阅读说明：本技术 用于消化器官中的药剂溶解试验的装置 (Device for dissolution test of medicament in digestive organ ) 是由 横林孝康 于 2020-04-30 设计创作，主要内容包括：本发明提供用于消化器官中的药剂溶解试验的装置。该用于溶解试验的装置包括：多个容器(12、14、16、18),与生物体的消化器官对应；消化液供给装置(20、24、40、42),向需要被供给消化液的容器供给该消化液；液状体输送路径(34、50、70),设置于各容器之间且从上游侧容器到达下游侧容器；输送驱动源(36、54、72),对液状体输送路径中的消化液与口服药剂的混合液状体施加流动力；以及控制装置(90),与生物体的消化器官中的从上游侧朝向下游侧的流量的随时间变化对应地控制输送驱动源(36、54、72)的输送速度。(The present invention provides a device for dissolution testing of an agent in a digestive organ. The apparatus for dissolution testing comprises: a plurality of containers (12, 14, 16, 18) corresponding to digestive organs of a living body; a digestive juice supply device (20, 24, 40, 42) for supplying the digestive juice to a container to which the digestive juice is to be supplied; liquid material conveying paths (34, 50, 70) which are provided between the containers and reach the downstream container from the upstream container; a transport drive source (36, 54, 72) that applies a flow force to a mixed liquid material of the digestive juice and the oral drug in the liquid material transport path; and a control device (90) that controls the transport speed of the transport drive sources (36, 54, 72) in accordance with the time-dependent change in the flow rate from the upstream side to the downstream side in the digestive organ of the living body.)

1. An apparatus for dissolution testing of a pharmacological agent in a digestive organ, comprising:

a plurality of containers corresponding to digestive organs of an organism;

a digestive juice supply device for supplying the digestive juice to a container to which the digestive juice is to be supplied;

a liquid material transport path provided between the containers and extending from the upstream container to the downstream container;

a transport driving source that applies a flow force to a mixed liquid of the digestive juice and the oral drug in the liquid transport path; and

and a control device that controls the transport speed of the transport drive source in accordance with a change over time in the flow rate from the upstream side to the downstream side in the digestive organ of the living body.

2. The apparatus for dissolution testing of pharmacological agents in a digestive organ according to claim 1, further comprising a mouthpiece which is opened through a bottom of the container on the upstream side communicating with the liquid body transfer path so as to be able to transfer the oral pharmacological agent inside the container on the upstream side to the container on the downstream side without remaining.

3. The apparatus for dissolution test of a drug in a digestive organ according to claim 1 or 2, wherein the control means controls the transport speed of the transport drive source in accordance with a temporal change in excretion speed from each digestive organ of a living body.

4. The apparatus for dissolution test of medicinal agent in digestive organs according to any one of claims 1 to 3, wherein the control means controls the amount of liquid in each container over time by controlling the transport speed of the transport driving source.

5. The apparatus for dissolution testing of pharmaceutical agents in digestive organs according to claim 4, further comprising a liquid volume detecting means for detecting the volume of liquid within each container.

6. Device for dissolution testing of a pharmacological agent in a digestive organ according to claim 4 or 5, characterised in that a drain is provided at the most downstream container for controlling the amount of liquid body within the most downstream container over time.

7. The apparatus for dissolution testing of pharmaceutical agents in digestive organs according to any of claims 4 to 6, wherein the control means determines the presence or absence of apparatus failure based on the amount of liquid in each container.

8. The apparatus for dissolution testing of a medicinal agent in a digestive organ according to any one of claims 1 to 7, wherein the apparatus for dissolution testing is capable of inputting, as a test condition, an online calculation result for at least one of a liquid amount in each vessel, a pH value in each vessel, and a flow rate from an upstream side to a downstream side.

9. The device for dissolution testing of pharmaceutical agents in digestive organs according to any of claims 1 to 8,

further comprises a conveying speed detection device for detecting the conveying speed of the conveying driving source,

the control device controls the conveying speed of the conveying drive source based on the detection result of the conveying speed detection device.

10. The device for dissolution testing of pharmaceutical agents in digestive organs according to any of claims 1 to 9,

also comprises a stirring device which is used for stirring the liquid in each container,

the stirring device can change the position according to the change of the amount of the liquid in each container.

11. The apparatus for testing drug dissolution in a digestive organ according to any one of claims 1 to 10, wherein a container corresponding to a small intestine of a living body contains a liquid material having an organic phase and an aqueous phase, and a stirring device for stirring the liquid material in the container is provided in the container corresponding to the small intestine, and the stirring device has an organic phase paddle and an aqueous phase paddle, and the organic phase paddle is a floating paddle.

12. The apparatus according to any one of claims 1 to 11, further comprising a net-like housing means, wherein the apparatus is configured to immerse the drug in the digestive juice of the container corresponding to the stomach of the living body in a state in which the drug that is not dissolved in the stomach of the living body is housed in the housing means, and then transport the drug from the container corresponding to the stomach of the living body to the container corresponding to the small intestine of the living body in a state in which the drug is housed in the housing means, and then immerse the drug in the digestive juice of the container corresponding to the small intestine of the living body.

Technical Field

The present invention relates to a device for a drug dissolution test in a digestive organ, and more particularly to a device for an ex vivo drug dissolution test.

Background

As a device for a drug dissolution test in a digestive organ, there is known one as follows: the digestive system is provided with a plurality of vessels for accommodating artificial digestive juices corresponding to the digestive organs of the living body. The vessel of the known device for dissolution testing is configured: in order to investigate the dissolution state of a drug such as a tablet after oral administration of the drug in a human or to study the absorption process of a pharmaceutically effective component, the dissolution state of the drug, the pH of a digestive solution into which the drug is dissolved, and the like can be investigated over time.

However, in known devices, the vessels are independent of each other and are not associated with each other. This is different from an actual living body.

To eliminate this, JP3787322B proposes the following device: the stomach, bowel and circulation chambers are connected in series and a pump is provided for pumping the liquid of each chamber into the different chambers. Further, JP3787322B describes a method of analyzing a liquid, a method of calculating a volume of the liquid in a chamber, a method of calculating a flow rate at the time of liquid feeding, and the like.

Disclosure of Invention

The present invention is further directed to an improvement of the technique described in JP3787322B, and an object of the present invention is to enable more accurate dissolution test of a drug by more accurately simulating the digestive system of a living body such as a human.

To achieve the object, the device for dissolution test of an agent in a digestive organ of the present invention comprises: a plurality of containers corresponding to digestive organs of an organism; a digestive juice supply device for supplying the digestive juice to a container to which the digestive juice is to be supplied; a liquid material transport path provided between the containers and extending from the upstream container to the downstream container; a transport driving source that applies a flow force to a mixed liquid of the digestive juice and the oral drug in the liquid transport path; and a control device that controls the transport speed of the transport drive source in accordance with a change over time in the flow rate from the upstream side to the downstream side in the digestive organ of the living body.

According to the device for a drug dissolution test in a digestive organ of the present invention, it is preferable that the device further comprises a mouthpiece which is opened at the bottom of the upstream side container by being communicated with the liquid material transfer path, so that the oral drug inside the upstream side container can be transferred to the downstream side container without being left.

According to the apparatus for dissolution test of the present invention, it is preferable that the control device controls the transport speed of the transport driving source in accordance with a temporal change in excretion speed from each digestive organ of a living body.

According to the apparatus for dissolution test of the present invention, it is preferable that the control means controls the amount of the liquid material in each container over time by controlling the transport speed of the transport driving source.

The apparatus for dissolution test according to the present invention preferably further comprises a liquid material amount detection device for detecting the amount of the liquid material in each container.

According to the apparatus for dissolution testing of the present invention, it is preferable that a discharge means for controlling the amount of liquid in the most downstream container with the passage of time is provided in the most downstream container.

According to the apparatus for dissolution test of the present invention, it is preferable that the control device determines the presence or absence of the apparatus failure based on the amount of the liquid material in each container.

According to the apparatus for dissolution test of the present invention, it is preferable that the control device is capable of inputting, as the test conditions, the results of on-line calculation for at least one of the liquid amount in each container, the pH value in each container, and the flow rate from the upstream side to the downstream side.

According to the apparatus for dissolution test of the present invention, it is preferable that the apparatus further comprises a conveying speed detecting means for detecting a conveying speed of the conveying drive source, and the control means controls the conveying speed of the conveying drive source based on a detection result of the conveying speed detecting means.

The apparatus for dissolution test according to the present invention preferably further comprises a stirring device for stirring the liquid material in each container, the stirring device being capable of changing its position according to a change in the amount of the liquid material in each container.

According to the apparatus for dissolution test of the present invention, it is preferable that a container corresponding to the small intestine of a living body contains a liquid material having an organic phase and an aqueous phase, and a stirring device for stirring the liquid material in the container is provided in the container corresponding to the small intestine, the stirring device includes an organic phase paddle and an aqueous phase paddle, and the organic phase paddle is a floating paddle.

The apparatus for dissolution test according to the present invention preferably further comprises a net-like housing device configured to immerse the drug in the digestive juice of the container corresponding to the stomach of the living body in a state where the drug is not dissolved in the stomach of the living body, and then transport the drug from the container corresponding to the stomach of the living body to the container corresponding to the small intestine of the living body in a state where the drug is housed in the housing device, and then immerse the drug in the digestive juice of the container corresponding to the small intestine of the living body.

According to the apparatus for testing the dissolution of a drug in a digestive organ of a living body of the present invention, the delivery speed of the delivery driving source for applying a hydrodynamic force to the mixed liquid body of the digestive juice and the oral drug in the liquid body delivery path between the containers is controlled in accordance with the time-dependent change in the flow rate from the upstream side to the downstream side in the digestive organ of the living body.

Drawings

Fig. 1 is a diagram showing the structure of an apparatus for drug dissolution test in a digestive organ according to an embodiment of the present invention.

Fig. 2 is an enlarged sectional view of a main portion in fig. 1.

Fig. 3 is an enlarged sectional view of the other main portion in fig. 1.

FIG. 4 is a graph showing the transition of pH in the human digestive system.

Fig. 5 is a graph showing what value the delivery rate of the liquid containing the drug takes at each time when the drug moves in the digestive organ.

Detailed Description

Fig. 1 shows a device for a drug dissolution test in a digestive organ according to an embodiment of the present invention. The device includes a plurality of containers 12, 14, 16, 18, and the plurality of containers 12, 14, 16, 18 correspond to respective organs of a human digestive organ, which is a living body. Receptacle 12 constitutes the gastric compartment, receptacle 14 constitutes the duodenal compartment, receptacle 16 constitutes the jejunal compartment, and receptacle 18 constitutes the ileal compartment. The duodenum, jejunum and ileum can be collectively referred to as the "small intestine".

Is configured to be able to supply an artificially adjusted gastric fluid 20 to the container 12 that forms the gastric cavity. Reference numeral 22 is a container for storing the gastric juice 20, and reference numeral 24 is a supply path for supplying the gastric juice from the container for storing 22 toward the container 12 constituting the gastric cavity. A peristaltic pump 26 is provided in the supply path 24. These components constitute a digestive juice supply device. The container 12 is provided with a stirring device 28 and a pH sensor 30.

In the apparatus of the present invention, an oral drug in the form of a tablet, capsule, or the like is injected into the gastric juice 20 in the container 12 constituting the gastric cavity. Therefore, a liquid material 32 in which the gastric juice 20 and the oral drug are mixed is present inside the container 12 constituting the gastric cavity. A supply path 34 serving as a liquid material supply path for supplying the liquid material 32 to the container 14 constituting the duodenal bulb chamber is provided. A peristaltic pump 36 as a conveyance drive source is provided in the supply path 34.

A supply path 42 for supplying the intestinal fluid 40 from the storage container 38 to the container 14 is directed to the container 14 constituting the duodenal bulb. A peristaltic pump 44 is provided in the supply path 42. These components also constitute a digestive juice supply device. The container 14 is provided with the same stirring means 46 and pH sensor 48 as in the case of the container 12 constituting the gastric cavity.

Reference numeral 50 denotes a supply path as a liquid material supply path for supplying the liquid material 52 present inside the container 14 constituting the duodenal lumen toward the container 16 constituting the jejunal lumen. A peristaltic pump 54 is provided in the supply path 50.

The liquid material 56 present inside the container 16 constituting the jejunal cavity is separated into an aqueous phase 58 and an oil phase 60 as an organic phase. The stirring device 62 and the pH sensor 64 are also provided in the container 16. The stirring device 62 includes an aqueous phase paddle 66 for stirring the aqueous phase 58 and an oil phase paddle 68 as an organic phase paddle for stirring the oil phase 60.

The receptacle 18 forming the ileal cavity is formed in the same configuration as the receptacle 16 forming the jejunal cavity. That is, reference numeral 70 denotes a supply path for supplying the liquid material 56 present inside the container 16 constituting the jejunal cavity toward the container 18 constituting the ileal cavity. A peristaltic pump 72 is provided in the supply path 70. The liquid 74 present inside the receptacle 18 forming the ileal cavity also separates into an aqueous phase 76 and an oil phase 78 which is an organic phase. The stirring device 80 and the pH sensor 82 are also provided in the container 18. The stirring device 80 includes an aqueous phase paddle 84 for stirring the aqueous phase 76 and an oil phase paddle 86 as an organic phase paddle for stirring the oil phase 78. Reference numeral 88 is an evacuation device for evacuating from the receptacle 18 forming the ileal cavity.

In the case of testing a drug that has been dissolved in the interior of the container 16 constituting the jejunal cavity, a structure may be adopted in which the container 18 constituting the ileal cavity is not provided.

In the case of testing an animal drug to be fed to an animal, for example, in the case where the animal is a bovine animal, the animal drug may be configured such that: a plurality of containers 12 constituting a gastric cavity are provided, and a supply path 24 for supplying a digestive juice from a single container 22 storing a gastric juice 20 as a digestive juice to the plurality of containers 12 is provided.

The following configuration may be adopted as necessary: in addition to the series connection of the containers 12, 14, … … constituting the chambers such as the stomach and the duodenum, a plurality of groups of such series-connected container rows are arranged in parallel. In addition to the illustrated structure, the supply paths 24 and 42 for digestive juice such as gastric juice 20 and the supply paths 34, 50, and … … connecting the containers 12, 14, and … … can be easily connected and disconnected by using connectors or the like, and the device structure can be changed as desired.

The stirring devices 28, 46, 62, 80 provided in the respective containers 12, 14, 16, 18 have a lifting function, and thus can follow the liquid level fluctuation when the liquid level of the containers 12, 14, 16, 18 fluctuates. The tests can also be carried out in only aqueous phases 58, 76 in container 16, which constitutes the jejunal cavity, and in container 18, which constitutes the ileal cavity. To cope with this, the stirring devices 62 and 80 may be configured such that the oil paddles 68 and 86 can be removed.

The apparatus for dissolution test shown in fig. 1 is configured to be controlled by the control device 90.

Fig. 2 shows a detailed structure of the container 12 constituting the gastric cavity. The container 12 is made of glass, for example, and the state of the inside thereof can be observed from the outside. The illustrated container 12 is cylindrical and has a bottom formed in a spherical shell shape. As a general example, a general oral drug is not completely dissolved in the stomach, but exists in the stomach in a finely divided solid state. Fig. 2 shows the medicine 92 in the above state.

The supply path 34 from the container 12 constituting the gastric cavity to the container 14 constituting the duodenal cavity takes the form of a suction nozzle 94 in the container 12 constituting the gastric cavity. The suction nozzle 94 opens at a position in the center of the bottom of the container 12. Specifically, if the bottom of the container 12 is formed in a spherical shell shape as shown in the drawing, the medicines 92 are gathered toward the center of the bottom of the container by gravity, and the suction nozzle 94 is opened so as to efficiently suck the medicines 92 gathered at the center of the bottom of the container 12.

The form of the container 12 is not limited to the bottom portion formed in a spherical shell shape as illustrated, and other suitable forms may be adopted. For example, if the bottom is flat, there is an advantage in that the paddle 96 of the stirring device 28 and the suction nozzle 94 do not easily interfere. The same applies to the container 14 and the like constituting the duodenal bulb.

In either case, the liquid material containing the medicine 92 can be transferred to the next container 14 on the downstream side without leaving the medicine 92 by opening the suction nozzle 94 at the bottom or the center of the bottom of the container 12.

Fig. 3 shows a detailed structure of the container 16 constituting the jejunal cavity. The container 16 itself is of the same construction as the container 12 that forms the gastric cavity. The oral drug dissolves in the container 16, and the liquid material 56 in the container 16 is separated into the water phase 58 and the oil phase 60 as described above. The supply path 70 is in the form of a suction nozzle 98 in the container 16, as in the case of fig. 2.

A nozzle, not shown, may be provided at the downstream end of the supply path 50 within the container 16, the supply path 50 extending from the container 14 constituting the duodenal lumen toward the container 16 constituting the jejunal lumen. Preferably, the nozzle is capable of moderate adjustment of its height. For example, in the case where it is necessary to supply the liquid material from the tank 14 to the aqueous phase 58 in the tank 16, a nozzle is provided near the lower end of the aqueous phase 58, so that the nozzle can be separated from the suction nozzle 98 of the supply path 70 located in the tank 16, the supply path 70 extending from the tank 16 constituting the jejunal cavity to the tank 18 constituting the ileal cavity. This enables an appropriate dissolution test to be performed. In addition, when it is not necessary to supply the liquid material to the water phase 58 or when the oil phase 60 is not present, it is possible to confirm whether or not the supply path 50 and the nozzles are not clogged by providing the nozzles above the liquid surface. The supply path 70 from the tank 16 constituting the jejunal cavity to the tank 18 constituting the ileal cavity can also be formed in the same configuration.

The oil phase paddle 68 of the stirring device 62 can be formed in a floating structure, and thus can favorably follow the change in the liquid level of the water phase 58 and the oil phase 60.

The control device 90 will be explained. One of the functions of the control device 90 is to control the pH in each container so as to match the pH in each digestive organ of the living body. Fig. 4 shows the progression of pH in the digestive system of a human, and also shows the change in pH around an orally-fed medicament. The vertical axis represents pH, and the horizontal axis represents elapsed time. The oral drug moves from the stomach to the duodenum and further to the jejunum and ileum with the passage of time. That is, the horizontal axis of fig. 4 represents the elapse of time, and also represents which organ the medicine 92 is present in when a predetermined time has elapsed.

In fig. 4, the position of the vertical axis on the horizontal axis indicates the timing when a person inserts a drug into the mouth, and the pH around the drug at this time is 6.8. The agent then reaches the stomach via the esophagus. t0 is the time when the drug reaches the stomach, i.e., the time when the dissolution test starts. The pH around the agent at this time was 1.2. t1 is the time when the drug is excreted from the stomach, t2 is the time when the drug is excreted from the duodenum, and t3 is the time when the drug is excreted from the jejunum. T4 is the time when the drug is excreted from the ileum, and the dissolution test is completed at this timing. According to fig. 4, the pH value tends to increase as it goes from the stomach to the jejunum through the duodenum.

The controller 90 controls the amount of the gastric juice 20 supplied to the container 12 constituting the gastric cavity and controls the amount of the intestinal juice 40 supplied to the container 14 constituting the duodenal cavity so that the pH of the liquid in each container corresponds to the value shown in fig. 4. This makes it possible to achieve the same pH as that of each organ of the actual human digestive organ in each of the vessels 12, 14, 16, and 18. The pH of the gastric juice 20 was set to 1.2, and the pH of the intestinal juice 40 was set to 6.3.

The controller 90 controls the amount of the liquid material in each of the containers 12, 14, 16, and 18. Specifically, the control device 90 detects the amount of the liquid material in each of the containers 12, 14, 16, and 18 by using a sensor that detects the mass of each container containing the liquid material, a sensor that detects the level (liquid level) of the liquid material in each container, a sensor that detects the flow rate of the peristaltic pumps 36, 54, and 72, and the like, and controls the operation of the peristaltic pumps 36, 54, and 72 and the peristaltic pumps 26 and 44 based on the amount of the liquid material. Thereby, the amount of the liquid material in each container is controlled.

In particular, by using a sensor for detecting the mass of the container, the amount of liquid to be fed can be appropriately controlled even in a situation where, for example, a temperature change occurs. Further, by using a sensor for detecting the level or flow rate of the liquid material, the amount of liquid to be fed can be appropriately controlled even when a plurality of solutions are mixed during the test and the specific gravity of the liquid material changes. Further, by using such a plurality of kinds of sensors in combination, the amount of liquid to be fed can be appropriately controlled even under complicated test conditions.

Fig. 5 is a graph showing what value the flow rate of the liquid containing the drug, that is, the liquid sending amount (mL/min), takes at each time when the drug moves in the digestive organ, in other words, what value the sending speed takes at each time. The vertical axis is flow rate and the horizontal axis is time. Unlike the case of fig. 4, fig. 5 shows the characteristics of each digestive organ. As shown in fig. 5, the flow rate of the liquid material containing the chemical agent is in the form of a decreasing curve. The decreasing curve can be expressed by an appropriate mathematical expression, and thus the peristaltic pumps 36, 54, 72 can be appropriately controlled in accordance with the mathematical expression. As the mathematical expression, various expressions can be used as approximate expressions, and for example, the following expression (1) can be used.

V(t)＝(b/t²)+c……(1)

Where V (t) is the flow rate, t is the elapsed time, and b and c are constants.

The above formula is obtained as follows. That is, the flow rate from the stomach to the duodenum of a human, for example, i.e., the liquid supply amount is known in advance according to various conditions. In the case of the above equation, the constants b, c are determined based on the known values described above.

Specifically, fig. 5 shows the temporal change in the amount of liquid sent from the stomach to the duodenum by the peristaltic pump 36. In fig. 5, the behavior of the peristaltic pump 36 corresponding to the known values is plotted as discrete data on a coordinate graph over time. For example, if the elapsed time t is 60 seconds, the liquid sending amount is 20 mL/min. The liquid feed amount is 13mL/min if the elapsed time t is 180 seconds, and 10mL/min if the elapsed time t is 360 seconds. Further, if the elapsed time t is 1320 seconds, it is appropriate that the liquid feeding amount is 2 mL/min. The constants b and c in the above equation can be determined from the above data, and the above equation can be completed. Thus, the characteristics obtained for the peristaltic pump 36 are continuously defined. Then, the peristaltic pump 36 is controlled so as to be a decided equation.

The amount of liquid delivered from the duodenum to the jejunum and the amount of liquid delivered from the jejunum to the ileum were also controlled in the same manner. In the above case, the values of constants b and c are different in the above formula compared with the liquid amount sent from the stomach to the duodenum.

Further, for example, after the initial liquid amount in each of the containers 12, 14, 16, and 18 is known, the control amount of the liquid supply amount is updated every 1 second, for example, whereby the temporal change of the liquid amount (liquid amount) in each of the containers 12, 14, 16, and 18 can be calculated, and control can be performed in accordance with the temporal change. In this case, if the volume of the liquid material in the container at time t is denoted by A (t), the volume of the liquid material in the container at time t-1, which is 1 second before time t, can be denoted by A (t-1). Therefore, if A (t) is subtracted from A (t-1), the flow rate V (t) [ mL/min ] at time t can be obtained.

In detail, a (t) can be expressed using an exponential reduction function called "first order reaction rate equation" as:

A(t)＝A₀×e^-kt。

wherein A is₀Is an initial quantity, k is an initial quantity A₀Half the time required. In this case, A (t-1) can be expressed as:

A(t-1)＝A₀×e^-k(t-1)。

therefore, if the above-described subtraction is performed, it becomes:

A(t-1)-A(t)＝

V(t)＝A₀×e^-kt×(e^k-1)……(2)。

that is, the above formula (2) may be employed instead of the above formula (1).

The pH of the liquid in each container 12, 14, 16, 18 can be obtained by calculation from the initial pH of the liquid in each container 12, 14, 16, 18, the measured value or the predetermined value of the pH of the liquid flowing into/out of each container 12, 14, 16, 18, and the liquid feed amount obtained as described above. Based on the calculated values and the detection results of the pH sensors 30, 48, 64, and 82, the control device 90 can perform higher control.

By applying the above-described control method, the volume of the liquid material in each of the containers 12, 14, 16, and 18 can be controlled by the control device 90. That is, the volume of the liquid material in each of the containers 12, 14, 16, and 18 is increased or decreased in accordance with the actual increase or decrease of the internal liquid in each digestive organ based on the inflow from the upstream side and the outflow to the downstream side. Alternatively, the volume can also be kept constant. In the vessel 18 constituting the ileal cavity, the same operation as the outflow operation to the downstream side is performed by the discharging device 88. Further, by introducing a device for detecting the actual volume of the liquid material in each of the containers 12, 14, 16, 18 in real time, for example, a device capable of detecting the mass, the liquid level, the inflow/outflow amount, and the like, it is possible to monitor whether the target volume changes with time or whether the target volume is kept constant with time, at regular intervals or at any time. When the detection result is different from the target value, the operation of the peristaltic pumps 36, 54, 72 is controlled by the control device 90, and the liquid feed amount is corrected.

As can be understood from the above description, the values of the volumes of the liquid material in the containers 12, 14, 16, and 18 can be predicted in advance. Therefore, by performing the volume monitoring, it is possible to determine whether or not there is a failure, such as a failure in the liquid feeding device such as the peristaltic pumps 36, 54, 72 or another device, or a blockage in the supply paths 34, 50, 70.

As is apparent from the above description, the apparatus for dissolution testing according to the embodiment of the present invention may be configured such that various values calculated and simulated on-line, for example, the amount of the liquid material inside each of the vessels 12, 14, 16, and 18, the pH of the liquid material, the amount of the liquid material transferred between the vessels 12, 14, 16, and 18, an approximate expression representing an approximate change in the amount of the liquid material transferred, and constants thereof can be input to the illustrated apparatus as test conditions. With this configuration, drug dissolution tests under various conditions can be performed.

In the apparatus for dissolution test according to the embodiment of the present invention, the flow rate in the supply paths 34, 50, and 70, that is, the transport speed can be detected by using a flow meter or other measuring device. This enables to accurately control the flow rate, that is, the liquid feed rate, based on the detection result.

Further, a peristaltic pump is exemplified as the driving source for liquid feeding, and other types of pumps and other liquid feeding driving sources can be similarly applied.

Among oral agents, there are those which do not substantially dissolve in the stomach and start to dissolve after reaching the small intestine. Such agents are known as enteric formulations. In a dissolution test of such a drug, a net-like housing device such as a basket is used to reliably deliver the drug to the intestine via the stomach. Then, each of the containers is immersed in the liquid in the container 12 constituting the gastric cavity in a state where the medicine is contained therein, and then taken out, and this time immersed in the liquid in the container 14 constituting the duodenum. Then, the same operation is repeated in the small intestine including the next stage and thereafter until the dissolution is completed.

According to the apparatus for dissolution testing of the embodiment of the present invention, the digestive system of a living body such as a human can be simulated as much as possible, and the absorption rate according to the actual state can be measured even for a drug that is not easily dissolved in the digestive organ. In addition, the medicine can be completely discharged from the container 12 corresponding to the stomach by the mouthpiece 94. The liquid volume of the container 14 corresponding to the duodenum and the liquid level of the aqueous phases 58, 76 in the containers 16, 18 corresponding to the jejunum and ileum can be kept constant or varied as desired.