CN111356919A

CN111356919A - Auxiliary device for dissolution test

Info

Publication number: CN111356919A
Application number: CN202080000307.5A
Authority: CN
Inventors: 王立坤; 顾国祥; 张凤娥
Original assignee: Nanjing Haiwei Pharmaceutical Technology Co ltd
Current assignee: Nanjing Haiwei Pharmaceutical Technology Co ltd
Priority date: 2020-02-21
Filing date: 2020-02-21
Publication date: 2020-06-30
Also published as: WO2021163988A1

Abstract

The embodiment of the application discloses a dissolution test auxiliary device. The device comprises an absorption part and an adjusting part, wherein the absorption part comprises an absorption unit, and the adjusting part comprises an adjusting unit; the absorption part is communicated with the dissolving-out cup through a first pipeline; the adjusting part is communicated with the dissolving-out cup through a second pipeline and a third pipeline; a first liquid inlet pump, a second liquid inlet pump and a first liquid outlet pump are respectively arranged on the first pipeline, the second pipeline and the third pipeline; the first liquid inlet pump leads the dissolved liquid into the absorption part through a first pipeline, and the led dissolved liquid flows into the absorption unit; the second liquid inlet pump leads the dissolved liquid into the adjusting part through a second pipeline, the adjusting unit adjusts the pH and/or the volume of the led dissolved liquid, and the first liquid outlet pump leads the adjusted dissolved liquid back to the dissolving cup. The method utilizes the modes of filtration, liquid-liquid extraction and the like and combines the change condition of the pH inside the organism to simulate the specific process that the medicine is absorbed in the organism, thereby improving the accuracy of the detection result of the dissolution device.

Description

Auxiliary device for dissolution test

Technical Field

The application relates to the field of drug test equipment, in particular to a dissolution test auxiliary device for simulating drug absorption.

Background

Dissolution rate refers to the rate and extent of dissolution of the active pharmaceutical ingredient from a formulation such as a tablet, capsule or granule under defined conditions. Dissolution apparatuses, such as dissolution instruments, are used to examine the rate and extent of dissolution of a formulation, such as a pharmaceutical tablet or capsule, in a prescribed solvent. The dosage of the solvent adopted by the existing dissolution device is greatly different from the gastric juice or intestinal juice actually existing in a human body, and the existing dissolution device cannot reflect the actual dosage of the gastric juice and the intestinal juice in the human body. In addition, the dissolution apparatus generally realizes the dissolution of the drug by adding a surfactant into a solvent, and the drug dissolution process usually defaults to the absorption of the drug, but the human body is a process of dissolving the drug while absorbing the drug, and the dissolution and absorption time is related to the characteristics of the drug and the internal environment of the human body. In addition, the solubility of drugs, especially weakly basic drugs, varies under different conditions during the specific administration, for example, the drug may precipitate due to the difference in pH conditions during the course of the drug from the stomach environment (lower pH) to the intestinal environment (higher pH). Therefore, a device capable of further simulating dissolution and absorption of the simulated drug in the human body is needed so as to accurately evaluate the dissolution and absorption rules of the drug.

Disclosure of Invention

One aspect of the present application provides a dissolution test aid comprising an absorbent portion and an adjustment portion, wherein the absorbent portion comprises an absorbent unit and the adjustment portion comprises an adjustment unit; the absorption part is communicated with a dissolving-out cup of the medicine dissolving-out device through a first pipeline; the adjusting part is communicated with the dissolving-out cup through a second pipeline and a third pipeline; a first liquid inlet pump, a second liquid inlet pump and a first liquid outlet pump are respectively arranged on the first pipeline, the second pipeline and the third pipeline; wherein the first liquid inlet pump is configured to guide the dissolution liquid in the dissolution cup into the absorption part through the first pipeline, and the guided dissolution liquid flows into the absorption unit; the second liquid inlet pump is configured to guide the dissolution liquid in the dissolution cup into the adjusting part through the second pipeline, the adjusting unit is configured to adjust the pH and/or the volume of the introduced dissolution liquid, and the first liquid outlet pump is configured to guide the adjusted dissolution liquid back to the dissolution cup.

In some embodiments, the absorption unit comprises a liquid trap capable of collecting the leachate flowing in from the first conduit.

In some embodiments, the liquid trap is connected to an analysis device capable of analyzing the eluate collected by the liquid trap.

In some embodiments, the apparatus further comprises a fourth conduit, the fourth conduit connects the absorption unit and the dissolution cup, and at least a portion of the dissolution fluid flowing into the absorption unit flows back into the dissolution cup through the fourth conduit after flowing out.

In some embodiments, the absorption unit comprises a membrane filter configured to collect dissolved drug and/or part of the eluate from the eluate flowing in from the first conduit.

In some embodiments, the absorption unit comprises a liquid-liquid extractor configured to collect dissolved drug in the dissolution liquid flowing in from the first conduit; and a second liquid outlet pump is arranged on the fourth pipeline and is configured to guide the dissolved liquid after the extraction of the medicine back to the dissolution cup through the fourth pipeline.

In some embodiments, the adjusting unit comprises at least one pH adjusting substance storage bin communicated with the inside of the adjusting part through an adjusting pipeline and used for adding an adjusting substance into the dissolution liquid flowing through the adjusting part to adjust the pH of the dissolution liquid.

In some embodiments, different pH adjusting substance reservoirs contain different adjusting substances for adding different adjusting substances to the dissolution liquid flowing through the adjusting part at different time periods.

In some embodiments, the conditioning substance comprises at least one of: carbon dioxide gas, argon, nitrogen, helium, water, carbonate buffer, phosphate buffer, citrate buffer, acetate buffer, tris buffer, barbiturate buffer, phthalate buffer, ammonia-ammonium-halide buffer, and boric acid buffer.

In some embodiments, a flow pump is provided on the conditioning duct, configured to define the amount and/or flow rate of conditioning substance added.

In some embodiments, the regulating part further comprises an elution medium supplement unit which is communicated with the inside of the regulating part through a supplement pipeline and is used for adding elution medium for dissolving medicine into the elution liquid flowing through the regulating part.

In some embodiments, a flow pump is provided on the supplemental conduit configured to control the amount and/or flow rate of the dissolution medium added.

In some embodiments, the apparatus further comprises at least one pH detection unit disposed inside the adjustment portion and/or inside the dissolution cup or on the third conduit, configured to detect the pH value of the dissolution fluid.

In some embodiments, the apparatus further comprises a control device in communication with the pump within the apparatus via an electrical and/or wireless connection, configured to control the pump to adjust the amount and/or flow rate of the solution passing through the pump.

In some embodiments, the device further comprises a thermostatic unit for preheating and/or keeping warm the absorption portion and/or the conditioning portion.

Another aspect of the present application provides a dissolution test aid comprising an absorbent portion and an adjustment portion, wherein the absorbent portion comprises a diverter valve and an absorbent unit, and the adjustment portion comprises an adjustment unit; the absorption part is communicated with a dissolution cup of the medicine dissolution device through a first pipeline and is communicated with the regulation part through a second pipeline; the adjusting part is communicated with the dissolving-out cup through a third pipeline; a liquid inlet pump and a liquid outlet pump are respectively arranged on the first pipeline and the third pipeline; wherein the flow dividing valve is arranged on the first pipeline and divides the dissolution liquid from the dissolution cup through a liquid inlet pump, one part of the dissolution liquid flows into the absorption unit, and the other part of the dissolution liquid flows into the adjusting part; the adjusting unit of the adjusting part is arranged to adjust the pH of the dissolution liquid flowing into the adjusting part, and the liquid outlet pump is arranged to guide the pH-adjusted dissolution liquid back to the dissolution cup.

In some embodiments, the absorption unit includes a liquid trap capable of collecting a portion of the eluate diverted from the diverter pump.

In some embodiments, the conditioning substance comprises at least one of: carbon dioxide gas, argon, nitrogen, helium, water, carbonate buffer, phosphate buffer, citrate buffer, acetate buffer, tris buffer, barbiturate buffer, phthalate buffer, ammonia-ammonium halide buffer, and boric acid buffer.

In some embodiments, the apparatus further comprises at least one pH detection unit disposed inside the adjustment portion and/or inside the dissolution cup, configured to detect the pH value of the dissolution fluid.

In some embodiments, the device further comprises a thermostatic unit for preheating and/or keeping warm the absorption portion and/or the conditioning portion. For preheating and/or keeping warm the absorption chamber, the conditioning section and/or the dissolution cup.

Drawings

The present application will be further explained by way of exemplary embodiments, which will be described in detail by way of the accompanying drawings. These embodiments are not intended to be limiting, and in these embodiments like numerals are used to indicate like structures, wherein:

FIG. 1 is a schematic diagram of a dissolution test aid according to some embodiments of the present application;

FIG. 2 is a schematic diagram of a dissolution test aid employing membrane filtration to simulate absorption, according to some embodiments of the present application;

FIG. 3 is a schematic diagram of a dissolution test aid employing extraction mode simulated absorption according to some embodiments of the present application;

figure 4 is another schematic diagram of a dissolution test aid according to some embodiments of the present application.

Detailed Description

In order to more clearly illustrate the technical solutions of the embodiments of the present application, the drawings used in the description of the embodiments will be briefly introduced below. It is obvious that the drawings in the following description are only examples or embodiments of the application, from which the application can also be applied to other similar scenarios without inventive effort for a person skilled in the art. Unless otherwise apparent from the context, or otherwise indicated, like reference numbers in the figures refer to the same structure or operation.

As used in this application and the appended claims, the terms "a," "an," "the," and/or "the" are not intended to be inclusive in the singular, but rather are intended to be inclusive in the plural unless the context clearly dictates otherwise. In general, the terms "comprises" and "comprising" merely indicate that steps and elements are included which are explicitly identified, that the steps and elements do not form an exclusive list, and that a method or apparatus may include other steps or elements.

Various embodiments of dissolution test aids are described. It is to be understood that the invention is not limited to the particular embodiments described herein, but may be modified, amended and/or altered. The aspects described in connection with a particular embodiment are not necessarily limited to that embodiment and may be implemented in any other aspect. For example, while various embodiments have been described in connection with a dissolution meter, it should be understood that the present invention can also be implemented in other test devices, such as any other test device and/or apparatus capable of performing dissolution testing purposes. It is also to be understood that the terminology used herein is for the purpose of describing particular embodiments only, and is not intended to be limiting, since the scope of the present invention will be defined by the appended claims, along with the full scope of equivalents to which such claims are entitled. In addition, various embodiments are described with reference to the drawings. It should be noted that the drawings are not to scale and are merely intended to facilitate the description of specific embodiments. The drawings are not intended to be exhaustive or to limit the scope of the invention.

For convenience in describing relative positions, orientations, or spatial relationships in connection with the figures, various relative terms such as "upper," "above," "upper," "directly above," "above …," "below," "bottom," "upper," "lower," or similar terms may be used herein. The term "level" or "upper or lower level" may be used for ease of description of some embodiments. The use of relative terms should not be construed to imply any necessary orientation, or direction of structures or portions thereof during manufacture or use and should not be construed to limit the scope of the invention. As used in the specification and the appended claims, the singular forms "a", "an", and "the" may include plural referents unless the context clearly dictates otherwise. For example, a reference to "a direction" may include an opposite direction to the direction as well as directions parallel to the direction.

Figure 1 is a schematic diagram of a dissolution test aid according to some embodiments of the present application. As shown in fig. 1, the dissolution test aid may include an absorbent portion 110 and an adjustment portion 120. The absorption portion 110 may refer to a component for simulating the absorption and collection of the drug in the digestive tract (e.g., stomach and intestinal tract) of the body, and reflects the absorption of the drug by simulating the absorption process in the digestive tract of the body. The absorption profile may include the amount or concentration value of the substance that absorbs the drug at different time points or/and at different pH environments. For example, a drug is dissolved in the dissolution liquid of the dissolution cup 130, and 30min after the start of dissolution, the absorption process of the drug in the small intestine is simulated by the absorption part 110, and at this time, the amount or concentration of the drug in the dissolution liquid of the absorption part 110 is measured to reflect the absorption of the drug. The absorption part 110 may include an absorption unit 111-1, and the absorption unit 111-1 refers to a member for simulating absorption of a medicine into a digestive tract (e.g., stomach, intestinal tract) of a body.

The regulating part 120 may be a member for simulating the environment corresponding to the medicine in different parts of the body. The respective environments in different parts of the body may include the pH of the body fluid, the amount of body fluid or components in the body fluid, or any combination thereof. For example, the pH of gastric juice in the stomach of a human is normally in the range of 1.3-1.8, the pH of diluted gastric juice after a meal can rise to 3.5, and the pH of small intestinal juice in the small intestine of a human is about 8-9. In this embodiment, the pH value of the dissolution liquid in the adjustment part 120 can be changed to simulate the pH value of each part of the body. In some embodiments, the adjusting part 120 may include an adjusting unit 125, and the adjusting unit 125 may be used to adjust the pH and/or volume of the dissolution liquid introduced into the adjusting part 120. The adjusting part 120 may be a container having a rectangular parallelepiped shape, a cylindrical shape, a conical shape or an irregular shape, and the material of the adjusting part 120 may be amorphous inorganic non-metallic material (glass), Polyethylene (PE), polypropylene (PP), Polystyrene (PS), polyvinyl chloride (PVC), acrylonitrile-butadiene-styrene copolymer (ABS), polyethylene terephthalate (PET) or polybutylene terephthalate (PBT).

The absorption part 110 is communicated with the dissolution cup 130 of the drug dissolution device through a first pipe 112, the first pipe 112 is provided with a first liquid inlet pump 113, wherein the first liquid inlet pump 113 is configured to introduce the dissolution liquid in the dissolution cup 130 into the absorption part 110 through the first pipe 112, and the introduced dissolution liquid flows into the absorption unit 111-1. In some embodiments, the first pipe 112 can be a flexible pipe or a rigid pipe, and the first pipe 112 can be a metal pipe (e.g., steel pipe, stainless steel pipe, etc.), a plastic-clad metal pipe (e.g., aluminum-plastic composite pipe), a plastic pipe (e.g., PVC pipe, UPVC pipe, PE pipe, etc.). In some embodiments, the first liquid inlet pump 113 may include at least any one of a peristaltic pump, a centrifugal pump, a circulation pump, and a jet pump.

In some embodiments, the manner of connection between the first tube 112 and the dissolution cup 130, the absorption section 110 is not limited to the manner shown in FIG. 1 in which both ends of the first tube 112 extend directly into the dissolution cup 130 and the absorption section 110, respectively. In some embodiments, the top of the dissolution cup 130, the top of the absorption portion 110, may be provided with a corresponding top plate (not shown) having an aperture formed therein for the first tube 112 to extend into, where a corresponding fastener may be provided to secure the first tube 112. In some embodiments, the fixing member may be a bolt having a through hole, and the end of the first tube 112 may pass through the through hole of the bolt and extend into the dissolution cup 130 or the absorption part 110, and the height of the end of the first tube 112 may be adjusted by screwing the bolt. In some embodiments, the fixing member may also be a rubber plug having a through hole, and the height of the end of the fixing member can be adjusted by applying an external force to the first conduit 112. In some embodiments, the fastener may also optionally include a clamp (e.g., a clamp) that is secured to the top plate, and the height of the end of the first conduit 112 can be adjusted by controlling the tightness of the clamp.

In some embodiments, the connection manner between the first pipe 112 and the dissolution cup 130 and the absorption part 110 is not limited to the insertion from top to bottom along the vertical direction as shown in fig. 1, one end of the first pipe 112 may be connected to the side wall of the dissolution cup 120 or the absorption part 110 for communication, the other end may be inserted into the dissolution cup 120 or the absorption part 110 from top to bottom along the vertical direction, or the two ends of the first pipe 112 are respectively connected to the side walls of the dissolution cup 120 and the absorption part 110 for communication. Wherein the end of the first conduit 112 in the dissolution cup 120 is below the liquid level, and the end of the first conduit 112 in the absorption part 110 may be above the liquid level or below the liquid level.

The adjustment section 120 is in communication with the dissolution cup 130 via a second pipe 121 and a third pipe 122. The second tube 121 and the third tube 122 are two tubes independent of each other, and both ends of the second tube 121 are located in the adjustment part 120 and the dissolution cup 130, respectively, and both ends of the third tube 122 are located in the adjustment part 120 and the dissolution cup 130, respectively. Further, the second pipe 121 is provided with a second liquid inlet pump 123, and the third pipe 122 is provided with a first liquid outlet pump 124. Wherein the second inlet pump 123 is configured to introduce the dissolution liquid in the dissolution cup 130 into the adjustment part 120 through the second pipe 121, the adjustment unit 125 is configured to adjust the pH and/or volume of the introduced dissolution liquid, and the first outlet pump 124 is configured to introduce the adjusted dissolution liquid back to the dissolution cup 130. It should be noted that the types of the second pipe 121 and the third pipe 122 may refer to the first pipe 112, the connection manner between the second pipe 121 and the adjusting part 120 and the dissolution cup 130, and the connection manner between the third pipe 122 and the adjusting part 120 and the dissolution cup 130 may refer to the connection manner between the first pipe 112 and the dissolution cup 130 and the absorption part 110, and the types of the second liquid inlet pump 123 and the first liquid outlet pump 124 may refer to the first liquid inlet pump 113, which will not be described in detail herein. In addition, the end of the second pipe 121 located at the dissolution cup 130 is located below the liquid surface in the dissolution cup 130, and the end of the second pipe 121 located at the adjustment part 120 may be located above the liquid surface in the adjustment part 120 or below the liquid surface in the adjustment part 120. The third conduit 122 is located at the end of the dissolution cup 130 either above the liquid level in the dissolution cup 130 or below the liquid level in the dissolution cup 130, and the third conduit 122 is located at the end of the adjustment section 120 below the liquid level in the adjustment section 120.

In some embodiments, the first conduit 112 and the first liquid feed pump 113 may be included in the absorption unit 111-1. The absorption unit 111-1 is a member for simulating the absorption of drugs by the digestive tract (e.g. stomach and intestinal tract) of the body, and in this embodiment, the first pipe 112 and the first liquid inlet pump 113 introduce the dissolution liquid containing drugs in the dissolution cup 130 into the absorption portion and flow into the absorption unit, and in the process, the first pipe 112 and the first liquid inlet pump 113 play a role in simulating the absorption of drugs by the digestive tract.

In some embodiments, the first conduit 112 may also have a filter portion disposed thereon, which may include at least one filter head or screen. A filter head or screen may be mounted to the end of the first conduit 112 in the dissolution cup 130 and the screen may be mounted in the conduit of the first conduit 112. In some embodiments, the size of the filter head or/and filter mesh (e.g., mesh size, wire diameter, pore size) can be selected based on the molecular weight of the drug and experimental requirements. The filter head or/and the filter screen of the filter screen can be made of stainless steel, nickel, copper, polypropylene, acrylonitrile-butadiene-styrene copolymer, polytetrafluoroethylene, polyether sulfone, mixed cellulose ester, nylon, polyvinylidene fluoride and the like, and in addition, the filter screen can be selected according to the pH value of the dissolution liquid, for example, the filter screen with higher corrosion resistance is selected when the dissolution liquid becomes acidic or alkaline. In some embodiments, the filter portion may also include a Caco-2 monolayer of cell membranes or an animal (e.g., rat) isolated intestinal tube. The filter unit can prevent the undissolved drug in the dissolution cup 130 from entering the absorption unit 110, thereby improving the accuracy of the detection result.

In some embodiments, the second and

third pipes

121 and 122 may further have a filter portion disposed thereon. A filter head or screen may be installed at the end of the second conduit 121 in the dissolution cup 130 and the end of the third conduit 122 in the adjustment section 120, and a screen may be installed in the conduits of the second conduit 121 and the third conduit 122. For a detailed description of the filter portion in this paragraph, please refer to the filter portion in the first pipe 112, which is not described in detail herein.

In some embodiments, absorption unit 111-1 includes a liquid trap capable of collecting the leachate flowing in from first conduit 112. The liquid trap may refer to a container for collecting the leachate, which may comprise one or more containers (not shown in fig. 1), for example, the number of containers may be one, two, three, four or more. When the liquid collector comprises a plurality of containers, the dissolution liquid can be collected according to different time points. In some embodiments, the plurality of containers may be arranged in a single row, in multiple rows, or irregularly. The single-row placement means that a plurality of containers are placed in a horizontal row or a vertical row in sequence. Multiple rows of containers are defined as multiple rows (e.g., two, three, etc.) of containers, and the number of containers in each row may be the same or different when the containers are arranged in multiple rows. The irregular arrangement means that the containers are not arranged in a longitudinal row or a transverse row, but arranged in a circumferential direction or in an irregular shape. In some embodiments, the number of first conduits 112 may be one or more. When the number of the first pipes 112 is one and the number of the vessels in the liquid trap is one, the first liquid pump 113 can introduce the dissolution liquid in the dissolution cup 130 into a specific one of the vessels. When the number of the first tubes 112 is one and the number of the containers in the liquid trap is plural, the positions of the containers may be manually or mechanically adjusted so that the ends of the first tubes 112 are positioned directly above the respective containers. When the number of the first tubes 112 is plural, the plural first tubes 112 may be located just above the plural containers so as to collect the plural sample solutions at the same time.

In some embodiments, the liquid trap is connected to an analysis device capable of analyzing the eluate collected by the liquid trap. The analytical equipment may include any one or more of a balance, an acidimeter, a conductivity meter, an automatic positioning titrator, a permanent stop titrator, a karl fischer moisture meter, a high performance liquid chromatograph, a visible spectrophotometer, an ultraviolet-visible spectrophotometer, an atomic absorption spectrophotometer, a colorimeter, a gas chromatograph, a polarimeter, and a sugar meter. The liquid collector and the analysis equipment can be connected through corresponding pipelines, for example, the liquid collector and the high performance liquid chromatograph are connected through a pipeline, the acidimeter, the conductivity meter, the saccharimeter and the like can be directly arranged in the liquid collector, and the balance can be directly arranged below the liquid collector.

In some embodiments, the adjusting unit 125 may include at least one pH adjusting material storage bin communicated with the inside of the adjusting part 120 through an adjusting pipe 125-1 for adding an adjusting material to the dissolution liquid flowing through the adjusting part 120 to adjust the pH of the dissolution liquid. The pH adjusting material storage means a container for containing the adjusting material, and the pH adjusting material storage may include one or more, and different pH adjusting material storage may contain the same or different adjusting materials. The adjusting substance may be used to adjust the pH of the dissolution liquid in the adjusting part 120, and may include any one of gas, liquid, and solid. The pH adjusting substance storage compartment is not limited to being located outside the adjusting part 120 as shown in fig. 1, but may be located inside the adjusting part 120. As an example, the adjustment part 120 is a closed structure or a top plate is disposed on the top of the adjustment part 120, and the pH adjusting material storage bin may be fixed to the top of the adjustment part 120 by any one of welding, riveting, and bonding.

In some embodiments, different pH adjusting substance reservoirs may contain different adjusting substances for adding different adjusting substances to the dissolution liquid flowing through the adjustment section at different time periods. The adjusting part 120 is used to simulate the pH change of each part in the body, the circulation time of the drug in the whole device can be regarded as the action time in the body, and the part of the drug in the body changes with the time, that is, the environment of the drug changes, and specifically can be embodied in the pH value and/or the adjusting substance in the body fluid. The pH adjusting material storage bin can be used to adjust the pH value of the dissolution liquid in the adjusting portion 120, and can change the adjusting material contained in the dissolution liquid in the adjusting portion 120, so as to further improve the simulation degree of the dissolution and absorption of the drug. As an example, the change of the pH value of the drug in the human digestive tract with time is known, and the pH value and the adjusting substance in the adjusting portion 120 are adjusted for the change of the pH value at these known time periods. As to the connection manner between the adjusting pipe 125-1 and the adjusting part 120 and the material of the adjusting pipe 125-1, reference is made to the detailed description between the first pipe 112 and the dissolving cup 130 or the absorbing part 110, which will not be described in detail herein.

In some embodiments, the conditioning substance includes at least one of: carbon dioxide gas, argon, nitrogen, helium, water, carbonate buffer, phosphate buffer, citrate buffer, acetate buffer, tris buffer, barbiturate buffer, phthalate buffer, ammonia-ammonia buffer, and boric acid buffer. It should be noted that the adjusting substance in the present specification is not limited to the above-mentioned examples, and the adjusting substance functions to adjust the pH of the dissolution liquid, but any substance that can achieve the function may be the adjusting substance, and the selection of the adjusting substance may be determined by a specific experiment, and is not further limited herein.

In some embodiments, a flow pump 125-2 is disposed on conditioning duct 125-1 and is configured to limit the amount and/or flow rate of conditioning substance added. The flow pump 125-2 can be set to a corresponding flow rate, which can be calculated by the flow rate and the inner diameter of the regulating tube 125-1. As an example, a target pH of the drug at a corresponding time point in the device may be set according to the time and pH change of the drug in the body, and the actual pH of the solution in the adjustment portion 120 may be measured, so that the addition of the corresponding adjustment substance may be calculated according to the target pH and the actual pH, and then a corresponding volume or a corresponding amount of the adjustment substance may be delivered. In some embodiments, the flow pump 125-2 can be a gas flow pump or a liquid flow pump, and the type of the flow pump 125-2 can be selected according to the form of the regulating substance, for example, if the regulating substance in the pH regulating substance storage is carbon dioxide gas, then a gas flow pump is selected; and if the regulating substance in the pH regulating substance storage bin is carbonate solution, a liquid flow pump is selected. In some embodiments, a pump and solenoid valve may be provided in the regulated line 125-1 for delivering a flow of regulated fluid. The pump herein may include at least any one of a peristaltic pump, a centrifugal pump, a circulation pump, and a jet pump.

In some embodiments, the conditioning portion 120 further comprises a dissolution medium supplement unit 126, the dissolution medium supplement unit 126 communicating with the interior of the conditioning portion 120 through a supplement conduit 126-1 for adding dissolution medium for dissolving the drug to the dissolution liquid flowing through the conditioning portion 120. The connection of the dissolution medium supplement unit 126 with the interior of the adjustment part 120 via the supplement pipe 126-1 is not described in detail herein, referring to the connection of the pH-adjusting material storage tank with the interior of the adjustment part 120 via the adjustment pipe 125-1. In some embodiments, the dissolution medium may include, but is not limited to, water, hydrochloric acid solution, acetate buffer, or phosphate buffer, or any combination thereof. In some embodiments, the pH of the dissolution medium may be selected to simulate body fluids in various parts of the body, for example, simulated gastric fluid may be selected to be a hydrochloric acid solution having a pH of 1.2. As another example, a phosphate buffer with a pH of 6.0 may be selected for the simulated intestinal fluid. In some embodiments, the dissolution media may also include components in body fluids of the human body, such as, for example, any one or more of inorganic salts, enzymes, monosaccharides, amino acids, fatty acids, glycerol, water-soluble vitamins, fat-soluble vitamins, and the like.

In some embodiments, the make-up line 126-1 is provided with a flow pump 126-2 configured to limit the amount and/or flow rate of the dissolution medium added for control. For the flow pump 126-2, reference is made to the detailed description of the flow pump 125-2, which is not detailed herein.

In some embodiments, the apparatus further comprises at least one pH detection unit disposed inside the adjustment part 120 and/or inside the dissolution cup 130, configured to detect the pH value of the dissolution liquid. In some embodiments, the pH detecting unit 150 may be disposed in the adjusting part 120, and the pH detecting unit 150 is configured to detect and monitor the pH value of the dissolution liquid in the adjusting part 120, and according to the detected actual pH value and the target pH value of the corresponding time period, the adjusting substance in the adjusting unit 125(pH buffer storage bin) is conveyed into the adjusting part 120 through the adjusting pipeline 125-1 and the flow pump 125-2, so that the pH value of the dissolution liquid in the adjusting part 120 is adjusted to the target pH value. In some embodiments, the pH detecting unit 140 may be disposed in the dissolution cup 130, in which case the pH detecting unit 140 may be configured to detect the pH value of the dissolution liquid in the dissolution cup 130, and according to the detected actual pH value and the target pH value of the corresponding time period, the adjusting substance in the adjusting unit 125(pH buffer storage bin) is conveyed to the adjusting portion 120 through the adjusting pipe 125-1 and the flow pump 125-2 to adjust the pH value of the dissolution liquid in the adjusting portion 120, since the adjusting portion 120 is communicated with the dissolution cup 130 through the second pipe 121 and the third pipe 122, the adjusting portion 120 and the dissolution liquid in the dissolution cup 130 may form a dynamic circulation system, and the pH value of the dissolution liquid in the dissolution cup 130 may be indirectly adjusted by adjusting the pH value of the dissolution liquid in the adjusting portion 120. In some embodiments, the adjusting part 120 and the dissolution cup 130 may be respectively provided with corresponding pH detecting units so as to keep the pH values of the dissolution liquid in the adjusting part 120 and the dissolution cup 130 consistent, and the specific adjusting process may refer to the description that the pH detecting units are provided in the adjusting part 120 or the dissolution cup 130. In some embodiments, the pH detecting unit may be disposed on the second pipe 121 or/and the third pipe 122. In some embodiments, the pH detecting unit may not be disposed in the adjusting part 120 or the dissolution cup 130, and when the dissolution liquid of the adjusting part 120 or/and the dissolution cup 130 needs to be detected, the pH detecting unit is disposed in the adjusting part 120 or/and the dissolution cup 130, and the specific adjusting process may refer to the description that the pH detecting unit is disposed in the adjusting part 120 or the dissolution cup 130.

In some embodiments, the apparatus may further comprise a control device in communication with the pump within the apparatus via an electrical and/or wireless connection, configured to control the pump to adjust the amount and/or flow rate of the solution passing through the pump. In some embodiments, the control device may include a switch controller, a pressure controller, a flow controller, or the like, or combinations thereof. In some embodiments, the electrical connection may include an electrical direct connection, an electrical indirect connection, an electrical inductive connection, an electrical coupling connection, and the like, or any combination thereof. The wireless connection includes a Local Area Network (LAN), a Wide Area Network (WAN), bluetooth, wireless personal area network, Near Field Communication (NFC), and the like, or any combination thereof.

In some embodiments, the apparatus may further include a thermostatic unit (not shown in fig. 1) for preheating and/or maintaining the temperature of the absorption part 110 and/or the adjustment part 120. Since the adjustment part 120 and the dissolution cup 130 are communicated with each other through the second pipe 121 and the third pipe 122, heating the dissolution liquid in the adjustment part 120 is equivalent to heating or keeping the temperature of the dissolution liquid in the entire apparatus to simulate the temperature of the digestive juice in the body, for example, 37.5 ℃. The heating manner of the constant temperature unit to the absorption part 110 and/or the adjustment part 120 may be, but is not limited to, electromagnetic heating, infrared heating, resistance heating, or the like, or any combination thereof.

The method for determining the dissolution rate of the medicine can comprise a rotating basket method, a paddle method, a small cup method, a flow cell method, a reciprocating barrel method, a cylinder method, a paddle-disk method, a reciprocating frame method and the like, and different determination methods can be selected according to the types of preparations, and the determination equipment corresponding to the different determination methods is different. In the examples provided herein, the drug may be dissolved in the dissolution cup 130, which is used to simulate the process of dissolution of the drug inside the body. The particular dissolution method may depend on the particular assay device, for example, when a rotary basket method is used, the drug is placed in a rotary basket that rotates in a dissolution cup containing the dissolution fluid to effect dissolution of the drug. For example, in the paddle method, the drug is placed on the bottom of an elution cup containing the dissolution liquid, and the drug is dissolved by stirring with a paddle. When the medicine is dissolved out, the dissolution liquid containing the medicine in the dissolution cup 130 is conveyed to the adjusting part 120 through the second pipeline 121 and the second liquid inlet pump 123, the dissolution medium in the adjusting part 120 is used for simulating the environment (such as pH) of different parts in the body, the process is used for simulating the environment of the medicine at different parts in the body, the environment of different parts in the body is different, the solubility of the medicine is changed, and the pH adjusting material storage bin is used for adjusting the environment at the adjusting part 120 in the process. After the drug-containing eluate is processed in the adjustment unit 120, the drug-containing eluate is transported to the elution cup 130 through the third pipe 122 and the first liquid outlet pump 124, and at the same time, the drug-containing eluate is transported to the absorption unit 110 through the first pipe 112 and the first liquid inlet pump 113, and the drug-containing eluate transported to the absorption unit 110 is a portion to be absorbed by the living body. In some embodiments, the volume of the dissolution fluid in the dissolution cup 130 can be controlled, in particular by adjusting the flow rates of the second inlet pump 123 and the first outlet pump 124. For example, when the second influent pump 123 and the first effluent pump 124 are at the same flow rate, the amount of the eluate in the dissolution cup is kept within a certain range. For example, when the amount of the dissolution liquid in the dissolution cup 130 is reduced, the flow rate of the first liquid outlet pump 124 may be reduced while the flow rate of the second liquid inlet pump 123 is kept constant. For another example, when the amount of the dissolution liquid in the dissolution cup 130 is increased, the flow rate of the first liquid outlet pump 124 may be increased while the flow rate of the second liquid inlet pump 123 is kept constant.

It should be noted that the above description is merely for convenience of description and is not intended to limit the present application. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the principles of the present application. For example, in some embodiments, the pH adjusting substance storage bin may be disposed above the adjustment part 120 or inside the adjustment part 120. In some embodiments, the adjusting unit 125 may also be provided with more pH adjusting substance storage bins, and the adjusting substances in the pH adjusting substance storage bins may be the same or different.

Figure 2 is a schematic diagram of a dissolution test aid employing membrane filtration to simulate absorption, according to some embodiments of the present application. As shown in FIG. 2, the apparatus further comprises a fourth pipe 114, the fourth pipe 114 connects the absorption unit 111-2 and the dissolution cup 130, and at least a part of the dissolution liquid flowing into the absorption unit 111-2 flows out and then flows back into the dissolution cup 130 through the fourth pipe 114. In this embodiment, the absorption unit 111-2 has a different structure from the absorption unit 111-1 in the embodiment corresponding to fig. 1.

In some embodiments, the absorption unit 111-2 comprises a membrane filter configured to collect dissolved drug and/or a portion of the eluate in the eluate flowing from the first conduit 112. In some embodiments, the membrane filter may comprise an ultrafiltration device. During ultrafiltration, the drug-containing eluate flows across the surface of the ultrafiltration membrane of the membrane filter under pressure, and the solvent (water) and small solutes in the eluate, which are smaller than the membrane pores, permeate the ultrafiltration membrane to become a filtrate, which flows into the collector 216 through the conduit 214. The undissolved particles in the dissolution liquid larger than the membrane pores are retained and flow back into the dissolution cup through the fourth pipe 114.

In some embodiments, the membrane material of the membrane filter may include, but is not limited to, cellulose and its derivatives, polycarbonate, polyvinyl chloride, polyvinylidene fluoride, polysulfone, polyacrylonitrile, polyamide, polysulfone amide, sulfonated polysulfone, cross-linked polyvinyl alcohol, modified acrylic acid polymers. The membrane material and the pore size of the filter membrane can be selected according to the type of the medicine and the molecular weight of the medicine.

In some embodiments, the membrane filter is in communication with an eluent supply reservoir 215 via an eluent inlet conduit 213. An eluent inlet pump 211 is arranged on the eluent inlet pipeline 213, the eluent inlet pump 211 is used for conveying eluent in the eluent supply bin 215 to the membrane filter, and the ultrafiltration efficiency can be adjusted by adjusting the liquid inlet speed of the liquid inlet pump 211 and the liquid outlet speed of the liquid outlet pump 212.

In some embodiments, the membrane filter is in communication with an eluent recovery bin 216 through an eluent outlet line 214. An eluent outlet pump 212 is arranged on the eluent inlet pipeline 214, the eluent outlet pump 212 is used for conveying eluent containing medicines to the eluent recovery bin 216, and the medicines entering the eluent recovery bin 216 simulate the medicines absorbed by human bodies.

Please refer to the detailed description of the first pipeline 112 about the fourth pipeline 114, the eluent inlet pipeline 213 and the eluent outlet pipeline 214. For eluent pump 211 and eluent pump 212, please refer to the detailed description of first liquid pump 113.

It should be noted that the above description is merely for convenience of description and is not intended to limit the present application. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the principles of the present application. For example, in some embodiments, the specific number of eluent supply bins 215 and eluent recovery bins 216 is not limited to the one shown in fig. 2, and multiple eluent supply bins 215 and eluent recovery bins 216 may be provided in the apparatus, respectively. In some embodiments, a plurality of eluent supply bins 215 can each contain a different eluent.

Figure 3 is a schematic diagram of a dissolution test aid employing extraction mode simulated absorption according to some embodiments of the present application. The auxiliary device provided by this embodiment of the present application has substantially the same structure as the auxiliary device provided by the embodiment shown in fig. 2, the most significant difference being the absorption pattern. As shown in fig. 3, the absorption unit 111-3 includes a liquid-liquid extractor configured to collect the drug dissolved in the dissolution liquid flowing in from the first pipe 112, and the dissolution cup 130 communicates with the inside of the liquid-liquid extractor through the first pipe 112. The liquid-liquid extractor is communicated with the dissolution cup 130 through a fourth pipeline 114, a second liquid pump 115 is arranged on the fourth pipeline 114, and the second liquid pump 115 is configured to guide the dissolution liquid after the extraction of the drug back to the dissolution cup 130 through the fourth pipeline 114. The liquid-liquid extractor is a container for holding the organic phase solvent. The material of the liquid-liquid extractor may include, but is not limited to, amorphous inorganic non-metallic material (glass), Polyethylene (PE), polypropylene (PP), Polystyrene (PS), polyvinyl chloride (PVC), acrylonitrile-butadiene-styrene (ABS), polyethylene terephthalate (PET), or polybutylene terephthalate (PBT). The organic phase solvent in the liquid-liquid extractor may include, but is not limited to, benzene, toluene, chloroform, carbon tetrachloride, hexane, cyclohexane, diethyl ether, ketones, esters, thioethers, sulfoxides, crown ethers.

In some embodiments, a stirring device may also be provided in the liquid-liquid extractor. The stirring device may include an anchor stirrer, a paddle stirrer, a propeller stirrer, a turbine stirrer, a ribbon stirrer, or the like, or any combination thereof. The drug-containing solution in the dissolution cup 130 flows into the liquid-liquid extractor through the first pipe 112, and the organic phase solvent and the drug-containing solution are stirred in the liquid-liquid extractor by the stirring device, so that the drug molecules and the organic phase solvent are fully mixed, and the extraction efficiency is improved. . In some embodiments, the organic phase solvent may be located in an upper layer or a lower layer. For example, when dichloromethane, chloroform, carbon tetrachloride or dichloroethane is used as the organic phase solvent, the organic phase solvent is located in the lower layer.

In some embodiments, the liquid-liquid extractor is communicated with the extraction liquid supply bin 315 through an extraction liquid inlet pipeline 313, an extraction liquid inlet pump 311 is disposed on the extraction liquid inlet pipeline 313, and the extraction liquid inlet pump 311 may be used to supply the organic phase solvent to the liquid-liquid extractor. The liquid-liquid extractor is communicated with an extraction liquid receiving bin 316 through an extraction liquid outlet pipeline 314, an extraction liquid outlet pump 312 is arranged on the extraction liquid outlet pipeline 314, and the extraction liquid outlet pump 312 can be used for conveying the organic phase containing the medicine to the extraction liquid recovery bin 316 for collection.

In some embodiments, extract feed pump 311 and/or extract drain pump 312 may be moved up and down relative to the liquid-liquid extractor by a lift mechanism. In some embodiments, the lifting device may include, but is not limited to, a lifting bar, a lifting column, a lifting platform. The lifting device can be realized by a cylinder, a hydraulic cylinder, a gear, a transmission chain, a conveying belt, a screw rod and the like. For example, the liquid-liquid extraction pump 311 and/or the liquid-liquid extraction pump 312 are fixed by an air cylinder or a hydraulic cylinder, and the height of the liquid-liquid extraction pump 311 and/or the liquid-liquid extraction pump 312 is adjusted by adjusting the stroke of a piston rod of the air cylinder or the hydraulic cylinder. For another example, the lead screw is fixed to the extract inlet pump 311 and/or the extract outlet pump 312, and the height of the extract inlet pump 311 and/or the extract outlet pump 312 is adjusted by rotating the lead screw nut. For example, the height of the extract feed pump 311 and/or extract discharge pump 312 may be adjusted by changing the length of the drive chain or belt in cooperation with the pulleys.

In some embodiments, where the organic phase solvent has a density less than water (e.g., ethyl acetate), the organic phase solvent is in the upper layer and the aqueous phase solvent is in the lower layer. For example, when the drug-containing eluate in the dissolution cup 130 enters the liquid-liquid extractor, the boundary line between the organic phase and the aqueous phase moves upward due to the gradual addition of the eluate, and at this time, the height of the extraction liquid outlet pump 312 may be adjusted so that the extraction liquid inlet pipe 313 and/or the extraction liquid outlet pipe 314 is/are located above the boundary between the organic phase solvent and the aqueous phase, and the extraction liquid outlet pump 312 and the extraction liquid outlet pipe 314 are used to transport the drug-containing organic phase located in the upper layer to the extraction liquid recovery bin 316 for collection. In some embodiments, where the organic phase solvent has a density greater than water (e.g., carbon tetrachloride), the organic phase solvent is located in the lower layer and the aqueous phase solvent is located in the upper layer. For example, the drug-containing eluate in the dissolution cup 130 enters the liquid-liquid extractor, the height of the port of the extraction liquid outlet pump 312 is adjusted so that the port of the extraction liquid outlet pipe 314 is located at the bottom of the liquid-liquid extractor, and the organic phase containing the drug and located in the lower layer is transported to the extraction liquid recovery bin 316 by the extraction liquid outlet pump 312 and the extraction liquid outlet pipe 314 for collection. The amount of organic phase solvent added to the liquid-liquid extractor can affect the efficiency of the drug extraction. For example, when the amount of the organic phase solvent added is large, the extraction efficiency of the drug is correspondingly high. For example, when the amount of the organic phase solvent added is small, the extraction efficiency of the drug is low. The amount of organic phase added in the liquid-liquid extractor affects the two-phase boundary line of the organic phase solvent and the aqueous phase solvent. For example, when the density of the organic phase solvent is lower than that of water, the boundary line between the organic phase and the aqueous phase moves downward as the volume of the dissolution liquid flowing into the liquid-liquid extractor decreases, and when the organic phase containing the drug is collected, the height of the extraction liquid pump 312 may be adjusted so that the extraction liquid pump 312 is located above the boundary line between the two phases. As another example, when the density of the organic phase solvent is greater than that of water, the height of the extraction effluent pump 312 may be adjusted such that the extraction effluent pump 312 is at the bottom of the liquid-liquid extractor.

For the above-mentioned extract liquid inlet pipe 313 and extract liquid outlet pipe 314, please refer to the detailed description of the first pipe 112. For the liquid inlet pump 311 and the liquid outlet pump 312, please refer to the first liquid inlet pump 113.

It should be noted that the above description is merely for convenience of description and is not intended to limit the present application. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the principles of the present application. For example, in some embodiments, the specific number of the extract supply bin 315 and the extract recovery bin 316 is not limited to one shown in fig. 3, and a plurality of extract supply bins 315 and extract recovery bins 316 may be provided in the apparatus, respectively. In some embodiments, the plurality of extraction liquid supply chambers 315 may contain different organic solvents.

Figure 4 is another schematic diagram of a dissolution test aid according to some embodiments of the present application. As shown in fig. 4, the dissolution test aid may include an absorbent portion 410 and an adjustment portion 420. In some embodiments, the absorption part 410 and the adjustment part 420 are in a container, and a partition is provided inside the container to separate the absorption part 410 and the adjustment part 420. In some embodiments, the absorbing portion 410 and the regulating portion 420 may be two separate portions. Wherein the absorption part 410 comprises a flow dividing valve 414 and an absorption unit 413, the adjusting part 420 comprises an adjusting unit 422, and the adjusting unit 422 is configured to adjust the pH of the dissolution liquid flowing into the adjusting part. The absorption part 410 is communicated with the dissolution cup 430 of the drug dissolution apparatus through a first pipe 411, and the absorption part 410 is communicated with the adjustment part 420 through a second pipe 421. The first conduit 411 is provided with a liquid inlet pump 412, and the liquid inlet pump 412 is used for conveying the dissolution liquid in the dissolution cup 430 through the first conduit 411. The flow dividing valve 414 is disposed in the first pipe 411, the first flow dividing pipe 415 and the second pipe 421 are connected to the flow dividing valve 414, respectively, the flow dividing valve 414 divides the dissolution liquid from the dissolution cup 430 by the liquid feed pump 412, a part of the dissolution liquid flows into the absorption unit 413 through the first flow dividing pipe 415, and the other part of the dissolution liquid flows into the adjustment section 420 through the second pipe 421.

In some embodiments, absorption unit 413 comprises a liquid trap, which is in communication with first conduit 411 via first diversion conduit 415, and which is capable of collecting a portion of the eluate diverted from diverter valve 414. The liquid trap is connected to an analysis device which is capable of analyzing the eluate collected by the liquid trap.

In some embodiments, the adjusting unit 422 comprises at least one pH adjusting substance storage bin communicated with the inside of the adjusting part 420 through an adjusting pipe 422-1 for adding an adjusting substance to the dissolution liquid flowing through the adjusting part 420 to adjust the pH of the dissolution liquid. In some embodiments, different pH adjusting substance reservoirs contain different adjusting substances for adding different adjusting substances to the dissolution liquid flowing through the adjusting section at different time periods. In some embodiments, the conditioning substance includes at least one of: carbon dioxide gas, argon, nitrogen, helium, water, carbonate buffer, phosphate buffer, citrate buffer, acetate buffer, tris buffer, barbiturate buffer, phthalate buffer, ammonia-ammonium-halide buffer, and boric acid buffer.

In some embodiments, a flow pump 422-2 is disposed on the conditioning conduit 422-1 and is configured to limit the amount and/or flow rate of conditioning substance added. In some embodiments, the regulating part 420 further comprises an elution medium supplementing unit 423, wherein the elution medium supplementing unit 423 is communicated with the inside of the regulating part 420 through a supplementing pipeline 423-1 and is used for adding elution medium for dissolving medicine into the elution liquid flowing through the regulating part 420. In some embodiments, the supplemental line 423-1 is provided with a flow pump 423-2 configured to limit the amount and/or flow rate of dissolution medium added for control.

In some embodiments, the apparatus further comprises at least one pH detection unit disposed inside the conditioning section 420 and/or inside the dissolution cup 430, e.g., a pH detection unit 450 disposed at the conditioning section 420, a pH detection unit 440 disposed in the dissolution cup 430, the pH detection unit configured to detect the pH value of the dissolution fluid.

In some embodiments, the apparatus further comprises a thermostatic unit for preheating and/or maintaining the temperature of the absorption part 410 and/or the conditioning part 420. The thermostatic unit is used to preheat and/or keep warm the absorption section 410, conditioning section 420 and/or dissolution cup 430. The absorbing part 410, the adjusting part 420, the units in each component, the pump, the material of the pipes, the connection mode between each pipe and the component, and the like in this embodiment can refer to the embodiment shown in fig. 1, and will not be described in detail here.

In the examples provided herein, the drug may be dissolved in the dissolution cup 430, which is used to simulate the process of dissolution of the drug inside the body. After the drug is dissolved out, the dissolution liquid containing the drug in the dissolution cup 430 is respectively conveyed to the absorption part 410 and the adjustment part 420 through the first pipeline 411, the liquid inlet pump 412 and the flow dividing valve 414, the dissolution medium in the adjustment part 420 is used for simulating the environment (such as pH) of different parts in the body, the process is used for simulating the environment of the drug at different parts in the body, the environment of different parts in the body is different, the solubility of the drug is also changed, and the pH adjusting material storage bin is used for adjusting the environment at the adjustment part 420 in the process. After the drug-containing eluate is processed in the adjustment unit 420, it is transported to the elution cup 430 through the third pipe 431 and the outlet pump 424, and at this time, the drug-containing eluate is transported to the absorption unit 410 through the first diversion pipe 415, and the drug-containing eluate transported to the absorption unit 410 is a portion to be absorbed by the living body, and in this process, since the amount of body fluid in the living body is dynamically balanced, the eluate transported to the absorption unit 410 needs to be supplemented by the elution medium supplementing unit 423 or the adjustment unit 422, so that the eluate of the entire apparatus is maintained within a certain range. In some embodiments, the volume of dissolution fluid in the dissolution cup 430 may be controlled, in particular by adjusting the flow rates of the inlet pump 412 and the outlet pump 424. For example, the amount of dissolution fluid in the dissolution cup 430 may be maintained within a certain range when the flow rates of the inlet pump 412 and the outlet pump 424 are the same. For example, when the amount of the dissolution liquid in the dissolution cup 430 is reduced, the flow rate of the liquid pump 424 may be reduced while the flow rate of the liquid pump 412 is kept constant. For another example, the amount of eluate in the elution cup 430 may be increased by increasing the flow rate of the effluent pump 424 while maintaining the flow rate of the influent pump 412.

It should be noted that the above description is merely for convenience of description and is not intended to limit the present application. It will be understood by those skilled in the art that various changes in form and details may be made therein without departing from the principles of the present application. For example, in some embodiments, the absorbing portion 410 and the regulating portion 420 may be two portions independent of each other. For another example, the pH adjusting substance storage bin may be provided outside the adjustment part 420. As another example, in some embodiments, the adjusting unit 422 may also be provided with more pH adjusting substance storage bins, and the adjusting substances in the pH adjusting substance storage bins may be the same or different.

Based on the embodiment shown in fig. 4, the present application provides another embodiment which is substantially the same as the embodiment provided in the present application, the most significant difference is the difference of the absorption unit, in this embodiment, the apparatus further comprises a fourth pipeline which is communicated with the absorption unit and the dissolution cup, and after at least part of the dissolution liquid flowing into the absorption unit flows out, the dissolution liquid flows back into the dissolution cup 430 through the fourth pipeline. In this embodiment, the absorption unit comprises a membrane filter configured to collect dissolved drug and/or part of the eluate flowing from the first shunt conduit 415 into the eluate. The membrane filter is communicated with the eluent supply bin through an eluent inlet pipeline. An eluent inlet pump is arranged on the eluent inlet pipeline and used for conveying eluent in the eluent supply bin to the membrane filter, and the eluent can elute the medicine dissolved out of the membrane filter. The membrane filter is communicated with the eluent recovery bin through an eluent outlet pipeline. An eluent liquid outlet pump is arranged on the eluent liquid inlet pipeline and used for conveying the eluent containing the medicine to an eluent recovery bin, and the medicine entering the eluent recovery bin simulates the medicine absorbed by a human body. The specific contents in this embodiment can refer to the description in fig. 2 and its corresponding embodiment.

Based on the above embodiments, the present application provides another embodiment which is substantially the same as the above embodiments, and the most difference is the absorption manner. In this embodiment, the absorption unit comprises a liquid-liquid extractor configured to collect drug dissolved in the dissolution liquid flowing in from the first conduit, the dissolution cup communicating with the interior of the liquid-liquid extractor through the first conduit, the diverter valve and the first diverter conduit. The liquid-liquid extractor is communicated with the dissolution cup through a fourth pipeline, a second liquid outlet pump is arranged on the fourth pipeline, and the second liquid outlet pump is configured to guide the dissolution liquid after the medicine extraction to the dissolution cup through the fourth pipeline. In some embodiments, the liquid-liquid extractor is communicated with the extraction liquid supply chamber through an extraction liquid inlet pipeline, and an extraction liquid inlet pump is disposed on the extraction liquid inlet pipeline, and the extraction liquid inlet pump can be used for supplying the organic phase solvent to the liquid-liquid extractor. The liquid-liquid extractor is communicated with the extraction liquid supply bin through an extraction liquid outlet pipeline, an extraction liquid outlet pump is arranged on the extraction liquid outlet pipeline, and the extraction liquid outlet pump can be used for conveying the organic phase containing the medicine to the extraction liquid recovery bin for collection. The details of this embodiment can be referred to the description of fig. 3 and its corresponding embodiment.

Having thus described the basic concept, it will be apparent to those skilled in the art that the foregoing detailed disclosure is to be considered merely illustrative and not restrictive of the broad application. Various modifications, improvements and adaptations to the present application may occur to those skilled in the art, although not explicitly described herein. Such modifications, improvements and adaptations are proposed in the present application and thus fall within the spirit and scope of the exemplary embodiments of the present application.

Also, this application uses specific language to describe embodiments of the application. Reference throughout this specification to "one embodiment," "an embodiment," and/or "some embodiments" means that a particular feature, structure, or characteristic described in connection with at least one embodiment of the present application is included in at least one embodiment of the present application. Therefore, it is emphasized and should be appreciated that two or more references to "an embodiment" or "one embodiment" or "an alternative embodiment" in various places throughout this specification are not necessarily all referring to the same embodiment. Furthermore, some features, structures, or characteristics of one or more embodiments of the present application may be combined as appropriate.

Similarly, it should be noted that in the preceding description of embodiments of the application, various features are sometimes grouped together in a single embodiment, figure, or description thereof for the purpose of streamlining the disclosure aiding in the understanding of one or more of the embodiments. This method of disclosure, however, is not intended to require more features than are expressly recited in the claims. Indeed, the embodiments may be characterized as having less than all of the features of a single embodiment disclosed above.

The entire contents of each patent, patent application publication, and other material cited in this application, such as articles, books, specifications, publications, documents, and the like, are hereby incorporated by reference into this application. Except where the application is filed in a manner inconsistent or contrary to the present disclosure, and except where the claim is filed in its broadest scope (whether present or later appended to the application) as well. It is noted that the descriptions, definitions and/or use of terms in this application shall control if they are inconsistent or contrary to the statements and/or uses of the present application in the material attached to this application.

Finally, it should be understood that the embodiments described herein are merely illustrative of the principles of the embodiments of the present application. Other variations are also possible within the scope of the present application. Thus, by way of example, and not limitation, alternative configurations of the embodiments of the present application can be viewed as being consistent with the teachings of the present application. Accordingly, the embodiments of the present application are not limited to only those embodiments explicitly described and depicted herein.

Claims

1. A dissolution test aid, the device comprising: the device comprises an absorption part and an adjusting part, wherein the absorption part comprises an absorption unit, and the adjusting part comprises an adjusting unit;

the absorption part is communicated with a dissolving-out cup of the medicine dissolving-out device through a first pipeline;

the adjusting part is communicated with the dissolving-out cup through a second pipeline and a third pipeline;

a first liquid inlet pump, a second liquid inlet pump and a first liquid outlet pump are respectively arranged on the first pipeline, the second pipeline and the third pipeline;

wherein the first liquid inlet pump is configured to guide the dissolution liquid in the dissolution cup into the absorption part through the first pipeline, and the guided dissolution liquid flows into the absorption unit;

the second liquid inlet pump is configured to guide the dissolution liquid in the dissolution cup into the adjusting part through the second pipeline, the adjusting unit is configured to adjust the pH and/or the volume of the introduced dissolution liquid, and the first liquid outlet pump is configured to guide the adjusted dissolution liquid back to the dissolution cup.

2. The apparatus of claim 1, wherein the absorption unit includes a liquid trap capable of collecting the leachate flowing from the first conduit.

3. The apparatus according to claim 2, wherein the liquid trap is connected to an analysis device capable of analyzing the leachate collected by the liquid trap.

4. The apparatus of claim 1, further comprising a fourth conduit communicating between said absorption unit and said dissolution cup, wherein at least a portion of the dissolution fluid flowing into said absorption unit flows out and then flows back into said dissolution cup through said fourth conduit.

5. The device according to claim 4, wherein the absorption unit comprises a membrane filter configured to collect dissolved drug and/or part of the eluate in the eluate flowing in from the first conduit.

6. The apparatus of claim 4, wherein the absorption unit comprises a liquid-liquid extractor configured to collect dissolved drug in the dissolution liquid flowing in from the first conduit;

and a second liquid outlet pump is arranged on the fourth pipeline and is configured to guide the dissolved liquid after the extraction of the medicine back to the dissolution cup through the fourth pipeline.

7. The apparatus according to any one of claims 1 to 6, wherein the adjusting unit comprises at least one pH adjusting substance storage bin communicated with the inside of the adjusting part through an adjusting pipe for adding an adjusting substance to the dissolution liquid flowing through the adjusting part to adjust the pH of the dissolution liquid.

8. The apparatus according to any one of claims 1 to 7, wherein different pH adjusting substance storage bins contain different adjusting substances for adding different adjusting substances to the dissolution liquid flowing through the adjusting part at different time periods.

9. The device according to any one of claims 7 or 8, wherein the conditioning substance comprises at least one of: carbon dioxide gas, argon, nitrogen, helium, water, carbonate buffer, phosphate buffer, citrate buffer, acetate buffer, tris buffer, barbiturate buffer, phthalate buffer, ammonia-ammonium halide buffer, and boric acid buffer.

10. Device according to any of claims 7-9, characterized in that the regulating conduit is provided with a flow pump configured to define the amount and/or flow rate of the regulating substance added.

11. The device according to any one of claims 1 to 10, wherein the regulating part further comprises an elution medium replenishing unit which is communicated with the inside of the regulating part through a replenishing pipe and is used for adding an elution medium for dissolving the drug into the elution liquid flowing through the regulating part.

12. The apparatus according to claim 11, wherein a flow pump is provided on the supplementary conduit configured to control defining the amount and/or flow rate of the dissolution medium to be fed.

13. The apparatus according to any one of claims 1 to 12, further comprising at least one pH detection unit disposed inside the conditioning section and/or inside the dissolution cup or on the third conduit, configured to detect the pH value of the dissolution fluid.

14. The apparatus of any one of claims 1-13, further comprising a control device in communication with the pump within the apparatus via an electrical and/or wireless connection configured to control the pump to adjust the amount and/or flow rate of the solution passing through the pump.

15. The device according to any one of claims 1 to 14, further comprising a thermostatic unit for preheating and/or keeping warm the absorption section and/or the conditioning section.

16. A dissolution test aid, the device comprising: the absorption part comprises a shunt valve and an absorption unit, and the adjusting part comprises an adjusting unit;

the absorption part is communicated with a dissolution cup of the medicine dissolution device through a first pipeline and is communicated with the regulation part through a second pipeline;

the adjusting part is communicated with the dissolving-out cup through a third pipeline;

a liquid inlet pump and a liquid outlet pump are respectively arranged on the first pipeline and the third pipeline;

wherein the flow dividing valve is arranged on the first pipeline and divides the dissolution liquid from the dissolution cup through a liquid inlet pump, one part of the dissolution liquid flows into the absorption unit, and the other part of the dissolution liquid flows into the adjusting part;

the adjusting unit of the adjusting part is arranged to adjust the pH of the dissolution liquid flowing into the adjusting part, and the liquid outlet pump is arranged to guide the pH-adjusted dissolution liquid back to the dissolution cup.

17. The apparatus of claim 16, wherein the absorption unit includes a liquid trap capable of collecting a portion of the eluate diverted from the diverter valve.

18. The apparatus of claim 17, wherein the liquid trap is connected to an analysis device capable of analyzing the leachate collected by the liquid trap.

19. The apparatus according to any one of claims 16 to 18, wherein the adjusting unit comprises at least one pH adjusting substance storage bin communicating with the inside of the adjusting part through an adjusting pipe for adding an adjusting substance to the dissolution liquid flowing through the adjusting part to adjust the pH of the dissolution liquid.

20. An apparatus according to any one of claims 16 to 19, wherein different pH modifying substance reservoirs contain different modifying substances for adding different modifying substances to the dissolution fluid flowing through the modifying section at different time periods

21. The device of any one of claims 19 or 20, wherein the conditioning substance comprises at least one of: carbon dioxide gas, argon, nitrogen, helium, water, carbonate buffer, phosphate buffer, citrate buffer, acetate buffer, tris buffer, barbiturate buffer, phthalate buffer, ammonia-ammonium halide buffer, and boric acid buffer.

22. Device according to any of claims 19-21, characterized in that the regulating conduit is provided with a flow pump configured to define the amount and/or flow rate of the regulating substance to be fed.

23. The apparatus according to any one of claims 16-22, wherein the conditioning section further comprises a dissolution medium replenishment unit communicating with the interior of the conditioning section via a replenishment conduit for adding dissolution medium to the dissolution fluid flowing through the conditioning section.

24. The apparatus according to claim 23, wherein a flow pump is provided on the supplementary conduit configured to control defining the amount and/or flow rate of the dissolution medium to be fed.

25. The apparatus according to any one of claims 16-24, further comprising at least one pH detection unit disposed inside the conditioning section and/or inside the dissolution cup configured to detect the pH of the dissolution fluid.

26. The apparatus of any one of claims 16-25, further comprising a control device in communication with the pump within the apparatus via an electrical and/or wireless connection configured to control the pump to adjust the amount and/or flow rate of the solution through the pump.

27. The apparatus according to any one of claims 16 to 26, further comprising a thermostatic unit for preheating and/or keeping warm the absorption section and/or the conditioning section;

for preheating and/or keeping warm the absorption chamber, the conditioning section and/or the dissolution cup.