Dissolution test system

Abstract

The utility model discloses a dissolution test system, which is used for testing the dissolution condition of a medicament in a solvent or the combination condition of the medicament and a solute in the solvent under the oscillation state of a shaking table, and comprises a dissolution bottle for accommodating the solvent; the connecting rod is fixedly connected with the dissolution bottle and comprises a bottom end, and the bottom end extends into the dissolution bottle in the axial direction of the dissolution bottle; the mesh basket is connected with the bottom end of the connecting rod, is suspended in the dissolution bottle and is used for accommodating medicaments; and the dissolution bottle is placed on the shaking table. The in-vivo release of the medicament can be more accurately simulated, the adhesion phenomenon of the medicament and the bottom of the dissolution bottle is reduced, the nonuniform dispersion of the medicament is avoided, the accuracy and the reliability of the in-vitro experiment result of the medicament are improved, and the uniformity and the repeatability of the experiment are improved.

Description

Technical Field

[0001] The utility model belongs to the field of pharmaceutical testing, and relates to a dissolution test system. Background Art

[0002] Oral solid pharmaceuticals play an important role in the research and production of drugs, and their quality is directly related to the safety and effectiveness of drugs. In order to ensure the good release and absorption of oral solid pharmaceuticals in vivo, in vitro dissolution experiments have become a key link in evaluating the quality of drugs.

[0003] In in vitro dissolution experiments, the shaker method is considered to have a high degree of simulation because it can simulate the natural movement mode of the human gastrointestinal tract. Compared with other devices, the shaker method can more truly reflect the behavior of drugs in the gastrointestinal tract. Therefore, drug regulatory agencies recommend using the shaker method for in vitro evaluation of some drugs.

[0004] The existing experimental techniques usually directly put solid pharmaceuticals into dissolution bottles and then place them in a shaker for in vitro dissolution experiments. This experimental device is simple and easy to operate, and can meet the needs of in vitro dissolution experimental research of oral solid pharmaceuticals to a certain extent. However, when the solid pharmaceuticals are heavy, there are certain problems with the shaker method. The solid pharmaceuticals are prone to quickly sink to the bottom after entering the conical flask, resulting in adhesion between the outer shell of the solid pharmaceuticals and the bottom of the dissolution bottle. The degree of adhesion is random, thus affecting the parallelism of test results.

[0005] The existing technology conducts dissolution tests by directly placing pharmaceuticals in dissolution bottles and placing them in a shaker. The problems of how to more accurately simulate the release of drugs in vivo, improve the accuracy and reliability of in vitro experimental results of pharmaceuticals, and improve the uniformity and repeatability of experiments have not been effectively solved. Summary of the Utility Model

[0006] The purpose of the utility model is to solve the problems of how to more accurately simulate the release of drugs in vivo, improve the accuracy and reliability of in vitro experimental results of pharmaceuticals (such as dissolution tests, the combination of pharmaceuticals and in vivo elements), and improve the uniformity and repeatability of experiments.

[0007] The utility model provides a dissolution test system for testing the dissolution of pharmaceuticals in a solvent or the combination with solutes in a solvent under the oscillating state of a shaker, including:

[0008] A dissolution bottle for containing a solvent;

[0009] A connecting rod fixedly connected to the dissolution bottle, including a bottom end that extends into the dissolution bottle along the axial direction of the dissolution bottle;

[0010] A wire basket connected to the bottom end of the connecting rod and suspended in the dissolution bottle for containing pharmaceuticals;

[0011] A shaker, with the dissolution bottle placed on the shaker.

[0012] Adopting the above technical solution can more accurately simulate the release of the medicament in the body, reduce the adhesion of the medicament to the bottom of the dissolution bottle, avoid uneven dispersion of the medicament, improve the accuracy and reliability of the in vitro experimental results of the medicament, and improve the uniformity and repeatability of the experiment.

[0013] According to another specific embodiment of the present invention, the connecting rod includes:

[0014] A rod body, including an external thread extending along the axial direction of the rod body;

[0015] A fixing member, fixedly connected to the dissolution bottle, sleeved on the outer periphery of the rod body, and threadedly connected to the rod body;

[0016] The rod body and the fixing member move relatively along the axial direction through screw drive, so as to adjust the length of the rod body extending into the dissolution bottle.

[0017] According to another specific embodiment of the present invention, the dissolution test system further includes:

[0018] A height fixing device, one end of which is fixedly connected to the bottom of the wire basket, and the other end abuts against the bottom of the dissolution bottle, for fixing the distance between the bottom of the wire basket and the bottom of the dissolution bottle.

[0019] According to another specific embodiment of the present invention, the axial length of the height fixing device is adjustable, and the adjustment range of the length is 2 mm - 50 mm.

[0020] According to another specific embodiment of the present invention, it includes height fixing devices with different axial length specifications, and the axial lengths of the height fixing devices with different axial length specifications are 2 mm - 50 mm.

[0021] According to another specific embodiment of the present invention, the bottom end of the connecting rod is detachably connected to the wire basket.

[0022] According to another specific embodiment of the present invention, the bottom end of the connecting rod is snap-connected to the wire basket.

[0023] According to another specific embodiment of the present invention, the connecting rod and the wire basket are integrally formed.

[0024] According to another specific embodiment of the present invention, the mesh number of the wire basket is 10 mesh to 200 mesh.

[0025] According to another specific embodiment of the present invention, the material of the connecting rod is stainless steel or plastic.

[0026] According to another specific embodiment of the present utility model, the connecting rod is made of polytetrafluoroethylene (PTFE) or perfluoroalkoxy polymer (PFA). Description of the Drawings

[0027] Figure 1 Schematic diagram of the partial cross-sectional structure of the dissolution test system in the embodiment of the present utility model Figure 1 ;

[0028] Figure 2 Schematic diagram of the partial cross-sectional structure of the dissolution test system in the embodiment of the present utility model Figure 2 ;

[0029] Figure 3 Schematic diagram of the semi-cross-sectional structure of the wire basket in the embodiment of the present utility model;

[0030] Figure 4 Schematic diagram of the structure of the dissolution test system in the embodiment of the present utility model Figure 1 .

[0031] Symbol Explanation

[0032] 1 Connecting rod, 11 Fixing piece, 12 Rod body, 2 Wire basket, 3 Constant height device, 4 Shaker, 5 Dissolution bottle, 10 Dissolution test system. Specific Embodiments

[0033] The following specific embodiments illustrate the implementation manners of the present utility model. Those skilled in the art can easily understand other advantages and effects of the present utility model from the content disclosed in this specification. Although the description of the present utility model will be introduced in conjunction with preferred embodiments, this does not mean that the features of this utility model are limited to this implementation manner. On the contrary, the purpose of introducing the utility model in conjunction with the implementation manner is to cover other alternatives or modifications that may be extended based on the claims of the present utility model. To provide a deep understanding of the present utility model, many specific details will be included in the following description. The present utility model can also be implemented without these details. In addition, to avoid confusion or obscuring the key points of the present utility model, some specific details will be omitted in the description. It should be noted that, without conflict, the embodiments in the present utility model and the features in the embodiments can be combined with each other.

[0034] It should be noted that in this specification, similar reference numerals and letters denote similar items in the following drawings. Therefore, once an item is defined in one drawing, it does not need to be further defined and explained in subsequent drawings.

[0035] To make the purpose, technical solutions and advantages of the present utility model clearer, the implementation manners of the present utility model will be further described in detail below with reference to the drawings.

[0036] The shaking table method is applied to the dissolution test field because it can simulate the natural movement mode of the human gastrointestinal tract. When the solid medicament is relatively heavy, there are certain problems with the shaking table method. After the solid medicament enters the conical flask, it is likely to quickly sink to the bottom, resulting in the adhesion of the outer shell of the solid medicament to the bottom of the dissolution flask. The degree of adhesion is random, thus affecting the parallelism and accuracy of the test results. The inventor thought of designing a basket structure suspended in the dissolution flask in the shaking table, placing the medicament in the basket, and then testing the dissolution of the medicament in the solvent under the oscillating state of the shaking table, which can avoid the adhesion phenomenon of the medicament that occurs when directly placing the medicament in the dissolution flask and using the shaking table method, affecting the accuracy of the dissolution test.

[0037] Based on the above principle, on the first aspect, the present invention provides a dissolution test system 10, as Figure 4 shown, for testing the dissolution of the medicament in the solvent or the binding of the medicament with the solute in the solvent under the oscillating state of the shaking table, including:

[0038] A dissolution flask 5 for containing the solvent;

[0039] A connecting rod 1 fixedly connected to the dissolution flask 5, including a bottom end that extends axially into the dissolution flask 5 along the axis of the dissolution flask 5;

[0040] A basket 2 connected to the bottom end of the connecting rod 1, suspended in the dissolution flask for containing the medicament;

[0041] A shaking table 4 with the dissolution flask 5 placed on the shaking table 4.

[0042] Adopting the above technical solution can more accurately simulate the release of the medicament in the body, reduce the adhesion phenomenon between the medicament and the bottom of the dissolution flask 5, avoid uneven dispersion of the medicament, improve the accuracy and reliability of the in vitro experimental results of the medicament, and improve the uniformity and repeatability of the experiment. The medicament in the basket 2 of the present invention is mainly dissolved fully by the oscillation of the shaking table 4 without applying additional power (such as electric power) for stirring or rotating, which more accurately simulates the scenario of the medicament release in the human body, and avoids the uneven flow state of the solvent liquid caused by the high-speed circular rotation of the basket 2 during the dissolution test, and also avoids the shear force generated during rotation from affecting the dissolution or binding behavior of some medicaments.

[0043] Specifically, the connecting rod 1 is suspended in the dissolution flask 5. One end of the connecting rod 1 is fixedly connected to the bottle mouth of the dissolution flask 5, and the other end is fixedly connected to the basket 2. The medicament to be tested is placed inside the basket 2. The basket 2 is fixedly connected to the bottom of the connecting rod 1. The basket 2 is suspended in the dissolution flask 5, and the solvent in the dissolution flask 5 submerges the medicament to be tested. Among them, the medicament includes solid preparations such as capsules and tablets, and semi-solid preparations.

[0044] Further, the dissolution bottle 5 is an Erlenmeyer flask or a conical flask. There may be one or more dissolution bottles 5, and the dissolution bottles 5 are placed in the shaker 4 for dissolution testing.

[0045] According to another specific embodiment of the present invention, as Figure 1 shown and Figure 4 , the connecting rod 1 includes: a rod body 12, including an external thread extending along the axial direction of the rod body 12; a fixing member 11; fixedly connected to the dissolution bottle 5, the fixing member 11 is sleeved on the outer periphery of the rod body 12 and is threadedly connected to the rod body 12, and the rod body 12 and the fixing member 11 move relative to each other along the axial direction through screw drive, so as to adjust the length of the rod body 12 extending into the dissolution bottle 5. By adopting the above technical solution, the length of the rod body 12 extending into the dissolution bottle 5 can be adjusted, which is convenient for adapting to different dissolution test experimental conditions.

[0046] In this embodiment, referring to Figure 1 and Figure 4 , the rod body 12 rotates relative to the fixing member 11 to adjust the length of the rod body 12 extending into the dissolution bottle 5. In addition, the rod body 12 and the fixing member 11 do not rotate relative to the dissolution bottle 5, that is, the rod body 12 is fixed to the dissolution bottle 5 through the fixing member 11. During the dissolution test, the rod body 12 and the fixing member 11 do not rotate, and the oscillation of the shaker 4 promotes the dissolution of the medicament in the solvent.

[0047] Specifically, continue to refer to Figure 1 , there is a through hole passing through the fixing member 11 in the fixing member 11, the through hole is an internal thread hole, and one end of the rod body 12 connected to the fixing member 11 has an external thread extending along the axis of the rod body 12. By rotating the fixing member 11, screw drive is performed to change the relative position of the rod body 12 and the fixing member 11, so that the rod body 12 and the fixing member 11 move relative to each other in the axial direction of the rod body 12, and further adjust the length of the rod body 12 extending into the dissolution bottle. The rod body 12 is fixedly connected to the wire basket 2.

[0048] Further, the length of the rod body 12 can be matched according to the sizes of different dissolution bottles. For example, the length range of the rod body is 5 - 30 cm. Preferably, the length of the rod body 12 is 12 - 15 cm. By changing the relative position of the rod body 12 and the fixing member 11, the length of the rod body 12 can be changed between 12 - 15 cm.

[0049] According to another specific embodiment of the present invention, as Figure 2 and Figure 4As shown in the figure, the dissolution test system further includes: a height fixer 3, one end of which is fixedly connected to the bottom of the basket 2, and the other end abuts against the bottom of the dissolution bottle 5, for fixing the distance between the bottom of the basket 2 and the bottom of the dissolution bottle 5. The connecting rod 1 includes a rod body 12 and a fixing member 11. One end of the basket 2 is fixedly connected to the rod body 12 of the connecting rod 1, and the other end of the basket 2 is fixedly connected to the height fixer 3. The length of the rod body 12 extending into the dissolution bottle 5 can be adjusted by screw drive. The height fixer 3 is fixedly connected to the basket 2. By rotating the fixing member 11, the length of the rod body 12 extending into the dissolution bottle 5 is changed. The height fixer 3 abuts against the bottom of the dissolution bottle 5, so that the position of the basket 2 in the dissolution bottle 5 is fixed, that is, the distance between the bottom of the basket 2 and the bottom of the dissolution bottle 5 is equal. By adopting the above technical solution, the depth of each dose of medicine immersed in the solvent in the dissolution test experiment is equal, ensuring the consistency of the dissolution test.

[0050] According to another specific embodiment of the present invention, the axial length of the height fixer 3 is adjustable, and the adjustment range of the length is 2 mm - 50 mm. For example, when there are multiple dissolution bottles 5 and corresponding baskets 2 and connecting rods 1 for parallel experiments, the multiple height fixers 3 are adjusted to the same height for dissolution testing. For another example, when testing the influence of different immersion depths on the dissolution test, the height fixers 3 are respectively adjusted to different heights for dissolution testing. By adopting the above technical solution, the axial length of the height fixer 3 is adjustable, and it can match and adapt to different dissolution test experimental conditions.

[0051] According to another specific embodiment of the present invention, it includes height fixers 3 with different axial length specifications, and the axial lengths of the height fixers 3 with different axial length specifications are 2 mm - 50 mm. For example, multiple height fixers 3 with different axial lengths can be used in the dissolution test to match different requirements of dissolution test conditions. By adopting the above technical solution, it can adapt to different dissolution test experimental conditions.

[0052] In the above embodiments, the height fixer 3 can also be multiple identical height fixers 3, which are convenient for cooperating with multiple identical dissolution bottles, connecting rods 1 and baskets 2 for parallel experiments.

[0053] According to another specific embodiment of the present invention, the bottom end of the connecting rod 1 is detachably connected to the basket 2. By adopting the above technical solution, it is convenient for cleaning and maintenance and for replacing damaged parts.

[0054] According to another specific embodiment of the present invention, the bottom end of the connecting rod 1 is connected to the basket 2 by a buckle. Specifically, it is connected by the buckle at the bottom of the connecting rod 1 and / or the buckle at the top of the basket 2. By adopting the above technical solution, the basket 2 can be quickly disassembled and installed, which can reduce the experimental preparation time and improve the experimental efficiency.

[0055] Optionally, there is a sealing ring between the connecting rod 1 and the wire basket 2 to increase the tightness and stability of the connection.

[0056] In the above embodiments, openings are provided at the top and / or bottom and / or side of the wire basket 2 to facilitate the placement of the medicament.

[0057] According to another specific embodiment of the present invention, the connecting rod 1 and the wire basket 2 are integrally formed. With the above technical solution, the dissolution test device has a stable structure, and the integrally formed design makes the structures of the connecting rod 1 and the wire basket 2 more firm and not easily deformed, so as to maintain stable performance during long-term use or repeated experiments.

[0058] Figure 3 FIG. 10 is a schematic half-sectional structure view of the wire basket 2 in the embodiment of the present invention. In this embodiment, the wire basket 2 is a cylinder. When the wire basket 2 is a cylinder, the diameter range of the wire basket 2 is 1-100 mm, the diameter range of the wire basket 2 is preferably 6 mm-35 mm, the length range of the wire basket 2 in the axial direction is 1-100 mm, and the length range of the wire basket 2 in the axial direction is preferably 6 mm-45 mm. The shape of the wire basket 2 is a cylinder or a prism. The shape of the wire basket 2 can also be other shapes such as a sphere or a polyhedron. The material of the wire basket 2 is stainless steel, titanium alloy or nickel alloy.

[0059] According to another specific embodiment of the present invention, the mesh number of the wire basket 2 is 2 to 200 meshes. Further, the mesh number of the wire basket 2 is preferably 5-50 meshes. Still further, the mesh number of the wire basket 2 is preferably 10-20 meshes. With the above technical solution, it is suitable for dissolution test experiments under different conditions.

[0060] According to another specific embodiment of the present invention, the material of the connecting rod 1 is stainless steel or plastic, especially polytetrafluoroethylene (PTFE) or perfluoroalkoxy polymer (PFA). With the above technical solution, the connecting rod 1 has corrosion resistance and is not easily dissolved, and has stability in use.

[0061] In a second aspect, the present invention also discloses a dissolution test method, which uses the above dissolution test system, including:

[0062] Place the solvent in the dissolution bottle 5;

[0063] Place the medicament in the wire basket 2;

[0064] Insert the connecting rod 1 connected to the wire basket 2 into the dissolution bottle 5 so that the medicament is immersed in the solvent;

[0065] Place the dissolution bottle 5 on the shaker 4, and dissolve the medicament in the solvent under the oscillating state of the shaker to test the dissolution of the medicament.

[0066] By adopting the above technical solution, it is possible to more accurately simulate the release of the medicament in the body, improve the accuracy and reliability of the in vitro experimental results of the medicament, and improve the uniformity and repeatability of the experiment.

[0067] Specifically, the solvent is placed in the dissolution bottle 5, and the dissolution bottle 5 is placed in the shaker 4 and preheated under the conditions of a preset temperature and a preset rotation speed. Among them, the preset temperature and the preset rotation speed are set according to conditions such as the medicament, the type of solvent, and the measured value. For example, in some specific embodiments, the preset temperature is 37 °C and the preset rotation speed is 100 r / min. The preset temperature and the preset rotation speed can be adjusted according to actual needs. The medicament is loaded into the basket 2, the basket 2 is fixedly connected to the connecting rod 1, the connecting rod 1 extends into the dissolution bottle 5, the length of the adjusting rod 12 extending into the dissolution bottle 5 is adjusted, and the connecting rod 1 is fixed to the mouth of the dissolution bottle 5. The medicament is wetted in the solvent, and the dissolution bottle 5 is placed on the shaker 4 for dissolution testing at the preset temperature and the preset rotation speed. Since the basket 2 is reticular, the contact area between the basket 2 and the medicament is small, and when the medicament quickly disintegrates, it slowly falls into the dissolution bottle, avoiding the adhesion of the outer shell of the medicament to the bottom of the dissolution bottle 5. The release or reaction of the drug in the human body is simulated under the oscillating state of the shaker 4.

[0068] In a third aspect, the present invention also discloses a method for testing the phosphate binding capacity, which is used to test the phosphate binding capacity of the medicament in the solvent. The solute in the solvent is phosphate, and the solvent is a phosphate buffer solution. The testing method includes:

[0069] The solvent is filled in the dissolution bottle, and the concentration of the solute in the solvent is concentration C1;

[0070] The medicament is placed in the basket 2, and the connecting rod 1 connected to the basket 2 extends into the dissolution bottle 5 to wet the medicament in the solvent;

[0071] The dissolution bottle is placed on the shaker 4, and the combination of the medicament and phosphate in the solvent is carried out under the oscillating state of the shaker 4; the concentration C2 of the solute in the solvent is detected;

[0072] According to the difference between the concentration C1 and the concentration C2, the phosphate binding capacity of the medicament in the solvent is calculated.

[0073] By adopting the above technical solution, it is possible to simulate the phosphate binding capacity after the medicament is fully disintegrated in the body, improve the accuracy and reliability of the in vitro experimental results of the medicament, and improve the uniformity and repeatability of the experiment.

[0074] In the above testing method, the phosphate includes potassium dihydrogen phosphate and / or sodium dihydrogen phosphate.

[0075] The following introduces a more specific embodiment for testing the phosphate binding capacity of the medicament in the solvent.

[0076] Examples 1 - 6 used the dissolution test system of the present utility model. Among them, the wire basket 2 had a mesh size of 10 meshes, and the medicament was a capsule. Examples 7 - 12 used the dissolution test system of the present utility model. Among them, the wire basket 2 had a mesh size of 20 meshes, and the medicament was a capsule. In Comparative Examples 1 - 6, the medicament was directly added to the dissolution bottle 5 and placed on the shaker 4. Among them, the medicament was a capsule. In Control Groups 1 - 6, the medicament was directly added to the dissolution bottle 5 and placed on the shaker 4. Among them, the medicament was the capsule content.

[0077] Reagents and materials: Purified water, potassium dihydrogen phosphate, sodium chloride, N,N-(2-hydroxyethyl)-2-aminoethanesulfonic acid (BES), sodium hydroxide, 36% - 38% hydrochloric acid, 10.0 mg / mL phosphorus standard solution.

[0078] Instruments and equipment: Inductively coupled plasma optical emission spectrometer (ICP-OES), water bath shaker, pH meter, thermometer, tachometer, centrifuge, electronic balance, ultrapure water instrument, the dissolution test system of the present utility model.

[0079] ICP-OES instrument parameters: Plasma gas flow rate: 15 L / min; Auxiliary gas flow rate: 0.5 L / min; Nebulizer flow rate: 0.85 L / min; RF power: 1400 W; Observation distance: 15.0; Plasma observation: Radial; Sample flow rate: 1.50 mL / min; Wavelength: 213.617 nm; Delay time: 40 s; Number of repetitions: 3 times.

[0080] Preparation of solutions:

[0081] 6% hydrochloric acid solution (w / v): Transfer 80 mL of 36% - 38% hydrochloric acid to a 500 mL volumetric flask, and make up the volume to the mark with pure water and mix well.

[0082] 1N sodium hydroxide solution: Weigh approximately 4.0 g (accurate to 0.01 g) of sodium hydroxide into a 100 mL beaker, dissolve it with pure water and transfer it to a 100 mL volumetric flask. Make up the volume to the mark with pure water and mix well.

[0083] pH 2.0 buffer solution: Weigh approximately 96.0 g (accurate to 0.01 g) of BES and 20.88 g (accurate to 0.01 g) of NaCl into a suitable container, dissolve them in 4500 mL of pure water. Adjust the pH to 2.00 ± 0.03 using 6% HCl solution and / or 1N NaOH solution.

[0084] Diluent: Transfer 200 mL of pH 2.0 buffer solution and 1800 mL of pure water into a 2 L bottle and mix well.

[0085] Solvent (15 mM KH₂PO₄ solution with pH 2.0): Weigh approximately 8.16 g (accurate to 0.01 g) of KH₂PO₄ into a suitable container, dissolve it in 4000 mL of pH 2.0 buffer solution, sonicate for about 30 minutes until the KH₂PO₄ is completely dissolved, and mix well. Adjust the pH to 2.00 ± 0.03 using 6% HCl solution and / or 1N NaOH solution.

[0086] Linear solution: Dilute the 10.0 mg / mL phosphorus standard solution with the diluent to prepare a series of linear solutions of 10 - 50 μg / mL.

[0087] Blank: Transfer 200 mL of pH 2.0 buffer solution and 1800 mL of pure water into a 2 L bottle and mix well.

[0088] Standard solution 1: Dilute the 10.0 mg / mL phosphorus standard solution with the diluent to 30 μg / mL.

[0089] Standard solution 2: Dilute the 10.0 mg / mL phosphorus standard solution with the diluent to 30 μg / mL.

[0090] Control solution (1.5 mM KH₂PO₄ solution): Transfer 2.0 mL of the solvent into a 20 mL volumetric flask, make up the volume with pure water and mix well. Prepare two aliquots in parallel. It is used to ensure the stability of the ICP - OES instrument.

[0091] Operating steps for Examples 1 - 6: Accurately transfer 300 mL of the solvent into a 500 mL dissolution flask 5, place it in a water bath shaker 4, and preheat for half an hour at 37 °C and 100 revolutions per minute. Put 1 capsule into a 10 - mesh basket, fix the connection between the basket and the connecting rod, place it into the dissolution flask, fix the connecting rod 1 to the dissolution flask 5, and place it in the water bath shaker 4 for dissolution testing at 37 °C and 100 revolutions per minute for 24 hours, that is, incubate for 24 hours. After the dissolution test,

[0092] Take out the dissolution flask 5, gently shake to mix the solution, pour out two aliquots of about 10 mL of the suspension for centrifugation, filtration, and collect the remaining filtrate. Transfer 2.0 mL of the filtrate into a 20 mL volumetric flask, make up the volume with pure water and mix well.

[0093] Operating steps of Examples 7 - 12: Accurately transfer 300 mL of solvent into a 500 mL dissolution bottle 5, place it in a water bath shaker 4, and preheat for half an hour at 37°C and 100 revolutions per minute. Put 1 capsule into a 20 - mesh basket, fixedly connect the basket 2 and the connecting rod 1, place them into the dissolution bottle 5, fixedly connect the connecting rod 1 with the dissolution bottle 5, place it in the water bath shaker 4, and conduct dissolution test for 24 hours at 37°C and 100 revolutions per minute, that is, cultivate for 24 hours. After the dissolution test is completed, take out the dissolution bottle, gently shake to mix the solution, pour out 2 portions of about 10 mL of suspension for centrifugation respectively, filter and collect the remaining filtrate. Transfer 2.0 mL of the filtrate into a 20 mL volumetric flask, make up the volume with pure water and mix well.

[0094] Operating steps of Comparative Examples 1 - 6: Accurately transfer 300 mL of solvent into a 500 mL dissolution bottle, place it in a water bath shaker 4, and preheat for half an hour at 37°C and 100 revolutions per minute. Put 1 capsule into the dissolution bottle, tightly plug the bottle stopper, place it in the water bath shaker 4, and conduct dissolution test for 24 hours at 37°C and 100 revolutions per minute, that is, cultivate for 24 hours. After the dissolution test is completed, take out the dissolution bottle 5, gently shake to mix the solution, pour out 2 portions of about 10 mL of suspension for centrifugation respectively, filter and collect the remaining filtrate. Transfer 2.0 mL of the filtrate into a 20 mL volumetric flask, make up the volume with pure water and mix well.

[0095] Operating steps of Control Groups 1 - 6: Accurately transfer 300 mL of solvent into a 500 mL dissolution bottle 5, place it in a water bath shaker 4, and preheat for half an hour at 37°C and 100 revolutions per minute. Take 1 capsule, open the capsule shell, put the capsule content into the dissolution bottle 5, tightly plug the bottle stopper, place it in the water bath shaker, and conduct dissolution test for 24 hours at 37°C and 100 revolutions per minute, that is, cultivate for 24 hours. After the dissolution test is completed, take out the dissolution bottle 5, gently shake to mix the solution, pour out 2 portions of about 10 mL of suspension for centrifugation respectively, filter and collect the remaining filtrate. Transfer 2.0 mL of the filtrate into a 20 mL volumetric flask, make up the volume with pure water and mix well.

[0096] Establish a phosphorus standard curve, and the phosphorus concentrations in Examples 1 - 12, Comparative Examples 1 - 6 and Control Groups 1 - 6 are measured according to the phosphorus standard curve.

[0097]

[0098] Among them, W is the phosphate - binding capacity (mg / g), calculated based on the labeled amount. C0 is the concentration of phosphorus in the dilution solvent (μg / mL), C spl is the concentration of phosphorus in the sample solution (μg / mL), Mw(P) is the relative atomic mass of phosphorus, Mw(PO4 3- ) is the relative molecular mass of phosphate radical. LC is the labeled amount, 700 mg.

[0099] The experimental results are shown in Table 1.

[0100] Table 1 Phosphate binding capacity and relative standard deviation of the examples, comparative examples and control group

[0101]

[0102] As can be seen from Table 1, in Examples 1-6, the dissolution test system of the present utility model was adopted, wherein the wire basket 2 was 10 mesh, and the average value of the phosphate binding capacity of the medicament was measured to be 267 mg / g, and the relative standard deviation was 1.1%. In Examples 7-12, the dissolution test system of the present utility model was adopted, wherein the wire basket was 20 mesh, and the average value of the phosphate binding capacity of the medicament was measured to be 271 mg / g, and the relative standard deviation was 0.9%. The relative standard deviation (Relative Standard Deviation, RSD) was less than 2%. It shows that the dissolution test system of the present utility model has good parallelism and stable test results for the phosphate binding capacity.

[0103] In Comparative Examples 1-6, the medicament was directly added to the dissolution flask and placed on the shaker 4 for testing. The average value of the phosphate binding capacity of the medicament was measured to be 247 mg / g, and the relative standard deviation was 7.6%. It shows that the consistency of directly adding the medicament to the dissolution flask and placing it on the shaker 4 for testing is poor. And the phosphate binding capacity of Comparative Example 6 was 209 mg / g, which was much lower than the average phosphate binding capacity of the control group, 264 mg / g. It shows that the capsules in the comparative examples were not evenly dispersed and the results were inaccurate. Compared with directly putting it into the dissolution flask 5 and placing it on the shaker 4, the dissolution test system of the present utility model has a smaller relative standard deviation, better consistency and more accurate test results. The dissolution test system of the present utility model is particularly suitable for the detection of phosphate binding capacity.

[0104] The average value of the phosphate binding capacity of Examples 1-6 was 267 mg / g, the average value of the phosphate binding capacity of Examples 7-12 was 271 mg / g, and the average value of the phosphate binding capacity of Control Groups 1-6 was 264 mg / g. Control Groups 1-6 were the groups that removed the capsule shell and only added the capsule content, which could reflect the experimental results without the influence of the capsule shell and could be used as a control for the true results. The average values of the phosphate binding capacity of Examples 1-6, Examples 7-12 and Control Groups 1-6 had little difference, indicating that the device of the present utility model could enable the drug to fully combine with phosphate and make the medicament reflect the true efficacy results.

[0105] Although the present utility model has been illustrated and described with reference to certain preferred embodiments thereof, those of ordinary skill in the art should understand that the above content is a further detailed description of the present utility model in connection with specific embodiments, and it cannot be determined that the specific implementation of the present utility model is only limited to these descriptions. Those skilled in the art can make various changes in form and detail, including making several simple deductions or substitutions, without departing from the spirit and scope of the present utility model.

Claims

1. A dissolution test system, characterized in that, For testing the dissolution of a medicament in a solvent or its binding with a solute in a solvent under the oscillating state of a shaker, including: A dissolution bottle for containing the solvent; A connecting rod fixedly connected to the dissolution bottle, including a bottom end that extends into the dissolution bottle along the axial direction of the dissolution bottle; A wire basket connected to the bottom end of the connecting rod and suspended in the dissolution bottle for containing the medicament; A shaker on which the dissolution bottle is placed.

2. The dissolution test system according to claim 1, wherein The connecting rod includes: A rod body including an external thread extending along the axial direction of the rod body; A fixing member fixedly connected to the dissolution bottle, the fixing member sleeved on the outer periphery of the rod body and threadedly connected to the rod body; The rod body and the fixing member relatively move along the axial direction through screw drive, so as to adjust the length of the rod body extending into the dissolution bottle.

3. The dissolution test system according to claim 2, wherein, It further includes: A height fixer, one end of which is fixedly connected to the bottom of the wire basket and the other end of which abuts against the bottom of the dissolution bottle, for fixing the distance between the bottom of the wire basket and the bottom of the dissolution bottle.

4. The dissolution test system according to claim 3, wherein The length of the height fixer along the axial direction is adjustable, and the adjustment range of the length is 2 mm - 50 mm.

5. The dissolution test system according to claim 3, wherein Including height fixers with different axial length specifications, and the lengths of the height fixers with different axial length specifications along the axial direction are 2 mm - 50 mm.

6. The dissolution test system according to claim 1, wherein, The bottom end of the connecting rod is detachably connected to the wire basket.

7. The dissolution test system according to claim 1, wherein, The bottom end of the connecting rod and the wire basket are connected by a buckle.

8. The dissolution test system according to claim 1, wherein The connecting rod and the wire basket are integrally formed.

9. The dissolution test system according to claim 1, characterized in that, The mesh number of the wire basket is 10 mesh to 200 mesh.

10. The dissolution test system according to claim 1, characterized in that, The material of the connecting rod is stainless steel or plastic.

11. The dissolution test system according to claim 10, wherein The material of the connecting rod is polytetrafluoroethylene (PTFE) or perfluoroalkoxy polymer (PFA).

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