) of the solvent injection component 1, thereby simulating the secretion process of saliva in the human mouth and gradually dissolving the drug sample.

[0051] The disintegration test apparatus also includes a cleaning fluid container and a waste fluid container. The cleaning fluid container is used to clean the fluid flow lines in the instrument and keep the disintegration test apparatus clean. The waste fluid container is used to collect the waste cleaning fluid.

[0052] Example 1 Test experiment of quick-release disintegration test device

[0053] 1.1 Information on the test drug samples is shown in Table 1 and Figure 4 .

[0054] Table 1 Drug sample information

[0055]

[0056] 1.2 Appearance of test drug samples

[0057] The properties (mainly shape, color, texture, etc.) were observed with the naked eye, and the front length, bottom length and thickness were measured with a vernier caliper to calculate the corresponding surface area and volume. The measurements were repeated 6 times, and the measurement data are shown in Tables 2 and 3.

[0058] Table 2 Appearance test results of Montelukast sodium oral lyophilized tablets

[0059]

[0060]

[0061] Table 3 Appearance test results of montelukast sodium orally disintegrating film

[0062]

[0063] The same test items were used to measure different montelukast sodium preparations, with six parallel tests. Montelukast sodium oral lyophilized tablets are white, round lyophilized tablets that are wide at the top and narrow at the bottom. The front length is 11.21 mm, the bottom length is 6.03 mm, and the thickness is 3.02 mm. The upper surface area of ​​the lyophilized tablet is calculated to be 0.99 cm 2 , with a volume of 0.182 cm 3 , which is equivalent to a volume of about 0.2 mL, and occupies less than 1 cm in the mouth when taking the medicine 2 The orally dissolving film of montelukast sodium is a pink sheet-like film with a square shape, about 20.38 mm long and 19.95 mm wide, with negligible thickness and a surface area of ​​about 4.07 cm. 2 Its texture is flexible and has a certain hardness, but it occupies a large proportion in the oral cavity when taking the medicine (greater than 4cm 2 ), will stick to the palate or tongue, feel like a foreign body, take a certain amount of time to disintegrate, and remain in the mouth for a long time.

[0064] 1.3 Results of drug sample test using freeze-dried tablet disintegration device

[0065] Use a simple disintegration device (see Figure 4 ) Disintegration test was performed on the drug sample, and the specific process was as follows:

[0066] Take out one piece or one patch of the drug sample, place it in the sample placement (test sample holding chamber), use an adjustable clamp to fix the sample, install and fix the sieve plate at the same time, place a culture dish (disintegration liquid collection container) under the sieve plate to collect the disintegration liquid. Set the total solvent to 2mL, the dripping parameter to 0.05mL / drop, and the time interval between each drop to 1.5s. Start timing from the beginning of dripping, record the disintegration of the tablet, stop timing after observing that the tablet is completely disintegrated, record the final time, and observe the sieving situation. Finally, judge the entire disintegration process. If the sample does not change significantly under the specified solvent amount or titration time, the solvent amount or titration time should be appropriately increased. The results of the drug sample disintegration test are shown in Table 4.

[0067] Table 4 Disintegration results of different preparations using freeze-dried tablet disintegration test device

[0068]

[0069] The disintegration test of montelukast sodium oral lyophilized tablets was conducted using the above parameters. The tablets disintegrated the moment they came into contact with water and completely disintegrated within 3 seconds. Within 20 seconds, the disintegration liquid was able to pass through the sieve plate along the inner wall of the device as the solvent was added. The outflow did not contain insoluble particles, and only a small amount of excipients was adhered to the inner wall. After 2 mL of solvent was dripped, the adhered material was touched and there was no hard core, and there was no foreign matter on the sieve plate. It can be seen that the lyophilized tablets disintegrated rapidly and completely. Based on this, there is no foreign body sensation when taking the medicine, especially there is no possibility of choking for children, and the medicine can be taken smoothly.

[0070] A disintegration test was conducted on the orodissolving film of montelukast sodium. There was no change when the orodissolving film first came into contact with water, and there was still no change within 1 minute. Considering the material of the dosage form, it may take a long time for water immersion to disintegrate, so 3 mL of water was added for the disintegration test. After the dripping was completed, it was found that the orodissolving film was partially disintegrated, and the disintegrating liquid was able to pass through the sieve plate without foreign matter. However, a large amount of orodissolving film remained in the mouth, accounting for about 2 / 3 of the total. Therefore, when taking the medicine, the orodissolving film stays in the mouth for a long time, and there will be a foreign body sensation. In addition, due to the problem of the material of the dosage form, choking may occur during the medication process. In comparison, freeze-dried tablets have more advantages in the entire medication process.

[0071] The above description is merely an embodiment of the present invention and does not limit the patent scope of the present invention. Any equivalent structural transformation made using the contents of the present invention specification, or directly or indirectly applied in other related technical fields, is also included in the patent protection scope of the present invention.

Claims

1. A disintegration test device for immediate-release preparations, characterized in that: The disintegration test device comprises, from top to bottom, a solvent injection component, a test sample receiving chamber, and a disintegrating liquid outflow component; The test sample holding chamber is open at both ends, and is detachably connected to at least one of the solvent injection component and the disintegrating liquid outflow component; The solvent injection component includes a solvent injection port, a solvent inflow pipe and a solvent outflow port; The test sample holding chamber includes a sample fixing device for fixing the immediate-release preparation; The disintegrating liquid outflow component comprises a disintegrating liquid outflow pipe and a sieve plate, and the sieve plate is arranged on the cross section of the disintegrating liquid outflow pipe.

2. The disintegration test device according to claim 1, wherein: The solvent outflow port of the solvent injection component is porous, and the solvent flows out of the porous outflow port into the test sample containing cavity.

3. The disintegration test device according to claim 1, wherein: The test sample holding chamber is arranged at an angle of 45-90 degrees to the horizontal plane in the vertical direction.

4. The disintegration test device according to claim 1, wherein: The sample fixing device is a sample clamp arranged on the cavity wall of the test sample holding cavity, and is used to clamp the rapid-release preparation.

5. The disintegration testing device according to claim 1, wherein: The pore size of the sieve plate is 75-850 μm.

6. The disintegration testing device according to claim 1, wherein: The disintegration testing device further includes a disintegration liquid collecting container, which is arranged below the disintegration liquid outflow pipe.

7. The disintegration testing device according to claim 1, wherein: The disintegration test apparatus further comprises a solvent storage container, a peristaltic pump and a catheter; The solvent storage container is connected to the solvent injection port via a conduit, and the conduit is fixed on the peristaltic pump.

8. The disintegration testing device according to claim 7, wherein: The disintegration testing device further includes a controller electrically connected to the peristaltic pump, and the controller is used to control the peristaltic pump to pump the solvent in the solvent storage container into the solvent injection port.

9. The disintegration testing device according to claim 1, wherein: The disintegration test device further includes a bracket, which is used to fix the solvent injection component, the test sample accommodating chamber and the disintegrating liquid outflow component.

10. The disintegration testing device according to claim 1, wherein: The disintegration test device It also includes a cleaning liquid container and a waste liquid container, wherein the cleaning liquid container is used to clean the liquid flow pipeline in the instrument. The waste liquid container is used to collect cleaning waste liquid.

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