A solid preparation release structure and solid preparation release tester and test method

Abstract

The present invention belongs to the field of preparation inspection, and specifically provides a solid preparation release structure and a solid preparation release tester and a test method. The solid preparation release structure includes two types: a ball stirring release structure and a top floating release structure. The solid preparation release tester includes a water tank top plate structure, a water tank, a driving structure, a supporting structure, a rear box body, and a base support structure. The water tank top plate mounting port provides a release cup moving space, and the release cup fixing blocks on the water tank top plate and the left and right top plate covers are fixed to the release cup position. The water tank and the rear box body are fixed on the base support, and the driving structure is fixed to the hollow steel cylinder through the supporting plate and connected to the stirring structure. The test method tests the surface morphological characteristics, the state characteristics of the disintegrated material, and the release rate of the raw material in the in vitro release process of the solid preparation by optimizing the rigid ball diameter, the type and temperature of the release medium, the stirring speed, and the aperture of the stainless steel mesh, and comprehensively evaluates the in vitro release of the solid preparation in combination with data and phenomena.

Description

Technical Field

[0001] The invention belongs to the field of preparation inspection, and in particular relates to a solid preparation release structure and a solid preparation release tester and a test method. Background Art

[0002] Dissolution rate and disintegration time are conventional quality inspection indicators for marketed drugs. Pharmacopoeias of various countries have set corresponding test methods and index ranges for dissolution rate and disintegration time of drugs. The dissolution modes used by conventional drug dissolution testing instruments mainly include basket method and paddle method dissolution apparatus (such as Chinese patent document CN201220241217.8), reciprocating cylinder method dissolution apparatus (such as Chinese patent document CN201921215456.4), flow cell method dissolution apparatus and disintegration apparatus (such as Chinese patent document CN201911045888.X). Such drug dissolution testing instruments usually have a base for supporting the instrument, a water tank for regulating and maintaining temperature, a stirring or lifting structure for promoting drug movement and a corresponding control motor, a release cup for accommodating simulated digestive tract fluid or dissolution medium, a heating structure for regulating temperature, etc. The dissolution cup usually has a volume of 1000ml, and the motor for controlling the rotation of the stirring structure is usually a stepping motor. Typical drug release testing instruments include Tianda Tianfa RC12ADK dissolution tester, Fucosi FADT-800RC / 1200RC automatic dissolution apparatus, Hanson Research Elite 8 dissolution apparatus, Agilent 708-DS dissolution apparatus, Tianda Tianfa ZB-lE intelligent disintegration apparatus, etc. The release cup of this type of dissolution instrument is fixed in the water tank in a detachable manner. Usually, a large transparent cover is used to press all the dissolution cups by manually pulling down, and all the release cups are removed by manually lifting, or a fixing card consisting of a vertical shaft, a spring slidably sleeved with the vertical shaft, and a baffle arranged on the upper surface of the water tank and the bottom of the spring is set on the water tank plate. When the baffle is lifted, the spring contracts. At this time, the baffle can be rotated so that it cannot cover the release cup insertion port. After the release cup is inserted, the baffle is rotated to cover the release cup and the outside of the cup cover, and then the baffle is released. At this time, the baffle presses the release cup under the deformation of the spring. This type of dissolution instrument is equipped with temperature control and temperature detection structure, speed control and speed adjustment structure, and LCD display. Temperature information and speed information are displayed on the display. Its stirring structure is connected to the synchronous belt of the motor through the stirring shaft. When the motor rotates, it drives multiple shafts to rotate with the help of the synchronous belt, so that the shaft drives the stirring structure to rotate in the release cup to achieve the stirring function. The stirring structure is fixed on the same iron plate and is controlled by the lifting motor to lift and lower the release cup and stirring shaft, and to set the height of the paddle basket and sampling needle. Commonly used dissolution instruments such as the Raytor RT612 dissolution tester have a typical structure including a water tank, a rear box, a release cup, a motor, a controller, a paddle shaft, and a sampling needle lifting column.

[0003] However, the release data detected by these conventional dissolution and disintegration instruments on the market are mainly used as the batch-to-batch quality consistency evaluation of the same drug after approval or the quality consistency evaluation of the drug after process changes and the indicator detection of new preparation development. They are designed to be good at collecting release data but not good at observing detailed phenomena, which invisibly leads to the drawback of focusing on data and neglecting phenomena in the development process. Since the dissolution or disintegration phenomenon of solid preparations is usually more representative of the release characteristics than data in the development process, this makes ordinary dissolution and disintegration data more suitable for quality control rather than research and development.

[0004] For example: 1. In the paddle method dissolution test process, the solid preparation disintegrates or dissolves, and the accumulation deposited in the middle of the dissolution cup makes it difficult to observe and distinguish the release process. In severe cases, the dissolution data cannot truly reflect the release characteristics. Improving the stirring speed may make it difficult to ensure the method's discrimination ability.

[0005] 2. It is difficult to observe the release phenomenon of solid preparations in the basket using the basket method dissolution test.

[0006] 3. The reciprocating cylinder method for dissolution and disintegration time testing may not allow for clear observation of unilateral changes due to the rapid fluctuations in the movement of solid preparations.

[0007] 4. The flow cell dissolution method focuses on the application of slow-release drugs, but has insufficient observation capabilities for the release phenomenon of immediate-release solid preparations, and it is difficult to reflect the movement state of solid preparations.

[0008] Based on the above situation, it is necessary to develop a new in vitro release test device for solid preparations, which can make the solid preparations move slowly and dynamically on the curved surface to simulate the continuous relaxation and contraction movement pattern of the gastrointestinal tract and ensure the clear observation, in-depth analysis and reasonable judgment of the disintegration or dissolution phenomenon of the solid preparations. Summary of the invention

[0009] In view of the above-mentioned prior art, one of the purposes of the present invention is to provide a solid preparation release structure to overcome the disadvantage that it is difficult for conventional dissolution instruments or disintegration instruments to observe in detail the in vitro release behavior of solid preparations, including the changing morphology of the tablet surface and disintegrated particles, so that it can not only be used to test and observe the disintegration characteristics and the release degree of the active ingredients of the solid preparations, but also enable the solid preparations to move continuously on the "S"-shaped interface in the instrument, which is more conducive to simulating the physical effects of the continuous relaxation and contraction movement mode of the gastrointestinal tract in the body on the solid preparations.

[0010] To achieve the above object, the technical solution of the present invention is as follows: For non-floating solid preparations, the main components of the solid preparation release structure of the present invention include a release cup and a ball-type stirring structure. The release cup is in the shape of a hollow cylinder, with a bottom in the shape of an arc, an inverted cone or a flat bottom, and is used as a container to contain a release medium for testing the in vitro release behavior of the solid preparation. The ball-type stirring structure is used to stir the balls in the release cup to drive the solid preparation to be tested to move. In order to maintain the stability of stirring, the vertical center axis of the ball-type stirring structure must be coaxial with the vertical center axis of the release cup.

[0011] Different from the dissolution structure of the paddle method, basket method and reciprocating cylinder method in the prior art, the ball-type stirring structure of the solid preparation release structure includes a stirring shaft, an upper cone, a lower cylinder, a stirring blade, a first stainless steel mesh, a rigid ball, and a ring-shaped vertical glass. Wherein, the upper cone and the lower cylinder are preferably hollow structures. The stirring shaft is used to drive the upper cone and the lower cylinder to rotate, so the lower part of the stirring shaft is fixedly connected to the upper cone, and the lower part of the upper cone is fixedly connected to the top of the lower cylinder. In order to make the rotation more stable and improve the stability of the structural connection, the circular interface between the upper cone and the lower cylinder can be a circular plate, and its material is the same as that of the upper cone and the lower cylinder, that is, the upper cone, the lower cylinder, and the circular plate are fixedly connected at the interface. The lower part of the stirring shaft is fixedly connected to the center of the circular plate and the top of the upper cone. The upper cone and the lower cylinder can also be solid structures. At this time, the lower part of the stirring shaft of the ball-type stirring structure is fixedly connected to the upper cone. However, this ball-type stirring structure itself is heavy.

[0012] The stirring blade is fixedly connected to the lower outer wall of the lower end cylinder, the vertical center axis of the stirring shaft is coaxial with the vertical center axis of the annular vertical glass; the annular vertical glass is located at the lower inner side of the release cup, the annular vertical glass and the inner wall of the release cup are integrally formed, the bottom of the annular vertical glass is detachably fixedly connected to a first stainless steel net, and a rigid ball is placed on the first stainless steel net. The rigid ball can be a small elastic sphere such as a stainless steel ball, a glass ball, a polymerized plastic ball, or a glass ball wrapped with PVC.

[0013] After the release medium and the solid preparation to be tested are added to the release cup, the external motor drives the stirring shaft to rotate, and the rigid balls on the first stainless steel net of this structure move driven by the stirring blades. The uneven changes in the balls present an "S"-shaped interface, so that the solid preparation is slowly moved and slightly collided on the interface to simulate the continuous relaxation and contraction movement mode of the gastrointestinal tract. The squeezing effect of the solid preparation on the solid preparation. Since the gap between the balls can accommodate the disintegrating materials, together with the movement effect, it can be avoided that the accumulation of the drug after disintegration affects the dissolution effect. At the same time, the disintegration speed and phenomenon on the surface of the solid preparation, as well as the shape and size of the disintegrating materials floating in the medium, flattened on the ball-bead interface, and sunk in the ball can be clearly observed, which is convenient for fully analyzing the in vitro release characteristics of the solid preparation, and also better simulates the disintegration and release characteristics of the solid preparation in the gastrointestinal tract.

[0014] In a preferred embodiment, the rigid balls are glass beads; 2 to 6 stirring blades are selected, and 3 are optimal in consideration of the limit of stirring action and economic cost; an inward and downward annular slope structure is formed between the upper end of the annular vertical glass and the inner wall of the release cup to prevent the solid preparation from falling on the plane and failing to enter the stirring structure when it is put into the glass; to facilitate the installation and disassembly of the first stainless steel mesh, the lower end of the annular vertical glass protrudes inward laterally to form a skirt structure, and 2 to 6 skirt internal threaded through holes are vertically distributed on the skirt structure, preferably 3; therefore, the first stainless steel mesh can be detachably fixedly connected to the bottom of the annular vertical glass by screws and skirt internal threaded through holes, that is, the screws pass through the mesh holes of the first stainless steel mesh and are screwed into the skirt internal threaded through holes, and the threaded connection facilitates the installation and disassembly of the first stainless steel mesh.

[0015] In a further preferred embodiment, the release cup is selected to have an arc-shaped bottom; the thickness of the middle part of the annular vertical glass is 6-15 mm, preferably 10 mm; the width of the skirt structure at the lower end of the annular vertical glass is 5-25 mm, preferably 10 mm; the first stainless steel mesh is 10-50 mm away from the bottom of the release cup and 2-30 mm away from the bottom of the lower cylinder, preferably 25 mm away from the bottom of the release cup and 8 mm away from the bottom of the lower cylinder; the diameter of the lower cylinder is 20-60 mm and the height is 20-70 mm, preferably 40 mm in diameter and 40 mm in height; the lower cylinder is The side surface of the body is 10~30mm away from the annular vertical glass, preferably 20mm; the upper cone is 5~70mm high, preferably 20mm; the upper cone and the lower cylinder are made of 316 stainless steel; the diameter of the rigid ball is 1~5mm, and the laying thickness of the rigid ball is: after the ball-type stirring structure is fixed, the top of the rigid ball is 15~95mm away from the first stainless steel mesh, preferably 35mm; the stirring blade is flat arc-shaped, the stirring blade is 2~15mm high, 5~40mm wide, and 8~28mm long, preferably 5mm high, 12mm wide, and 16mm long.

[0016] In another further optimized solution, the top edge of the release cup is folded outward by 90 degrees. o An annular flange is formed, and the annular flange and the outer wall of the release cup are integrally formed by hot pressing with hard polypropylene to form an encapsulated flange. There is a release cup side ear with the same thickness as the encapsulated flange on each side of the encapsulated flange. The release cup side ear is 2~15mm high and 5~50mm wide, preferably 8mm high and 22mm wide; the upper outer wall of the stirring shaft is provided with an external thread. Since the stirring shafts of the existing similar solid preparation dissolution test devices are connected to the rotating shaft driven by the motor through threads. Therefore, the external thread of the upper outer wall of the stirring shaft provides a connection end for the connection between the solid preparation release structure and the existing solid preparation release test device. The encapsulated flange on the top edge of the release cup facilitates the fixation of the release cup.

[0017] For floating solid preparations, the main components of the solid preparation release structure of the present invention include a release cup and a floating stirring structure. The release cup is in the shape of a hollow cylinder, with a bottom in the shape of an arc, an inverted cone or a flat bottom, and is used as a container to contain a release medium for testing the in vitro release behavior of the solid preparation. The floating stirring structure is used to stir the release medium in the release cup to drive the solid preparation to be tested to move. In order to maintain the stability of stirring, the vertical center axis of the floating stirring structure must be coaxial with the vertical center axis of the release cup.

[0018] Different from the paddle method, basket method and reciprocating cylinder method in the prior art, the floating stirring structure of the solid preparation release structure of the present invention includes a stirring shaft, a top glass, a cylindrical peripheral glass, a columnar solid glass and a second stainless steel mesh. The top glass is fixedly connected to the top of the cylindrical peripheral glass; the top glass and the cylindrical peripheral glass are both transparent glass. The bottom surface of the top glass is fixedly connected to the top of the columnar solid glass. The vertical center axis of the top glass is coaxial with the vertical center axis of the columnar solid glass. The radius of the top glass is greater than the radius of the columnar solid glass. 2 to 6 flat arc-shaped protrusions are fixedly connected to the bottom wall of the top glass, preferably 4. A circular through hole is provided between the flat arc-shaped protrusions of the top glass for the floating particles generated during the dissolution of the solid preparation to pass through. At least one dosing port is also provided on the top glass, and the dosing port is provided in the middle of the flat arc-shaped protrusion, that is, an opening is provided in the middle of the flat arc-shaped protrusion, and the opening passes through the flat arc-shaped protrusions of the top glass and its bottom wall. In order to cover the medication port after medication is administered, a medication port top cover is also provided. The medication port top cover matches the opening shape of the medication port, and can be plugged into the medication port to play a blocking role. An upper protruding paddle is fixedly connected to the upper part of the medication port top cover, and the upper protruding paddle can play a role in driving the water flow during stirring, and can also be used as a handle of the medication port top cover for picking up and inserting the medication port top cover. When there are two medication ports, the medication ports are preferably arranged on two opposite flat arc-shaped protrusions. When there is only one medication port, another upper protruding paddle is preferably fixedly connected to the upper surface of the top glass corresponding to the opposite flat arc-shaped protrusion. The two upper protruding paddles can better drive the water flow during stirring and avoid the shaking of the stirring structure.

[0019] The flat arc-shaped protrusion in the present structure may also be a hollow structure, in which case the drug delivery port becomes the openings on the upper and lower surfaces of the flat arc-shaped protrusion.

[0020] Among them, two layers of second stainless steel mesh are detachably and fixedly connected to the bottom of the cylindrical outer peripheral glass, and the aperture of the upper second stainless steel mesh is larger than that of the lower second stainless steel mesh; the vertical center axis of the stirring shaft is coaxial with the vertical center axis of the top glass, and the lower part of the stirring shaft is fixedly connected to the top glass and the columnar solid glass.

[0021] After the medium and the solid preparation to be tested are added to the release cup, the external motor drives the stirring shaft to rotate, and the flat arc-shaped protrusions of the structure drive the liquid flow on the lower side of the top glass, so that the solid preparation can float horizontally in the space surrounded by the top glass, the cylindrical peripheral glass, the columnar solid glass and the second stainless steel net. The solid preparation floats in the medium and constantly touches the "S"-shaped interface presented by the flat arc-shaped protrusions of the top glass, so as to keep the solid preparation in the stirring state in the space surrounded by the top glass, the cylindrical peripheral glass, the columnar solid glass and the second stainless steel net. There is a certain longitudinal floating instead of being close to the top glass. Since the circular through holes on the top glass can pass the floating disintegration upward, the large and small mesh holes of the two layers of the second stainless steel net can intercept the sedimentation disintegration downward, and the morphology and proportion of disintegrations of different densities and sizes can be clearly distinguished, which is convenient for observing and analyzing the disintegration characteristics of floating solid preparations. The upper protruding paddles of the structure drive the liquid flow on the upper side of the top glass, thereby promoting the diffusion of the disintegration on the top glass for easy observation. At the same time, the disintegration rate and phenomenon on the surface of the solid preparation can be clearly observed, which is convenient for fully analyzing the in vitro release characteristics of the solid preparation. In a preferred embodiment, the top glass and the cylindrical peripheral glass are preferably integrally formed, and the top glass and the columnar solid glass are preferably integrally formed.

[0022] In a further preferred embodiment, the bottom of the release cup is arc-shaped, the diameter of the top glass is 40-80 mm, preferably 75 mm; the number of circular through holes on the top glass is 4×8-4×25, preferably 4×14, and the diameter of the circular through holes on the top glass is 0.4-3 mm, preferably 1 mm; the drug injection port is rectangular, 12-20 mm long, 7-15 mm wide, preferably 16 mm long, 9 mm wide; the upper protruding paddle is 5-20 mm high, 1-10 mm wide, preferably 8 mm high, 2 mm wide; the flat arc-shaped protrusion is 2-20 mm high, 5-30 mm wide, 10-30 mm long, preferably 8 mm high, 15 mm wide, 20 mm long; the columnar solid glass is 10-55 mm in diameter, 10-45 mm high, preferably straight The diameter is 35mm and the height is 25mm; the side of the columnar solid glass column is 10~30mm away from the inner wall of the cylindrical peripheral glass, preferably 20mm; the upper and lower layers of the second stainless steel mesh are 10~50mm apart, preferably 20mm, and the lower layer of the second stainless steel mesh is 10~50mm away from the bottom of the release cup, preferably 25mm; the upper and lower layers of the lower part of the cylindrical peripheral glass are provided with 6 to 12 peripheral internal threaded through holes, preferably 3 peripheral internal threaded through holes in each of the upper and lower layers; the second stainless steel mesh is fixedly connected to an annular outer wall made of stainless steel on the periphery, and the annular outer wall is provided with an annular outer wall internal threaded through holes matching the peripheral internal threaded through holes; the second stainless steel mesh is detachably fixedly connected to the bottom of the cylindrical peripheral glass by annular outer wall screws, peripheral internal threaded through holes, and annular outer wall internal threaded through holes.

[0023] In another further optimized solution, the top edge of the release cup is folded outward by 90 degrees. o A circular flange is formed, and the circular flange and the outer wall of the release cup are hot-pressed into one piece with hard polypropylene to form a wrapped flange. There is a release cup side ear on each side of the wrapped flange with the same thickness as the wrapped flange. The release cup side ear is 2~15mm high and 5~50mm wide, preferably 8mm high and 22mm wide; the upper outer wall of the stirring shaft is provided with an external thread.

[0024] The above-mentioned solid preparation release structures for non-floating solid preparations and floating solid preparations can be detachably fixedly connected to the stirring mechanism of the existing dissolution instrument with the aid of a stirring shaft, for example, they can be connected to the paddle method and basket method stirring mechanism of the Raytor RT612 dissolution tester. The release cups can be detachably fixedly connected to the existing dissolution instrument, for example, they can be inserted into the release cup jack of the Raytor RT612 dissolution tester and detachably fixedly connected with the aid of their fixed structures. Among them, a dissolution instrument can carry one or more identical or different solid preparation release structures, for example, a dissolution instrument can carry 2-6 of the above-mentioned solid preparation release structures for non-floating solid preparations or 2-6 of the above-mentioned solid preparation release structures for floating solid preparations, and can also carry 3 of the above-mentioned solid preparation release structures for non-floating solid preparations and 3 of the above-mentioned solid preparation release structures for floating solid preparations, etc.

[0025] The present invention also provides a solid dosage form release tester for detecting the in vitro release behavior of solid dosage forms using the above-mentioned solid dosage form release structure, i.e., the in vitro release kinetic characteristics of solid dosage forms, which has an overall structure that is partially similar to that of the Ruituo RT612 dissolution tester. The solid dosage form release tester includes a water tank top plate structure, a water tank, a drive structure, a support structure, a rear box body, a base support structure, and a control structure, and can be installed with any of the aforementioned solid dosage form release structures. Among them, the support structure and the control structure are located on the upper surface of the water tank top plate structure, the drive structure is located on the upper part of the support structure, the water tank top plate structure is located on the upper surface of the water tank, the rear box body is located below the water tank top plate structure and behind the water tank, and the base support structure is located below the water tank and the rear box body. The water tank top plate structure is detachably fixedly connected to the aforementioned release cup side ears; the drive structure is detachably fixedly connected to the stirring shaft of the aforementioned solid dosage form release structure; and the release cup cover is made of a transparent material.

[0026] In a preferred embodiment, the aforementioned water tank top plate structure includes a water tank top plate, a release cup lid, and an installation opening located on one side of the water tank top plate. The installation opening penetrates the upper and lower surfaces of the water tank top plate. Above the front and rear edges of the installation opening, two upper surface square protrusions are fixedly connected respectively, and the upper surface square protrusions are close to the left or right edge of the installation opening. Below the front and rear edges of the installation opening, lower surface protrusions corresponding to the positions of the upper surface square protrusions are fixedly connected. The lower surface protrusions are stepped, with a length covering the two upper surface square protrusions on the same side and being of the same length as the installation opening. On both the left and right sides of the installation opening, there are semi-circular release cup installation holes matching the release cup. For the case of installing two release cups: A left top plate cover and a right top plate cover are movably inserted between the upper surface square protrusion and the lower surface protrusion. There is a middle top plate cover in the middle of the left top plate cover and the right top plate cover that is not blocked by the upper surface square protrusion. On the left side of the left top plate cover and the right side of the right top plate cover, there are semi-circular holes matching the release cup installation holes. The diameter of the release cup lid matches the upper opening of the release cup. On both the left and right sides of the release cup lid, release cup lid side ears with the same shape and size as the release cup side ears are fixedly connected. On the front and rear side walls of the release cup lid side ears, raised latch blocks are fixedly connected. On both the left top plate cover, the right top plate cover, and the water tank top plate on both sides of the release cup, C-shaped release cup fixing blocks are fixedly connected. The release cup fixing blocks have a sector-shaped depression matching the release cup side ears and the release cup lid side ears, and on the release cup fixing blocks, there are bayonet openings matching the latch blocks. Among them, the bayonet openings of the release cup fixing blocks and the latch blocks of the release cup lid side ears can precisely fix the position of the release cup lid through snap connection, so that operations such as drug dosing, observation, sampling, and imaging on the release cup lid during the test do not affect the release cup, thereby maintaining the stable and precise placement position of the release cup. In addition, long threaded through holes for long screws to pass through are provided on the water tank top plate, the left top plate cover, the right top plate cover, the release cup side ears, and the release cup lid side ears, and the long screws can further play a role in fixing the release cup. For the case of installing three or more release cups: Then the above-mentioned left top plate cover and right top plate cover can be multiple. Except for the left top plate cover and the right top plate cover adjacent to the middle top plate cover, semi-circular holes matching the release cup installation holes are provided on both the left and right sides of other left top plate covers and right top plate covers, so as to insert the release cup through the semi-circular holes of the adjacent left top plate cover or right top plate cover.

[0027] The left and right sides of the water tank top plate and the lower part of the front wall are fixedly bonded with stainless steel half circles, which are used to lift and fix the water tank top plate above the water tank. The two ends of the stainless steel half circles are fixedly bonded to the rear box body; the release cup cover is provided with insertion holes for the camera, the mobile temperature probe, the stirring mother shaft, the stirring shaft and the sampling needle. Among them, the sampling needle can be sleeved with a rubber plug at the syringe part, and the height of the sampling needle can be fixed above the insertion hole with the help of the expanded rubber plug. The sampling needle needle can be made of 316 stainless steel. The sampling needle needle can also be a bent needle with a bending angle of 100° or 130°. The water tank can be an integrated seamless arc groove to facilitate the internal water flow distribution, or it can be a rectangular groove formed by bonding 5 transparent acrylic plates. When the water tank is an integrated seamless arc groove, the release cup should not overlap with the projection of the arc corner of the water tank after installation, that is, when observed from the front or left and right sides, the arc corner of the water tank does not block the release cup, and the arc corner obviously changes the image shape during observation.

[0028] In a preferred embodiment, the driving structure comprises a support plate, a stepper motor, a rotating shaft sleeve, a synchronous pulley, a transmission belt, a cross-shaped groove, a cross-shaped convex rod, an internally threaded top cap, an externally threaded column and a stirring mother shaft. The rotating shaft of the stepper motor is fixedly connected to the synchronous pulley, and the synchronous pulley and the rotating shaft sleeve are synchronously transmitted through the transmission belt. The rotating shaft sleeve is fixed to the support plate through a bearing, the outer ring of the bearing is fixedly connected to the support plate, the inner ring of the bearing is fixedly connected to the outer wall of the rotating shaft sleeve, the upper part of the rotating shaft sleeve is fixedly connected to the externally threaded column, the top of the externally threaded column is provided with a cross-shaped groove, the middle part of the externally threaded column is provided with a stirring mother shaft sleeve hole for inserting the stirring mother shaft, the stirring mother shaft sleeve hole passes through the externally threaded column, the rotating shaft sleeve and the support plate, the stirring mother shaft is slidably sleeved in the stirring mother shaft sleeve hole, the top of the stirring mother shaft is provided with a cross-shaped convex rod, the convexity of the cross-shaped convex rod matches the cross-shaped groove, the lower part of the stirring mother shaft is provided with an internally threaded connecting hole, the upper part of the stirring shaft is threadedly connected to the lower part of the stirring mother shaft, and the externally threaded column is threadedly connected to the internally threaded top cap. Insert the stirring mother shaft into the stirring mother shaft sleeve hole, the cross-shaped convex rod at the top is clamped with the cross-shaped groove, and the internal thread top cap is threadedly connected to the external thread column, so that the stirring mother shaft can rotate with the rotating shaft sleeve. When the internal thread top cap is unscrewed and the cross-shaped convex rod is lifted, the stirring mother shaft can not rotate with the rotating shaft sleeve. Preferably, the solid dosage release tester is also provided with a mother shaft fixing half ring, and the mother shaft fixing half ring can be movably clamped between the cross-shaped groove and the top of the cross-shaped convex rod; at least one positioning collar is fixedly bonded in the rotating shaft sleeve, and the positioning collar can be made of wear-resistant hard polyoxymethylene plastic; the stirring mother shaft and the positioning collar are slidably sleeved. Among them, the positioning collar can prevent the stirring mother shaft from shaking when rotating in the rotating shaft sleeve. Therefore, the number of positioning collars is preferably 2, distributed at the upper and lower ends of the inner cavity of the rotating shaft sleeve. The mother shaft fixing half ring can be used to insert between the cross-shaped groove and the top of the cross-shaped convex rod when the stirring mother shaft is lifted to prevent the stirring mother shaft from slipping. The female shaft fixing half ring is particularly suitable for temporary lifting and position fixing of a floating stirring structure.

[0029] In a preferred solution, the aforementioned support structure is cylindrical, including a hollow steel cylinder and a plastic cover, the rear end of the support plate is fixedly embedded in the middle inner cavity of the hollow steel cylinder, the stepper motor is located in the inner cavity of the hollow steel cylinder, the transmission belt passes through the outer wall of the steel cylinder and is rotatably connected to the shaft sleeve, the plastic cover covers the transmission belt and the shaft sleeve, the hollow steel cylinder vertically passes through the top plate of the water tank, the bottom of the hollow steel cylinder is horizontally extended to form an extension part, the extension part is provided with 3 to 9 extension part threaded through holes, the rear box base is provided with 3 to 9 base threaded through holes, the hollow steel cylinder is threadedly connected to the rear box base through the support structure fixing screws, the extension part threaded through holes, and the base threaded through holes. The support structure can be fixedly connected to the rear box base through the threaded connection of the extension part threaded through holes, the base threaded through holes and the support structure fixing screws.

[0030] In a preferred solution, the aforementioned base support structure includes an integrated square column, a support seat, a water tank support column, a lower iron plate of the water tank, a rear box base, a water heater, a water circulator and a water circulation pipeline. Four support seat threaded holes are provided at the four corners of the bottom of the integrated square column. The upper part of the support seat is fixedly connected to the support seat threaded column, and the support seat threaded column is threadedly connected to the support seat threaded hole. The upper front section of the integrated square column is fixedly connected to 4 to 6 water tank support columns. The water tank is placed on the water tank support column through the lower iron plate of the water tank. The rear box is placed on the rear box base, and the rear box base is placed on the upper rear section of the integrated square column. The water heater is fixed to the rear side of the integrated square column. The water circulator is fixedly connected to one side of the integrated square column. The water circulation pipeline is a three-head structure, one end of which opens at the upper part of one side of the water tank, one end of which opens at the bottom of the opposite side of the water tank, and one end is equipped with a faucet for drainage. For example, one end of the water circulation pipeline opens at the upper right side of the water tank, one end opens at the bottom of the left side of the water tank, and one end is equipped with a faucet for drainage. The water heater, the water circulator and the water tank are connected through a water circulation pipeline so as to control the temperature of the liquid in the water tank.

[0031] In a preferred solution, the control structure includes a PLC touch screen, a water tank temperature probe, and a mobile temperature probe. The top plate of the water tank is provided with a probe hole for inserting the water tank temperature probe. The front wall of the rear box body is provided with a mirror, which faces the side of the water tank, and the image of the rear of the release cup can be observed through the mirror. The side walls of the rear box body are respectively provided with a drive structure socket, a power switch, and a main power socket. The drive structure socket is connected to the stepper motor through a wire, and the main power socket is connected to the 220V indoor power supply and the power switch through a wire. The power switch is connected to the power supply, the water heater, and the water circulator through the lower PCB circuit board. The power supply provides 24V DC voltage and 10A rated current, and is connected to the stepper motor, the motor driver, the timer, the water tank temperature probe, the mobile temperature probe, the PLC touch screen, and the PLC controller through the lower PCB circuit board; the PLC touch screen is electrically connected to the PLC controller through the upper PCB circuit board, and the PLC controller is connected to the lower PCB circuit board through the upper PCB circuit board, and regulates the timer, the water heater, the water circulator, the stepper motor, the motor driver, the water tank temperature probe, and the mobile temperature probe signals. Among them, the water heater can be a PTC water heater. The drive structure socket and the stepper motor can be connected in a one-to-one manner, that is, each drive structure socket is connected in series with a stepper motor through a wire; or in a one-to-many manner, that is, multiple stepper motors are connected in parallel and then connected in series with a drive structure socket through a wire. The stepper motor can be connected with the wire of the plug, and when it is needed, the plug is inserted into the drive structure socket.

[0032] In a further preferred embodiment, the arc width of the aforementioned release cup side ear close to the release cup mounting hole accounts for 1 / 5 of the circumference of the release cup mounting hole; the middle top plate cover of the water tank top plate is 40~300mm long and 100~400mm wide, preferably 105mm long and 180mm wide; the left top plate cover and the right top plate cover are 80~300mm long and 100~400mm wide on both sides, preferably 115mm long and 180mm wide on both sides; the distance between the support plate and the water tank top plate is 90~250mm, preferably 140mm; the extension ring through hole fixedly connected to the bottom of the hollow steel cylinder and the threaded hole of the rear box base are preferably 6.

[0033] The stepper motor can be a 56BYG250CK stepper motor, and the temperature probe can be a TMP115 temperature probe. This type of stepper motor and temperature probe can be purchased directly on the Internet or in the market. The principle is a well-known technology in this field and will not be described here.

[0034] The present invention also provides a method for detecting the in vitro release behavior of a solid preparation used in conjunction with the above-mentioned solid preparation release tester: For non-floating solid preparations, the following steps are included: connect the drive structure socket with a wire to the drive structure, connect the household AC power supply to the main power socket, turn on the power switch, set the water tank temperature and the test speed, and start the water heater and the water circulator. When the drive structure socket is connected to the stepper motor in a one-to-one manner, connect one or more stepper motors that need to be started, that is, the stepper motors corresponding to the release cups that need to be used, to the corresponding drive structure sockets with a wire. When the drive structure socket is connected to the stepper motor in a one-to-many manner, the drive structure socket can be connected to the drive structure with a wire, and the unused release cups and the corresponding stirring components do not need to be installed.

[0035] Connect the first stainless steel mesh to the bottom of the annular vertical glass through the skirt screws and the inner threaded through holes of the skirt and tighten them. Slide the release cup horizontally through the water tank top plate mounting port to the release cup mounting hole. Insert the left top plate cover and / or the right top plate cover (i.e., the top plate cover corresponding to the release cup and stepper motor used) between the square protrusion on the upper surface and the protrusion on the lower surface. Move the left top plate cover to the left and / or the right top plate cover to the right to make them contact with the release cup. The middle top plate cover is stuck between the left top plate cover and the right top plate cover, and the release medium is added into the release cup.

[0036] Pass the stirring shaft of the ball-type stirring structure through the central circular hole of the release cup cover, screw it upward to the stirring mother shaft through the thread, insert the cross-shaped protruding rod on the top of the stirring mother shaft into the cross-shaped groove on the top of the rotating shaft sleeve, tighten the internal threaded top cap of the driving structure, lift the release cup cover and pour the glass balls, cover the release cup cover, insert the block of the release cup cover into the bayonet of the release cup fixing block, pass the long screw through the side ear through hole of the release cup cover, the side ear through hole of the release cup and the threaded through hole on the top plate of the water tank, tighten and fix the release cup.

[0037] Insert the mobile temperature probe into the release cup. When the temperature of the release medium in the release cup reaches the requirement, put the solid preparation to be tested into the release cup through the camera insertion hole on the cover of the release cup, and start stirring immediately to observe the in vitro release behavior of the solid preparation. When taking liquid for testing, insert the liquid collection needle into the corresponding insertion hole on the cover of the release cup to extract the liquid sample.

[0038] After the test, unscrew the long screw, unscrew the stirring mother shaft and the stirring shaft, lift the stirring mother shaft, remove the release cup cover and the middle top plate cover in turn, then pull out the left top plate cover and the right top plate cover, slide the release cup together with the stirring device to the middle of the installation port and take them out.

[0039] For floating solid preparations, the following steps are included: connecting the drive structure socket with a wire, connecting the household AC power supply to the main power socket, turning on the power switch, setting the water tank temperature and the test speed, and starting the water heater and the water circulator; The two layers of second stainless steel mesh are fixedly connected to the bottom of the glass of the cylindrical outer peripheral part through the annular outer wall screws, the outer peripheral inner threaded through holes, and the annular outer wall inner threaded through holes, respectively; the release cup is slid horizontally to the release cup mounting hole through the water tank top plate mounting opening; the left top plate cover or the right top plate cover is inserted between the square protrusion on the upper surface and the protrusion on the lower surface; the left top plate cover is moved to the left and / or the right top plate cover is moved to the right to make it contact with the release cup; and the middle top plate cover is clamped between the left top plate cover and the right top plate cover; The stirring shaft of the floating stirring structure is passed through the central circular hole of the release cup cover, and screwed upward to the stirring mother shaft through the thread, and the stirring mother shaft is lifted to the highest position. At this time, the floating stirring structure is higher than the upper edge of the release cup as a whole, and the release medium can be added to the release cup to prevent the floating stirring structure from contacting the medium too early, which will affect the test results. The mother shaft fixing half ring is placed under the cross-shaped protruding rod at the top of the stirring mother shaft, and the floating stirring structure is slowly lowered so that the upper surface of the top glass of the floating stirring structure is close to the lower surface of the release cup cover, and the release cup cover is placed on the release cup. At this time, the floating stirring structure is higher than the liquid level of the medium as a whole, which can prevent the floating stirring structure from contacting the medium too early.

[0040] Insert the mobile temperature probe into the release cup. When the temperature of the release medium in the release cup reaches the required level, lift the stirring shaft and the release cup cover. At this time, the top glass surface of the floating stirring structure is exposed, and the solid preparation can be added to the floating stirring structure through the dosing port. Then, pinch the upper protruding blade of the dosing port top cover to insert the dosing port top cover into the dosing port, and slowly lower the floating stirring structure so that the cross-shaped protruding rod on the top of the stirring shaft is placed on the fixed half ring of the shaft, ensuring that the top glass surface of the floating stirring structure is close to the lower surface of the release cup cover. At this time, the floating stirring structure is higher than the liquid level of the medium as a whole to prevent the solid preparation from contacting the medium before stirring, which will affect the test results. Then insert the block of the release cup cover into the block of the release cup fixing block, and pass the long screw through the side ear through hole of the release cup cover, the side ear through hole of the release cup and the threaded through hole on the top plate of the water tank to tighten and fix the release cup; remove the fixing half ring of the mother shaft, insert the cross-shaped protrusion on the top of the stirring mother shaft into the cross-shaped groove on the top of the rotating shaft sleeve, and immediately tighten the internal threaded top cap of the driving structure, and start stirring immediately, observe the in vitro release behavior of the solid preparation, and when taking liquid for testing, insert the liquid collection needle into the corresponding insertion hole on the release cup cover to extract the liquid sample. After the test, unscrew the long screw, unscrew the stirring mother shaft and the stirring shaft, lift the stirring mother shaft, remove the release cup cover and the middle top plate cover in turn, then pull out the left top plate cover and the right top plate cover, slide the release cup together with the stirring device to the middle of the installation port and take them out.

[0041] In a preferred embodiment, for the step of non-floating solid preparations: the rigid balls are glass balls with a diameter of 1-5 mm; the aperture of the first stainless steel mesh is one of 18, 20, 24, 30, 40, and 50 meshes; for the step of floating solid preparations: the aperture of the second stainless steel mesh is selected from any two of 18, 20, 24, 30, 40, and 50 meshes.

[0042] Furthermore, in the above method for detecting the in vitro release behavior of a solid preparation, the pH of the release medium is 1.0-8.0; the rotation speed of the stirring structure is 10-100 rpm, preferably 10-50 rpm; and the medium temperature is 20-45°C, preferably 37°C or 25°C.

[0043] Compared with the existing dissolution apparatus and disintegration apparatus, the solid preparation release structure for non-floating solid preparations or floating solid preparations of the present invention has the following advantages: Existing dissolution apparatus and disintegration apparatus are mainly used for batch-to-batch quality control of solid preparations after marketing, that is, to ensure that the dissolution and disintegration data of solid preparations are consistent or the variation range is acceptable between batches. However, they are not obviously suitable for distinguishing the differences in the excipient composition and process parameters of solid preparation granule intermediates. Since the paddle and basket dissolution processes are prone to form accumulation bodies, it is also difficult to simulate the decomposition and release behavior of solid preparations under the continuous relaxation and contraction movement mode of the gastrointestinal tract.

[0044] Since the solid preparation release structure for non-floating solid preparations of the present invention has rigid spheres, upper cones, lower cylinders, first stainless steel nets and other components, and the solid preparation release structure for floating solid preparations has flat arc-shaped protrusions, double-layer second stainless steel nets, top glass, cylindrical outer peripheral glass and other components, the stirring process avoids the generation of accumulation bodies, so that solid preparations of different densities can move in the "S"-shaped interface in the release structure, which is closer to the characteristics of the mechanical digestion process caused by the continuous relaxation and contraction movement mode of the gastrointestinal tract. At the same time, the two solid preparation release structures of the present invention can clearly observe and record the surface morphology and change characteristics of the solid preparations at various parts of the upper, middle and lower parts of the release cup, the movement state and particle size characteristics of the disintegrated materials, and the release speed and degree of the raw materials, and combine the data and phenomena to characterize the drug release in detail, so as to more reasonably optimize the prescription and process, analyze the in vitro release characteristics, and infer the in vivo release risk. It has reliable and obvious solving capabilities for the problems of inconvenient, unclear and insufficient observation of the release phenomenon in the research and development process and the problem of accumulation at the bottom of the dissolution cup affecting the analysis of the release results, and is particularly suitable for the development of solid preparations of generic drugs. In addition, the solid preparation release tester of the present invention reduces the cost of driving structure lifting and lowering control by fixing the driving structure and moving the release cup, while ensuring the fixing effect and efficiency of the release cup and its cup cover, and avoids the possibility of decreased accuracy due to frequent lifting or tilting of the driving structure. The instrument has a simple structure, low cost, a wide range of applicability, and is easy to promote and popularize. BRIEF DESCRIPTION OF THE DRAWINGS

[0045] In order to make the purpose, technical solution and beneficial effects of the present invention clearer, the present invention provides the following drawings: Figure 1 It is a structural schematic diagram of a solid preparation release structure for non-floating solid preparations of the present invention and its stirring structure and lower skirt structure; Figure 2 It is a schematic diagram of the structure of a solid preparation release structure for floating solid preparations of the present invention and its top glass, second stainless steel mesh and upper protruding paddles; Figure 3 It is a schematic diagram of the overall structure of a solid preparation release tester of the present invention; Figure 4 A schematic diagram of the installation port position of a water tank top plate structure of a solid dosage form release tester of the present invention; Figure 5 A schematic diagram of a release cup installation structure of a water tank top plate structure of a solid preparation release tester of the present invention; Figure 6 It is a schematic diagram of the split structure of the release cup mounting structure of a solid preparation release tester of the present invention; Figure 7It is a schematic diagram of a driving structure of a solid preparation release tester of the present invention; Figure 8 It is a schematic diagram of a support structure of a solid preparation release tester of the present invention; Fig. 9 It is a schematic diagram of a socket on the side wall of the rear box of a solid dosage form release tester of the present invention; Fig.10 It is a schematic diagram of the base support structure of a solid preparation release tester of the present invention; Fig.11 A schematic diagram of a control structure of a solid preparation release tester of the present invention; Fig.12 The present invention is a circuit connection diagram of a solid preparation release tester.

[0046] In the figure: 1-1 stirring shaft, 1-2 upper cone, 1-3 lower cylinder, 1-4 stirring blade, 1-5 first stainless steel mesh, 1-6 rigid ball, 1-7 annular vertical glass, 1-8 skirt screw; 2-1 top glass, 2-2 cylindrical peripheral glass, 2-3 columnar solid glass, 2-4 second stainless steel mesh, 2-5 flat arc protrusion, 2-6 circular through hole, 2-7 dosing port, 2-8 upper protruding blade, 2-9 wrapped flip 2-10 release cup side ear, 2-11 annular outer wall screw, 2-12 dosing port top cover, 2-13 mother shaft fixing half ring; 3 water tank top plate structure, 3-1 water tank top plate, 3-2 mounting port, 3-3 upper surface square protrusion, 3-4 lower surface protrusion, 3-5 left top plate cover, 3-6 right top plate cover, 3-7 middle top plate cover, 3-8 release cup mounting hole, 3-9 release cup cover, 3-10 release cup cover side ear, 3-11 block, 3- 12 release cup fixing block, 3-13 bayonet, 3-14 long screw, 3-15 stainless steel half circle, 3-16 probe hole; 4 water tank; 5 drive structure, 5-1 support plate, 5-2 stepper motor, 5-3 shaft sleeve, 5-4 synchronous pulley, 5-5 transmission belt, 5-6 cross groove, 5-7 cross convex rod, 5-8 internal thread top cap, 5-9 external thread column, 5-10 stirring mother shaft; 6 support structure, 6-1 hollow steel cylinder, 6-2 Plastic cover, 6-3 extension part, 6-4 support structure fixing screws; 7 rear box, 7-1 left drive structure socket, 7-2 right drive structure socket, 7-3 power switch, 7-4 main power socket; 8 base support structure, 8-1 integrated square column, 8-2 support seat, 8-3 water tank support column, 8-4 water tank lower iron plate, 8-5 rear box base, 8-6 water heater, 8-7 water circulator, 8-8 water circulation pipeline; 9 control structure, 9-1 PLC touch screen, 9-2 water tank temperature probe, 9-3 mobile temperature probe, 9-4 lower PCB circuit board, 9-5 power supply, 9-6 motor driver, 9-7 timer, 9-8 PLC controller, 9-9 upper PCB circuit board. DETAILED DESCRIPTION

[0047] The preferred embodiments of the present invention will be described in detail below in conjunction with the accompanying drawings. The test methods without specific conditions in the embodiments are usually based on conventional conditions or conditions recommended and specified by similar instruments and pharmacopoeias.

[0048] Example 1 A solid dosage form release structure for non-floating solid dosage forms like Figure 1As shown, this part provides a solid preparation release structure for non-floating solid preparations, which consists of a release cup with an arc-shaped bottom, a wrapped flange 2-9, a release cup side ear 2-10, a stirring shaft 1-1, an upper cone 1-2, a lower cylinder 1-3, a stirring blade 1-4, a first stainless steel mesh 1-5, a rigid ball 1-6, and an annular vertical glass 1-7.

[0049] The top edge of the release cup is folded outwards by 90 degrees. o An annular flange is formed, and the annular flange and the outer wall of the release cup are integrally formed by hot pressing with hard polypropylene to form a sheathed flange 2-9, and there is a release cup edge ear 2-10 of the same thickness on each side of the sheathed flange 2-9. After installation, the vertical center axis of the stirring shaft 1-1 is coaxial with the vertical center axis of the release cup. In this structure, a circular plate is fixedly connected between the upper cone 1-2 and the lower cylinder 1-3, the lower part of the upper cone 1-2 is fixedly connected to the top of the lower cylinder 1-3, and the lower part of the stirring shaft 1-1 is fixedly connected to the top of the upper cone 1-2 and the center of the circular plate. The stirring blade 1-4 is fixedly connected to the lower outer wall of the lower cylinder 1-3, and there are three stirring blades 1-4. The annular vertical glass 1-7 is located at the lower inner part of the release cup, and the annular vertical glass 1-7 is integrally formed with the inner wall of the release cup. The lower end of the bottom of the annular vertical glass 1-7 protrudes inwardly to form a skirt structure, and three skirt internal thread through holes are vertically distributed on the skirt structure. The first stainless steel mesh 1-5 is detachably fixedly connected to the bottom of the annular vertical glass 1-7 through the skirt screw 1-8 and the skirt internal thread through hole. An inward and downward annular slope structure is formed between the upper end of the annular vertical glass 1-7 and the inner wall of the release cup, which can prevent the solid preparation from falling on the plane of the upper wall when administering the medicine and being unable to enter the stirring structure. The upper cone 1-2 and the lower cylinder 1-3 can be made of 316 stainless steel. The rigid ball 1-6 is a glass ball. The stirring blade 1-4 is in the shape of a flat arc.

[0050] Among them, the sizes of different components of the solid preparation release structure are preferably: the thickness of the middle part of the annular vertical glass 1-7 is 10mm; the width of the skirt structure at the lower end of the annular vertical glass 1-7 is 10mm; the first stainless steel mesh 1-5 is 25mm away from the bottom of the release cup and 8mm away from the bottom of the lower cylinder 1-3; the diameter of the lower cylinder 1-3 is 40mm and the height is 40mm; the distance between the side of the lower cylinder 1-3 and the annular vertical glass 1-7 is 20mm; the upper cone 1-2 is 20mm high; the diameter of the rigid ball 1-6 is 2mm, and the laying thickness of the rigid ball 1-6 is: the distance between the top of the rigid ball 1-6 and the first stainless steel mesh 1-5 is 35mm; the stirring blade 1-4 is 5mm high, 12mm wide, and 16mm long. The release cup side ear 2-10 is 2~15mm high and 5~50mm wide; the upper outer wall of the stirring shaft 1-1 is provided with an external thread.

[0051] When the present invention is used, the release cup can be placed in the release cup jack of an existing solid preparation release tester such as the Raytor RT612 dissolution tester, so that the wrapped flange 2-9 and the release cup side ear 2-10 are stuck under the cup cover plate, and then the stirring shaft 1-1 is connected to the motor of the Raytor RT612 dissolution tester, and the stirring shaft 1-1 drives the stirring blade 1-4 to rotate.

[0052] Example 2 A solid dosage form release structure for floating solid dosage forms like Figure 2 As shown, this part provides a solid preparation release structure for floating solid preparations, including a coated flange 2-9, a release cup side ear 2-10, a stirring shaft 1-1, a top glass 2-1, a cylindrical peripheral glass 2-2, a columnar solid glass 2-3, a second stainless steel mesh 2-4, a flat arc-shaped protrusion 2-5, a circular through hole 2-6, a dosing port 2-7 and an upper protruding paddle 2-8.

[0053] The top edge of the release cup is folded outwards by 90 degrees. o A circular flange is formed, and the circular flange and the outer wall of the release cup are integrally formed by hot pressing with hard polypropylene to form a wrap-around flange 2-9, and there is a release cup edge ear 2-10 of the same thickness on each side of the wrap-around flange 2-9. The top glass 2-1, the columnar solid glass 2-3 and the cylindrical peripheral glass 2-2 can be integrally formed, or they can be manufactured separately and then the top glass 2-1 is fixedly connected to the columnar solid glass 2-3 and the cylindrical peripheral glass 2-2. The stirring shaft 1-1 is fixedly connected to the top glass 2-1. A hole can also be punched at the center of the top glass 2-1 and the columnar solid glass 2-3, and the stirring shaft 1-1 is inserted into the hole and fixedly bonded to the top glass 2-1 and the columnar solid glass 2-3. The second stainless steel mesh 2-4 is divided into two layers, upper and lower. The top glass 2-1, the cylindrical outer peripheral glass 2-2, the columnar solid glass 2-3, and the second stainless steel mesh 2-4 together form a cylindrical cavity.

[0054] Four flat arc-shaped protrusions 2-5 are fixedly connected to the bottom wall of the top glass 2-1, one of the flat arc-shaped protrusions 2-5 is provided with a medicine feeding port 2-7, an upper protruding paddle 2-8 is fixedly connected to the upper part of the medicine feeding port top cover 2-12, and an upper protruding paddle 2-8 is fixedly connected to the upper surface of the top glass 2-1 corresponding to the flat arc-shaped protrusion 2-5 at the symmetrical position of the flat arc-shaped protrusion 2-5 where the medicine feeding port 2-7 is located. Circular through holes 2-6 are provided between the flat arc-shaped protrusions 2-5 of the top glass 2-1. The lower part of the cylindrical outer peripheral glass 2-2 is provided with 6 outer peripheral internal threaded through holes in the upper and lower layers. The outer periphery of the second stainless steel mesh 2-4 is fixedly connected with an annular outer wall made of stainless steel, and the annular outer wall is provided with an annular outer wall internal threaded through hole matching the outer peripheral internal threaded through hole; the second stainless steel mesh 2-4 is detachably connected to the bottom of the cylindrical outer peripheral glass 2-2 through the annular outer wall screws 2-11, the outer peripheral internal threaded through holes, and the annular outer wall internal threaded through holes Among them, the sizes of different components of the solid preparation release structure are preferably as follows: the top glass 2-1 has a diameter of 75mm; the number of circular through holes 2-6 on the top glass 2-1 is 4×14 and the diameter is 1.0mm; the medication port 2-7 is rectangular, 16mm long and 9mm wide; the upper protruding paddle 2-8 is 8mm high and 2mm wide; the flat arc-shaped protrusion 2-5 is 8mm high, 15mm wide and 20mm long; the diameter of the columnar solid glass 2-3 is 35mm and 25mm high; the side surface of the columnar solid glass 2-3 is 20mm away from the inner wall of the cylindrical outer peripheral glass 2-2; the upper layer and the lower layer of the second stainless steel mesh 2-4 are 20mm apart, and the lower layer of the second stainless steel mesh 2-4 is 25mm away from the bottom of the release cup; the release cup side ear 2-10 is 2~15mm high and 5~50mm wide; the upper outer wall of the stirring shaft 1-1 is provided with an external thread.

[0055] When the present invention is used, the release cup can be placed in the release cup jack of an existing solid preparation release tester such as the Raytor RT612 dissolution tester, so that the wrapped flange 2-9 and the release cup side ear 2-10 are stuck under the cup cover plate, and then the stirring shaft 1-1 is connected to the motor of the Raytor RT612 dissolution tester, and the stirring shaft 1-1 drives the stirring blade 1-4 to rotate.

[0056] Example 3 A solid dosage form release tester like Figures 3 to 12 As shown, this section provides a solid dosage form release tester that carries the solid dosage form release structures shown in Example 1 and Example 2. Figure 3As shown, the solid dosage form release tester comprises a water tank top plate structure 3, a water tank 4, a driving structure 5, a supporting structure 6, a rear box body 7, a base support structure 8, a control structure 9, and the solid dosage form release structures shown in Examples 1 and 2. The water tank top plate structure 3 is located above the water tank 4, the rear box body 7 is located behind the water tank 4, the base support structure 8 is located below the water tank 4 and the rear box body 7, and the driving structure 5, the supporting structure 6, and the control structure 9 are located above the water tank top plate structure 3.

[0057] Among them, the water tank top plate structure 3 is related to the installation of the release cup. Figures 4 to 6 As shown, the water tank top plate structure 3 includes a water tank top plate 3-1, a mounting opening 3-2, a square protrusion 3-3 on the upper surface, a protrusion 3-4 on the lower surface, a left top plate cover 3-5, a right top plate cover 3-6, a middle top plate cover 3-7, a release cup mounting hole 3-8, a release cup cover 3-9, a release cup cover side ear 3-10, a clamping block 3-11, a release cup fixing block 3-12, a clamping port 3-13, a long screw 3-14, and a stainless steel half ring 3-15. Among them, a mounting opening 3-2 is provided on the water tank top plate 3-1. Two square protrusions 3-3 on the upper surface are fixedly connected above the edges of the front and rear walls of the mounting opening 3-2, and a step-shaped protrusion 3-4 on the lower surface is fixedly connected below the corresponding edges. The stainless steel half ring 3-15 is fixedly bonded to the left, right and lower front walls of the water tank top plate 3-1.

[0058] The left top plate cover 3-5 and the right top plate cover 3-6 can be inserted between the square protrusion 3-3 on the upper surface and the protrusion 3-4 on the lower surface. The middle top plate cover 3-7 is located between the left top plate cover 3-5 and the right top plate cover 3-6 and is not covered by the square protrusion 3-3 on the upper surface, so as to facilitate the removal and installation of the middle top plate cover 3-7. Semicircular release cup mounting holes 3-8 matching the release cup are provided on the left and right sides of the mounting opening 3-2, and semicircular holes matching the release cup mounting holes 3-8 are also provided on the outer sides of the left top plate cover 3-5 and the right top plate cover 3-6. When the left top plate cover 3-5 and the right top plate cover 3-6 are moved to the left and right respectively, they can be combined with the semicircular release cup mounting holes 3-8 on both sides of the mounting opening 3-2 to form a circular hole for inserting the release cup. Figure 5 , Figure 6As shown, the release cup cover side ear 3-10 has the same shape as the release cup side ear 2-10 at the release cup mouth, and both the release cup side ear 2-10 and the release cup cover side ear 3-10 are provided with side ear through holes, the water tank top plate 3-1 is provided with a threaded through hole, the release cup cover side ear 3-10 is provided with a clamping block 3-11 on the outside, and the U-shaped release cup fixing block 3-12 is provided with a clamping port 3-13 matching the clamping block 3-11. When the release cup is inserted into the release cup mounting hole 3-8, the release cup fixing block 3-12 can be fixed to the release cup cover side ear 3-10 by means of the engagement of the clamping port 3-13 and the clamping block 3-11, and the long screw 3-14 is inserted into the side ear through hole to fix the fixed release cup on the water tank top plate 3-1. A probe hole 3-16 for inserting the water tank temperature probe 9-2 is provided on the water tank top plate 3-1, and insertion holes for inserting a camera, a movable temperature probe 9-3, a stirring mother shaft 5-10 and a sampling needle are respectively provided on the release cup cover 3-9. The sampling needle is fixed at a height on the release cup cover 3-9 by a rubber stopper provided therewith.

[0059] like Figure 7 As shown, the driving structure 5 is composed of two sets including a support plate 5-1, a stepper motor 5-2, a rotating shaft sleeve 5-3, a synchronous pulley 5-4, a transmission belt 5-5, a cross-shaped groove 5-6, a cross-shaped protruding rod 5-7, an internal threaded top cap 5-8, an external threaded column 5-9, and a stirring mother shaft 5-10. The rotating shaft of the stepper motor 5-2 is fixedly connected to the synchronous pulley 5-4, and the synchronous pulley 5-4 is synchronously driven with the rotating shaft sleeve 5-3 through the transmission belt 5-5. The upper part of the rotating shaft sleeve 5-3 is fixedly connected to the external threaded column 5-9, and the top of the external threaded column 5-9 is provided with a cross-shaped groove 5-6. The protrusion of the cross-shaped protruding rod 5-7 matches the cross-shaped groove 5-6, and the external threaded column 5-9 is threadedly connected with the internal threaded top cap 5-8. The stirring mother shaft 5-10 is detachably fixedly connected to the stirring shaft 1-1 through a thread, and then the stirring shaft 1-1 is driven by the stepper motor 5-2 to achieve the stirring effect. The inner cavity of the external thread column 5-9 is provided with a stirring mother shaft sleeve hole for inserting the stirring mother shaft 5-10, and the stirring mother shaft sleeve hole passes through the external thread column 5-9, the rotating shaft sleeve 5-3 and the support plate 5-1. Two positioning collars are fixedly bonded in the rotating shaft sleeve 5-3, and the stirring mother shaft 5-10 is slidably sleeved with the positioning collars to prevent the stirring mother shaft 5-10 from shaking when rotating in the rotating shaft sleeve 5-3. The two positioning collars are distributed at the upper and lower ends of the inner cavity of the rotating shaft sleeve.

[0060] like Figure 8As shown, the support structure 6 is composed of two sets including a hollow steel column 6-1, a support structure fixing screw 6-4, and a plastic cover 6-2. The rear end of the support plate 5-1 is fixedly embedded in the middle inner cavity of the hollow steel column 6-1, the stepper motor 5-2 is located in the inner cavity of the hollow steel column 6-1, the transmission belt 5-5 passes through the outer wall of the hollow steel column 6-1 and is rotatably connected to the shaft sleeve 5-3, the plastic cover 6-2 covers the transmission belt 5-5 and the shaft sleeve 5-3, the hollow steel column 6-1 vertically passes through the water tank top plate 3-1, the bottom of the hollow steel column is horizontally extended to form an extension part 6-3, the extension part 6-3 is provided with 3 extension part threaded through holes, the rear box base 8-5 is provided with 3 base threaded through holes, and the hollow steel column is threadedly connected to the rear box base 8-5 through the support structure fixing screw 6-4, the extension part threaded through hole, and the base threaded through hole.

[0061] like Fig. 9 As shown, the side walls of the rear box 7 are respectively provided with a left drive structure socket 7-1, a right drive structure socket 7-2, a power switch 7-3, and a main power socket 7-4. The left drive structure socket 7-1 is connected to the stepper motor 5-2 in the left drive structure through a wire, the right drive structure socket 7-2 is connected to the stepper motor 5-2 in the right drive structure through a wire, the main power socket 7-4 connects the power plug and the power switch 7-3, the power switch 7-3 is connected to the power supply 9-5, the PTC water heater 8-6, and the water circulator 8-7 through the lower PCB circuit board 9-4, the power supply 9-5 provides 24V DC voltage and 10A rated current, and is connected to the stepper motor 5-2, the motor driver 9-6, the timer 9-7, the water tank temperature probe 9-2, the mobile temperature probe 9-3, the PLC touch screen 9-1, and the PLC controller 9-8 through the lower PCB circuit board 9-4.

[0062] like Fig.10 As shown, the base support structure 8 includes an integrated square column 8-1, a support seat 8-2, a water tank support column 8-3, a water tank lower iron plate 8-4, a rear box base 8-5, a water heater 8-6, a water circulator 8-7, and a water circulation pipeline 8-8. Four support seat threaded holes are provided at the four corners of the bottom of the integrated square column 8-1, and the upper part of the support seat 8-2 is fixedly connected to the support seat threaded column, and the support seat threaded column is threadedly connected to the support seat threaded hole. The upper front section of the integrated square column 8-1 is fixedly connected to five water tank support columns 8-3, the water tank 4 is placed on the water tank support column 8-3 through the lower iron plate 8-4 of the water tank, the rear box body 7 is placed on the rear box body base 8-5, and the rear box body base 8-5 is placed on the upper rear section of the integrated square column 8-1, the water heater 8-6 is fixed to the rear side of the integrated square column 8-1, the water circulator 8-7 is fixed to the left side of the integrated square column 8-1, the water circulation pipe 8-8 is a three-head structure, one end is opened at the upper right side of the water tank 4, one end is opened at the bottom of the left side of the water tank 4, and one end is installed with a faucet for drainage; the water heater 8-6, the water circulator 8-7, and the water tank 4 are connected through the water circulation pipe 8-8.

[0063] like Fig.11 and Fig.12 As shown, the control structure 9 includes a PLC touch screen 9-1, a water tank temperature probe 9-2, and a mobile temperature probe 9-3. The PLC touch screen 9-1 is electrically connected to a PLC controller 9-8 through an upper PCB circuit board 9-9. The PLC controller 9-8 is connected to a lower PCB circuit board 9-4 through an upper PCB circuit board 9-9, and controls the timer 9-7, the PTC water heater 8-6, the water circulator 8-7, the stepper motor 5-2, the motor driver 9-6, the water tank temperature probe 9-2 and the mobile temperature probe 9-3 signals.

[0064] Among them, the sizes of different components of the solid dosage form release tester are preferably as follows: the arc width of each release cup side ear 2-10 close to the release cup mounting hole 3-8 accounts for 1 / 5 of the circumference of the release cup mounting hole 3-8; the middle top plate cover 3-7 is 105mm long and 180mm wide; the left top plate cover 3-5 and the right top plate cover 3-6 are 115mm long and 180mm wide on both sides; the distance between the support plate 5-1 and the water tank top plate 3-1 is 140mm.

[0065] When using the solid dosage form release tester, if the solid dosage form release structure for non-floating solid dosage forms of Example 1 is installed, the operating steps are as follows: Connect the left drive structure socket 7-1 and the right drive structure socket 7-2 to the drive structure 5 with plugs respectively, connect the household AC power supply to the main power socket 7-4, turn on the power switch 7-3, set the temperature and standby speed of the water tank 4, and start the water heater 8-6 and the water circulator 8-7.

[0066] Tighten the first stainless steel mesh 1-5 to the bottom of the annular vertical glass 1-7 through the skirt screws 1-8 and the inner threaded through holes of the skirt, slide the release cup horizontally through the mounting port 3-2 of the water tank top plate 3-1 to the release cup mounting hole 3-8, insert the left top plate cover 3-5 or the right top plate cover 3-6 between the square protrusion 3-3 on the upper surface and the protrusion 3-4 on the lower surface, move the left top plate cover 3-5 to the left or move the right top plate cover 3-6 to the right to make it contact with the release cup, and insert the middle top plate cover 3-7 between the left top plate cover 3-5 and the right top plate cover 3-6, and add the release medium into the release cup.

[0067] Pass the stirring shaft 1-1 of the ball-type stirring structure through the central circular hole of the release cup cover 3-9, screw it upward to the stirring mother shaft 5-10 through threads, insert the cross-shaped protruding rod 5-7 on the top of the stirring mother shaft 5-10 into the cross-shaped groove 5-6 on the top of the rotating shaft sleeve 5-3, tighten the internal threaded top cap 5-8 of the driving structure 5, lift the release cup cover 3-9 and pour the glass beads to the standard height, cover the release cup cover 3-9, insert the block 3-11 of the release cup cover 3-9 into the bayonet 3-13 of the release cup fixing block 3-12, and pass the long screw 3-14 through the release cup cover side ear through hole, the release cup side ear 2-10 through hole and the threaded through hole on the water tank top plate 3-1 to tighten and fix the release cup.

[0068] Insert the mobile temperature probe 9-3 into the release cup. When the temperature of the release medium in the release cup reaches the requirement, put the solid preparation to be tested into the release cup through the camera insertion hole of the release cup cover 3-9, and start stirring immediately to observe the in vitro release behavior of the solid preparation. When taking liquid for testing, insert the liquid collection needle into the corresponding insertion hole on the release cup cover 3-9 to extract the liquid sample.

[0069] After the test, unscrew the long screw 3-14, unscrew the stirring mother shaft 5-10 and the stirring shaft 1-1, lift the stirring mother shaft 5-10, remove the release cup cover 3-9 and the middle top plate cover 3-7 in turn, then pull out the left top plate cover 3-5 and the right top plate cover 3-6, slide the release cup together with the stirring device to the middle of the installation port 3-2 and take them out.

[0070] When the solid dosage form release tester is used, if the solid dosage form release structure for floating solid dosage forms of Example 2 is installed, the operating steps are as follows: Connect the left drive structure socket 7-1 and the right drive structure socket 7-2 to the drive structure 5 with plugs respectively, connect the household AC power supply to the main power socket 7-4, turn on the power switch 7-3, set the temperature and standby speed of the water tank 4, and start the water heater 8-6 and the water circulator 8-7.

[0071] The two layers of the second stainless steel mesh 2-4 are fixedly connected to the bottom of the cylindrical outer peripheral glass 2-2 through the annular outer wall screws, the outer peripheral internal threaded through holes, and the annular outer wall internal threaded through holes respectively, the release cup is slid horizontally to the release cup mounting hole 3-8 through the water tank top plate mounting port 3-2, the left top plate cover 3-5 or the right top plate cover 3-6 is inserted between the upper surface square protrusion 3-3 and the lower surface protrusion 3-4, the left top plate cover 3-5 is moved to the left or the right top plate cover 3-6 is moved to the right to make it contact with the release cup, and the middle top plate cover 3-7 is stuck between the left top plate cover 3-5 and the right top plate cover 3-6.

[0072] Pass the stirring shaft 1-1 of the floating stirring structure through the central circular hole of the release cup cover 3-9, screw it upward to the stirring mother shaft 5-10 through threads, lift the stirring mother shaft 5-10 to the highest position, add the release medium into the release cup, place the mother shaft fixing half ring 2-13 under the cross-shaped protruding rod 5-7 on the top of the stirring mother shaft 5-10, slowly lower the floating stirring structure, so that the upper surface of the top glass 2-1 of the floating stirring structure is close to the lower surface of the release cup cover 3-9, and the release cup cover 3-9 is placed on the release cup.

[0073] Insert the mobile temperature probe 9-3 into the release cup. When the temperature of the release medium in the release cup reaches the required level, lift the stirring mother shaft 5-10 and the release cup cover 3-9, add the solid preparation into the floating stirring structure through the dosing port 2-7, pinch the upper protruding blade 2-8 of the dosing port top cover 2-12 by hand to insert the dosing port top cover 2-12 into the dosing port 2-7, and slowly lower the floating stirring structure so that the cross-shaped protruding rod 5-7 on the top of the stirring mother shaft 5-10 is placed on the mother shaft fixed half ring 2-13, ensure that the upper surface of the top glass 2-1 of the floating stirring structure is close to the lower surface of the release cup cover 3-9, and put the release cup cover 3-9 Insert the block 3-11 into the bayonet 3-13 of the release cup fixing block 3-12, and pass the long screw 3-14 through the through hole of the release cup cover ear, the through hole of the release cup ear 2-10 and the threaded through hole on the water tank top plate 3-1 to tighten and fix the release cup; remove the mother shaft fixing half ring 2-13, insert the cross-shaped protruding rod 5-7 on the top of the stirring mother shaft 5-10 into the cross-shaped groove 5-6 on the top of the rotating shaft sleeve 5-3, and immediately tighten the internal threaded top cap 5-8 of the driving structure 5, and start stirring at the same time, observe the in vitro release behavior of the solid preparation, and when taking liquid for testing, insert the liquid collection needle into the corresponding insertion hole on the release cup cover 3-9 to extract the liquid sample; After the test, unscrew the long screw 3-14, unscrew the stirring mother shaft 5-10 and the stirring shaft 1-1, lift the stirring mother shaft 5-10, remove the release cup cover 3-9 and the middle top plate cover 3-7 in turn, then pull out the left top plate cover 3-5 and the right top plate cover 3-6, slide the release cup together with the stirring device to the middle of the installation port 3-2 and take them out.

[0074] Example 4 Testing and performance comparison of in vitro release behavior of solid preparations The solid preparation release tester of Example 3 and the ZB-1E intelligent disintegration tester (test temperature 37 oC, the release medium is water), Shenzhen Ruituo Instrument Equipment Co., Ltd. RT612 dissolution apparatus (paddle method, rotation speed 50 rpm, test temperature 37 ° C, release medium is water), the conventional excipients of solid preparations lactose, microcrystalline cellulose (Microcrystalline cellulose, MCC), cross-linked carboxymethyl cellulose sodium (Croscarmellose sodium, CCNa), magnesium stearate (Magnesiumstearate, MS) are mixed, granulated and tableted, and the test device and method of the present invention are tested for the ability to distinguish the release process of granules and tablets prepared with different process parameters and material ratios.

[0075] Table 1-1. Test of the ability of the ball stirring release structure and solid dosage form release tester and test method of the present invention to distinguish between the proportion of conventional excipients and the processing technology of tablets (test temperature 37°C, rotation speed 25rpm, release medium is water) Table 1-2 Test of the ability of the top floating release structure and solid preparation release tester and test method of the present invention to distinguish the proportion of conventional auxiliary materials and processing technology of particles (test temperature 37°C, rotation speed 35rpm, release medium is water) Note: (1) The tablet weight of the prepared tablet is 250±20 mg, the diameter is 8 mm, and the hardness is 90±10N.

[0076] (2) The parameters of the same process used for tablets and granules are the same, such as the mill speed is 25000 rpm and the time is 90 s, the hopper mixer mixing speed is 15 rpm and the time is 45 min, the wet granulator mixing speed is 700 rpm and the time is 15 min, the dry granulator air pressure is 0.4 mPa, the feeding speed is 14 rpm, the roller speed is 2 rpm, the roller gap is 0.2 mm, and the granulation speed is 285 rpm.

[0077] Table 2 Results of the ability of the in vitro release structure and solid preparation release tester and test method of the present invention to distinguish between conventional excipient ratios and processing techniques The results in Tables 1-1, 1-2 and 2 show that the testing device and method proposed in the present invention have obvious ability to distinguish the dosage and process of common materials in solid preparations, while the ability of the dissolution instrument to distinguish is mainly on the release time, and there is no ability to distinguish on the disintegration phenomenon. The ability of the disintegration instrument to distinguish is also mainly on the release time, and the ability to distinguish on the disintegration phenomenon is insufficient. The disintegration time of tablets tested by the three devices is similar.

[0078] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions proposed by the present invention and are not intended to limit the present invention. It should be understood by those skilled in the art that any changes, similar substitutions, or improved solutions that do not deviate from the corresponding concepts of the technical features of the present invention are included in the protection scope of the present invention. Contents not described in detail in this specification belong to the prior art known to professional and technical personnel in the field.

Claims

1. A solid preparation release structure, characterized in that: It includes a release cup and a ball-type stirring structure; the release cup is in the shape of a hollow cylinder, and the bottom is in the shape of an arc, an inverted cone or a flat bottom; the ball-type stirring structure includes a stirring shaft, an upper cone, a lower cylinder, a stirring blade, a first stainless steel mesh, a rigid ball, and an annular vertical glass; the lower part of the stirring shaft is fixedly connected to the upper cone, and the lower part of the upper cone is fixedly connected to the top of the lower cylinder; the stirring blade is fixedly connected to the lower outer wall of the lower cylinder, and the vertical center axis of the stirring shaft is coaxial with the vertical center axes of the annular vertical glass, the upper cone and the lower cylinder; the annular vertical glass is located at the lower inner side of the release cup, and the annular vertical glass is integrally formed with the inner wall of the release cup, and the bottom of the annular vertical glass is detachably and fixedly connected to the first stainless steel mesh, and the rigid ball is placed on the first stainless steel mesh; the stirring blade is 5 mm high, 12 mm wide and 16 mm long.

2. The solid preparation release structure according to claim 1, characterized in that: The rigid spherical beads are glass beads; the number of the stirring blades is 2 to 6; an inward and downward annular slope structure is formed between the upper end of the annular vertical glass and the inner wall of the release cup; the lower end of the annular vertical glass protrudes inward laterally to form a skirt structure, and the skirt structure is vertically provided with 2 to 6 skirt internal threaded through holes, and the first stainless steel mesh is detachably fixedly connected to the bottom of the annular vertical glass through skirt screws and skirt internal threaded through holes.

3. The solid preparation release structure according to claim 2, characterized in that: The bottom end of the release cup is arc-shaped; the middle part of the annular vertical glass is 6~15mm thick, the skirt structure width of the lower end of the annular vertical glass is 5~25mm, the first stainless steel mesh is 10~50mm away from the bottom of the release cup and 2~30mm away from the bottom of the lower cylinder; the diameter of the lower cylinder is 20~60mm and the height is 20~70mm, and the side of the lower cylinder is 10~30mm away from the annular vertical glass; the upper cone is 5~70mm high; the upper cone and the lower cylinder are made of 316 stainless steel material; the diameter of the rigid ball is 1~5mm, and the laying thickness of the rigid ball is: the top of the rigid ball is 15~95mm away from the first stainless steel mesh; the stirring blade is flat arc-shaped, and there are 3 stirring blades.

4. The solid preparation release structure according to any one of claims 1 to 3, characterized in that: The top edge of the release cup is folded outward by 90° o A circular flange is formed, and the circular flange and the outer wall of the release cup are integrally formed by hot pressing with hard polypropylene to form a wrapped flange. There is a release cup side ear with the same thickness on each side of the wrapped flange; the release cup side ear is 2-15mm high and 5-50mm wide; the upper outer wall of the stirring shaft is provided with an external thread.

5. A solid dosage form release tester, comprising a water tank top plate structure, a water tank, a driving structure, a supporting structure, a rear box body, a base support structure, and a control structure; the water tank top plate structure is located on the upper surface of the water tank, the driving structure is located on the upper part of the supporting structure, the supporting structure and the control structure are located on the upper surface of the water tank top plate structure, the rear box body is located below the water tank top plate structure, and the base support structure is located below the water tank and the rear box body; characterized in that, The solid dosage form release tester is equipped with the solid dosage form release structure as claimed in claim 4; the water tank top plate structure is detachably fixedly connected to the release cup side ear as claimed in claim 4; the driving structure is detachably fixedly connected to the stirring shaft of the solid dosage form release structure as claimed in claim 4; and the release cup cover is made of a transparent material.

6. The solid preparation release tester according to claim 5, characterized in that: The water tank top plate structure includes a water tank top plate, a release cup lid, and an installation opening located on one side of the water tank top plate. The installation opening penetrates the upper and lower surfaces of the water tank top plate. Above the front and rear edges of the installation opening, two upper surface square protrusions are respectively fixedly connected. The upper surface square protrusions are close to the left or right edge of the installation opening. Below the front and rear edges of the installation opening, lower surface protrusions corresponding to the positions of the upper surface square protrusions are fixedly connected. The lower surface protrusions are stepped, with a length covering the two upper surface square protrusions on the same side and being of the same length as the installation opening. A left top plate cover and a right top plate cover are movably inserted between the upper surface square protrusions and the lower surface protrusions. A middle top plate cover that is not blocked by the upper surface square protrusions is provided between the left top plate cover and the right top plate cover. Semi-circular release cup installation holes matching the release cup are provided on both left and right sides of the installation opening. Semi-circular holes matching the release cup installation holes are provided on the left top plate cover and the right top plate cover. The diameter of the release cup lid matches the upper opening of the release cup. On both left and right sides of the release cup lid, release cup lid side ears with the same shape and size as the release cup side ears are fixedly connected. On the front and rear side walls of the release cup lid side ears, protruding latch blocks are fixedly connected. On the left top plate cover, right top plate cover, and water tank top plate on both sides of the release cup, U-shaped release cup fixing blocks are fixedly connected. The release cup fixing blocks have fan-shaped depressions matching the release cup side ears and the release cup lid side ears. On the release cup fixing blocks, bayonet openings matching the latch blocks are provided. Long threaded through holes for long screws to pass through are provided on the water tank top plate, left top plate cover, right top plate cover, release cup side ears, and release cup lid side ears. Stainless steel half rings are bonded to the lower parts of the left, right, and front walls of the water tank top plate above the water tank. The two ends of the stainless steel half rings are fixedly bonded to the rear box body. The drive structure includes a support plate, a stepping motor, a rotating shaft sleeve, a synchronous belt pulley, a transmission belt, a cross-shaped groove, a cross-shaped convex rod, an internal thread top cap, an external thread column, and a stirring mother shaft. The rotating shaft of the stepping motor is fixedly connected to the synchronous belt pulley. The synchronous belt pulley and the rotating shaft sleeve are synchronously driven by the transmission belt. The rotating shaft sleeve is fixed on the support plate through a bearing. The outer ring of the bearing is fixedly connected to the support plate, and the inner ring of the bearing is fixedly connected to the outer wall of the rotating shaft sleeve. An external thread column is fixedly connected above the rotating shaft sleeve. A cross-shaped groove is provided at the top of the external thread column. A stirring mother shaft sleeve hole for inserting the stirring mother shaft is provided in the inner cavity of the external thread column. The stirring mother shaft sleeve hole penetrates the external thread column, the rotating shaft sleeve, and the support plate. The stirring mother shaft is slidably sleeved in the stirring mother shaft sleeve hole. A cross-shaped convex rod is provided at the top of the stirring mother shaft. The protrusions of the cross-shaped convex rod match the cross-shaped groove. An internal thread connection hole is provided at the lower part of the stirring mother shaft. The upper part of the stirring shaft is threadedly connected to the lower part of the stirring mother shaft. The external thread column is threadedly connected to the internal thread top cap;The support structure is cylindrical, including a hollow steel cylinder and a plastic cover. The rear end of the support plate is fixedly embedded in the middle inner cavity of the hollow steel cylinder. The stepper motor is located in the inner cavity of the hollow steel cylinder. The transmission belt passes through the outer wall of the steel cylinder and is rotatably connected to the rotating shaft sleeve. The plastic cover covers the transmission belt and the rotating shaft sleeve. The hollow steel cylinder vertically passes through the top plate of the water tank. The bottom of the hollow steel cylinder is horizontally extended to form an extension part. The extension part is provided with 3 to 9 extension part threaded through holes. The rear box base is provided with 3 to 9 base threaded through holes. The hollow steel cylinder is threadedly connected to the rear box base through the support structure fixing screws, the extension part threaded through holes, and the base threaded through holes. The base bracket structure includes an integrated square column, a support seat, and a water tank. The integrated square column comprises a support column, a lower iron plate for the water tank, a rear box body base, a water heater, a water circulator and a water circulation pipeline. The four corners of the bottom of the integrated square column are provided with 4 support seat threaded holes. The upper part of the support seat is fixedly connected to the support seat threaded column. The support seat threaded column is threadedly connected to the support seat threaded hole. The upper front section of the integrated square column is fixedly connected to 4 to 6 water tank support columns. The water tank is placed on the water tank support column through the lower iron plate of the water tank. The rear box body is placed on the rear box body base, and the rear box body base is placed on the upper rear section of the integrated square column. The water heater is fixed to the rear side of the integrated square column. The water circulator is fixedly connected to one side of the integrated square column. The water circulation pipeline is a three-head structure, one end of which is opened at the upper part of one side of the water tank, one end is opened at the bottom of the opposite side of the water tank, and one end is installed with A faucet for drainage, the water heater, water circulator, and water tank are connected through a water circulation pipeline; the control structure includes a PLC touch screen, a water tank temperature probe, and a mobile temperature probe, and a probe hole for inserting the water tank temperature probe is provided on the top plate of the water tank; there is a mirror on the front wall of the rear box body, and the side walls of the rear box body are respectively provided with a drive structure socket, a power switch, and a main power socket, the drive structure socket is connected to the stepper motor through a wire, the main power socket is connected to the 220V indoor power supply and the power switch through a wire, the power switch is connected to the power supply, the water heater, and the water circulator through the lower PCB circuit board, the power supply provides 24V DC voltage, 10A rated current, and is connected to the stepper motor, Motor driver, timer, water tank temperature probe, mobile temperature probe, PLC touch screen, PLC controller; the PLC touch screen is electrically connected to the PLC controller through the upper PCB circuit board, the PLC controller is connected to the lower PCB circuit board through the upper PCB circuit board, and regulates the timer, water heater, water circulator, stepper motor, motor driver, water tank temperature probe and mobile temperature probe signals; the release cup cover is respectively provided with insertion holes for the camera, mobile temperature probe, stirring mother shaft, stirring shaft and sampling needle; the middle top plate cover of the water tank top plate is 40~300mm long and 100~400mm wide, and the left top plate cover and the right top plate cover are 80~300mm long and 100~400mm wide on both sides;The distance between the support plate and the top plate of the water tank is 90-250 mm. ; 7. The solid dosage form release tester according to claim 6, characterized in that: The solid preparation release tester is also provided with a mother shaft fixing half ring, which is movably clamped between the cross-shaped groove and the top of the cross-shaped protruding rod; at least one positioning collar is fixedly bonded in the rotating shaft sleeve, and the positioning collar is made of wear-resistant hard polyformaldehyde plastic; the stirring mother shaft is slidably sleeved with the positioning collar.

8. The solid preparation release tester according to claim 7, characterized in that: The driving structure and the supporting structure each have two sets; the water heater is a PTC water heater; the driving structure socket on the side wall of the rear box body is divided into a left driving structure socket and a right driving structure socket, the left driving structure socket is connected to the stepper motor in the left driving structure through a wire; the right driving structure socket is connected to the stepper motor in the right driving structure through a wire; two positioning rings are fixedly bonded in the rotating shaft sleeve, and the positioning rings are located at the upper and lower ends of the inner cavity of the rotating shaft sleeve.

9. A method for detecting the in vitro release behavior of a solid preparation, characterized in that Using the solid preparation release tester according to claim 8, the method comprises the following steps: M1: Connect the left drive structure socket and / or the right drive structure socket to the corresponding drive structure with a wire, connect the household AC power supply to the main power socket, turn on the power switch, set the water tank temperature and the test speed, and start the water heater and water circulator; The first stainless steel mesh is connected to the bottom of the annular vertical glass through the skirt screws and the inner threaded through holes of the skirt, and tightened. The release cup is slid horizontally to the release cup mounting hole through the water tank top plate mounting opening. The left top plate cover and / or the right top plate cover are inserted between the square protrusion on the upper surface and the protrusion on the lower surface. The left top plate cover is moved to the left and / or the right top plate cover is moved to the right to make it contact with the release cup. The middle top plate cover is stuck between the left top plate cover and the right top plate cover, and the release medium is added into the release cup. The stirring shaft of the ball-type stirring structure is passed through the circular hole in the center of the release cup cover, and is screwed upward to the stirring mother shaft through a thread, and the cross-shaped protruding rod on the top of the stirring mother shaft is inserted into the cross-shaped groove on the top of the rotating shaft sleeve, and the internal threaded top cap of the driving structure is tightened, and the release cup cover is lifted and the glass balls are poured in, and the release cup cover is covered, and the block of the release cup cover is inserted into the bayonet of the release cup fixing block, and the long screw is passed through the side ear through hole of the release cup cover, the side ear through hole of the release cup, and the threaded through hole on the top plate of the water tank, and the release cup is tightened and fixed; Insert the mobile temperature probe into the release cup. When the temperature of the release medium in the release cup reaches the requirement, put the solid preparation to be tested into the release cup through the camera insertion hole on the cover of the release cup, and immediately start the stepper motor to observe the in vitro release behavior of the solid preparation. When taking liquid for testing, insert the liquid collection needle into the corresponding insertion hole on the cover of the release cup to extract the liquid sample; After the test, unscrew the long screw, unscrew the stirring mother shaft and the stirring shaft, lift the stirring mother shaft, remove the release cup cover and the middle top plate cover in turn, then pull out the left top plate cover and the right top plate cover, slide the release cup together with the stirring device to the middle of the installation port and take them out.

10. The method for detecting the in vitro release behavior of a solid preparation according to claim 9, characterized in that: The rigid balls in M1 are glass balls with a diameter of 1-5 mm; the aperture of the first stainless steel mesh in M1 is one of 18, 20, 24, 30, 40, and 50 meshes; the pH of the release medium in M1 is 1.0-8.0; the rotation speed of the stirring structure is 10-100 rpm; and the medium temperature is 20-45°C.

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