A disintegration measuring device and method for orally disintegrating tablets capable of simulating oral environment

Abstract

The present invention discloses an orodisintegrating tablet disintegration measuring device that can simulate the oral environment, including a medium cup, a sample basket for placing a sample to be tested, a pressure control system and a water circulation control system; the sample basket is suspended in the medium cup, and the lower half of the sample basket is a screen structure; the pressure control system includes a test end for applying pressure to the sample to be tested in the sample basket; the water circulation control system includes a water inlet end and at least two water outlet ends, the water outlet end includes an upper water outlet end facing the top of the test end and a lower water outlet end facing the bottom of the sample basket, and water outlet holes are distributed on the test end; the present invention also discloses an orodisintegrating tablet disintegration measuring method. The present invention can more accurately, conveniently and normatively measure the disintegration time of orodisintegrating tablets, and detect the disintegration speed of orodisintegrating tablets close to the actual situation.

Description

Technical Field

[0001] The invention relates to the technical field of drug detection, and in particular to an orodisintegrating tablet disintegration measuring device and a measuring method capable of simulating an oral environment. Background Art

[0002] Orally disintegrating tablets refer to tablets that can quickly disintegrate or dissolve in the mouth without the need for water. Due to the particularity of its administration method and absorption route, the disintegration rate is an important indicator for the quality evaluation of orally disintegrating tablets. At present, the pharmacopoeias of various countries examine the disintegration rate through the <Disintegration Time Limit Test>. Among them, the 2020 edition of the "Chinese Pharmacopoeia" requires that the disintegration medium of the measuring instrument is 900mL, the lifting bracket moves up and down a distance of 10mm, and the round-trip frequency is 30 times per minute. This type of evaluation method is very different from the actual oral administration environment, the detection method has a single structure, and there are problems such as large water consumption and large tablet amplitude. It cannot truly reflect the disintegration behavior of orally disintegrating tablets in the mouth, and it is difficult to effectively evaluate the quality of orally disintegrating tablets.

[0003] The disintegration process of orally disintegrating tablets is affected by many factors. In addition to the tablet structure, it is also related to the temperature of the disintegration environment, the medium, the stirring of the tongue, the pressure of the orally disintegrating tablet in the mouth, etc. Drug review agencies in various countries are also actively exploring how to accurately measure the disintegration time, and there is no unified standard yet. The "Minutes of the Dosage Form Characteristics and Quality Control Meeting of Orally Disintegrating Tablets" issued by the Center for Drug Evaluation (CDE) of the State Food and Drug Administration requires control points: the disintegration time is within one minute, the medium is preferably water, the amount should be less than 2ml, the temperature should be 37°C, a static method should be used, and there should be a particle size control item (should be less than 0.71mm for dispersible tablets).

[0004] The patent specification with publication number CN109507376A discloses an orally disintegrating tablet disintegration time limit measuring instrument, which has structures such as a guide rail frame, a housing, a guide rail, and a guide rail slider. Compared with the original disintegration device, this solution reduces the oscillation amplitude of the orally disintegrating tablet, reduces the number of samples in the measuring basket, and reduces the liquid volume in the stainless steel tube.

[0005] The patent specification with announcement number CN209894801U discloses a disintegration instrument, which includes a constant temperature water bath, a disintegration cup and a lifting mechanism. The disintegration cup is provided with an elastic bag and a transparent oral palate phantom to simulate the movement of an orally disintegrating tablet in the oral cavity and increase the accuracy of disintegration time detection.

[0006] The paper "Study on Disintegration Time Detection Method for Orally Disintegrating Tablets" discloses a self-made orally disintegrating tablet disintegration detection device consisting of a sieve basket and a beaker, as well as an inspection method.

[0007] The above schemes cannot simulate the real environment in the oral cavity, and cannot more accurately, conveniently and normatively determine the disintegration time of orally disintegrating tablets. Summary of the invention

[0008] One object of the present invention is to provide an orally disintegrating tablet disintegration measuring device that can simulate the oral environment, and can more accurately, conveniently and standardizedly measure the disintegration time of orally disintegrating tablets, and detect the disintegration speed of orally disintegrating tablets close to the actual situation.

[0009] The technical solution is as follows:

[0010] A disintegration measuring device for orally disintegrating tablets capable of simulating an oral environment comprises a medium cup, a sample basket for placing a sample to be tested, a pressure control system and a water circulation control system; the sample basket is suspended in the medium cup, and the lower half of the sample basket is a screen structure; the pressure control system comprises a test end for extending into the sample basket to apply pressure to the sample to be tested; the water circulation control system comprises a water inlet end and at least two water outlet ends, the water outlet ends comprising an upper water outlet end facing the top of the test end and a lower water outlet end facing the bottom of the sample basket, and water outlet holes are distributed on the test end.

[0011] The test end of the pressure control system simulates the resistance of the upper palate of the mouth; the screen around the sample basket simulates the dispersion path of the disintegrated particles; the medium volume in the medium cup is small, simulating the saliva volume in the mouth.

[0012] In addition, the disintegration medium flows out from the upper water outlet, flows to the surface of the sample to be tested through the water outlet hole on the test end, moistening the sample and simulating the wetting of the tablet by the upper jaw of the mouth; the disintegration medium flows out from the lower water outlet, providing water flow, simulating the stirring effect of the tongue on the oral fluid and the flushing effect on the sample to be tested.

[0013] This program simulates the oral environment in multiple dimensions and measures the disintegration behavior of orally disintegrating tablets under conditions close to reality, providing a guarantee for the effective evaluation of the quality of orally disintegrating tablets.

[0014] Preferably, the test end is disc-shaped, and the upper water outlet end and the lower water outlet end are both discs with water outlets.

[0015] In this solution, the water outlets are distributed in a ring shape on the disc, so that the water outlet is more uniform and the oral environment is simulated more realistically.

[0016] More preferably, the diameters of the test end and the upper water outlet end are both 2-10 mm, and the diameter of the lower water outlet end is 2-16 mm.

[0017] More preferably, the diameters of the test end and the upper water outlet end are both 8 mm, and the diameter of the lower water outlet end is 10 mm.

[0018] Preferably, the medium cup is a cylindrical structure with a diameter of 10 to 20 mm and a height of 10 to 20 mm.

[0019] More preferably, the medium cup has a diameter of 16 mm and a height of 18 mm.

[0020] Preferably, the sample basket has a diameter of 8 to 15 mm, a height of 8 to 15 mm, and a sieve mesh aperture of 500 to 800 μm.

[0021] More preferably, the sample basket has a diameter of 10 mm and a height of 10 mm, the sample basket has a sieve structure with a height of less than 5 mm, and the pore size of the periphery and the bottom is 710 μm.

[0022] Preferably, a pressure sensor for sensing pressure changes is provided on the test end.

[0023] In this solution, the test end can apply a vertical pressure of 10 to 150 g to the sample to be tested, simulating the squeezing force of the upper palate on the orodisintegrating tablet; the pressure sensor can sense pressure changes, and the sudden change in pressure can sense the disintegration of the orodisintegrating tablet; the control end of the pressure control system can adjust the force applied to the sample to be tested and sense pressure changes.

[0024] Another object of the present invention is to provide a method for determining the disintegration of an orally disintegrating tablet, comprising the following steps:

[0025] (1) adding the disintegration medium into the medium cup of the above-mentioned orally disintegrating tablet disintegration test device;

[0026] The disintegration medium is 2 ml of water; at this time, the liquid level is about 10 mm from the bottom of the medium cup and about 2 mm from the bottom of the sample basket, which can ensure that the sample to be tested is partially immersed in the medium and not submerged;

[0027] (2) Place the device in a water bath and adjust the water bath temperature;

[0028] Before testing, you need to prepare a water bath temperature control device that can adjust the water bath temperature;

[0029] (3) Place the sample to be tested in the sample basket;

[0030] The sample to be tested is generally ≤10mm;

[0031] (4) Turn on the water circulation control system and the pressure control system, adjust the water flow rate and pressure, observe the disintegration process of the sample to be tested, and record the disintegration time.

[0032] Preferably, the water bath temperature in step (2) is 36.3-37.2°C.

[0033] When testing the sample, first place the device without the sample in a constant temperature water bath, adjust the temperature to 36.3℃-37.2℃ according to the experimental conditions, add about 2ml of medium to the medium cup, and after the temperature is balanced, put the sample to be tested, adjust the pressure controller to apply pressure to the sample to be tested, adjust the water circulation system controller to adjust the medium flow rate at the water absorption end and the two water outlet ends to the appropriate size, start the measurement, and record the disintegration process and disintegration time.

[0034] Beneficial effects of the present invention:

[0035] The present invention can more accurately, conveniently and normatively measure the disintegration time of orally disintegrating tablets, and at the same time establish an in vitro orally disintegrating tablet disintegration measurement method with stronger in vivo and in vitro correlation, simulate the oral environment in multiple dimensions, and measure the disintegration behavior of orally disintegrating tablets under conditions close to reality, thereby providing a guarantee for effectively evaluating the quality of orally disintegrating tablets. BRIEF DESCRIPTION OF THE DRAWINGS

[0036] Figure 1 It is a structural schematic diagram of the present invention;

[0037] Figure 2 It is a top view of the upper water outlet;

[0038] Figure 3 It is a top view of the lower water outlet;

[0039] Figure 4 is a side view of the sample basket;

[0040] In the figure: 1. medium cup; 2. sample basket; 3. controller; 4. pneumatic cylinder; 5. test end; 6. micro circulating water pump; 7. water inlet pipe; 8. first water outlet pipe; 9. second water outlet pipe; 10. upper water outlet end; 11. lower water outlet end. DETAILED DESCRIPTION

[0041] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0042] like Figure 1 As shown, an orodisintegrating tablet disintegration measuring device capable of simulating an oral environment comprises a medium cup 1, a sample basket 2, a pressure control system and a water circulation control system.

[0043] The medium cup 1 is used to contain the disintegration medium. In this embodiment, the disintegration medium is water. The medium cup 1 is cylindrical in structure, with a cross-sectional diameter of 16 mm and a height of 18 mm.

[0044] The sample basket 2 is suspended in the medium cup 1, such as Figure 4 As shown, hooks are provided on both sides of the sample basket 2 for hanging on the side wall of the medium cup 1 .

[0045] The sample basket 2 is also cylindrical in structure, with a cross-sectional diameter of 10 mm and a height of 10 mm. The lower half of the sample basket 2 is a screen structure, which is used to simulate the dispersion path of disintegrated particles. Specifically, small holes are provided on the outer circumference and bottom of the portion below 5 mm of the sample basket 2, with a pore diameter of 710 μm. During the test, the sample to be tested is placed at the bottom of the sample basket 2.

[0046] The pressure control system comprises a test end 5 for extending into the sample basket 2 to apply pressure to the sample to be tested.

[0047] In this embodiment, the pressure control system includes a controller 3, a pneumatic cylinder 4 and a test end 5. The test end 5 is fixed to the movable end of the pneumatic cylinder 4 and is used to contact the sample to be tested. The controller 3 controls the pneumatic cylinder 4 to drive the test end 5 to apply a certain pressure to the sample to be tested. At the same time, a pressure sensor for sensing pressure changes is provided on the test end 5, which can feedback the pressure of the sample to be tested and judge the disintegration time of the sample to be tested by the pressure change. Among them, the pneumatic cylinder 4 can also be replaced by a hydraulic cylinder or a spring screw rod. The controller 3 controls the pneumatic cylinder 4 or the hydraulic cylinder or the spring screw rod to move, which is a conventional operation well known to those skilled in the art and will not be described in detail here.

[0048] The water circulation control system includes a water inlet and at least two water outlets, wherein the water outlets include an upper water outlet 10 and a lower water outlet 11 .

[0049] In this embodiment, the water circulation control system includes a micro-circulation water pump 6, which includes a water inlet and two water outlets. The water inlet is connected to the inside of the medium cup 1 through a water inlet pipe 7 for absorbing the medium, and the two water outlets are respectively connected to a first water outlet pipe 8 and a second water outlet pipe 9. The micro-circulation water pump 6 can adjust the flow rate of the upper water outlet end 10 and the lower water outlet end 11. Usually, the flow rate of the upper water outlet end 10 is less than the flow rate of the lower water outlet end 11.

[0050] The first water outlet pipe 8 and the second water outlet pipe 9 have an upper water outlet end 10 and a lower water outlet end 11 respectively, and the micro-circulation water pump 6 transports the medium to the upper water outlet end 10 and the lower water outlet end 11 respectively through the first water outlet pipe 8 and the second water outlet pipe 9. Among them, the upper water outlet end 10 is arranged opposite to the test end 5, and the lower water outlet end 11 is arranged opposite to the bottom of the sample basket 2.

[0051] The test end 5, the upper water outlet end 10 and the lower water outlet end 11 are all disc structures, the test end 5 is provided with water outlet holes, and the upper water outlet end 10 and the lower water outlet end 11 are also evenly provided with water outlets; Figure 2 and 3As shown, the water outlets are distributed in a ring shape on the disc, so that the water outlet is more uniform and the oral environment is simulated more realistically.

[0052] Water flows out from the water outlet of the upper water outlet end 10, flows to the surface of the sample to be tested through the water outlet hole on the test end 5, moistening the sample, simulating the wetting of the tablet by the upper jaw of the oral cavity; water flows out from the water outlet of the lower water outlet end 11, providing a surge of water flow, simulating the stirring effect of the tongue on the oral fluid and the flushing effect on the sample to be tested.

[0053] A method for measuring disintegration of an orally disintegrating tablet comprises the following steps: firstly preparing the above-mentioned orally disintegrating tablet disintegration measuring device, a water bath temperature control device and a sample to be measured.

[0054] The method specifically comprises the following steps:

[0055] (1) disintegration medium added to the medium cup of the orally disintegrating tablet disintegration test apparatus;

[0056] The disintegration medium is 2 ml of water; at this time, the liquid level is about 10 mm from the bottom of the medium cup and about 2 mm from the bottom of the sample basket, which can ensure that the sample to be tested is partially immersed in the medium and not submerged;

[0057] (2) Place the device in a water bath and adjust the water bath temperature;

[0058] Place the device containing the medium in a water bath and adjust the water bath temperature so that the temperature of the disintegration medium generally reaches 36.3-37.2°C;

[0059] (3) Place the sample to be tested in the sample basket;

[0060] The sample to be tested is ≤10mm;

[0061] (4) Turn on the water circulation control system and the pressure control system, adjust the water flow rate and pressure, observe the disintegration process of the sample to be tested, and record the disintegration time.

[0062] The present invention can more accurately, conveniently and normatively measure the disintegration time of orally disintegrating tablets, and at the same time establish an in vitro orally disintegrating tablet disintegration measurement method with stronger in vivo and in vitro correlation, simulate the oral environment in multiple dimensions, and measure the disintegration behavior of orally disintegrating tablets under conditions close to reality, thereby providing a guarantee for effectively evaluating the quality of orally disintegrating tablets.

[0063] Although the present invention has been described in detail with reference to the aforementioned embodiments, it is still possible for those skilled in the art to modify the technical solutions described in the aforementioned embodiments, or to make equivalent substitutions for some of the technical features therein. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the protection scope of the present invention.

Claims

1. An orodisintegrating tablet disintegration measuring device capable of simulating an oral environment, characterized in that: The invention comprises a medium cup, a sample basket for placing a sample to be tested, a pressure control system and a water circulation control system; the sample basket is suspended in the medium cup, and the lower half of the sample basket is a screen structure; the pressure control system comprises a test end for applying pressure to the sample to be tested in the sample basket, the test end applies a vertical pressure of 10 to 150 g to the sample to be tested, simulating the squeezing force of the upper jaw on the orodisintegrating tablet; the water circulation control system comprises a water inlet end and at least two water outlet ends, the water outlet ends comprise an upper water outlet end facing the top of the test end and a lower water outlet end facing the bottom of the sample basket, the test end is provided with water outlet holes, the disintegrating medium flows out from the upper water outlet end, flows to the surface of the sample to be tested through the water outlet holes on the test end, plays a role in wetting the sample, simulating the wetting of the tablet by the upper jaw of the oral cavity, and the disintegrating medium flows out from the lower water outlet end, provides the surge of water flow, simulates the stirring effect of the tongue on the oral fluid and the flushing effect on the sample to be tested.

2. The orally disintegrating tablet disintegration measuring device according to claim 1, characterized in that: The test end is in the shape of a disc, and the upper water outlet end and the lower water outlet end are both discs with water outlets.

3. The orally disintegrating tablet disintegration measuring device according to claim 2, characterized in that: The diameters of the test end and the upper water outlet end are both 2-10 mm, and the diameter of the lower water outlet end is 2-16 mm.

4. The orodisintegrating tablet disintegration measuring device according to claim 1, characterized in that: The medium cup is a cylindrical structure with a diameter of 10 to 20 mm and a height of 10 to 20 mm.

5. The orally disintegrating tablet disintegration measuring device according to claim 1, characterized in that: The sample basket has a diameter of 8 to 15 mm, a height of 8 to 15 mm, and a sieve mesh aperture of 200 to 800 μm.

6. The orodisintegrating tablet disintegration measuring device according to claim 1, characterized in that: The test end is provided with a pressure sensor for sensing pressure changes.

7. A method for measuring disintegration of orally disintegrating tablets, characterized in that: The following steps are involved: (1) adding the disintegration medium into the medium cup of the orally disintegrating tablet disintegration test device according to any one of claims 1 to 6; (2) Place the device in a water bath and adjust the water bath temperature; (3) Place the sample to be tested in the sample basket; (4) Turn on the water circulation control system and the pressure control system, adjust the water flow rate and pressure, observe the disintegration process of the sample to be tested, and record the disintegration time.

8. The method for measuring disintegration of orally disintegrating tablets according to claim 7, characterized in that: In step (2), the water bath temperature is 36.3-37.2°C.

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