JP7134048B2 - Measurement evaluation device and evaluation method using it - Google Patents

Description

Application of Article 30, Paragraph 2 of the Patent Act Powder Industry Association 2018 Spring Research Presentation May 16, 2018 The 33rd Pharmaceutical Society of Japan May 31, 2018

TECHNICAL FIELD The present invention relates to a measurement evaluation device for measuring mass change due to permeation of a liquid into a sample such as a tablet to evaluate the wettability (affinity) of the sample, and an evaluation method using the same.

For tablets, particularly orally disintegrating tablets, so-called OD (Oral Disintegration) tablets, evaluation of disintegration is important in tablet development/design, quality control, and the like.

As an apparatus for measuring such disintegration, for example, Patent Document 1 discloses a container containing a solution, a weighting means for applying a load to a tablet, and both applying a load to the tablet and immersing the tablet in the solution. A disintegration measuring device is disclosed comprising a measuring means for measuring the time from filling to disintegration of the tablet.

Further, for example, Patent Document 2 discloses a sample tablet receiver for placing a sample tablet at a position slightly contacting the liquid surface of a disintegration test liquid filled in a disintegration test container, and a sample tablet placed on the receiver. A sample disintegrating device is disclosed that includes a pressing tool that presses a sample lock from above.

Japanese Patent Application Laid-Open No. 2001-141718 Japanese Patent Application Laid-Open No. 2004-233332

The disintegration measuring device disclosed in Patent Document 1 measures the disintegration of a tablet while applying a load to the tablet by a weighting means. A sample tablet placed on the tool is pressed from above by a pressing tool to disintegrate the tablet.

In this way, in all cases, the tablet is disintegrated by being absorbed by the liquid while the tablet is subjected to an action such as a load. It is desirable to be able to perform various evaluations by

The present invention has been made with a focus on such a situation, and various evaluations such as liquid absorbency of a sample are performed by measuring the mass change in a state in which a sample such as a tablet is absorbed by the force alone. The purpose is to enable

In order to achieve the above object, the present invention is configured as follows.

( 1 ) In the evaluation method using the measurement evaluation apparatus of the present invention, a sample holder that holds a sample and is suspended and supported by a mass measuring device is arranged above a container that stores a liquid, and the sample holder is: A sample mounting portion on which the sample is mounted is provided, the sample mounting portion has a peripheral wall portion, and a plurality of liquid inflow holes into which the liquid flows are formed in the bottom surface of the sample mounting portion. The container and the sample holder are moved up and down relative to each other, the liquid surface of the container is brought into contact with the bottom surface of the sample mounting portion, and the change in mass caused by the permeation of the liquid into the sample is measured by the mass measurement. An evaluation method using a measurement evaluation device that measures over time with a device,
The hardness of the sample is evaluated based on the permeation rate coefficient determined by measuring the mass change.

According to the present invention, when the sample holder holding the sample and the liquid surface are brought relatively close to each other and the bottom surface of the sample mounting portion is immersed in a suitable amount of liquid, the liquid flows into the sample mounting portion through the liquid inflow hole. The liquid comes into contact with the entire lower end of the sample, and by maintaining this state, the liquid gradually penetrates into the sample.
At this time, since the sample mounting part has a peripheral wall part, when the sample mounting part is immersed in the liquid, the liquid does not flow beyond the peripheral wall part and contact the outer peripheral surface of the sample. Permeation of the liquid only from the lower end portion can be performed with good reproducibility.
According to the present invention, there is a correlation, as described below, between the permeation rate coefficient obtained in a state in which the sample is absorbed only by the force of the sample, without any action such as a load, and the hardness of the sample. As such, the hardness of the sample can be evaluated based on the permeation rate coefficient determined. This makes it possible, for example, to determine whether or not the hardness of the sample is appropriate for obtaining the permeation rate coefficient that exhibits the required liquid absorbency.

( 2 ) In the evaluation method using the measurement evaluation apparatus of the present invention, a sample holder that holds a sample and is suspended and supported by a mass measuring device is arranged above a container that stores a liquid, and the sample holder is: A sample mounting portion on which the sample is mounted is provided, the sample mounting portion has a peripheral wall portion, and a plurality of liquid inflow holes into which the liquid flows are formed in the bottom surface of the sample mounting portion. The container and the sample holder are moved up and down relative to each other, the liquid surface of the container is brought into contact with the bottom surface of the sample mounting portion, and the change in mass caused by the permeation of the liquid into the sample is measured by the mass measurement. An evaluation method using a measurement evaluation device that measures over time with a device,
The hardness of the sample is evaluated based on the maximum absorption, which is the maximum amount of the liquid absorbed by the sample due to permeation into the sample, determined by measuring the mass change.

According to the present invention, there is a correlation, as will be described later, between the maximum absorption amount obtained when the sample is absorbed only by the force of the sample, without any action such as a load, and the hardness of the sample. As can be seen, the hardness of the sample can be evaluated based on maximum absorption. By this, for example, it is determined whether or not the hardness of the tablet is suitable for suppressing the maximum amount of absorption of liquid such as water and artificial saliva until the tablet as a sample disintegrates and making it easy to disintegrate. It is possible to do

( 3 ) In the evaluation method using the measurement evaluation apparatus of the present invention, a sample holder that holds a sample and is suspended and supported by a mass measuring device is arranged above a container that stores a liquid, and the sample holder is: A sample mounting portion on which the sample is mounted is provided, the sample mounting portion has a peripheral wall portion, and a plurality of liquid inflow holes into which the liquid flows are formed in the bottom surface of the sample mounting portion. The container and the sample holder are moved up and down relative to each other, the liquid surface of the container is brought into contact with the bottom surface of the sample mounting portion, and the change in mass caused by the permeation of the liquid into the sample is measured by the mass measurement. An evaluation method using a measurement evaluation device that measures over time with a device,
Based on the permeation rate coefficient obtained by measuring the mass change and the maximum absorption amount, which is the maximum amount of the liquid absorbed by the sample due to permeation into the sample, reaching the quasi-maximum absorption calculated according to the following formula Evaluate time.

Time to reach quasi-maximal absorption = (maximum absorption) ² / (permeation rate coefficient)
According to the present invention, the quasi-maximum absorption amount is calculated according to the above formula from the maximum absorption amount and the permeation rate coefficient obtained in a state in which the sample is absorbed only by the force of the sample without applying an action such as a load. Arrival times can be evaluated. This quasi-maximum absorption reaching time corresponds to the time required for the sample to reach the maximum absorption amount, i.e., the time close to the time required to reach the maximum absorption amount. is. Therefore, it is possible to roughly grasp the time required for the liquid absorption amount of the sample to reach the maximum absorption amount from this quasi-maximum absorption reaching time.

( 4 ) In embodiment ( 3 ) above, the sample is a tablet, and the disintegration time of the tablet may be evaluated based on the time to reach the quasi-maximal absorption and the hardness of the tablet.

According to this embodiment, the relationship between the time to reach the quasi-maximal absorption of the tablet as a sample and the hardness of the tablet approximates the relationship between the disintegration time of the tablet and the hardness of the tablet, as described later. The degree of disintegration time can be evaluated from the relationship between the time to reach the maximum absorption amount and the hardness of the tablet.

( 5 ) In the measurement and evaluation apparatus of the present invention, a sample holder that holds a sample and is suspended and supported by the mass measuring device is arranged above a container that stores a liquid, and the sample holder holds the sample. A sample mounting portion to be mounted is provided, the sample mounting portion has a peripheral wall portion, and a plurality of liquid inflow holes into which the liquid flows are formed in the bottom surface of the sample mounting portion, The container and the sample holder are moved up and down relative to each other, and the liquid surface of the container is brought into contact with the bottom surface of the sample mounting portion. A measurement evaluation device that measures
An image capturing means for capturing an image of the sample placed on the sample mounting portion of the sample holder is provided, and the image capturing means captures an image of the sample swollen by permeation of the liquid.

According to the present invention, when the sample holder holding the sample and the liquid surface are brought relatively close to each other and the bottom surface of the sample mounting portion is immersed in a suitable amount of liquid, the liquid flows into the sample mounting portion through the liquid inflow hole. The liquid comes into contact with the entire lower end of the sample, and by maintaining this state, the liquid gradually penetrates into the sample.

At this time, since the sample mounting part has a peripheral wall part, when the sample mounting part is immersed in the liquid, the liquid does not flow beyond the peripheral wall part and contact the outer peripheral surface of the sample. Permeation of the liquid only from the lower end portion can be performed with good reproducibility.

In this way, the process of the sample absorbing and swelling can be observed as an image captured by the imaging means in a state in which the sample is absorbed only by the force of the sample and no load or other action is applied to the sample.

( 6 ) The evaluation method by the measurement evaluation device of the present invention is the evaluation method by the measurement evaluation device of ( 5 ) above,
A swelling rate of the sample obtained based on the image captured by the imaging means is evaluated.

According to the present invention, the swelling rate of the sample can be evaluated as the swelling process in a state in which the sample is absorbed only by the force of the sample without applying an action such as a load.

( 7 ) The evaluation method by the measurement evaluation device of the present invention is the evaluation method by the measurement evaluation device of ( 5 ) above,
A swelling speed of the sample obtained based on the image captured by the imaging means is evaluated.

According to the present invention, the swelling rate can be evaluated as the swelling process of a sample in a state in which the sample is absorbed only by the force of the sample without applying an action such as a load.

( 8 ) The evaluation method by the measurement evaluation device of the present invention is the evaluation method by the measurement evaluation device of ( 5 ) above,
A maximum swelling amount of the sample obtained based on the image captured by the imaging means is evaluated.

According to the present invention, the maximum amount of swelling can be evaluated as the process in which a sample swells in a state in which the sample is absorbed only by the force of the sample, without any action such as a load being applied to the sample.

( 9 ) The evaluation method by the measurement evaluation device of the present invention is the evaluation method by the measurement evaluation device of ( 5 ) above,
Based on the swelling speed and the maximum swelling amount of the sample obtained based on the image captured by the imaging means, the semi-maximal swelling amount arrival time calculated according to the following equation is evaluated.

Semi-maximal swelling amount reaching time = (maximum swelling amount) / (swelling speed)
According to the present invention, the swelling process of the sample in a state where the sample is absorbed by the force of only the sample without any action such as a load is calculated according to the above formula from the swelling rate and the maximum swelling amount. , can be evaluated as the time to reach the quasi-maximal swelling amount. The semi-maximal swelling amount reaching time corresponds to the time required for the sample to reach the maximum swelling amount, that is, the time close to the time required to reach the maximum swelling amount. Therefore, it is possible to roughly grasp the time required for the swelling amount of the sample to reach the maximum swelling amount from this semi-maximum swelling amount reaching time.

( 10 ) In embodiment ( 9 ) above, the sample is a tablet, and the disintegration time of the tablet may be evaluated based on the time to reach the semi-maximal swelling amount and the hardness of the sample.

According to this embodiment, the relationship between the time to reach the semi-maximal swelling amount of the tablet as a sample and the hardness of the tablet approximates the relationship between the disintegration time of the tablet and the hardness of the tablet, as described later. The degree of disintegration time can be evaluated from the relationship between the maximum swelling amount reaching time and tablet hardness.

(11) In the above embodiments (1), ( 2 ), ( 3 ), (5), ( 6 ), ( 7 ), ( 8 ) or ( 9 ), the sample may be a tablet.

According to this embodiment, it is possible to evaluate the absorbability of liquids such as water and artificial saliva with respect to the tablet in a state closer to the time of administration.

( 12 ) In the embodiment of ( 4 ), ( 10 ) or ( 11 ) above, the tablet may be an orally disintegrating tablet.

According to this embodiment, the absorbability of liquids such as water and artificial saliva to the orally disintegrating tablet can be evaluated in a state closer to the time of ingestion.

In the present invention, the above (1) to ( 10 ) may be combined as appropriate. For example, (1 ) and at least one of ( 2 ), ( 3 ), ( 6 ) to ( 9 ) may be combined, ( 2 ) and ( 3 ), ( 6 ) to ( 9 ) ) may be combined with at least one of ( 3 ) and at least one of ( 6 ) to ( 9 ) may be combined, ( 6 ) and ( 7 ) to ( 9 ) At least one of them may be combined, ( 7 ) may be combined with ( 8 ) or ( 9 ), or ( 8 ) and ( 9 ) may be combined.

By such a combination, the samples can be evaluated from various angles, and useful information can be obtained, for example, in the development/design and quality control of tablets as samples.

As described above, according to the present invention, various evaluations can be performed by obtaining the permeation rate coefficient and the like in a state in which the sample is absorbed only by the force of the sample without applying an action such as a load.

As a result, for example, the affinity (wettability) between a tablet as a sample and a liquid such as water or artificial saliva can be evaluated in a state closer to the time of ingestion.

It is an external appearance perspective view of the main body of a measurement evaluation apparatus. It is a side view of the main body of a measurement evaluation apparatus. It is the front view which notched a part of sample holder. FIG. 3 is a perspective view of a sample holder; It is a figure which shows the bilayer OD tablet as a sample, (a) is a top view, (b) is a side view. FIG. 4 is a diagram showing the measurement results of the water absorption of a double-layer OD tablet. FIG. 10 is a diagram showing a captured image of changes in a two-layer OD tablet due to water absorption. FIG. 3 is a diagram showing the measurement results of the amount of water absorbed when the first layer and the second layer of a double-layer OD tablet are on the water landing side. FIG. 3 is a graph showing temporal changes in permeation rate coefficients when the first layer and the second layer of a two-layer OD tablet are placed on the water landing surface side. FIG. 10 is a diagram showing changes over time in permeation rate coefficients of bilayer OD tablets with different compression pressures. FIG. 2 is a diagram showing the relationship between tableting pressure and tablet hardness for bilayer OD tablets. FIG. 3 is a diagram showing the relationship between the permeation rate coefficient and tablet hardness of bilayer OD tablets. FIG. 3 is a diagram showing the relationship between maximum absorption and tablet hardness of bilayer OD tablets. FIG. 4 is a diagram showing the relationship between the disintegration time and tablet hardness of a bilayer OD tablet, and the relationship between the time to reach the semi-maximal absorption and tablet hardness. It is a schematic block diagram of the measurement evaluation apparatus of other embodiment of this invention. FIG. 3 is a diagram showing the relationship between the swelling rate and tablet hardness of a bilayer OD tablet. FIG. 10 is a diagram showing a captured image of a swollen state due to water absorption of a double-layer OD tablet. FIG. 3 is a diagram showing the relationship between the swelling rate and tablet hardness of bilayer OD tablets. FIG. 2 is a diagram showing the relationship between the disintegration time and tablet hardness of a bilayer OD tablet, and the relationship between the semi-maximal swelling amount reaching time and tablet hardness.

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, embodiments of the present invention will be described with reference to the drawings.

First, a measurement evaluation device used for the evaluation method according to the embodiment of the present invention will be described.

1 and 2 show the main body A of the measurement and evaluation device. A main body A of this measurement evaluation apparatus is configured to be placed on a table and used. A measuring unit 3 installed on the unit 2, a lifting table 5 arranged in a processing space 4 surrounded by the base 1, the driving unit 2, and the measuring unit 3, and the processing space 4 can be freely opened and closed from the front, left and right. transparent cover 6, etc.

The main body A of this measurement evaluation apparatus is connected to a control device such as a personal computer (not shown), and the control device controls the driving of the platform 5, which will be described later, processes measurement data from the measurement unit 3, displays the processing results in a graph, and the like. is performed. That is, the measurement evaluation device of this embodiment includes a main body A and a control device.

The measurement unit 3 is equipped with a mass measurement device 7 using an electronic balance, and a hook 8 for mass measurement is suspended from the bottom surface of the measurement unit 3 into the processing space 4. A sample holder 9 as a sample cell containing a certain sample w is suspended and supported.

The elevating table 5 supports and elevates a container 12 containing a liquid f to be permeated into the sample, such as water, and has an L-shaped side surface so that the container 12 can be placed thereon. The lift table 5 is supported by a vertical slide guide means 10 built in the drive unit 2 so as to be able to move up and down in parallel, and is configured to be lifted and lowered by a stepping motor 11 as a driving device built into the drive unit 2 by means of a screw feed. It is

The sample holder 9 is suitable for a single sample w, such as a tablet, having an outer diameter of, for example, several millimeters to ten-odd millimeters. and suspension portions 14 connected to two locations on the outer periphery of the sample mounting portion 13 .

The sample mounting portion 13 is made of, for example, a stainless steel plate having a thickness of about 0.2 mm, and is formed by press-molding a blanked material to have a peripheral wall portion 13a along the entire outer circumference of the circular bottom portion. there is A connecting piece 13b for connecting the suspending portion 14 extends upward from a diagonal portion of the peripheral wall portion 13a.

The height of the peripheral wall portion 13a is sufficiently lower than the thickness of the sample w to be placed and accommodated, so that the sample w can be easily picked up with fingertips or tweezers and placed on the sample placement portion 13. .

The outer diameter of the sample mounting portion 13 is set slightly larger than the outer diameter of the sample w to be measured. A small gap is formed between the outer circumference of the sample w and the peripheral wall portion 13a when the sample w is placed and accommodated in the center of the sample placement portion 13. As shown in FIG.

In the bottom surface of the sample mounting portion 13, a large number of small holes 15 as liquid inflow holes through which the liquid f to be brought into contact with the sample w flows into the sample mounting portion 13 are punched in a predetermined pitch pattern. there is This small hole 15 has a sufficiently small diameter (for example, about 0.3 to 0.7 mm) relative to the size of the sample w, and is arbitrarily selected according to the size of the sample w, the disintegration characteristics of the tablet described later, etc. set.

Further, in this embodiment, a raised portion 13c having a circular planar shape and protruding downward is press-molded in the central portion of the bottom surface of the sample mounting portion 13 . The diameter of the raised portion 13 c is set to include several small holes 15 , and when the container 12 is raised with respect to the sample holder 9 , the liquid surface of the liquid f comes into contact with the sample mounting portion 13 . At this time, the liquid surface first contacts the protruding portion 13c, and the liquid f flows into the central portion of the sample mounting portion 13 through the small holes 15 of the protruding portion 13c.

The suspending portion 14 is made of, for example, a stainless steel plate having a thickness of about 0.3 mm, and is formed with a vertically elongated locking hole 16 that is hooked and connected to the hook 8 made of a metal plate at its upper end. A pair of support arms 14a for connecting and supporting the sample mounting section 13 are provided in a continuous manner in the lower part thereof in an inwardly curved shape.

The inward ends of the support arms 14a facing each other inward are connected to the upper end of the connecting piece 13b extending from the peripheral wall portion 13a of the sample mounting portion 13, and are connected to the upper end of the connecting piece 13b. are soldered together and joined together.

3 and 4, between the two support arms 14a in a state in which the sample mounting portion 13 is joined to the plate-like hanging portion 14, there is a partial circular shape with a large space above the sample mounting portion 13, as shown in FIGS. A space 18 is formed. Since the upper portion of the sample mounting portion 13 is thus largely open and exposed, the sample w can be easily taken in and out of the sample mounting portion 13 through this large space 18 .

In addition, the suspending portion 14 functions as a weight that prevents the entire sample holder 9 from floating off the hook 8 due to buoyancy when the sample mounting portion 13 contacts the liquid surface of the container 12 . Its mass is set so as to demonstrate

This prevents the entire sample holder 9 from floating due to buoyancy when immersed in the liquid f, even if the sample placement section 13 for placing a single sample w is small and lightweight. Therefore, the mass can be accurately transmitted to the mass measuring device 7 .

Next, a procedure for measuring the permeation rate of the sample w using the measurement evaluation apparatus will be described.

First, as a preparatory step, the sample w is mounted and accommodated in the central portion of the sample mounting portion 13 of the sample holder 9 as described above, and the suspending portion 14 of the sample holder 9 is attached to the hook 8 of the mass measuring device 7. A transparent container 12, which is supported by suspension and stores the liquid f as the penetrating solvent at a predetermined level, is placed on the elevator table 5 in the lowered standby position so as to be positioned substantially directly below the suspended sample holder 9. .

In the measurement, a jacket (not shown) is provided around the container 12, and a heat medium is passed through the jacket to control the temperature of the liquid in the container 12 to a constant temperature.

When a measurement start command (lift command) is issued, the stepping motor 11 is started to rotate forward and the lift table 5 starts to move up. In this case, the container 12 is driven upward at a preset high speed until the liquid surface of the container 12 reaches a preset height near the lower end of the sample holder 9, and the container 12 quickly approaches the sample holder 9 and rises. be done. The number of driving pulses of the stepping motor 11 can be set for the lifting of the platform 5 until it reaches the set height.

After the liquid level of the container 12 reaches a predetermined height, the stepping motor 11 is pulse-controlled so that the upward driving speed becomes medium speed, and the container 12 is gently raised so that the liquid level does not undulate. be.

When the liquid level of the container 12 reaches the raised portion 13c, which is the lower end of the sample holder 9, the stepping motor 11 is pulse-controlled so that the upward movement speed becomes low, and the liquid level rises from the lower end of the sample holder 9 to a predetermined level. The container 12 is raised a height more gently and stops.

When the liquid surface of the container 12 reaches the raised portion 13c at the lower end of the sample holder 9, the value measured by the mass measuring device 7 changes. It can be recognized that the liquid surface of the container 12 has reached the lower end of the sample holder 9 .

When the liquid surface approaches the lower end of the sample holder 9, the raised portion 13c of the sample mounting portion 13 is first immersed in the liquid. flow into the center. After that, the entire lower end of the sample mounting portion 13 is immersed in the liquid f, so that the liquid f flows into the sample mounting portion 13 through all the small holes 15, and the entire lower end of the sample w is filled with the liquid f. comes into contact. By maintaining this state for a set time, the liquid f gradually permeates the sample w from the bottom surface of the sample w, the mass increases, and this mass change is measured over time by the mass measuring device 7, By processing the measurement data based on a predetermined arithmetic expression, the permeation speed of the liquid with respect to the sample w can be obtained.

After the measurement process is completed, when the container lowering command is issued, the container is lowered to the lowering standby position at the same high speed as the initial rising speed or at a faster speed than this.
Here, the calculation of the permeation speed of the liquid will be briefly described.

The affinity between a sample and a liquid is generally expressed by the following Washburn equation.

W _L ² /t=(Sερ _L ) ²・(rγ _L cos θ/2η _L )
W _L : permeation mass of liquid, t: time, S: powder layer cross-sectional area, ε: void ratio ρ _L : liquid density, r: capillary radius formed by particles in the powder layer γ _L : liquid surface tension, η _L : liquid viscosity, θ: contact angle between liquid and solid surface When the liquid and the sample are brought into contact with each other for a certain period of time, the sample absorbs the liquid due to capillary action and the mass increases. Measurement time and mass change at this time are measured and displayed as a graph with horizontal axis: time and vertical axis: mass. At the time of analysis, the graph is converted into a graph with horizontal axis: time and vertical axis: square of mass, and the slope of the tangent line is calculated. The slope of this tangent line is called the permeation rate coefficient (W _L ² /t), which is equal to the left side of the above Washburn equation. The larger this value, the higher the permeation rate, and the better the affinity between the sample and the liquid. be. The contact angle θ between the liquid and the solid surface can also be obtained from the above Washburn equation using the calculated permeation rate coefficient ( _WL ² /t).

As described above, the measurement and evaluation apparatus of the present embodiment absorbs liquid only by the force of the sample w, so compared to the above-mentioned Patent Documents 1 and 2, in which the sample, for example, a tablet, absorbs liquid in a state where an action such as a load is applied. Therefore, it is possible to evaluate liquid penetration/absorbency in a state similar to when a tablet is ingested.

Using this measurement and evaluation device, tests were conducted to evaluate the absorption rate of water as a liquid (permeation rate coefficient) and the maximum absorption amount, which is the maximum amount of water that can be absorbed, for OD tablets, which are orally disintegrating tablets. gone. In this test, the water temperature in container 12 was controlled at 37° C., corresponding to body temperature, by a heat transfer medium flowing through a jacket around container 12 .

First, the OD tablet used in this test will be described. As the OD tablet, a bilayer OD tablet having one layer and two layers shown in Table 1 below was used.

図５は、この二層ＯＤ錠２０を示す図であり、図５では、裏面層である１層目２１と表面層である２層目２２との形状は、同一であって、青色着色剤を含有する２層目２２の外観は、青色である。この二層ＯＤ錠２０は、平面視が円形の丸型であって、中央部がやや膨らんでいる。

FIG. 5 is a diagram showing this bilayer OD tablet 20. In FIG. 5, the shape of the first layer 21, which is the back layer, and the second layer 22, which is the surface layer, are the same. The appearance of the second layer 22 containing is blue. This double-layer OD tablet 20 has a circular shape when viewed from above, and has a slightly bulging central portion.

Two-layer OD tablets were produced using a rotary two-layer tableting machine (HT-GS32MS-E/2L, manufactured by Hata Iron Works Co., Ltd.).

The tableting punches are circular (diameter Φ: 10 mm, R13), the rotation speed of the rotating disc is constant at 15 rpm, the tableting powder is supplied by a stirring feed shoe, and the number of punches is 32.

The process parameters (tabletting conditions) are as follows: 1st layer suction depth 5-7 mm, 1st layer punch tip spacing 2-5 mm, 2nd layer suction depth 4.5-5.5 mm, 2nd layer punch The tip spacing is 2 to 2.5 mm, preload (kN), and tableting pressure (main pressure) (kN).

The design of the bilayer OD tablet was carried out by the central composite method of the experimental design method. 1 to No. 27 of 27 bilayer OD tablets were manufactured.

Tablet hardness (N), tablet weight (mg), weight CV (%), friability (%), and disintegration time (sec) were measured as product physical properties of the manufactured bilayer OD tablet.

Specifically, the weight, thickness, diameter and hardness of the tablets were measured using a fully automatic tablet property measurement system (MultiCheck6ERWEKA, manufactured by Erweka, Germany), with 10 tablets being measured.

The friability was measured according to the Japanese Pharmacopoeia using a friability tester (TFT-1200, manufactured by Toyama Sangyo).

The disintegration time was measured by the disintegration test method of the Japanese Pharmacopoeia.

In addition, the water absorption permeation curve, permeation rate coefficient (g ² /s), maximum absorption amount (g), swelling amount, etc. were measured using the above measurement evaluation apparatus and the measurement evaluation apparatus described later.

First, in order to understand the water absorption process of the double-layered OD tablet 20, the amount of water absorbed by the double-layered OD tablet 20 was measured. The measurement results are shown in FIG. In FIG. 6 , the horizontal axis is time (sec) and the vertical axis is water absorption (g), showing both the tableting pressure of the first layer 21 and the second layer 22 and the hardness of the two-layer OD tablet 20. ing.

FIG. 7 shows images of the water absorption process of the double-layered OD tablet 20 captured by a camera, which will be described later, and shows the observation results of the water absorption and swelling process of the double-layered OD tablet 20 .

In FIGS. 6 and 7, No. 1 to No. No. of 27 bilayer OD tablets. Results are shown for 27 bilayer OD tablets. This No. The tableting pressure of the first layer 21 of the bilayer OD tablet No. 27 was 0.07 kN, the tableting pressure of the second layer 22 was 10.25 kN, and the hardness was 51.5N.

Moreover, in this measurement, the first layer 21 was positioned on the water landing surface side, that is, the lower side, and water was permeated from the first layer 21 .

As shown in FIG. 6, the water absorption process is a region 1, which is a period in which liquid water comes into contact with the two-layer OD tablet 20, and apparently the amount of water absorption increases rapidly due to the action of the surface tension of the water. After that, in the region 2, which is a period in which the amount of water absorption increases as water permeates and absorbs the double-layer OD tablet 20, and the amount of water absorption reaches a steady state with the passage of the measurement time. can be divided into region 3, which is the period in which the

The permeation rate coefficient is determined mainly in Region 2. Further, in region 3, the maximum amount of water absorbed by the bilayer OD tablet 20 is the maximum absorption amount.

Here, the maximum absorption amount is calculated according to the following formula.

Maximum absorption = [(mass of double layer OD tablet after measurement) + (mass of sample holder)]
-[(mass of bilayer OD tablet before measurement) + (mass of sample holder)]
(1)
Note that the transition region in region 2 in FIG. 7 is around the point at which water permeation transitions from the first layer 21, which is the layer on the water landing surface side of the double-layer OD tablet 20, to the second layer 22, which is not on the water landing surface side. be.

As a result of observing the water absorption process of the bilayer OD tablet 20, the following findings were obtained. First, in region 1, water contacts the lower portion of the sample holder 9 and spreads over the entire bottom surface of the sample holder 9. As shown in FIG. Next, in region 2, water was absorbed from the lower portion of the double-layered OD tablet 20 due to water absorption, and the double-layered OD tablet 20 was swollen. Furthermore, in region 3, it was found that the shape of the bilayer OD tablet 20 did not change significantly.

Contrary to FIG. 6, FIG. 8 shows the change in water absorption with time when the second layer 22 of the two-layer OD tablet 20 is placed on the water-receiving surface side. FIG. 8 also shows the change over time when the first layer 21 of FIG. 6 is placed on the landing surface side and measured. In FIG. 8, line L1 shows the time change when the first layer 21 of the two-layer OD tablet 20 is measured as the water landing surface side, and line L2 shows the time change when the second layer 22 is the water landing surface side. , respectively.

It can be seen that both line L1 and line L2 show substantially the same change.

In this way, since water is absorbed by the force of the double-layered OD tablet 20 alone, the water absorption of the double-layered OD tablet 20, that is, the affinity between the double-layered OD tablet 20 and water, is maintained in a state similar to when the double-layered OD tablet 20 is taken. (wettability) can be evaluated.

In addition, according to the above formula (1), the maximum absorption amount of water permeated and absorbed by the bilayer OD tablet 20 is calculated. It is useful for designing formulations of OD tablets that disintegrate even in people with a small amount of saliva.

FIG. 9 is a diagram showing a permeation rate coefficient calculated from the measured water absorption amount.

As described above, the permeation rate coefficient can be obtained as the slope of the tangent line in a graph in which the horizontal axis is time and the vertical axis is the square of mass (water absorption). The higher the permeation rate coefficient, the higher the permeation rate, the higher the affinity with water, and the faster the permeation.

In FIG. 9, line L3 shows the change when the first layer 21 of the two-layer OD tablet 20 is measured with the water landing surface side, and line L4 shows the change when the measurement is made with the second layer 22 on the water landing surface side. showing change. FIG. 9 shows the above-described regions 1 to 3, and in the case of line L4, near the time t1 when water penetration transitions from the second layer 22 to the first layer 21 of the double-layer OD tablet 20, and In the case of the line L3, the permeation of water indicates a time point t2 near the transition from the first layer 21 to the second layer 22, respectively.

As shown in FIG. 9, the line L4 measured with the second layer 22 on the landing surface side shows a rapid increase in the water absorption rate at the initial stage of landing on the water. After that, the water absorption rate decreases after the water permeation shifts to the first layer 21 after passing around the time t1 when the water permeation transitions from the second layer 22 to the first layer 21 .

Conversely, the line L3 measured with the first layer 21 as the landing surface side is gentle in the initial stage of landing on water, but after passing around the time t2 when the water permeation transitions from the first layer 21 to the second layer 22, the water After the permeation of the water moves to the second layer 22, the water absorption rate rises sharply.

Therefore, the water absorption of the first layer 21 and the second layer 22 is based on the time change of the permeation rate coefficient obtained by measuring the two-layer OD tablet 20 with the first layer 21 and the second layer 22 on the water landing side. Speed can be evaluated, and in this bilayer OD tablet 20:
It can be seen that the second layer 22 has a faster water absorption rate and a better affinity with water than the first layer 21 .

In this way, the water absorbency of each layer 22, 21 on the front and back surfaces of the bilayer OD tablet 20 can be evaluated.

FIG. 10 is a diagram showing changes over time in permeation rate coefficients of bilayer OD tablets 20 with different compression pressures/tablet hardnesses. In this FIG. 10, the No. 1 to No. Of the 27 bilayer OD tablets 20 of No. 27, No. 2 indicated by line L5. 27 bilayer OD tablet 20, no. 22 bi-layer OD tablet 20 and No. 22 indicated by line L7. 4 shows the measurement results for the bilayer OD tablet 20 of No. 4.

The tableting pressure of the second layer, which is the main pressure of the double-layer OD tablet 20 indicated by line L5, is 10.25 kN, and the tablet hardness is 51.5 N. The tableting pressure of 13.20 kN and the tablet hardness of 76.3 N, and the tableting pressure of the second layer of the double layer OD tablet indicated by line L7 is 16.61 kN and the tablet hardness is 108.6 N.

In FIG. 10, the measurement was performed with the first layer 21 of each double-layer OD tablet 20 on the water landing surface side.

In FIG. 10, the peak of the permeation rate coefficient within 5 seconds after landing on the water is a very narrow peak, not due to the components of the double-layer OD tablet 20, but the sample holder. This is due to the surface tension of water acting at the moment 9 lands on the water and the initial penetration into the bilayer OD tablet 20 .

Therefore, attention is paid to the permeation rate coefficient after the elapsed time from landing on the water exceeds 5 seconds.

The elapsed time from landing on the water exceeds 5 seconds, and the time at which the penetration rate coefficient peaks (maximum point) is the earliest in the line L5 with the lowest tableting pressure/hardness, and the highest in the line with the highest tableting pressure/hardness. L7 was the slowest, with line L6 in between,
Thus, the time at which the peak of the permeation rate coefficient is shown tends to be slower as the tableting pressure/hardness increases, and the tableting pressure/hardness of the bilayer OD tablet 20 can be evaluated from the time at which the peak of the permeation rate coefficient appears. can be done.

The higher the compression pressure/tablet hardness of the double-layer OD tablet 20, the slower the peak of the permeation rate coefficient and the longer the permeation time. It is suggested that the disintegration time of OD tablet 20 is increased.

In addition, although not shown, the result of measurement with the second layer 22 of the double-layer OD tablet 20 as the water-landing surface also showed the same tendency as above.

FIG. 11 is a diagram showing the relationship between the tablet hardness and the tableting pressure (main pressure) of the bilayer OD tablet 20. As shown in FIG. According to the above design of experiments No. 1 to No. 27 shows measurement results for 27 bilayer OD tablets.

As shown in FIG. 11, a good correlation is obtained between the tablet hardness of the bilayer OD tablet 20 and the tableting pressure (main pressure).

Therefore, focusing on the tablet hardness of the bilayer OD tablet 20, the above measurement results were further considered.

FIG. 12 is a diagram showing the relationship between tablet hardness and permeation rate coefficient. The permeation rate coefficient on the vertical axis is the average value of the permeation rate coefficients in the range of 3 to 20 seconds elapsed from the start of water absorption after landing on the water.

The reason why the range of 3 seconds to 20 seconds is set is that at the earliest stage of water absorption when the elapsed time from the start of water absorption is less than 3 seconds, as described above, the sample holder 9 is not caused by the components of the tablet. This is due to the surface tension of water acting at the moment of landing on the water and the initial penetration into the double-layer OD tablet 20, and the reproducibility is poor. Also, in the latter stage of water absorption, when the elapsed time from the start of water absorption exceeds 20 seconds, there are also tablets in which the rate of permeation is attenuated.

The time range for obtaining the permeation rate coefficient is not limited to the above 3 seconds to 20 seconds, and may of course be changed as appropriate according to the items to be evaluated.

In addition, FIG. 12 also shows the main pressure Tp=5 kN, 11 kN, and 22 kN corresponding to the tablet hardness.

In FIG. 12, the open squares show the results of measurement with the first layer 21 of the two-layer OD tablet 20 as the water landing surface side, and the black circles show the results of measurement with the second layer 22 as the water landing surface side. .

As shown in FIG. 12, there is a correlation between the permeation rate coefficient and tablet hardness, and the permeation rate coefficient decreases as the tablet hardness increases or decreases.

If the permeation rate coefficient becomes smaller, the permeation rate becomes slower and the disintegration time of the bilayer OD tablet 20 becomes longer, which is not preferable.

Therefore, from the relationship between tablet hardness and permeation rate coefficient shown in FIG. can be evaluated.

FIG. 13 is a diagram showing the relationship between the tablet hardness of the bilayer OD tablet 20 and the maximum absorption calculated by the formula (1). The maximum absorption amount on the vertical axis is the average value of the maximum absorption amount measured with the first layer 21 of the two-layer OD tablet 20 as the water landing surface side and the maximum absorption amount measured with the second layer 22 as the water landing surface side. .

As shown in FIG. 13, there is a correlation between the maximum absorbed amount and tablet hardness, and the maximum absorbed amount increases as the tablet hardness increases. The degree of hardness can be evaluated.

As the tablet hardness/tabletting pressure of the bilayer OD tablet 20 increases, the maximum absorption amount, which is the maximum water absorption amount that the bilayer OD tablet can contain, increases. will increase, which is not desirable.

Therefore, it can be seen that a high tablet hardness/compression pressure is not suitable for designing a bilayer OD tablet 20 with a small maximum absorption.

FIG. 14 is a diagram showing the relationship between tablet hardness and disintegration time of bilayer OD tablet 20, and the relationship between tablet hardness and semi-maximal absorption reaching time. In FIG. 14, the horizontal axis is tablet hardness (N), the left vertical axis is disintegration time (s), and the right vertical axis is time to reach sub-maximal absorption (s).

The disintegration time is the disintegration time measured by the disintegration test method of the Japanese Pharmacopoeia.

Here, the quasi-maximum absorption reaching time is newly defined in the present invention, and is calculated according to the following formula based on the maximum absorption and the permeation rate coefficient.

Time to reach quasi-maximal absorption = (maximum absorption) ² / (permeation rate coefficient)
(2)
The maximum absorption amount and the permeation rate coefficient were measured with the first layer 21 of the two-layer OD tablet 20 as the water landing surface side. Mean values of permeation rate coefficients in the range of seconds to 20 seconds.

The semi-maximal absorption reaching time corresponds to the time required to reach the maximum absorption at which the amount of water absorbed by the bilayer OD tablet 20 is maximized, that is, the time required to reach the maximum absorption. It's almost time. Therefore, it is possible to roughly grasp the time required for the water absorption of the double-layer OD tablet 20 to reach the maximum absorption by this semi-maximum absorption reaching time.

As shown in FIG. 14, the relationship between tablet hardness and time to reach quasi-maximal absorption shows substantially the same tendency as the relationship between tablet hardness and disintegration time.

Also, the disintegration time of the bilayer OD tablet indicated by the left vertical axis is shorter than the time to reach the sub-maximal absorption indicated by the right vertical axis.

Since the relationship between tablet hardness and time to reach quasi-maximum absorption approximates the relationship between tablet hardness and time to disintegration, disintegration time can be evaluated from the relationship between tablet hardness and time to reach quasi-maximum absorption.

For example, it is possible to roughly grasp the disintegration time of a bilayer OD tablet with a certain tablet hardness from the obtained time to reach the quasi-maximal absorption amount.

In this way, the disintegration time of OD tablets can be evaluated from the time to reach the quasi-maximum absorption amount, which is obtained when the OD tablet is absorbed by the force of only the OD tablet, and no load is applied. It is useful in design, quality control, etc.

As described above, according to the present embodiment, the force of the two-layer OD tablet alone is enough to absorb water, so that the water absorption and the like can be evaluated in a state similar to when the two-layer OD tablet is ingested.

Moreover, based on the permeation rate coefficient of each layer 21, 22 of the bilayer OD tablet 20, the water absorption in each layer 21, 22 can be evaluated.

Furthermore, by calculating the maximum absorption amount of the bilayer OD tablet 20, it is possible to grasp the amount of saliva required for the bilayer OD tablet 20 to absorb water, swell and disintegrate. useful for

In addition, based on the relationship between the permeation rate coefficient, maximum absorption amount, and tablet hardness, information on tablet hardness/tabletting pressure useful for tablet design can be obtained.

In this embodiment, as shown in FIG. 9, the water absorption of each layer 21, 22 of the bilayer OD tablet 20 is evaluated based on the permeation rate coefficient, and as shown in FIG. Evaluate the hardness/tabletting pressure of the bilayer OD tablet 20 based on the time of appearance of OD, as shown in FIG. 12, evaluate the hardness of the bilayer OD tablet 20, and As shown in Figure 14, the tablet hardness is evaluated based on the maximum absorption amount, and the disintegration time is evaluated based on the time to reach the quasi-maximal absorption amount and the tablet hardness as shown in Fig. 14, so these It is possible to perform multifaceted evaluation by combining them, but the present invention does not necessarily need to evaluate all of them, and it is sufficient if at least one of them can be evaluated.

Next, an evaluation method by a measurement evaluation device according to another embodiment of the present invention will be described.

As shown in the schematic configuration diagram of FIG. 15, the measurement evaluation apparatus of this embodiment includes a camera 25 as imaging means for imaging a sample in addition to the main body A of the measurement evaluation apparatus described above.

This camera 25 is installed beside the sample holder 9 of the main body A of the measurement evaluation apparatus, and is used to image the state of the two-layer OD tablet 20, which is a sample that swells when it absorbs water. and the captured image is displayed on a display unit such as a liquid crystal display of the control device.

In this embodiment, this measurement evaluation device was used to measure the swelling amount of the bilayer OD tablet 20 to determine the relationship between tablet hardness and swelling rate, and the relationship between tablet hardness and swelling rate.

FIG. 16 is a diagram showing the relationship between tablet hardness and swelling rate of bilayer OD tablet 20. FIG.

Here, the swelling rate was calculated according to the following formula.

Swelling rate = (swelling amount + tablet thickness) / (tablet thickness) (3)
In the above formula (3), the amount of swelling was calculated according to the following formula.

Swelling amount = π x (tablet diameter/2) ² x swelling thickness (4)
The tablet thickness in the formula (3) is the thickness of the bilayer OD tablet 20 before measurement, and the tablet diameter in the formula (4) is the diameter of the bilayer OD tablet 20 before measurement. Measurement was performed using a fully automatic tablet property measurement system (MultiCheck6ERWEKA, manufactured by Erweka, Germany).

The swelling thickness in the above formula (4) is the upper portion of the double-layer OD tablet 20 before swelling at the moment the double-layer OD tablet 20 hits the water, as shown in FIG. Each distance D1 between the reference straight line L8 passing through the vertex and virtual straight lines L9 and L10 passing through the upper vertex of the double-layer OD tablet 20 after swelling (during swelling) shown in FIGS. , D2. 17(a), (b), and (c) are the same as the regions 1, 2, and 3 in FIG.

Swelling was measured with the first layer 21 of the two-layer OD tablet 20 as the water landing surface side.

The process in which the bilayer OD tablet 20 as shown in FIG. 17 absorbs water and swells can be evaluated as a swelling rate.

The swelling rate in FIG. 16 is the average value in the range of 3 seconds to 20 seconds after the start of water absorption.

As shown in FIG. 16, it can be seen that the higher the tablet hardness, the higher the swelling ratio.

Therefore, the tablet hardness can be evaluated from the swelling rate.

FIG. 18 is a diagram showing the relationship between the tablet hardness and the swelling rate of the bilayer OD tablet 20. FIG.

The swelling rate is the amount of change in the amount of swelling per unit time. This swelling speed is an average value in the range of 3 seconds to 20 seconds after the start of water absorption.

As shown in FIG. 18, there is a correlation between the swelling rate and tablet hardness, and the swelling rate decreases as the tablet hardness increases or decreases.

FIG. 19 is a diagram showing the relationship between tablet hardness and disintegration time of bilayer OD tablet 20, and the relationship between tablet hardness and semi-maximal swelling amount reaching time. In FIG. 19, the horizontal axis is tablet hardness (N), the left vertical axis is disintegration time (s), and the right vertical axis is time to reach semi-maximal swelling (s).

The disintegration time is the disintegration time measured by the disintegration test method of the Japanese Pharmacopoeia.

Here, the time to reach the semi-maximal swelling amount is newly defined in the present invention, and is calculated according to the following formula based on the maximum swelling amount, which is the maximum swelling amount of the bilayer OD tablet, and the swelling rate. .

Semi-maximal swelling amount reaching time = (maximum swelling amount) / (swelling speed) (5)
Here, the swelling speed is the average value in the range of 3 seconds to 20 seconds after the start of water absorption, as described above.

The semi-maximal swelling amount reaching time is the time corresponding to the time required for the bilayer OD tablet 20 to reach the maximum swelling amount, that is, the time close to the time required to reach the maximum swelling amount. be. Therefore, it is possible to roughly grasp the time required for the swelling amount of the bilayer OD tablet 20 to reach the maximum swelling amount from this semi-maximum swelling amount reaching time.

As shown in FIG. 19, the relationship between tablet hardness and time to reach the semi-maximal swelling shows substantially the same tendency as the relationship between tablet hardness and disintegration time.

Also, the disintegration time indicated by the left vertical axis is shorter than the quasi-maximal swelling degree reaching time indicated by the right vertical axis.

Since the relationship between the tablet hardness and the time to reach the semi-maximal swelling approximates the relationship between the tablet hardness and the disintegration time, the disintegration time can be evaluated from the relationship between the tablet hardness and the time to reach the semi-maximal swelling.

For example, it is possible to roughly grasp the disintegration time of a bilayer OD tablet with a certain tablet hardness from the obtained time to reach the quasi-maximal swelling amount.

In this way, the disintegration time of the OD tablet can be evaluated from the time to reach the semi-maximal swelling amount, which is obtained in the state where the OD tablet absorbs water and swells only by the force of the OD tablet, without any action such as a load being applied. It is useful in development/design and quality control.

In this embodiment, the swelling of the bilayer OD tablet was explained, but it is of course possible to evaluate the water absorbency and the like in the same manner as in the above embodiment.

According to this embodiment, water is absorbed only by the force of the double-layered OD tablet, so the swelling process in a state similar to the time of taking the double-layered OD tablet is evaluated as the swelling rate, the swelling rate, and the time to reach the semi-maximal swelling amount. In addition, the disintegration time of the bilayer OD tablet can be evaluated from the relationship between the tablet hardness and the time to reach the semi-maximal swelling amount.

As described above, according to the above-described embodiments, in a state close to the time of dosing, in which an action such as a load is not applied to the double-layer OD tablet 20, during the process of water absorption and permeation and the swelling process of the double-layer OD tablet 20, Permeation rate coefficient, maximum absorption amount, time to reach quasi-maximum absorption amount, swelling rate, swelling rate, time to reach quasi-maximum swelling amount, and the relationship between them and hardness/compression pressure of bilayer OD tablet 20, etc. Therefore, useful information can be obtained as a basis for developing and designing bilayer OD tablets.

[Other embodiments]
The present invention can also be implemented in the following forms.

(1) In the above-described embodiment, the container 12 storing the liquid f is raised to contact the sample w suspended at a predetermined height, but the sample w is suspended by fixing the container 12. It is also possible to implement in a form in which the supported hook 8 is lowered.

(2) In the above embodiment, the sample w is applied to a two-layer OD tablet, but the sample w is not limited to a two-layer OD tablet, and may be an OD tablet having three or more layers, other than an OD tablet. It may be a tablet other than the tablet, or it may be a ceramic chip or the like other than the tablet.

Moreover, the liquid is not limited to water, and can be applied to various liquids such as artificial saliva and colored water.

REFERENCE SIGNS LIST 1 base 1a leg 2 driving unit 3 measuring unit 4 processing space 5 lifting table 6 transparent cover 7 mass measuring device 8 hook 9 sample holder 10 vertical slide guide means 11 stepping motor 12 container 13 sample mounting unit 13a peripheral wall 13b connecting piece 13c raised portion 14 hanging portion 14a support arm 15 small hole (liquid inflow hole)
16 locking hole 18 space f liquid w sample

Claims (12)

A sample holder that holds a sample and is suspended and supported by the mass measuring device is disposed above the container that stores the liquid, and the sample holder includes a sample placement section on which the sample is placed, The sample mounting portion has a peripheral wall portion, and the bottom surface of the sample mounting portion is formed with a plurality of liquid inflow holes into which the liquid flows, so that the container and the sample holder can be moved up and down relative to each other. and the liquid surface of the container is brought into contact with the bottom surface of the sample mounting portion, and the mass change accompanying the permeation of the liquid into the sample is measured over time by the mass measuring device. There is
Evaluating the hardness of the sample based on the permeation rate coefficient obtained by measuring the mass change,
An evaluation method using a measurement evaluation device characterized by: A sample holder that holds a sample and is suspended and supported by the mass measuring device is disposed above the container that stores the liquid, and the sample holder includes a sample placement section on which the sample is placed. The sample mounting portion has a peripheral wall portion, and the bottom surface of the sample mounting portion is formed with a plurality of liquid inflow holes into which the liquid flows, so that the container and the sample holder can move up and down relative to each other. and the liquid surface of the container is brought into contact with the bottom surface of the sample mounting portion, and the mass change accompanying the permeation of the liquid into the sample is measured over time by the mass measuring device. and
Evaluating the hardness of the sample based on the maximum absorption amount, which is the maximum amount of the liquid absorbed by the sample due to permeation into the sample, determined by measuring the mass change;
An evaluation method using a measurement evaluation device characterized by: A sample holder that holds a sample and is suspended and supported by the mass measuring device is disposed above the container that stores the liquid, and the sample holder includes a sample placement section on which the sample is placed, The sample mounting portion has a peripheral wall portion, and the bottom surface of the sample mounting portion is formed with a plurality of liquid inflow holes into which the liquid flows, so that the container and the sample holder can be moved up and down relative to each other. and the liquid surface of the container is brought into contact with the bottom surface of the sample mounting portion, and the mass change accompanying the permeation of the liquid into the sample is measured over time by the mass measuring device. There is
Based on the permeation rate coefficient obtained by measuring the mass change and the maximum absorption amount, which is the maximum amount of the liquid absorbed by the sample due to permeation into the sample, reaching the quasi-maximum absorption calculated according to the following formula evaluate time,
Time to reach quasi-maximal absorption = (maximum absorption) ² / (permeation rate coefficient)
An evaluation method using a measurement evaluation device characterized by: the sample is a tablet,
Evaluate the disintegration time of the tablet based on the time to reach the quasi-maximal absorption amount and the hardness of the tablet,
An evaluation method using the measurement evaluation device according to claim 3 . A sample holder that holds a sample and is suspended and supported by the mass measuring device is disposed above the container that stores the liquid, and the sample holder includes a sample placement section on which the sample is placed, The sample mounting portion has a peripheral wall portion, and the bottom surface of the sample mounting portion is formed with a plurality of liquid inflow holes into which the liquid flows, so that the container and the sample holder can be moved up and down relative to each other. the liquid surface of the container is brought into contact with the bottom surface of the sample mounting portion, and the mass change accompanying the permeation of the liquid into the sample is measured over time by the mass measuring device ,
An image capturing means for capturing an image of the sample placed on the sample mounting portion of the sample holder, wherein the image capturing means captures an image of the sample that swells due to permeation of the liquid.
A measurement evaluation device characterized by: An evaluation method by the measurement evaluation device according to claim 5,
Evaluating the swelling rate of the sample obtained based on the image captured by the imaging means;
An evaluation method using a measurement evaluation device characterized by: An evaluation method by the measurement evaluation device according to claim 5,
Evaluating the swelling speed of the sample obtained based on the image captured by the imaging means;
An evaluation method using a measurement evaluation device characterized by: An evaluation method by the measurement evaluation device according to claim 5 ,
Evaluating the maximum amount of swelling of the sample obtained based on the image captured by the imaging means;
An evaluation method using a measurement evaluation device characterized by: An evaluation method by the measurement evaluation device according to claim 5 ,
Based on the swelling speed and the maximum swelling amount of the sample obtained based on the image captured by the imaging means, the time to reach the semi-maximal swelling amount calculated according to the following formula is evaluated.
Semi-maximal swelling amount reaching time = (maximum swelling amount) / (swelling speed)
An evaluation method using a measurement evaluation device characterized by: the sample is a tablet,
Evaluate the disintegration time of the tablet based on the time to reach the semi-maximal swelling amount and the hardness of the sample,
An evaluation method using the measurement evaluation device according to claim 9 . the sample is a tablet,
10. An evaluation method using the measurement evaluation device according to claim 1, 2, 3, 5, 6, 7, 8, or 9 . The tablet is an orally disintegrating tablet,
An evaluation method using the measurement evaluation device according to claim 4 , 10 or 11 .

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