JP3965372B2 - Sample tablet disintegration apparatus, disintegration test apparatus and disintegration / dissolution test system using the same, and sample tablet disintegration test method - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a disintegration device for a sample tablet, a disintegration test device, a disintegration / dissolution test system using the same, and a disintegration test method, and more particularly, a so-called intraoral rapidly disintegrating tablet that disintegrates rapidly by a small amount of saliva present in the oral cavity. The present invention relates to an apparatus and method for measuring the disintegration time of in vitro with good reproducibility.
[0002]
[Prior art]
As a general method for evaluating the disintegration time of a sample tablet, there is a disintegration test method defined in the Japanese Pharmacopoeia (commonly called “Pharmacopeia”). In this disintegration test method, a disintegration test container is filled with 900 ml of test solution, the sample tablet is immersed in the test solution and moved up and down, the sample tablet is disintegrated, and the disintegration time is measured visually. .
[0003]
[Problems to be solved by the invention]
However, since the disintegration test method specified in the above pharmacopoeia assumes disintegration of the sample tablet in the stomach (or in the digestive tract), 900 ml of the test solution is used. Therefore, even sample tablets that are inherently difficult to disintegrate in the oral cavity may disintegrate rapidly, and the disintegration property of the sample in the oral cavity is not sufficiently reflected, and a small amount of liquid (the actual amount of saliva in the oral cavity) It is difficult to evaluate the disintegration rate of so-called intraoral rapidly disintegrating tablets that are required to disintegrate rapidly in about 1 ml). In addition, after a long period of storage or after a severe test, when the state of the surface of the sample tablet changes and it becomes difficult for the disintegration test solution to penetrate into the sample tablet, an apparent disintegration time delay is observed. There was a case. In the oral cavity, both the dissolution of the sample tablet composition due to the infiltration of the test solution and the destruction of the interparticle bonding structure due to swelling and the breaking stress that holds the tablet between the tongue and the upper jaw in the oral cavity. Despite taking
This is because in the pharmacopoeia disintegration test method, only the former dissolution and swelling are loaded on the sample tablet.
In order to solve the above-mentioned problems, there is a method (sensory test) in which a human actually includes a quick-disintegrating tablet in the mouth and measures the time for the quick-disintegrating tablet to disintegrate in the oral cavity. This method may solve the problem of delay in decay time, but because it is a sensual evaluation by humans, there are concerns about easy implementation from the viewpoint of safety. There were problems of lack of objectivity and poor reproducibility.
[0004]
[Means for Solving the Problems]
An object of the present invention is to provide a sample tablet disintegration device closer to a living body that can detect the disintegration time of a sample tablet even in the presence of a small amount of water, a disintegration test device using the sample tablet disintegration device, and disintegration / elution It is to provide a test system and a disintegration test method.
[0005]
The first sample tablet disintegration device of the present application disintegrates the sample tablet that is the subject of the disintegration test in the disintegration test solution filled in the disintegration test container, and the disintegration filled in the disintegration test container A sample lock holder for placing the sample tablet at a position slightly contacting the liquid surface of the test solution and a presser for pressing the sample lock placed on the holder from above are provided.
[0006]
The second sample tablet disintegrating device of the present application is the first sample tablet disintegrating device, in which the receiving device and the pressing device relatively move with the sample tablet sandwiched therebetween, thereby applying a breaking stress to the sample tablet. A friction mechanism is provided.
[0007]
In the third sample tablet disintegrating device of the present application, in the second sample tablet disintegrating device, the friction mechanism is a mechanism in which one or both of the receiving tool and the pressing tool rotate.
[0008]
The fourth sample tablet disintegrating device of the present application is the second sample tablet disintegrating device, wherein the friction mechanism is a mechanism in which one or both of the receiving member and the pressing member reciprocate in a direction horizontal to the liquid level of the disintegrating test solution. It is what is.
[0009]
The fifth sample tablet disintegrating device of the present application is such that, in any of the first to fourth sample tablet disintegrating devices, the force with which the presser presses the sample lock from above can be adjusted.
[0010]
The sixth sample tablet disintegrating device of the present application is a hole through which the receiving member penetrates from the upper surface to the lower surface in any of the first to fifth sample tablet disintegrating devices, the size of which is larger than the size of the sample tablet. Is also equipped with small things.
[0011]
The seventh sample-tablet disintegrating device of the present application is the sixth sample-tablet disintegrating device, wherein the receiver is a mesh.
[0012]
The eighth sample tablet disintegrating device of the present application is the seventh sample tablet disintegrating device, wherein the mesh interval of the receiving tool is 0.01 to 2.0 mm.
[0013]
The ninth sample tablet disintegrating device of the present application is the sample tablet disintegrating device according to any one of the first to eighth sample disintegrating devices, in which the sample lock disposed on the receiving member is disintegrated based on the contact between the receiving member and the pressing member. It is provided with a detecting means for detecting that it has happened.
[0014]
The disintegration test device of the present application is a device for measuring the time required for the sample tablet to disintegrate, and the first disintegration test device is a disintegration test device using any one of the sample tablet disintegration devices. The disintegration test container for disintegrating the sample tablet is provided below the sample tablet disintegrating device.
[0015]
The second disintegration test apparatus of the present application is a combination of a sample tablet disintegration apparatus and a disintegration test container, and the disintegration test container of the first disintegration test apparatus is a Japanese Pharmacopoeia dissolution test beaker.
[0016]
The disintegration / dissolution test system of the present application is a system configured such that a sample tablet can be disintegrated by combining a sample tablet disintegration device and a dissolution test container and then transferred to a dissolution test as it is. The first disintegration / dissolution test system is a disintegration / dissolution test system using any of the sample tablet disintegration devices, and includes a disintegration test container for disintegrating the sample tablets below the sample tablet disintegration device. And a discharge means for discharging the disintegration test liquid in the disintegration test container, and an elution test container for receiving the disintegration test liquid discharged by the discharge means.
[0017]
In the first sample tablet disintegration / dissolution test method of the present application, the sample tablet placed on the receiver is placed in a position slightly in contact with the liquid level of the disintegration test solution, wetted with the disintegration test solution, and pressed. In this method, the disintegration time or dissolution time is measured by disintegrating the sample tablet in the disintegration test solution by applying pressure from above to the sample tablet with a tool.
[0018]
The second sample tablet disintegration / dissolution test method of the present application is a method in which the receiving tool and the presser are relatively moved in the first disintegration / dissolution test method.
[0019]
The third sample tablet disintegration / dissolution test method of the present application is a method of rotating one or both of the receiving tool and the pressing tool in the second disintegration / dissolution test method.
[0020]
The fourth sample tablet disintegration / dissolution test method of the present application is the same as that of the second disintegration / dissolution test method, wherein one or both of the support and the holding part are reciprocated in a direction horizontal to the liquid surface of the disintegration test solution. It is a method to make it.
[0021]
The sample tablets of the present application refer to tablets, tablets coated with an appropriate coating agent, pills, capsules, semi-solid preparations, gel preparations, mucosal patch preparations, granules and the like.
[0022]
DETAILED DESCRIPTION OF THE INVENTION
(Embodiment of sample tablet disintegrating apparatus)
An embodiment of a sample tablet disintegrating apparatus according to the present invention is shown in FIG. The sample tablet disintegrating device in the present embodiment is used in a state of being installed in the disintegration test container 6, and has a receiving tool 1 and a pressing tool 2. The disintegration test solution is infiltrated into the sample tablet 12 placed on the upper surface of the receiving device 1 arranged just below the liquid surface of the disintegration test solution filled in the disintegration test vessel 6, and pressure is applied downward by the presser 2. Thus, the sample tablet 12 is disintegrated in the disintegration test container 6. In the sample tablet disintegration apparatus shown in FIG. 1, a receiver 1 is arranged near the water surface of the disintegration test solution filled in the disintegration test container 6 so as to be immersed up to the upper surface of the receiver 1, and above the receiver 1. The support tool 13 for instruct | indicating the presser 2 is arrange | positioned, and the presser 2 is installed in the lower part of the support tool 13. FIG.
[0023]
The receiver 1 is a member for slightly immersing the sample tablet 12 in the disintegration test solution with the sample tablet 12 placed on the upper surface thereof. The size of the receiving device 1 is only required to have a size on which a normal tablet can be placed. Usually, a disc shape of about 20 mmφ is preferable, but the size and shape are not limited to this and can be arbitrarily selected. You can do it. The material of the receiver 1 is not particularly limited, but it is preferable to use a material made of a material that is inert to a disintegration test solution such as stainless steel or a material coated with an inert material such as a fluororesin. Good. In order to facilitate the infiltration of the disintegration test solution by the sample tablet 12 installed on the upper surface of the receptacle 1 and the disintegration into the disintegration test container 6 (dropping of the sampled tablet into the disintegration test solution). In addition, it is preferable to provide a hole 3 penetrating from the upper surface to the lower surface of the receiver 1, and in this case, it is particularly preferable that the receiver 1 has a mesh shape (mesh shape). The mesh size when the receptacle 1 is made into a mesh shape is not particularly limited, and can be selected depending on the size and type of the sample tablet to be measured, and the sample tablet 12 does not fall directly into the disintegration test container 6. The size may be of the order of magnitude, and is usually 8.6 to 200 mesh of JIS standard, preferably 30 to 36 mesh. At the periphery of the receiver 1, a locking portion 14 is raised and installed at the periphery in order to prevent the sample tablet 12 from falling directly into the disintegration test container 6 from the periphery of the receiver 1.
As described above, the disintegration test solution needs to be infiltrated into the sample tablet 12 placed on the upper surface of the receptacle 1 during the disintegration time measurement. However, if the sample tablet 12 infiltrates into the disintegration test solution before the measurement, accurate disintegration is required. Since the time cannot be measured, it is necessary to configure the sample tablet 12 so as not to infiltrate the disintegration test solution before the measurement. As the configuration, the sample tablet 12 can be infiltrated into the disintegration test solution by moving the receptacle 1 to a position slightly below the liquid level at the start of measurement. In addition, the receptacle 1 having a slightly convex shape is disposed near the liquid surface, and the sample tablet 12 is placed in a state where the convex portion is not immersed in the disintegration test solution. The disintegration test is started by placing it on the convex part, and the convex part on the support 1 is slightly bent downward by the pressure of the presser 2 to simultaneously start the measurement of the disintegration time. It can also be set as the structure which makes the sample tablet 12 infiltrate a disintegration test liquid. The distance from the liquid level to the upper surface of the receiver 1 at the time of disintegration time measurement is 0.01 to 2.0 mm, preferably about 0.5 to 1.0 mm. In the disintegration test apparatus shown in FIG. 1, an apparatus is shown in which the receiving device 1 is fixed to a leg 15 that is set up from the bottom of the disintegration test container 6, but the method of installation is limited to this. For example, it may be fixed by being suspended from above the disintegration test container 6.
[0024]
The pressing tool 2 is a member for pressing the sample lock 12 disposed on the receiving tool 1 downward. Since the pressing tool 2 applies a breaking stress by pressing the sample tablet 12 against the receiving tool 1, the sample tablet 12 is easily disintegrated, and the sample tablet 12 can be disintegrated in a state closer to the oral cavity. . As shown in FIG. 2, the presser 2 is provided with a guide hole 21 penetrating from the upper surface to the lower surface at the center, and is used in a state where the support tool 13 is inserted into the guide hole 21. Since the presser 2 is only restricted in the horizontal direction by the support 13 and is not restricted in the vertical direction, the weight of the presser 2 is directly applied to the sample lock 12 on the receiver 1. It has come to take. As shown in FIG. 4, it is preferable that the pressure for pressing the sample lock 12 can be adjusted by placing a weight 28 of arbitrary weight on the upper part of the presser 2 or by using different pressers 2 having different weights. In order to adjust the frictional force of the contact surface, a sponge, a wire mesh or the like may be attached to the lower surface of the presser 2 (the contact surface with the sample tablet). At this time, the presser 2 may be provided with a mechanism for fixing the sample lock using a needle or a jig. The size, shape, material, and the like of the presser 2 are suitable to use the same as those of the receiver, but are not limited thereto and may be arbitrarily selected.
[0025]
The sample tablet disintegrating device in this embodiment includes a friction mechanism 4. The friction mechanism 4 applies a breaking stress to the sample lock by the relative movement of the upper surface of the holder 1 and the lower surface of the holder 2 with the holder 1 and the holder 2 sandwiching the sample lock 12. This is a mechanism, and by applying a pressure imitating the tongue or upper jaw to the sample tablet 12 by this mechanism, the sample tablet disintegration test can be performed in a state closer to the oral cavity. As the friction mechanism 4, for example, as shown in FIG. 2, a guide groove 22 is provided in a direction perpendicular to the side surface of the guide hole 21, and a protrusion 23 that fits into the guide groove 22 is provided on the side surface of the support 13. In the state in which the protrusion 23 is fitted to the support 22, the support 13 is rotated in the direction A so that the presser 2 is interlocked and rotated in the direction A. Although FIG. 2 shows two pairs of guide grooves 22 and protrusions 23, the number of these is not limited and can be any number. Moreover, as a structure of the friction mechanism 4, it is good also as a mechanism which mutually reciprocates by attaching a motor etc. to either one or both of the receiving device 1 or the pressing device 2, and is further limited to these. Any mechanism can be used. When the friction mechanism 4 is a mechanism in which one or both of the presser 2 and the receiver 1 rotate, it is preferable that the conditions for the collapse can be optimized by making the rotation speed variable. In this case, the rotation speed is preferably about 1 to 120 rotations per minute, more preferably about 10 to 50 rotations per minute.
[0026]
The sample tablet disintegrating device in the present embodiment is provided with detecting means 5 for detecting that the sample lock 12 on the receiving member 1 has been disintegrated. For example, the detection means 5 may have a structure as shown in FIG. A sensor set 26 is attached to the support 13 and the presser 2. The sensor set 26 is attached so as to operate when the sensor 26 sets come close to each other when the lower surface of the presser 2 comes into contact with the upper surface of the receiver 1. Before the sample tablet 12 collapses, both sensor sets 26 are separated (FIG. 3 (a)). However, the sample tablet 12 collapses and the sensor set 26 approaches to detect the collapse of the sample lock 12. (FIG. 3B). The detecting means 5 may be any means as long as it can detect that the sample tablet 12 has collapsed and the upper surface of the holder 1 and the lower surface of the presser 2 are in contact with each other (the distance between them is lost). An arbitrary structure can be used without being performed.
[0027]
The liquidity and volume of the disintegration test solution depend on the assumed test conditions (for example, about 1 ml of purified water when assuming disintegration in the oral cavity, and the Japanese Pharmacopoeia disintegration test when disintegration in the stomach is assumed. The first liquid etc.) can be arbitrarily selected and used. Although the disintegration test container 6 can be arbitrarily selected and used, it is preferable to use a glass container having a capacity of about 0.5 to 1000 ml.
Further, by using the disintegration test container 6 as a beaker for a pharmacopeiale elution test, it is possible to proceed to an elution test determined by the pharmacopoeia following a disintegration time measurement experiment. In that case, as shown in FIG. 4, a paddle defined in the pharmacopoeia for stirring the dissolution test container 6 may be used as the support 13.
[0028]
The sample tablet disintegrating device may be configured as shown in FIG. In this sample lock disintegrating device, the presser 2 is fixed to the support 13, and the receiver 1 rotates while the presser 2 presses the sample lock 12 from above. A leg 15 made of a material having a characteristic of being attracted by magnetism is attached to the lower portion of the receiving device 1. It is preferable to use iron, nickel, cobalt, or the like as a material having a characteristic attracted by magnetism. When using a material that is corroded by an acid, it is preferable to use an acid-resistant coating. A magnet 31 is installed below the collapse test container 6. A rotating shaft 32 is attached to the magnet 31, and the rotating shaft 32 and a motor 33 are connected by a belt 34. The receiver 1 is rotated by rotating the motor 33. In the case of this configuration, the presser 2 may rotate, but it is not necessary to rotate. Also in this case, it is preferable to attach the detection means 5 to the sample tablet disintegrating device. As the configuration thereof, the following configurations can be adopted in addition to those described above.
A displacement detection bar 35 is provided on the upper portion of the support 13, and an electrically conductive lid 36 is installed on the collapse test container 6. The displacement detection bar 35 and the lid 36 are connected to a collapse end point detector 37 through a conductive wire. Has been. The collapse end point detector 37 can capture a change in electrical resistance between the displacement detection bar 35 and the lid 36. The distance between the displacement detection bar 35 and the lid 36 is adjusted to be the same as the distance between the receiving tool 1 and the pressing tool 2, and the sample is sandwiched between the receiving tool 1 and the pressing tool 2. When the lock 12 is collapsed, the displacement detection bar 35 and the lid 36 come into contact with each other. When the displacement detection bar 35 and the lid 36 come into contact with each other, the collapse end point detector 37 detects a change in the electrical resistance to detect the collapse of the sample tablet.
[0029]
(Embodiment of disintegration and dissolution test system)
The disintegration / dissolution test system is equipped with a discharge means 8 for sending out disintegration test liquid containing powder of the disintegrated sample tablet in the disintegration test container 6 of the disintegration test apparatus, and the discharged disintegration test liquid is dissolved in the dissolution test container. This is a system that leads to 7. With this configuration, the dissolution test can be performed in a solution different from the disintegration test solution after the sample tablet is disintegrated.
[0030]
The sample tablet disintegrating device used in the disintegration / dissolution test system may be the one shown in the above embodiment. As shown in FIG. 6, the disintegration test container 6 is provided with a discharge port 41 for discharging the disintegration test solution, and the disintegration test solution is discharged through a tube 42 connected to the discharge port 41. Is discharged out of the collapse test container 6. In order to discharge the disintegrated sample tablet, the discharge port 41 is suitably installed on the side surface or the lower surface of the disintegration test container 6. A cock 49 is preferably installed outside the discharge port 41. For example, a roller pump, a tube pump, or a gear pump can be used as the discharge means 8 for the disintegration test container, but the discharge means 8 can be arbitrarily selected without being limited thereto. Moreover, the structure which introduce | transduces the tube 42 into the container from the upper opening of the disintegration test container 6 and discharges | disintegrates the disintegration test liquid may be sufficient. The sample tablet disintegrates, and the disintegration test liquid containing the disintegrated powder is sent into the dissolution test container 7 by the discharge means 8. In this case, it is preferable that the components of the sample tablet remaining in the disintegration test container 6 are washed out in the dissolution test container 7 by refluxing the dissolution test solution between the disintegration test container 6 and the dissolution test container 7. . In the disintegration / dissolution test system shown in FIG. 6, a tube 42 connected to the discharge means 8 is introduced from the upper opening of the dissolution test container 7, and the dissolution test solution is sucked up from the dissolution test container 7 to enter the collapse test container 6. Although it is made to recirculate | reflux, the introduction position of the tube 42 introduce | transduced into the elution test container 7 is not limited to this, You may introduce in arbitrary positions.
As the dissolution test container 7, it is suitable to use a dissolution test beaker prescribed by the pharmacopoeia, but any container can be used without being limited thereto. The dissolution test solution filled in the dissolution test container 7 can be arbitrarily selected from water, artificial gastric juice, artificial intestinal fluid and the like. The test liquid discharged from the disintegration test container 6 is injected into the dissolution test container 7 and can shift to a normal dissolution test.
In the disintegration / dissolution test using this system, the liquid properties of the disintegration test solution and the dissolution test solution can be changed, so that the liquid property in the organ in which the sample tablet disintegrates differs from the liquid property in the eluting organ. It is particularly suitable for evaluation of disintegration / dissolution time of intraoral rapidly disintegrating tablets that disintegrate in the oral cavity and dissolve in the stomach.
[0031]
(Optimization test of presser weight and support rotation speed)
The test example about the change of the disintegration time of a sample tablet at the time of changing the weight of a holding tool and the rotation speed of a support using the sample tablet disintegration apparatus concerning this invention is shown below. In this test, a sample tablet that does not contain a main ingredient and exhibits rapid disintegration was disintegrated in a ROwater (purified water) solution. FIG. 7 is a graph showing the relationship between the weight of the presser and the disintegration time of the sample tablet when the sample tablet is disintegrated using the sample tablet disintegrating apparatus according to the present invention. In this test, the rotation speed of the support tool was fixed at 10 rotations per minute, the weight of the pressing tool was changed to 1, 15, and 30 g, and the time until the sample tablet collapsed was measured. As can be seen from the graph, the disintegration time of the sample tablet shortened as the weight of the presser increased. Under this condition, the time when the weight of the presser was set to 15 g was the closest to the disintegration time (rightmost column) when the person actually disintegrated the sample tablet in the mouth.
FIG. 8 is a graph showing the relationship between the rotation speed of the support and the collapse time. In this test, the weight of the presser was fixed at 15 g, the rotation speed of the support was changed to 10, 25, and 50 revolutions per minute, and the time until the sample tablet collapsed was measured. As can be seen from the graph, the disintegration time of the sample tablet was shortened as the number of rotations of the support increased. Under this condition, it was the time when the rotation speed of the support was set to 10 rotations per minute that was closest to the disintegration time (the rightmost column) when the person actually disintegrated the sample tablet in the mouth. . As can be seen from these graphs, the time for the sample tablet to disintegrate can be adjusted by changing the weight of the presser and the rotational speed of the support, and by optimizing these values, A test similar to the disintegration test can be reproduced.
[0032]
(Results of disintegration test of sample tablets containing active ingredients)
The result of the disintegration test of the sample tablet using the disintegration test apparatus according to the present invention is shown in FIG. The sample tablet used in this disintegration test is a sample tablet containing an active ingredient compound which is a hydrochloride, and is a tablet containing 0 mg (placebo), 5 mg or 10 mg of the active ingredient compound, respectively. The tablet weight is about 280 mg, the tablet diameter is about 9.5 mm, and the tablet thickness is about 4.0 mm. Changes in disintegration time of sample tablets when stored at 60 ° C. and 75% relative humidity for 10 days (severe test), and disintegrated into ROwater (purified water) or 0.1 N HCl as a disintegration test solution before and after the same severe Is shown. In this disintegration test, a 15 g presser was used, and the rotation speed of the support was 10 revolutions per minute. FIG. 10 shows the results when the same test was performed using a conventional disintegration test apparatus, and FIG. 11 shows the results of the human sensory test.
As shown in FIG. 10, in the case of the test using the conventional disintegration test apparatus, the disintegration time is delayed in the sample tablet containing the active ingredient. This is considered to be due to a change in the surface of the sample tablet due to the severe test. In addition, when 0.1 N HCl was used as the disintegration test solution, the longer the disintegration time due to the severe test, the greater the sample tablet with a higher content of active ingredient. This is presumably because the disintegration rate was reduced due to the common salt effect in the sample tablets containing the hydrochloride compound as an active ingredient. On the other hand, when the disintegration test apparatus according to the present invention is used, it can be seen that the disintegration time is hardly delayed. This is the same as the result of the sensory test shown in FIG. 11, and no delay in disintegration time due to the severe test was observed.
[0033]
(Correlation with sensory test using placebo)
FIG. 12 shows a graph showing the correlation between a disintegration test using the disintegration test apparatus according to the present invention or a conventional disintegration test apparatus and a human sensory test. In this test, the disintegration test was performed using placebo sample tablets whose disintegration time in human sensory tests was about 5 to 25 seconds. The sample tablet was placed in a desiccator soaked with a saturated NaCl solution and stored at 60 ° C. (75% RH) for 1 week, and then the disintegration time was measured by a disintegration test apparatus according to the present invention, a conventional disintegration test apparatus, and a human sensory test. The correlation with human sensory tests was examined.
As shown in FIG. 12, in the conventional disintegration test apparatus, the inclination is 3 or more, and the disintegration time is extended three times or more as compared with the sensory test by humans. On the other hand, in the disintegration test apparatus according to the present invention, the inclination is approximately 1, and it can be seen that the disintegration time is substantially equal to the result of the sensory test by humans. Therefore, it is clear that the disintegration test apparatus according to the present invention more faithfully reproduces the state in the human oral cavity.
[0034]
【The invention's effect】
The present invention has the following effects.
(1) The disintegration time of sample tablets (especially intraoral rapidly disintegrating tablets) can be quantitatively measured by escaping from the current situation where disintegration time was measured in a state far from the process of disintegrating sample tablets in the oral cavity. . This makes it possible to more scientifically study the formulation design of sample tablets that disintegrate or dissolve in the oral cavity, and can be used for quality control of products.
(2) In stability tests under warming / humidification conditions, the disintegration time of the conventional pharmacopoeia and dissolution test are apparently lower than the initial disintegration time even though there is almost no delay in the oral cavity. Even when a delay is observed, if the sample tablet disintegration test apparatus of the present invention is used, the disintegration time is hardly observed as in the oral cavity, and the evaluation can be performed in a state closer to the oral cavity.
(3) Elution of a sample tablet that disintegrates easily in a neutral pH solution or water, but in a solution with a high chloride ion concentration, the active ingredient that does not disintegrate due to the common ion effect is a chloride salt. Properly evaluate the profile.
(4) Disintegration in the oral cavity of the rapidly disintegrating tablet in the oral cavity and subsequent dissolution of the active ingredient in the oral cavity, stomach and digestive tract can be evaluated simultaneously.
(5) When the disintegration / dissolution test system according to the present invention is used, first, the disintegration test can be performed with a test liquid having a pH of 1.2 corresponding to gastric juice after being disintegrated with a neutral test liquid corresponding to oral saliva. It can be evaluated in a state closer to the actual dosage form.
[Brief description of the drawings]
FIG. 1 is an explanatory diagram showing an example of a disintegration test apparatus according to the present invention.
FIG. 2 is a cross-sectional view of the presser of the sample tablet disintegrating device of the present invention.
FIGS. 3A and 3B are explanatory diagrams showing an example of the detection means of the present invention, in which FIG. 3A shows a state before the sample tablet is collapsed, and FIG. 3B shows a state after the sample tablet is collapsed.
FIG. 4 is an explanatory view showing another example of the disintegration test apparatus of the present invention.
FIG. 5 is an explanatory view showing another example of the disintegration test apparatus of the present invention.
FIG. 6 is an explanatory diagram showing an example of a disintegration / elution test system of the present invention.
FIG. 7 is a graph showing the relationship between the weight of the presser and the disintegration time of the sample tablet.
FIG. 8 is a graph showing the relationship between the rotation speed of the support and the disintegration time of the sample tablet.
FIG. 9 is a graph showing the results of a disintegration test using the disintegration test apparatus of the present invention.
FIG. 10 is a graph showing the results of a disintegration test using a conventional disintegration test apparatus.
FIG. 11 is a graph showing the results of a human sensory test.
FIG. 12 is a graph showing a correlation between a disintegration test using the disintegration test apparatus of the present invention and a disintegration test using a conventional disintegration test apparatus and a human sensory test.
[Explanation of symbols]
1 Receiver
2 Presser
3 Friction mechanism
4 holes
5 Detection means
6 Disintegration test container
7 Dissolution test container
8 Discharge means

Claims (10)

A sample tablet disintegrating device that disintegrates an intraoral rapidly disintegrating tablet, which is an object of disintegration test, in a disintegration test solution filled in a disintegration test container,
A receptacle for disposing the intraoral rapidly disintegrating tablet at a position of 0.01 to 2.0 mm downward from the surface of the disintegration test liquid filled in the disintegration test container;
A presser for pressing the intraoral quick disintegration placed on the receiver from above;
In a state where the receiving tool and the pressing tool sandwich the intra-oral quick-disintegrating tablet , one or both of the receiving tool and the pressing tool are rotated, or one or both of the receiving tool and the pressing tool is a disintegration test solution. Reciprocating in a direction horizontal to the liquid level of, and a friction mechanism that imparts a breaking stress to the intraoral quick disintegration ,
During disintegration time measurement, wherein the arranged side into orally rapidly disintegrating tablet of the receptacle infiltrated the disintegration test liquid, disrupting the orally rapidly disintegrating tablet by the friction mechanism, the sample tablet disintegration apparatus. The sample tablet disintegrating device according to claim 1, wherein the pressing tool can adjust the force for pressing the intraoral quick disintegrating tablet from above. 3. The sample tablet disintegrating device according to claim 1 or 2, wherein the receptacle is a hole that penetrates from the upper surface to the lower surface, and the size of the hole is smaller than the size of the intraoral quick disintegrating tablet. apparatus.   4. The sample tablet disintegrating device according to claim 3, wherein the receiving member has a mesh shape.   The sample tablet disintegration device according to claim 4, wherein the mesh interval of the receiver is 0.01 to 2.0 mm. The sample tablet disintegrating device according to any one of claims 1 to 5, wherein the intraoral quick disintegrating tablet disposed on the receiving device has collapsed based on the contact between the receiving device and the pressing device. A sample tablet disintegrating device comprising detecting means for detecting. A disintegration test device using the sample tablet disintegration device according to any one of claims 1 to 6,
A disintegration test container for disintegrating the intraoral quick disintegrating tablet is provided below the sample tablet disintegrating device,
Disintegration test equipment.   The disintegration test apparatus according to claim 7, wherein the disintegration test container is a Japanese Pharmacopoeia dissolution test beaker. A disintegration / dissolution test system using the sample tablet disintegrating device according to any one of claims 1 to 7,
A disintegration test container for disintegrating the intraoral quick disintegration device is provided below the sample tablet disintegration device, a discharge means for discharging the disintegration test solution in the disintegration test container, and a disintegration test discharged by the discharge means A disintegration / dissolution test system comprising a dissolution test container for receiving a liquid. When disintegration time is measured, infiltrate with the disintegration test solution from the side where the disintegration test solution is placed on the receiving device of the oral disintegrating tablet placed on the receiving device at a position of 0.01 to 2.0 mm downward In a state where the pressing tool and the receiving tool sandwich the intraoral quick-disintegrating tablet , one or both of the receiving tool or the pressing tool is rotated, or one or both of the receiving tool or the pressing tool is subjected to a disintegration test. disintegration test method reciprocates in a horizontal direction to the liquid surface of the liquid, the breaking stress is given to the orally rapidly disintegrating tablet, to disintegrate the orally rapidly disintegrating tablet.

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