CN119619429A

CN119619429A - A solid preparation release structure and solid preparation release tester and test method

Info

Publication number: CN119619429A
Application number: CN202411824078.5A
Authority: CN
Inventors: 刘超; 宗剑飞; 孟庆廷
Original assignee: Qingzhou Yaowang Pharmaceutical Co ltd
Current assignee: Qingzhou Yaowang Pharmaceutical Co ltd
Priority date: 2020-10-23
Filing date: 2020-10-23
Publication date: 2025-03-14
Also published as: CN119738539A; CN112285306A; CN112285306B

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

Solid preparation release structure, solid preparation release tester and solid preparation release testing method

Technical Field

The invention belongs to the field of preparation inspection, and particularly relates to a solid preparation release structure, a solid preparation release tester and a solid preparation release testing method.

Background

The dissolution rate and disintegration time limit are conventional quality inspection indexes of medicines which are already marketed, and the dissolution rate and disintegration time limit of the medicines are provided with corresponding detection methods and index ranges in the pharmacopoeia of each country. The dissolution modes adopted by the conventional medicine dissolution detection instrument mainly comprise a basket method dissolution instrument and a paddle method dissolution instrument (such as a patent document CN201220241217.8 in China), a reciprocating cylinder method dissolution instrument (such as a patent document CN201921215456.4 in China), a flow tank method dissolution instrument and a disintegration instrument (such as a patent document CN201911045888.X in China). Such drug dissolution testing apparatus typically have a base for supporting the apparatus, a water tank for regulating and maintaining the temperature, a stirring or lifting structure for causing movement of the drug and corresponding control motors, a release cup for containing simulated digestive tract fluid or dissolution medium, a heating structure for regulating the temperature, etc., the dissolution cup typically being 1000ml in volume, and the motor for controlling rotation of the stirring structure typically being a stepper motor. Typical drug release detection instruments are a Tian Fa RC12ADK dissolution tester, a Fu Ke Si FADT-800RC/1200RC automatic dissolution tester, a Hanson RESEARCH ELITE 8 dissolution tester, an Agilent 708-DS dissolution tester, a Tian Fa ZB-lE intelligent disintegration tester and the like.

The release cup of this kind of dissolution appearance adopts detachable mode to be fixed in the water tank, is usually with a big transparent cover through manual pull down's mode push down all dissolution cups, leave all release cups through manual lifting mode, perhaps set up by the vertical axis, with the spring that vertical axis slip cup jointed and the fixation clamp that sets up the separation blade of water tank upper surface and spring bottom constitute at the water tank board, when lifting the separation blade, the spring shrink, rotatable separation blade makes it can not cover the release cup inserted port this moment, after waiting to insert the release cup, rotatory separation blade makes it cover release cup and bowl cover outside thereof, then release the separation blade, the separation blade compresses tightly the release cup under the spring deformation effect this moment. The dissolution instrument is provided with a temperature control and temperature detection structure, a rotating speed regulation and control and rotating speed regulation structure and a liquid crystal display screen, and temperature information, rotating speed information and the like are displayed on the display screen. The stirring structure is connected with the synchronous belt of the motor through the stirring shaft, and when the motor rotates, the synchronous belt drives the rotating shafts to rotate, so that the rotating shafts drive the stirring structure to rotate in the release cup, and the stirring function is realized. The stirring structure is fixed on the same iron plate and is controlled to lift by a lifting motor so as to realize the taking and placing of the release cup and the stirring shaft and the height setting of the paddle basket and the sampling needle position. A conventional dissolution instrument, such as a Rui Tuo RT612 dissolution experimental instrument, has a typical structure including a water tank, a rear box body, a release cup, a motor, a controller, a paddle shaft, a sampling needle lifting column and the like.

However, the release data detected by the conventional dissolution and disintegration apparatuses in the market are mainly used for evaluating the quality consistency between batches in the production process of the same medicine after batch acquisition or evaluating the quality consistency of the medicine after process change and detecting indexes of new preparation research and development, are longer than release data acquisition in design and shorter than detail phenomenon observation, and intangibly cause the defects of heavy data and light phenomenon in the research and development process. Since erosion or disintegration of solid formulations is generally more representative of the expression release profile during development than data, this allows for more adaptation of common dissolution and disintegration data to quality control than research and development.

For example:

1. The solid preparation is disintegrated or eroded in the paddle method dissolution detection process, the accumulation body deposited in the middle of the dissolution cup is difficult to observe and distinguish the release process, the dissolution data cannot truly embody the release characteristics when severe, and the method distinguishing force is difficult to guarantee when the stirring speed is improved.

2. The dissolution rate detection by the basket method is difficult to observe the release phenomenon of the solid preparation in the basket.

3. The dissolution rate and disintegration time limit detection by the reciprocating cylinder method can be fast due to the fluctuation of the solid preparation movement, and the one-sided change condition can not be clearly observed.

4. The dissolution rate of the flow cell method pays attention to the application of slow release drugs, has insufficient observation capability on the release phenomenon of a quick release solid preparation, and is difficult to embody the movement state of the solid preparation.

Based on the above circumstances, it is necessary to develop a new device for testing the in vitro release phenomenon of solid preparation, so that the solid preparation moves on a curved surface dynamically at a slow speed to simulate the continuous diastole and systole movement modes of the gastrointestinal tract, and ensure clear observation, deep analysis and reasonable judgment of the disintegration or erosion phenomenon of the solid preparation.

Disclosure of Invention

Aiming at the prior art, one of the purposes of the invention is to provide a solid preparation release structure, so as to overcome the defect that the conventional dissolution instrument or disintegration instrument is difficult to observe in-vitro release behaviors of the solid preparation in detail, including the changing forms of tablet surfaces and disintegration particles, so that the solid preparation release structure can be used for testing and observing the disintegration characteristics of the solid preparation and the release degree of active ingredients, and the solid preparation can continuously move on an S-shaped interface in the instrument, thereby being more beneficial to simulating the physical effect of continuous diastole and contraction movement modes of gastrointestinal tracts in vivo on the solid preparation.

In order to achieve the above purpose, the technical scheme of the invention is as follows:

For non-buoyant solid formulations, the major components of the solid formulation delivery structure of the present invention include a delivery cup and a ball-and-bead stirring structure. The release cup is hollow cylindrical, and the bottom of the release cup is arc-shaped or inverted cone-shaped or flat-bottom-shaped and is used as a container for containing a release medium for testing the in-vitro release behavior of the solid preparation. The ball type stirring structure is used for stirring balls in the release cup and driving the solid preparation to be tested to move. To maintain agitation stability, the vertical central axis of the ball-and-socket agitation structure must be coaxial with the vertical central axis of the release cup.

Unlike the dissolving out structure of paddle, basket and reciprocating cylinder in the prior art, the ball stirring structure of the solid preparation releasing structure comprises a stirring shaft, an upper cone, a lower cylinder, stirring blades, a first stainless steel net, rigid balls and annular vertical glass. Wherein the upper cone and the lower cylinder are preferably hollow structures. The stirring shaft is used for driving the upper cone and the lower cylinder to rotate, so that the lower part of the stirring shaft is fixedly connected with the upper cone, and the lower part of the upper cone is fixedly connected with the top of the lower cylinder. In order to make the rotation more stable and improve the stability of structural connection, the circular interface between the upper cone and the lower cylinder can be a circular plate, and the material of the circular interface is the same as that of the upper cone and the lower cylinder, namely, 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 with the center of the circular plate and the top of the upper cone. The upper cone and the lower cylinder may also be solid structures. At this time, the lower part of the stirring shaft of the ball-type stirring structure is fixedly connected with the upper cone. But such bead-type stirring structures are themselves heavy.

The stirring blade is fixedly connected with the outer wall of the lower part of the lower end cylinder, the vertical center shaft of the stirring shaft is coaxial with the vertical center shaft of the annular vertical glass, the annular vertical glass is positioned at the lower part of the 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 and fixedly connected with a first stainless steel net, and the rigid ball is arranged on the first stainless steel net. Wherein, the rigid ball can be stainless steel ball, glass ball, polymeric plastic ball or PVC-coated glass ball.

After a release medium and a solid preparation to be detected are added into a release cup, an external motor drives a stirring shaft to rotate, rigid balls on a first stainless steel net of the structure move under the drive of stirring paddles, and the ball is staggered, concave-convex and changed to present an S-shaped interface, so that the solid preparation is slowly moved and slightly collided on the interface, and the extrusion effect of continuous diastole and systole movement modes of gastrointestinal tracts on the solid preparation is simulated. The ball gaps can contain the disintegrating matters and the movement effect, so that the phenomenon that the dissolution effect is influenced due to accumulation bodies after the medicine disintegrates can be avoided. Meanwhile, the disintegration speed and phenomenon on the surface of the solid preparation, the morphology and the size of the disintegrated substance floating in the medium, spreading on the interface of the ball and sinking in the ball can be clearly observed, the in-vitro release characteristics of the solid preparation can be conveniently and fully analyzed, and the disintegration and release characteristics of the solid preparation in the gastrointestinal tract can be better simulated.

In a preferred scheme, the rigid ball is glass balls, the stirring blades are 2-6, 3 stirring blades are optimal in consideration of the limit and economic cost of stirring, an inward 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 a plane and not entering the stirring structure when being put into the stirring structure, the lower end of the annular vertical glass transversely protrudes inwards to form a skirt structure, and 2-6 skirt internal thread through holes, preferably 3 skirt internal thread through holes, are vertically distributed on the skirt structure, so that the first stainless steel mesh can be detachably and fixedly connected with the bottom of the annular vertical glass through screws and the skirt internal thread through holes, namely the screws are screwed into the skirt internal thread through holes after penetrating through meshes of the first stainless steel mesh, and the threaded connection is convenient for mounting and dismounting the first stainless steel mesh.

In a further preferred scheme, the release cup is a circular arc-shaped release cup with the bottom end, the thickness of the middle part of the annular vertical glass is 6-15 mm, preferably 10mm, the width of the skirt structure at the lower end of the annular vertical glass is 5-25 mm, preferably 10mm, the first stainless steel mesh is 10-50 mm from the bottom of the release cup and 2-30 mm from the bottom of the lower cylinder, preferably 25mm from the bottom of the release cup and 8mm from the bottom of the lower cylinder, the diameter of the lower cylinder is 20-60 mm, the height is 20-70 mm, preferably 40mm and the height is 40mm, the side surface of the lower cylinder is 10-30 mm, preferably 20mm from the annular vertical glass, the height of the upper cone is 5-70 mm, preferably 20mm, the upper cone and the lower cylinder are made of 316 stainless steel materials, the diameter of rigid steel balls is 1-5 mm, the laying thickness of the rigid ball tops are 15-95 mm, preferably 35mm from the first stainless steel mesh after the ball stirring structure is fixed, the heights of the stirring paddles are flat, the heights of 15-2 mm-30 mm, the heights of the rigid steel balls are 40mm, the heights of the 15-40 mm, the heights of the rigid steel balls are 28-12 mm, and the lengths of the circular arc-shaped paddles are 28mm, and the heights of the rigid balls are 28mm and 15-12 mm.

In another further optimized scheme, the top edge of the release cup is turned outwards by 90 ^o to form a circular flange, the circular flange and the outer wall of the release cup are integrally formed into a cladding flange by hard polypropylene through hot pressing, two sides of the cladding flange are respectively provided with a release cup side lug with the same thickness as the cladding flange, the height of the release cup side lug is 2-15 mm, the width of the release cup side lug is 5-50 mm, the height is 8mm, the width is 22mm preferably, and the outer wall of the upper part of the stirring shaft is provided with external threads. As the stirring shafts of the existing similar solid preparation dissolution testing device are connected with the rotating shaft driven by the motor through threads. Therefore, the external thread of the outer wall of the upper part of the stirring shaft provides a connecting end for the connection of the solid preparation release structure and the existing solid preparation release testing device. The wrapping type flanging at the top edge of the release cup is convenient for fixing the release cup.

For a buoyant solid formulation, the major components of the solid formulation delivery structure of the present invention include a delivery cup and a buoyant agitation structure. The release cup is hollow cylindrical, and the bottom of the release cup is arc-shaped or inverted cone-shaped or flat-bottom-shaped and is used as a container for containing a release medium for testing the in-vitro release behavior of the solid preparation. The floating stirring structure is used for stirring a release medium in the release cup and driving the solid preparation to be tested to move. To maintain agitation stability, the vertical central axis of the floating agitator structure must be coaxial with the vertical central axis of the release cup.

Unlike the paddle method, basket method and reciprocating cylinder method in the prior art, the floating stirring structure of the solid preparation releasing structure comprises a stirring shaft, top glass, cylindrical peripheral glass, columnar solid glass and a second stainless steel net. The top glass is fixedly connected with the top of the cylindrical outer periphery glass, and the top glass and the cylindrical outer periphery glass are transparent glass. The bottom surface of the top glass is fixedly connected with 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 larger than that of the columnar solid glass. The diapire fixedly connected with of top glass is 2~6 flat arcuation protruding bodies, preferably 4. A circular through hole is arranged between the flat arc-shaped protruding bodies of the top glass for the floatable particles generated in the solid preparation dissolution and release process to pass through, at least one administration port is also arranged on the top glass, the administration port is arranged in the middle of the flat arc-shaped protruding bodies, namely, an opening is arranged in the middle of the flat arc-shaped protruding bodies, and the opening penetrates through the flat arc-shaped protruding bodies of the top glass and the bottom wall of the top glass. In order to cover the administration port after administration, an administration port top cover is also arranged. The top cover of the dosing opening is matched with the opening of the dosing opening in shape, can be inserted into the dosing opening to play a role in blocking, the upper part of the top cover of the dosing opening is fixedly connected with an upper protruding blade, the upper protruding blade can play a role in driving water flow during stirring, and the top cover of the dosing opening can also be used as a handle of the top cover of the dosing opening for picking up and inserting the top cover of the dosing opening. When the number of the administration openings is two, the administration openings are preferably arranged on the two opposite flat arc-shaped bulges. When the medicine feeding port is one, the other upper protruding blade is preferably fixedly connected with the upper surface of the top glass corresponding to the opposite side flat arc-shaped protruding body. The two upper protruding paddles can better drive water flow during stirring and avoid shaking of the stirring structure.

The flat arc-shaped bulge in the structure can also be a hollow structure, and the administration port is an opening on the upper surface and the lower surface of the flat arc-shaped bulge.

The bottom of the glass at the cylindrical periphery is detachably and fixedly connected with two layers of second stainless steel nets, the aperture of the second stainless steel net at the upper layer is larger than that of the second stainless steel net at the lower layer, the vertical center shaft of the stirring shaft is coaxial with the vertical center shaft of the top glass, and the lower part of the stirring shaft is fixedly connected with the top glass and the columnar solid glass.

After a medium and a solid preparation to be tested are added into the release cup, the external motor drives the stirring shaft to rotate, and the flat arc-shaped protruding body of the structure drives liquid at the lower side of the top glass to flow, so that the solid preparation is promoted to transversely float in a space surrounded by the top glass, the cylindrical peripheral glass, the columnar solid glass and the second stainless steel mesh. The solid preparation floats in the medium and continuously contacts with the S-shaped interface of the flat arc-shaped bulge body of the top glass, so that the solid preparation can float longitudinally in a space surrounded by the top glass, the cylindrical peripheral glass, the columnar solid glass and the second stainless steel mesh rather than tightly contact with the top glass under the stirring state. The circular through holes on the top glass can penetrate the floating disintegrants upwards, the big and small meshes of the two layers of second stainless steel meshes can intercept the settling disintegrants downwards, the morphology and the proportion of the disintegrants with different densities and sizes can be obviously distinguished, and the disintegration characteristics of the floating solid preparation can be conveniently observed and analyzed. The upper protruding paddle of the structure drives the liquid on the upper side of the top glass to flow, so that the disintegrants on the top glass are promoted to diffuse so as to be convenient for observation. Meanwhile, the disintegration speed and phenomenon on the surface of the solid preparation can be clearly observed, and the in-vitro release characteristics of the solid preparation can be conveniently and fully analyzed. 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.

In a further preferred scheme, the bottom end of the release cup is arc-shaped, the diameter of the top glass is 40-80 mm, preferably 75mm, the number of circular through holes in the top glass is 4× 8~4 ×25, preferably 4×14, the diameter of the circular through holes in the top glass is 0.4-3 mm, preferably 1mm, the administration opening is rectangular, the length is 12-20 mm, the width is 7-15 mm, preferably 16mm, the width is 9mm, the upper protruding blades are 5-20 mm, the width is 1-10 mm, preferably 8mm, the width is 2mm, the flat arc-shaped protrusions are 2-20 mm, the width is 5-30 mm, the length is 10-30 mm, preferably 8mm, the width is 15mm, the length is 20mm, the diameter of the circular through holes in the top glass is 10-45 mm, preferably 35mm, the side surface of the cylindrical solid glass cylinder is 10-30 mm, preferably 20mm from the inner wall of the cylindrical outer periphery, the upper layer and the lower layer of the second stainless steel mesh are separated from each other by a distance of 16-50 mm, the upper annular stainless steel mesh is preferably 10-50 mm, the annular stainless steel mesh is connected with the outer periphery of the inner periphery of the two annular stainless steel through holes, the annular stainless steel inner periphery and the annular stainless steel wire is preferably connected with the outer periphery of the annular stainless steel is formed by the annular stainless steel inner periphery, and the annular stainless steel wire is preferably has the annular stainless steel inner through holes and the annular stainless steel wire is formed by the annular stainless steel inner stainless steel and the inner stainless steel has the stainless steel wire has the inner through holes.

In another further optimized scheme, the top edge of the release cup is turned outwards by 90 ^o to form a circular flange, the circular flange and the outer wall of the release cup are integrally formed into a cladding flange by hard polypropylene through hot pressing, two sides of the cladding flange are respectively provided with a release cup side lug with the same thickness as the cladding flange, the height of the release cup side lug is 2-15 mm, the width of the release cup side lug is 5-50 mm, the height is 8mm, the width is 22mm preferably, and the outer wall of the upper part of the stirring shaft is provided with external threads.

The solid preparation release structures for the non-floatable solid preparation and the floatable solid preparation can be detachably and fixedly connected with the stirring mechanism of the existing dissolution instrument by means of a stirring shaft, such as a paddle method and basket method stirring mechanism which can be connected with a Rui Tuo RT612 dissolution experimental instrument. The release cup can be detachably and fixedly connected with the existing dissolution instrument, such as a release cup jack which can be placed into the Rui Tuo RT612 dissolution experiment instrument, and can be detachably and fixedly connected with the release cup jack by virtue of a fixing structure. Wherein one dissolution instrument may carry one or more identical or different solid formulation release structures, for example, one dissolution instrument may carry 2 to 6 of the above solid formulation release structures for non-buoyant solid formulations or 2 to 6 of the above solid formulation release structures for buoyant solid formulations, and may also carry 3 of the above solid formulation release structures for non-buoyant solid formulations and 3 of the above solid formulation release structures for buoyant solid formulations, etc.

The invention also provides a solid preparation release tester for detecting the solid preparation in-vitro release behavior, namely the in-vitro release dynamic characteristic of the solid preparation by using the solid preparation release structure, which has an overall structure partially similar to that of a Rui Tuo RT612 dissolution experiment instrument. The solid preparation release tester comprises a water tank top plate structure, a water tank, a driving structure, a supporting structure, a rear box body, a base bracket structure and a control structure, and can be provided with any solid preparation release structure. Wherein, bearing structure and control structure are located water tank roof structure upper surface, and drive structure is located bearing structure upper portion, and water tank roof structure is located water tank upper surface, and the rear box is located water tank roof structure below and the rear of water tank, and base support structure is located water tank, rear box below. The water tank top plate structure is detachably and fixedly connected with the release cup side lug, the driving structure is detachably and fixedly connected with the stirring shaft of the solid preparation release structure, and the release cup cover is made of transparent materials.

In a preferred scheme, the water tank top plate structure comprises a water tank top plate, a release cup cover and a mounting opening positioned at one side of the water tank top plate, wherein the mounting opening penetrates through the upper surface and the lower surface of the water tank top plate, two upper surface square protruding parts are fixedly connected above the front edge and the rear edge of the mounting opening respectively, the upper surface square protruding parts are close to the left side edge or the right side edge of the mounting opening, lower surface protruding parts corresponding to the positions of the upper surface square protruding parts are fixedly connected below the front edge and the rear edge of the mounting opening, and the lower surface protruding parts are in a step shape, cover the two upper surface square protruding parts at the same side in length and are equal in length with the mounting opening. Semicircular release cup mounting holes matched with the release cups are formed in the left side and the right side of the mounting opening. In 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 protruding part and the lower surface protruding part, a middle top plate cover which is not blocked by the upper surface square protruding part is arranged between the left top plate cover and the right top plate cover, and semicircular holes matched with the release cup installing holes are formed in the left side of the left top plate cover and the right side of the right top plate cover. The diameter of the cup cover of the release cup is matched with that of an upper opening of the release cup, the left side and the right side of the cup cover of the release cup are fixedly connected with cup cover side lugs which are the same as the cup side lugs in shape and size, the front side wall and the rear side wall of the cup cover side lugs of the release cup are fixedly connected with raised clamping blocks, the left top plate cover, the right top plate cover and the top plate of the water tank on two sides of the release cup are fixedly connected with 匚 -shaped release cup fixing blocks, the release cup fixing blocks are provided with sector-shaped depressions matched with the cup side lugs and the cup cover side lugs, and the release cup fixing blocks are provided with bayonets matched with the clamping blocks. The bayonet of the release cup fixing block and the clamping block of the side lug of the release cup cover can accurately fix the position of the release cup cover through clamping, so that operations such as medicine administration, observation, sampling, shooting and the like on the release cup cover in the test process do not influence the release cup, and further the stable and precise placement position of the release cup is kept. In addition, a long thread through hole for a long screw to pass through is arranged on the top plate, the left top plate cover, the right top plate cover, the edge lug of the release cup cover and the edge lug of the release cup cover, and the long screw can further play a role in fixing the release cup. In the case of installing three or more release cups, the left top plate cover and the right top plate cover can be multiple, and semicircular holes matched with the release cup installing holes are formed on the left side and the right side of the left top plate cover and the right top plate cover except for the left top plate cover and the right top plate cover adjacent to the middle top plate cover so as to insert the release cups through the semicircular holes of the left top plate cover or the right top plate cover adjacent to the middle top plate cover.

The left, right and lower parts of the front wall of the water tank top plate are fixedly adhered with a stainless steel half ring which is used for lifting and fixing the water tank top plate above the water tank, two ends of the stainless steel half ring are fixedly adhered with a rear tank body, and the cup cover of the release cup is respectively provided with an insertion hole for inserting a camera, a movable temperature probe, a stirring mother shaft, a stirring shaft and a sampling needle. The sampling needle can be sleeved with the rubber plug at the needle cylinder part, and the sampling needle is fixed to the height above the insertion hole by means of the expanded rubber plug. The sampling needle head can be made of 316 stainless steel. The needle head of the sampling needle can also be a bent needle head, and the bent angle is 100 degrees or 130 degrees. The water tank can be an integrated seamless circular arc groove so as to facilitate the water flow distribution in the interior, and can also be a rectangular groove formed by bonding 5 transparent acrylic plates. When the water tank is an integrated seamless circular arc groove, the release cup is not overlapped with the projection of the circular arc corner of the water tank after being installed, namely, the circular arc corner of the water tank does not shade the release cup when being observed from the front side or the left side and the right side, and the shape of an image is obviously changed by the circular arc corner in the observation process.

In a preferred scheme, the aforesaid drive structure includes backup pad, step motor, the pivot sleeve, synchronous pulley, a driving belt, the cross recess, cross protruding pole, internal thread hood, external screw thread post and stirring female axle, step motor's pivot fixed connection synchronous pulley, synchronous pulley passes through drive belt synchronous drive with the pivot sleeve, the pivot sleeve is fixed in the backup pad through the bearing, the outer lane and the backup pad fixed connection of bearing, the inner circle and the pivot cover outer wall fixed connection of bearing, pivot sleeve top fixed connection external screw thread post, external screw thread post top is equipped with cross recess, the middle part of external screw thread post is equipped with and supplies stirring female axle male stirring female axle sleeve hole, stirring female axle sleeve hole link up external screw thread post, pivot sleeve and backup pad, stirring female axle slip cup joints in stirring female axle sleeve hole, stirring female axle top is equipped with cross protruding pole, the protruding and cross recess phase-match of cross protruding pole, stirring female axle lower part is equipped with the internal thread connecting hole, stirring female axle upper portion and stirring female axle lower part threaded connection, external screw thread post and internal screw thread hood threaded connection. The stirring female shaft is inserted into the sleeve hole of the stirring female shaft, the cross-shaped protruding rod at the top end is clamped with the cross-shaped groove, the internal thread top cap is in threaded connection with the external thread column, and the stirring female shaft can rotate along with the rotating shaft sleeve. When the internal thread top cap is unscrewed and the cross-shaped convex rod is lifted, the stirring female shaft can not rotate along with the rotating shaft sleeve. Preferably, the solid preparation release tester is further provided with a female shaft fixing half ring, the female shaft fixing half ring is movably clamped between the cross-shaped groove and the top end of the cross-shaped protruding rod, at least one positioning sleeve ring is fixedly adhered in the rotating shaft sleeve, the positioning sleeve ring can be made of wear-resistant hard polyoxymethylene plastic, and the stirring female shaft is in sliding sleeve joint with the positioning sleeve ring. Wherein, the locating lantern ring can prevent that the stirring female shaft from taking place to rock when rotating in the pivot sleeve. Therefore, the number of the positioning lantern rings is preferably 2, and the positioning lantern rings are distributed at the upper end and the lower end of the inner cavity of the rotating shaft sleeve. The female axle retainer half ring can be used for inserting between cross recess and the cross protruding pole top when the female axle of stirring lifts, prevents the female axle of stirring landing. The female shaft retainer half ring is particularly suitable for temporary lifting and position fixing of a floating stirring structure.

In a preferred scheme, the supporting structure is cylindrical and comprises a hollow steel column body and a plastic outer cover, the rear end of the supporting plate is fixedly embedded into the middle inner cavity of the hollow steel column body, the stepping motor is located in the inner cavity of the hollow steel column body, the transmission belt penetrates through the outer wall opening of the steel column body and is rotationally connected with the rotating shaft sleeve, the plastic outer cover covers the transmission belt and the rotating shaft sleeve, the hollow steel column body vertically penetrates through the water tank top plate, the bottom of the hollow steel column body horizontally extends to form an extension part, 3-9 extension part threaded through holes are formed in the extension part, 3-9 base threaded through holes are formed in the base of the rear box body, and the hollow steel column body is in threaded connection with the base of the rear box body through supporting structure fixing screws and the extension part threaded through holes. The support structure can be fixedly connected to the rear box base through the extension portion threaded through hole, the base threaded through hole and the threaded connection of the support structure fixing screw.

In a preferred scheme, the base support structure comprises an integrated square column, a support seat, a water tank support column, a lower water tank iron plate, a rear box base, a water heater, a water circulator and a water circulation pipeline, wherein 4 support seat threaded holes are formed in four corners of the bottom of the integrated square column, the upper part of the support seat is fixedly connected with a support seat threaded column, and the support seat threaded column is in threaded connection with the support seat threaded holes. 4~6 water tank support columns of integration square column upper portion anterior segment fixed connection, water tank are placed on the water tank support column through the water tank lower iron plate, and the back box is placed on the back box base, and the integration square column upper portion rear segment is placed to the back box base, and the water heater is fixed in integration square column rear side. The water circulator is fixedly connected to one side of the integrated square column, the water circulation pipeline is of a three-head structure, one end of the water tank is opened at the upper part of one side of the water tank one end of the water tank is opened at the bottom of the opposite side of the water tank one end is provided with a water tap for draining water. For example, a water circulation pipe is opened at one end to the upper right side of the water tank, at one end to the bottom left side of the water tank, and at one end is provided with a water tap for draining water. The water heater, the water circulator and the water tank are communicated through the water circulation pipeline so as to regulate and control the temperature of the liquid in the water tank.

In a preferred scheme, the control structure comprises a PLC touch screen, a water tank temperature probe and a movable temperature probe, wherein a probe hole for inserting the water tank temperature probe is formed in a top plate of the water tank, a mirror is arranged on the front wall of the rear box body, the mirror faces one side of the water tank, and images at the rear part of the release cup can be observed through the mirror. The side wall of the rear box body is respectively provided with a driving structure socket, a power switch and a total power socket, the driving structure socket is connected with a stepping motor through a wire, the total power socket is connected with a 220V indoor power supply and the power switch through a wire, the power switch is connected with a power supply device, a water heater and a water circulator through a lower PCB circuit board, the power supply device provides 24V direct-current voltage and 10A rated current, the stepping motor, a motor driver, a timer, a water tank temperature probe, a movable temperature probe, a PLC touch screen and a PLC controller are connected through the lower PCB circuit board, the PLC controller is connected with the lower PCB circuit board through the upper PCB circuit board, and signals of the timer, the water heater, the water circulator, the stepping motor, the motor driver, the water tank temperature probe and the movable temperature probe are regulated and controlled. Wherein, the water heater can select PTC water heater. The driving structure sockets and the stepping motors can be connected in a one-to-one mode, namely, each driving structure socket is connected in series with one stepping motor through a wire, or in a one-to-many mode, namely, a plurality of stepping motors are connected in parallel and then connected in series with one driving structure socket through a wire. The plug can be connected with the stepping motor by using the lead of the plug, and the plug is inserted into the driving structure socket when the stepping motor needs to be used.

In a further preferred scheme, the arc width of one side of the edge lug of the release cup close to the mounting hole of the release cup is 1/5 of the circumference of the mounting hole of the release cup, the length of the middle top plate cover of the water tank top plate is 40-300 mm, the width is 100-400 mm, the length is 105mm, the longitudinal width is 180mm, the transverse length of two sides of the left top plate cover and the right top plate cover is 80-300 mm, the longitudinal width is 100-400 mm, the transverse length of two sides is 115mm, the longitudinal width is 180mm, the distance between the supporting plate and the water tank top plate is 90-250 mm, the distance between the supporting plate and the water tank top plate is 140mm, and the number of the extending ring through holes fixedly connected with the bottom of the hollow steel cylinder and the threaded holes of the base of the rear box body is 6.

The stepper motor can be a 56BYG250CK type stepper motor, the temperature probe can be a TMP115 type temperature probe, the stepper motor and the temperature probe can be directly purchased in a network or the market, and the principle is a well-known technology of the person skilled in the art and will not be described herein.

The invention also provides a method for detecting the in-vitro release behavior of the solid preparation, which is matched with the solid preparation release tester for use:

The non-floatable solid preparation includes the steps of connecting the socket of the driving structure to the driving structure via wire, connecting the household AC power source to the socket of the main power source, turning on the power switch, setting the temperature of the water tank and the rotation speed for test, and starting the water heater and the water circulator. When the driving structure sockets are connected with the stepping motors one by one, the stepping motors corresponding to the 1 or more stepping motors to be started, namely the release cups to be used, are communicated with the corresponding driving structure sockets through wires. When the driving structure socket is connected with the stepping motor in a one-to-many mode, the driving structure socket can be connected with the driving structure through a wire, and a release cup and corresponding components required for stirring which are not used are not required to be installed.

The first stainless steel net is screwed with the annular vertical glass bottom through the skirt screw and the skirt internal thread through hole, the release cup transversely slides to the release cup mounting hole through the water tank top plate mounting hole, the left top plate cover and/or the right top plate cover (namely, the top plate cover corresponding to the used release cup and the stepping motor) are inserted between the square protruding part on the upper surface and the protruding part on the lower surface, the left top plate cover is moved left and/or the right top plate cover is moved right to be in contact with the release cup, the middle top plate cover is clamped between the left top plate cover and the right top plate cover, and release medium is added into the release cup.

The stirring shaft of the ball type stirring structure penetrates through a central round hole of the cup cover of the release cup, the stirring female shaft is screwed up through threads, a cross-shaped protruding rod at the top of the stirring female shaft is clamped into a cross-shaped groove at the top of the rotating shaft sleeve, an internal thread top cap of the driving structure is screwed, the cup cover of the release cup is lifted, glass balls are poured into the cup cover of the release cup, the cup cover of the release cup is covered, a clamping block of the cup cover of the release cup is inserted into a bayonet of a fixing block of the release cup, and a long screw penetrates through a lug through hole of the cup cover of the release cup, a lug through hole of the release cup and a threaded through hole on a top plate of the water tank to screw down and fix the release cup.

And inserting the movable temperature probe into the release cup, putting the solid preparation to be tested into the release cup through the camera insertion hole of the cup cover of the release cup after the temperature of the release medium in the release cup reaches the requirement, immediately starting stirring, observing the external release behavior of the solid preparation, and inserting the liquid taking needle into the corresponding insertion hole on the cup cover of the release cup to extract the liquid sample during liquid taking detection.

After the test is finished, the long screw is screwed out, the stirring female shaft and the stirring shaft are unscrewed, the stirring female shaft is lifted, the cup cover of the release cup and the middle top plate cover are sequentially taken down, the left top plate cover and the right top plate cover are pulled out, and the release cup and the stirring device are respectively slid towards the middle of the mounting opening and taken out.

The floating solid preparation comprises connecting the drive structure socket with a wire, connecting the household AC power supply with the main power socket, turning on the power switch, setting the water tank temperature and test rotation speed, and starting the water heater and water circulator;

The two layers of second stainless steel meshes are fixedly connected with the bottom of the cylindrical outer peripheral part glass through annular outer wall screws, outer peripheral inner thread through holes and annular outer wall inner thread through holes respectively, a release cup transversely slides to a release cup mounting hole through a water tank top plate mounting hole, a left top plate cover or a right top plate cover is inserted between an upper surface square protruding part and a lower surface protruding part, the left top plate cover is moved left and/or the right top plate cover is moved right to be contacted with the release cup, and a 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 penetrates through the central round hole of the cup cover of the release cup, and is screwed to the stirring female shaft upwards through threads, so that the stirring female shaft is lifted to the highest position, and at the moment, the whole floating stirring structure is higher than the upper edge of the release cup, so that release medium can be added into the release cup, and the influence on the test result caused by the fact that the floating stirring structure contacts with the medium too early is avoided. The female shaft retainer half ring is placed below the cross-shaped protruding rod at the top of the stirring female shaft, the floating stirring structure is slowly lowered, the upper surface of top glass of the floating stirring structure is abutted against the lower surface of the cup cover of the release cup, the cup cover of the release cup is placed on the release cup, and at the moment, the floating stirring structure is integrally higher than the liquid level of the medium, so that the floating stirring structure can be prevented from being in contact with the medium too early.

And inserting the movable temperature probe into the release cup, and lifting the positions of the stirring female shaft and the cup cover of the release cup after the temperature of the release medium in the release cup reaches the requirement, wherein the upper surface of the top glass of the floating stirring structure is exposed at the moment, so that the solid preparation can be added into the floating stirring structure through the administration port. Then the upper protruding blade of the hand pinching dosing opening top cover inserts the dosing opening top cover into the dosing opening, and slowly lowers the floating stirring structure, so that the lower part of the cross-shaped protruding rod at the top of the stirring female shaft is placed on the female shaft fixing half ring, the upper surface of the top glass of the floating stirring structure is guaranteed to be close to the lower surface of the cup cover of the release cup, and at the moment, the whole floating stirring structure is higher than the liquid level of a medium to avoid the solid preparation from contacting with the medium before stirring, and the test result is influenced. Then, a clamping block of the cup cover of the release cup is inserted into a bayonet of a fixing block of the release cup, and a long screw penetrates through a lug through hole of the cup cover of the release cup, a lug through hole of the side of the release cup and a threaded through hole on a top plate of the water tank to screw and fix the release cup; and taking down the female shaft fixing half ring, clamping the cross-shaped protruding rod at the top of the stirring female shaft into the cross-shaped groove at the top of the rotating shaft sleeve, immediately screwing the internal thread top cap of the driving structure, immediately starting stirring, observing the external release behavior of the solid preparation, and inserting the liquid taking needle into the corresponding insertion hole on the cup cover of the release cup to extract the liquid sample when liquid taking detection.

In a preferred scheme, the rigid body ball is glass ball with the diameter of 1-5 mm, the first stainless steel mesh is one of 18, 20, 24, 30, 40 and 50 meshes, and the second stainless steel mesh is any two of 18, 20, 24, 30, 40 and 50 meshes.

Further, in the method for detecting the in-vitro release behavior of the 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 temperature of the medium is 20-45 ℃, preferably 37 ℃ or 25 ℃.

Compared with the existing dissolution instrument and disintegration instrument, the solid preparation release structure for the non-floatable solid preparation or the floatable solid preparation has the following advantages:

The existing dissolution instrument and disintegration instrument are mainly used for controlling the quality of solid preparations among batches after marketing, namely ensuring that dissolution and disintegration data among the batches of the solid preparations are consistent or the variation range is acceptable, but are not obviously suitable for distinguishing the difference between the auxiliary material composition and the technological parameters of the solid preparation particle intermediate.

Because the solid preparation release structure for the non-floatable solid preparation has the elements such as the rigid ball, the upper cone, the lower cylinder, the first stainless steel net and the like, and the solid preparation release structure for the floatable solid preparation has the elements such as the flat arc-shaped protruding body, the double-layer second stainless steel net, the top glass, the cylindrical peripheral glass and the like, the generation of a stacking body is avoided in the stirring process, and the solid preparation with different densities can move at an S-shaped interface in the release structure, so that the solid preparation is more similar to the characteristics of a mechanical digestion process caused by a continuous diastole and contraction movement mode of a gastrointestinal tract. Meanwhile, the two solid preparation release structures can clearly observe and record the surface morphology and change characteristics of the solid preparation, the movement state and granularity characteristics of the disintegrating matters and the release speed and degree of the bulk drugs at the upper, middle and lower positions in the release cup, and the drug release condition is represented in detail by combining data and phenomena so as to more reasonably optimize the prescription and process, analyze the external release characteristics and infer the internal release risk. The method has reliable and obvious solving capability for the problems of inconvenient, unclear and insufficient observation of the release phenomenon in the research and development process and the problem of influence on analysis of the release result caused by accumulation at the bottom of the dissolution cup, and is particularly suitable for development of simulated pharmaceutical solid preparations. In addition, the solid preparation release tester reduces the cost of lifting control of the driving structure on the premise of ensuring the fixing effect and efficiency of the release cup and the cup cover thereof by fixing the driving structure and moving the release cup, avoids the possibility of precision reduction caused by frequent lifting or lifting of the driving structure, has simple structure, lower cost and wide applicable range, and is convenient to popularize.

Drawings

In order to make the objects, technical solutions and advantageous effects of the present invention clearer, the present invention provides the following drawings:

FIG. 1 is a schematic view showing a solid preparation releasing structure for a non-floating solid preparation, a stirring structure and a lower skirt structure of the present invention;

FIG. 2 is a schematic view showing a solid preparation releasing structure for floating solid preparation, and a top glass, a second stainless steel net and upper projecting blades thereof according to the present invention;

FIG. 3 is a schematic diagram showing the overall structure of a solid preparation release tester according to the present invention;

FIG. 4 is a schematic view showing the position of the mounting opening of the top plate structure of the water tank of the solid preparation release tester according to the present invention;

FIG. 5 is a schematic diagram showing a release cup mounting structure of a tank top plate structure of a solid preparation release tester according to the present invention;

FIG. 6 is a schematic diagram showing a split structure of a release cup mounting structure of a solid preparation release tester according to the present invention;

FIG. 7 is a schematic diagram showing a driving structure of a solid preparation release tester according to the present invention;

FIG. 8 is a schematic view of a support structure of a solid preparation release tester according to the present invention;

FIG. 9 is a schematic view of a rear housing sidewall socket of a solid formulation release tester of the present invention;

FIG. 10 is a schematic view of a base support structure of a solid preparation release tester according to the present invention;

FIG. 11 is a schematic diagram showing a control structure of a solid preparation release tester according to the present invention;

Fig. 12 is a schematic diagram showing the circuit connection of a solid preparation release tester according to the present invention.

In the figure, a stirring shaft 1-1, a cone at the upper end 1-2, a cylinder at the lower end 1-3, stirring paddles 1-4, a first stainless steel mesh 1-5, rigid body balls 1-6, annular vertical glass 1-7 and skirt screws 1-8; 2-1 top glass, 2-2 cylindrical peripheral glass, 2-3 columnar solid glass, 2-4 second stainless steel mesh, 2-5 flat arc-shaped protruding bodies, 2-6 round through holes, 2-7 dosing ports, 2-8 upper protruding paddles, 2-9 cladding flanges, 2-10 release cup lugs, 2-11 annular outer wall screws, 2-12 dosing port top covers and 2-13 female shaft fixing half rings; 3 water tank top plate structure, 3-1 water tank top plate, 3-2 mounting opening, 3-3 upper surface square protruding part, 3-4 lower surface protruding part, 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 fixture block, 3-12 release cup fixing block, 3-13 bayonet, 3-14 long screw, 3-15 stainless steel half ring, 3-16 probe hole, 4 water tank, 5 driving structure, 5-1 supporting plate, 5-2 stepping motor, 5-3 rotating shaft sleeve, 5-4 synchronous pulley, 5-5 driving belt, 5-6 cross groove, 5-7 cross protruding rod, 5-8 internal screw top cap, 5-9 external screw thread column, 5-1 supporting plate, 5-7 cross protruding rod, 5-8 internal screw thread top cap, 5-9 external screw thread column, the stirring box comprises a 5-10 stirring box shaft, a 6-1 hollow steel column, a 6-2 plastic housing, a 6-3 extension part, a 6-4 support structure fixing screw, a 7 rear box body, a 7-1 left drive structure socket, a 7-2 right drive structure socket, a 7-3 power switch, a 7-4 total power socket, an 8 base support structure, an 8-1 integrated square column, an 8-2 support base, an 8-3 water tank support column, an 8-4 lower iron plate, an 8-5 rear box body base, an 8-6 water heater, an 8-7 water circulator and an 8-8 water circulation pipeline, a 9 control structure, a 9-1 PLC touch screen, a 9-2 water tank temperature probe, a 9-3 mobile temperature probe, a 9-4 lower PCB circuit board, a 9-5 power supply, a 9-6 motor driver, a 9-7 timer, a 9-8 PLC controller and a 9-9 upper PCB circuit board.

Detailed Description

Preferred embodiments of the present invention will be described in detail below with reference to the accompanying drawings. The test methods without specific conditions noted in the examples are generally carried out according to conventional conditions or conditions suggested and specified in the similar instruments and pharmacopoeias.

Example 1 solid preparation releasing Structure for non-Floating solid preparation

As shown in figure 1, the part provides a solid preparation release structure for a non-floating solid preparation, which consists of a release cup with a circular arc bottom, a cladding type flanging 2-9, a release cup edge lug 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 net 1-5, rigid ball beads 1-6 and annular vertical glass 1-7.

The top edge of the release cup is outwards turned over by 90 ^o to form a circular flange, the circular flange and the outer wall of the release cup are integrally formed into a cladding flange 2-9 by hard polypropylene hot pressing, and 1 release cup edge lug 2-10 with the same thickness is respectively arranged on two sides of the cladding flange 2-9. The vertical center axis of the stirring shaft 1-1 is coaxial with the vertical center axis of the release cup after installation. In the structure, a circular plate is fixedly connected between an upper cone 1-2 and a lower cylinder 1-3, the lower part of the upper cone 1-2 is fixedly connected with the top of the lower cylinder 1-3, and the lower part of a stirring shaft 1-1 is fixedly connected with the top of the upper cone 1-2 and the circle center of the circular plate. The stirring paddles 1-4 are fixedly connected with the outer wall of the lower part of the lower end cylinder 1-3, and the number of the stirring paddles 1-4 is 3. The annular vertical glass 1-7 is positioned at the lower part of the inner side of the release cup, the annular vertical glass 1-7 and the inner wall of the release cup are integrally formed, the lower end of the bottom of the annular vertical glass 1-7 transversely protrudes inwards to form a skirt structure, 3 skirt internal thread through holes are vertically distributed on the skirt structure, and the first stainless steel net 1-5 is detachably and fixedly connected with the bottom of the annular vertical glass 1-7 through skirt screws 1-8 and the skirt internal thread through holes. An inward downward annular slope structure is formed between the upper ends of the annular vertical glasses 1-7 and the inner wall of the release cup, so that the solid preparation can be prevented from falling on the plane of the upper wall and not entering the stirring structure during administration. The upper cone 1-2 and the lower cylinder 1-3 can be made of 316 stainless steel materials. The rigid body ball 1-6 is glass ball. The stirring blades 1-4 are in a flat arc shape.

The solid preparation releasing structure has the advantages that the sizes of different parts of the solid preparation releasing structure are preferably 10mm in the middle of annular vertical glass 1-7, 10mm in the width of a skirt edge structure at the lower end of the annular vertical glass 1-7, 25mm in the distance from the first stainless steel net 1-5 to the bottom of the releasing cup and 8mm in the distance from the bottom of the lower end cylinder 1-3, 40mm in the diameter and 40mm in the height of the lower end cylinder 1-3, 20mm in the distance from the side face of the lower end cylinder 1-3 to the annular vertical glass 1-7, 20mm in the height of an upper end cone 1-2, 2mm in the diameter of rigid body balls 1-6, and 35mm in the height and 5mm in the distance from the top of the rigid body balls 1-6 to the first stainless steel net 1-5 are paved, and the thickness of the rigid body balls 1-6 is 35mm in the height and 12mm and 16mm in the height of the stirring blades 1-4. The height of the release cup edge lug 2-10 is 2-15 mm, the width thereof is 5-50 mm, and the outer wall of the upper part of the stirring shaft 1-1 is provided with external threads.

When the invention is used, the release cup can be placed into a release cup jack of an existing solid preparation release tester such as a Rui Tuo RT612 dissolution experiment instrument, so that the coated flange 2-9 and the release cup edge ear 2-10 are clamped under the cup cover plate, then the stirring shaft 1-1 is connected with a motor of the Rui Tuo RT612 dissolution experiment instrument, and the stirring shaft 1-1 drives the stirring blade 1-4 to rotate.

Example 2 solid preparation releasing Structure for Floating solid preparation

As shown in FIG. 2, this section provides a solid preparation releasing structure for floating solid preparation, comprising a clad flange 2-9, a releasing cup lug 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 convex body 2-5, a circular through hole 2-6, a dosing port 2-7 and an upper protruding blade 2-8.

The top edge of the release cup is outwards turned over by 90 ^o to form a circular flange, the circular flange and the outer wall of the release cup are integrally formed into a cladding flange 2-9 by hard polypropylene hot pressing, and 1 release cup edge lug 2-10 with the same thickness is respectively arranged on two sides of the cladding flange 2-9. The top glass 2-1, the columnar solid glass 2-3 and the cylindrical peripheral glass 2-2 may be integrally molded, or the top glass 2-1 may be fixedly connected to the columnar solid glass 2-3 and the cylindrical peripheral glass 2-2 after being manufactured. Wherein the stirring shaft 1-1 is fixedly connected with the top glass 2-1. Or punching holes at the centers of the top glass 2-1 and the columnar solid glass 2-3, and fixedly bonding the stirring shaft 1-1 with the top glass 2-1 and the columnar solid glass 2-3 after inserting the stirring shaft 1-1 into the holes. The second stainless steel net 2-4 is divided into an upper layer and a lower layer. The top glass 2-1, the cylindrical peripheral glass 2-2, the columnar solid glass 2-3 and the second stainless steel mesh 2-4 jointly enclose 1 cylindrical cavity.

The bottom wall of the top glass 2-1 is fixedly connected with 4 flat arc-shaped protruding bodies 2-5, the 1 flat arc-shaped protruding bodies 2-5 are provided with drug administration ports 2-7, the upper parts of the top covers 2-12 of the drug administration ports are fixedly connected with upper protruding paddles 2-8, and the upper surfaces of the top glass 2-1 corresponding to the flat arc-shaped protruding bodies 2-5 at symmetrical positions of the flat arc-shaped protruding bodies 2-5 where the drug administration ports 2-7 are positioned are fixedly connected with the upper protruding paddles 2-8. A circular through hole 2-6 is arranged between the flat arc-shaped protruding bodies 2-5 of the top glass 2-1. The upper and lower layers of the lower part of the cylindrical peripheral part glass 2-2 are provided with 6 peripheral internal thread through holes, the periphery of the second stainless steel net 2-4 is fixedly connected with an annular outer wall made of stainless steel, the annular outer wall is provided with an annular outer wall internal thread through hole matched with the peripheral internal thread through hole, and the second stainless steel net 2-4 is detachably connected with the bottom of the cylindrical peripheral part glass 2-2 through an annular outer wall screw 2-11, the peripheral internal thread through hole and the annular outer wall internal thread through hole

The solid preparation release structure is characterized in that the sizes of different parts of the solid preparation release structure are preferably 75mm in diameter of top glass 2-1, 4 x 14 circular through holes 2-6 in the top glass 2-1 are arranged, the diameter is 1.0mm, a dosing opening 2-7 is rectangular, the length is 16mm and the width is 9mm, an upper protruding blade 2-8 is 8mm in height and 2mm in width, a flat arc-shaped protruding body 2-5 is 8mm in height, 15mm in width and 20mm in length, the diameter of columnar solid glass 2-3 is 35mm and 25mm in height, the side face of the columnar solid glass 2-3 is 20mm from the inner wall of the cylindrical peripheral glass 2-2, the upper layer and the lower layer of a second stainless steel net 2-4 are 20mm apart, the second stainless steel net 2-4 in the lower layer is 25mm from the bottom of a release cup, the height of a release cup side lug 2-10 is 2-15 mm and the width is 5-50 mm, and external threads are arranged on the outer wall of the upper part of a stirring shaft 1-1.

Example 3 solid preparation Release tester

As shown in fig. 3 to 12, this section provides a solid preparation release tester carrying the solid preparation release structures shown in example 1 and example 2. As shown in fig. 3, the solid preparation release tester includes a tank top plate structure 3, a tank 4, a driving structure 5, a supporting structure 6, a rear case 7, a base bracket structure 8, a control structure 9, and solid preparation release structures shown in embodiments 1 and 2. The water tank roof structure 3 is located water tank 4 top, and back box 7 is located water tank 4 rear, and base support structure 8 is located water tank 4 and back box 7 below, and drive structure 5, bearing structure 6, control structure 9 are located water tank roof structure 3 top.

Wherein the tank ceiling structure 3 is associated with the mounting of the release cup. As shown in fig. 4-6, the water tank top plate structure 3 comprises a water tank top plate 3-1, a mounting opening 3-2, an upper surface square protruding part 3-3, a lower surface protruding part 3-4, 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 lug 3-10, a clamping block 3-11, a release cup fixing block 3-12, a bayonet 3-13, a long screw 3-14 and a stainless steel half ring 3-15. Wherein, the water tank top plate 3-1 is provided with a mounting port 3-2. The upper parts of the edges of the front wall and the rear wall of the mounting opening 3-2 are respectively and fixedly connected with 2 square protruding parts 3-3 on the upper surface, and the lower parts of the corresponding edges are respectively and fixedly connected with 1 step-shaped protruding part 3-4 on the lower surface. The stainless steel half ring 3-15 is fixedly adhered below the left, right and front walls of the water tank top plate 3-1.

Wherein, a left top plate cover 3-5 and a right top plate cover 3-6 can be inserted between the upper surface square protruding part 3-3 and the lower surface protruding part 3-4. The middle top cover 3-7 is positioned between the left top cover 3-5 and the right top cover 3-6 without being covered by the upper surface square protruding part 3-3, so that the middle top cover 3-7 can be removed and installed. The left side and the right side of the mounting opening 3-2 are provided with semicircular release cup mounting holes 3-8 matched with the release cups, semicircular holes matched with the release cup mounting holes 3-8 are also formed in the outer sides of the left top plate cover 3-5 and the right top plate cover 3-6, and when the left top plate cover 3-5 and the right top plate cover 3-6 move leftwards and rightwards respectively, the semicircular holes can be combined with the semicircular release cup mounting holes 3-8 on the two sides of the mounting opening 3-2 to form circular holes for inserting the release cups. As shown in fig. 5 and 6, the shape of the release cup cover side lug 3-10 is the same as that of the release cup side lug 2-10 at the opening of the release cup, the release cup side lug 2-10 and the release cup cover side lug 3-10 are respectively provided with a side lug through hole, the water tank top plate 3-1 is provided with a threaded through hole, the outer side of the release cup cover side lug 3-10 is provided with a clamping block 3-11, and the 匚 -shaped release cup fixing block 3-12 is provided with a bayonet 3-13 matched with 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 fix the side lug 3-10 of the cup cover of the release cup by means of the jogged joint of the bayonet 3-13 and the clamping block 3-11, and the long screw 3-14 is inserted into the side lug through hole to fix the fixed release cup on the top plate 3-1 of the water tank. The water tank top plate 3-1 is provided with a probe hole 3-16 for inserting the water tank temperature probe 9-2, the release cup cover 3-9 is respectively provided with an insertion hole for inserting a camera, the movable temperature probe 9-3, the stirring female shaft 5-10 and a sampling needle, and the sampling needle is fixed on the release cup cover 3-9 in height through a rubber plug.

As shown in FIG. 7, the driving structure 5 comprises two sets of supporting plates 5-1, a stepping motor 5-2, a rotating shaft sleeve 5-3, a synchronous pulley 5-4, a driving belt 5-5, a cross-shaped groove 5-6, a cross-shaped protruding rod 5-7, an internal thread top cap 5-8, an external thread column 5-9 and a stirring female shaft 5-10. The rotating shaft of the stepping motor 5-2 is fixedly connected with a synchronous pulley 5-4, the synchronous pulley 5-4 and the rotating shaft sleeve 5-3 are synchronously driven by a driving belt 5-5, an external thread column 5-9 is fixedly connected above the rotating shaft sleeve 5-3, a cross-shaped groove 5-6 is arranged at the top of the external thread column 5-9, the bulge of a cross-shaped protruding rod 5-7 is matched with the cross-shaped groove 5-6, and the external thread column 5-9 is in threaded connection with an internal thread top cap 5-8. The stirring female shaft 5-10 is detachably and fixedly connected with the stirring shaft 1-1 through threads, and further the stirring shaft 1-1 is driven by the stepping motor 5-2 to realize stirring. Wherein the inner cavity of the external thread column 5-9 is provided with a stirring female shaft sleeve hole for inserting the stirring female shaft 5-10, and the stirring female shaft sleeve hole penetrates through the external thread column 5-9, the rotating shaft sleeve 5-3 and the supporting plate 5-1. 2 positioning lantern rings are fixedly adhered in the rotating shaft sleeve 5-3, and the stirring female shaft 5-10 is in sliding sleeve joint with the positioning lantern rings, so that the stirring female shaft 5-10 can be prevented from shaking when rotating in the rotating shaft sleeve 5-3. The 2 positioning lantern rings are distributed at the upper end and the lower end of the inner cavity of the rotating shaft sleeve.

As shown in FIG. 8, the support structure 6 comprises two sets of hollow steel columns 6-1, support structure fixing screws 6-4 and a plastic housing 6-2. The rear end of the supporting plate 5-1 is fixedly embedded into the middle inner cavity of the hollow steel column 6-1, the stepping motor 5-2 is located in the inner cavity of the hollow steel column 6-1, the driving belt 5-5 penetrates through the outer wall of the hollow steel column 6-1 and is rotationally connected with the rotating shaft sleeve 5-3, the plastic outer cover 6-2 covers the driving belt 5-5 and the rotating shaft sleeve 5-3, the hollow steel column 6-1 vertically penetrates through the water tank top plate 3-1, the bottom of the hollow steel column horizontally extends to form the extension part 6-3, 3 extension part threaded through holes are formed in the extension part 6-3, 3 base threaded through holes are formed in the rear box base 8-5, and the hollow steel column is in threaded connection with the rear box base 8-5 through the supporting structure fixing screw 6-4, the extension part threaded through holes and the base threaded through holes.

As shown in fig. 9, the side wall of the rear case 7 is respectively provided with a left driving structure socket 7-1, a right driving structure socket 7-2, a power switch 7-3 and a main power socket 7-4. The left driving structure socket 7-1 is connected with the stepping motor 5-2 in the left driving structure through a wire, the right driving structure socket 7-2 is connected with the stepping motor 5-2 in the right driving structure through a wire, the total power socket 7-4 is connected with the power plug and the power switch 7-3, the power switch 7-3 is connected with the power supply 9-5, the PTC water heater 8-6 and the water circulator 8-7 through the lower PCB 9-4, the power supply 9-5 provides 24V direct current voltage and 10A rated current, and is connected with the stepping motor 5-2, the motor driver 9-6, the timer 9-7, the water tank temperature probe 9-2, the movable temperature probe 9-3, the PLC touch screen 9-1 and the PLC controller 9-8 through the lower PCB 9-4.

As shown in fig. 10, the base support structure 8 includes an integrated square column 8-1, a support seat 8-2, a tank support column 8-3, a tank lower iron plate 8-4, a rear tank base 8-5, a water heater 8-6, a water circulator 8-7, and a water circulation pipe 8-8. Four corners of the bottom of the integrated square column 8-1 are provided with 4 support seat threaded holes, the upper part of the support seat 8-2 is fixedly connected with a support seat threaded column, and the support seat threaded column is in threaded connection with the support seat threaded holes. The water tank 4 is arranged on the water tank support columns 8-3 through a lower iron plate 8-4 of the water tank, the rear box body 7 is arranged on a rear box body base 8-5, the rear box body base 8-5 is arranged on the rear section of the upper part of the integrated square column 8-1, the water heater 8-6 is fixed on the rear side of the integrated square column 8-1, the water circulator 8-7 is fixed on the left side of the integrated square column 8-1, the water circulation pipeline 8-8 is of a three-head structure, one end of the water circulator is opened on the upper right side of the water tank 4, the other end of the water circulator is opened on the bottom of the left side of the water tank 4, a water tap for water drainage is arranged at one end of the water circulator 8-6, the water circulator 8-7 and the water tank 4 are communicated through a water circulation pipeline 8-8.

As shown in fig. 11 and 12, 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, wherein the PLC touch screen 9-1 is electrically connected to a PLC controller 9-8 through an upper PCB circuit board 9-9, and the PLC controller 9-8 is connected to a lower PCB circuit board 9-4 through the upper PCB circuit board 9-9, and regulates signals of a timer 9-7, a PTC water heater 8-6, a water circulator 8-7, a stepper motor 5-2, a motor driver 9-6, the water tank temperature probe 9-2, and the mobile temperature probe 9-3.

The solid preparation release tester is characterized in that the sizes of different parts of the solid preparation release tester are preferably that the arc width of one side, close to the release cup mounting hole 3-8, of each release cup side ear 2-10 respectively occupies 1/5 of the circumference of the release cup mounting hole 3-8, the length of a middle top plate cover 3-7 is 105mm, the longitudinal width is 180mm, the transverse length of the left top plate cover 3-5 and the transverse length of the right top plate cover 3-6 are 115mm, the longitudinal width is 180mm, and the distance between a supporting plate 5-1 and a water tank top plate 3-1 is 140mm.

When the solid preparation release tester was used, if the solid preparation release structure for a non-floating solid preparation of example 1 was installed, the procedure was as follows:

The left driving structure socket 7-1 and the right driving structure socket 7-2 are respectively connected with the driving structure 5 by plugs, a household alternating current power supply is connected with the main power socket 7-4, the power switch 7-3 is turned on, the temperature and the standby rotating speed of the water tank 4 are set, and the water heater 8-6 and the water circulator 8-7 are started.

The first stainless steel net 1-5 is screwed with the bottom of the annular vertical glass 1-7 through the skirt screw 1-8 and the skirt internal thread through hole, the release cup transversely slides to the release cup mounting hole 3-8 through the water tank top plate 3-1 mounting hole 3-2, the left top plate cover 3-5 or the right top plate cover 3-6 is inserted between the upper surface square protruding part 3-3 and the lower surface protruding part 3-4, the left top plate cover 3-5 is moved left or the right top plate cover 3-6 is moved right to be contacted with the release cup, the middle top plate cover 3-7 is clamped between the left top plate cover 3-5 and the right top plate cover 3-6, and a release medium is added into the release cup.

The stirring shaft 1-1 of the ball type stirring structure penetrates through a central round hole of the release cup cover 3-9 and is screwed up to the stirring female shaft 5-10 through threads, a cross-shaped convex rod 5-7 at the top of the stirring female shaft 5-10 is clamped into a cross-shaped groove 5-6 at the top of the rotating shaft sleeve 5-3, an internal thread top cap 5-8 of the driving structure 5 is screwed, the release cup cover 3-9 is lifted and poured into glass balls to a standard height, the release cup cover 3-9 is covered, a clamping block 3-11 of the release cup cover 3-9 is inserted into a bayonet 3-13 of the release cup fixing block 3-12, and a long screw 3-14 penetrates through a release cup cover side lug through hole, a release cup side lug 2-10 through hole and a threaded through hole on the water tank top plate 3-1 to screw down and fix the release cup.

The mobile temperature probe 9-3 is inserted into a release cup, after the temperature of a release medium in the release cup reaches the requirement, a solid preparation to be tested is put into the release cup through a camera insertion hole of the release cup cover 3-9, stirring is started immediately, the external release behavior of the solid preparation is observed, and a liquid sample is extracted by inserting a liquid sampling needle into a corresponding insertion hole on the release cup cover 3-9 during liquid sampling detection.

After the test is finished, the long screw 3-14 is unscrewed, the stirring female shaft 5-10 and the stirring shaft 1-1 are unscrewed, the stirring female shaft 5-10 is lifted, the release cup cover 3-9 and the middle top plate cover 3-7 are sequentially taken down, the left top plate cover 3-5 and the right top plate cover 3-6 are pulled out, and the release cup and the stirring device are respectively slid towards the middle of the mounting port 3-2 and taken out.

When the solid preparation release tester was used, if the solid preparation release structure for floating solid preparation of example 2 was installed, the procedure was as follows:

The two layers of second stainless steel nets 2-4 are respectively and fixedly connected with the bottom of the cylindrical peripheral glass 2-2 through annular outer wall screws, peripheral inner thread through holes and annular outer wall inner thread through holes, a release cup transversely slides to a release cup mounting hole 3-8 through a water tank top plate mounting hole 3-2, a left top plate cover 3-5 or a right top plate cover 3-6 is inserted between an upper surface square protruding part 3-3 and a lower surface protruding part 3-4, the left top plate cover 3-5 is moved left or the right top plate cover 3-6 is moved right to be contacted with the release cup, and a middle top plate cover 3-7 is clamped between the left top plate cover 3-5 and the right top plate cover 3-6.

The stirring shaft 1-1 of the floating stirring structure penetrates through a central round hole of the cup cover 3-9 of the release cup, is screwed to the stirring female shaft 5-10 upwards through threads, the stirring female shaft 5-10 is lifted to the highest position, a release medium is added into the release cup, the female shaft fixing half ring 2-13 is placed below the cross-shaped protruding rod 5-7 at the top of the stirring female shaft 5-10, the floating stirring structure is slowly lowered, the upper surface of the top glass 2-1 of the floating stirring structure abuts against the lower surface of the cup cover 3-9 of the release cup, and the cup cover 3-9 of the release cup is placed on the release cup.

Inserting a movable temperature probe 9-3 into a release cup, lifting a stirring female shaft 5-10 and a release cup cover 3-9 after the temperature of a release medium in the release cup reaches the requirement, adding a solid preparation into a floating stirring structure through a dosing port 2-7, pinching an upper protruding blade 2-8 of a dosing port top cover 2-12 by hand to insert the dosing port top cover 2-12 into the dosing port 2-7, slowly lowering the floating stirring structure, placing the lower part of a cross-shaped protruding rod 5-7 at the top of the stirring female shaft 5-10 onto a female shaft fixing half ring 2-13, ensuring that the upper surface of a top glass 2-1 of the floating stirring structure abuts against the lower surface of the release cup cover 3-9, inserting a clamping block 3-11 of the release cup cover 3-9 into a bayonet 3-13 of a release cup fixing block 3-12, penetrating a long screw 3-14 through a threaded through hole in a side ear of the release cup cover, a side ear 2-10 through hole of the release cup and a threaded through hole in a water tank top plate 3-1, screwing and fixing the release cup, taking down the female shaft fixing half ring 2-13, placing the cross-shaped protruding rod 5-7 at the top of the stirring female shaft 5-10 into the female shaft fixing half ring 2-10 onto the female shaft fixing half ring, and simultaneously taking a liquid in a corresponding groove 5-6 of the vertical groove of the release cup, and taking out the solid preparation when the solid preparation is screwed into the vertical groove 5-6, and detecting the solid preparation, and opening the screw is screwed into the vertical groove, and the top cup, and the solid preparation, when the probe is screwed, and the probe is screwed;

Example 4 detection of in vitro Release behavior of solid formulations and comparison of Performance

The solid preparation conventional auxiliary materials lactose, microcrystalline cellulose (Microcrystalline cellulose, MCC), croscarmellose sodium (Croscarmellose sodium, CCNa) and magnesium stearate (Magnesiumstearate, MS) are mixed, granulated and tableted by using a solid preparation release tester of example 3, a ZB-1E intelligent disintegration tester of Tian-da-Tian-fa-Tech, tian-da-technology, inc. (test temperature 37 ^o C, release medium is water), a RT612 type dissolution tester of Shenzhen Rui-Tou instrument equipment, inc. (paddle method, rotation speed 50rpm, test temperature 37C, release medium is water), and the test device and method provided by the invention have the capability of distinguishing the release processes of granules and tablets prepared by different process parameters and materials.

Table 1-1. The ball-stirring type Release Structure and solid preparation Release tester and test method of the invention test the conventional auxiliary Material proportion and the treatment Process differentiation ability of the tablets (test temperature 37 ℃ C., rotation speed 25rpm, release Medium is Water)

Table 1-2 the top floating type release structure and solid preparation release tester and test method of the present invention test the proportion of conventional auxiliary materials to particles and the distinguishing ability of the treatment process (test temperature 37 ℃, rotation speed 35rpm, release medium is water)

Note that (1) the tablet weight of the prepared tablet was 250.+ -.20 mg, the diameter was 8mm, and the hardness was 90.+ -.10N.

(2) The parameters of the same type of process used for the tablets and the granules are the same, for example, the rotation speed of a pulverizer during pulverization is 25000rpm, the time is 90s, the mixing rotation speed of a hopper mixer is 15rpm, the time is 45min, the mixing rotation speed of a wet granulator is 700rpm, the time is 15min, the air pressure of the dry granulator is 0.4mPa, the feeding speed is 14rpm, the rotation speed of a pressing wheel is 2rpm, the distance between the pressing wheels is 0.2mm, and the granule finishing speed is 285rpm.

Table 2 the in vitro release structure and the solid preparation release tester and the test method of the invention can distinguish the conventional auxiliary materials proportion and the treatment process

The results in tables 1-1, 1-2 and 2 show that the testing device and the testing method provided by the invention have obvious distinguishing capability on the dosage and the process of common materials of the solid preparation, the distinguishing capability of the dissolution instrument is mainly on the release time, the distinguishing capability of the dissolution instrument is not on the disintegration phenomenon, the distinguishing capability of the disintegration instrument is also mainly on the release time, the distinguishing capability of the disintegration phenomenon is insufficient, and the disintegration time of tablets detected by three devices is similar.

Finally, it should be understood that the foregoing embodiments are merely illustrative of the technical solutions provided by the present invention, and not limiting, and those skilled in the art should understand that all changes, or similar alternatives and modifications that do not depart from the technical features of the present invention are included in the protection scope of the present invention. What is not described in detail in this specification is prior art known to those skilled in the art.

Claims

1. The method for detecting the external release behavior of the solid preparation is characterized in that the solid preparation release tester adopted by the method comprises a water tank top plate structure, a water tank, a driving structure, a supporting structure, a rear box body, a base bracket structure and a control structure, wherein the water tank top plate structure is positioned on the upper surface of the water tank, the driving structure is positioned on the upper part of the supporting structure, the supporting structure and the control structure are positioned on the upper surface of the water tank top plate structure, the rear box body is positioned below the water tank top plate structure, the base bracket structure is positioned below the water tank and the rear box body, and the solid preparation release tester is provided with the solid preparation release structure;

The solid preparation release structure comprises a release cup and a ball type stirring structure, wherein the release cup is hollow and cylindrical, the bottom of the release cup is in an arc shape or an inverted cone shape or a flat bottom shape, the ball type stirring structure comprises a stirring shaft, an upper end cone, a lower end cylinder, stirring paddles, a first stainless steel mesh, rigid balls and annular vertical glass, the lower part of the stirring shaft is fixedly connected with the upper end cone, the lower part of the upper end cone is fixedly connected with the top of the lower end cylinder, the stirring paddles are fixedly connected with the outer wall of the lower part of the lower end cylinder, the vertical center shaft of the stirring shaft is coaxial with the vertical center shafts of the annular vertical glass, the upper end cone and the lower end cylinder, the annular vertical glass is positioned at the lower part of the 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 and fixedly connected with the first stainless steel mesh, and the rigid balls are arranged on the first stainless steel mesh;

The stirring device comprises a stirring blade, an annular vertical glass, a skirt structure, a first stainless steel net, a second stainless steel net and a release cup, wherein the rigid ball is a glass ball, the number of the stirring blade is 2-6, an inward 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 transversely protrudes inwards to form the skirt structure, 2-6 skirt internal thread through holes are vertically distributed on the skirt structure, and the first stainless steel net is detachably and fixedly connected with the bottom of the annular vertical glass through skirt screws and the skirt internal thread through holes;

The bottom end of the release cup is arc-shaped, the thickness of the middle part of the annular vertical glass is 6-15 mm, the width of the skirt edge structure at the lower end of the annular vertical glass is 5-25 mm, the distance between the first stainless steel net and the bottom of the release cup is 10-50 mm, the distance between the first stainless steel net and the bottom of the lower cylinder is 2-30 mm, the diameter of the lower cylinder is 20-60 mm, the height of the lower cylinder is 20-70 mm, the lateral surface of the lower cylinder is 10-30 mm, the height of the upper cone is 5-70 mm, the upper cone and the lower cylinder are made of 316 stainless steel materials, the diameter of the rigid body ball is 1-5 mm, the laying thickness of the rigid body ball is 15-95 mm, the distance between the top of the rigid body ball and the first stainless steel net is 2-15 mm, the stirring paddles are in a flat arc shape, the height of the stirring paddles is 2-15 mm, the width of the stirring paddles is 5-40 mm, and the length of the stirring paddles is 8-28 mm;

The top edge of the release cup is outwards turned over by 90 ^o to form a circular flange, the circular flange and the outer wall of the release cup are integrally formed by hard polypropylene hot pressing to form a cladding flange, and two sides of the cladding flange are respectively provided with a release cup side lug with the same thickness as the cladding flange;

The water tank top plate structure is detachably and fixedly connected with the release cup side lug, the driving structure is detachably and fixedly connected with the stirring shaft of the solid preparation release structure, and the release cup cover is made of transparent materials;

The water tank top plate structure comprises a water tank top plate, a release cup cover and a mounting opening positioned at one side of the water tank top plate, wherein the mounting opening penetrates through the upper surface and the lower surface of the water tank top plate; the two upper surface square protruding parts are respectively and fixedly connected above the front edge and the rear edge of the mounting opening, the upper surface square protruding parts are close to the left side edge or the right side edge of the mounting opening, lower surface protruding parts corresponding to the positions of the upper surface square protruding parts are fixedly connected below the front edge and the rear edge of the mounting opening, the lower surface protruding parts are in a step shape, cover the two upper surface square protruding parts on the same side in length and are equal to the mounting opening, a left top plate cover and a right top plate cover are movably inserted between the upper surface square protruding parts and the lower surface protruding parts, a middle top plate cover which is not blocked by the upper surface square protruding parts is arranged between the left top plate cover and the right top plate cover, semicircular release cup mounting holes matched with release cups are formed in the left side and the right side of the mounting opening, semicircular holes matched with the release cup mounting holes are formed in the left top plate cover and the right top plate cover, the diameter of the release cups is matched with the upper opening of the release cups, and the left side and the right side of the release cups are fixedly connected with lug-shaped release cups The novel water tank comprises a water tank top plate, a left top plate cover, a right top plate cover, a release cup cover side lug with the same size, protruding clamping blocks are fixedly connected to the front side wall and the rear side wall of the release cup cover side lug, a 匚 -shaped release cup fixing block is fixedly connected to the left top plate cover, the right top plate cover and the water tank top plate on two sides of the release cup, the release cup fixing block is provided with a sector-shaped recess matched with the release cup side lug and the release cup cover side lug, a bayonet matched with the clamping blocks is arranged on the release cup fixing block, long threaded through holes for long screws to pass are formed in the water tank top plate, the left top plate cover, the right top plate cover, the release cup side lug and the release cup cover side lug, a stainless steel half ring is bonded below the left wall, the right top plate and the front wall of the water tank top part, two ends of the stainless steel half ring are fixedly bonded to a rear tank body, and the driving structure comprises a supporting plate, Step motor, pivot sleeve, synchronous pulley, driving belt, cross recess, cross protruding pole, internal thread hood, external screw thread post and stirring female axle, step motor's pivot fixed connection synchronous pulley, synchronous pulley passes through driving belt synchronous drive with the pivot sleeve, the pivot sleeve passes through the bearing to be fixed in the backup pad, the outer lane and the backup pad fixed connection of bearing, the inner circle and the pivot cover outer wall fixed connection of bearing, pivot sleeve top fixed connection external screw thread post, external screw thread post top is equipped with cross recess, the inner chamber of external screw thread post is equipped with the stirring female axle sleeve hole that supplies stirring female axle male, stirring female axle sleeve hole link up external screw thread post The stirring female shaft is sleeved with the stirring female shaft sleeve hole in a sliding mode, a cross-shaped protruding rod is arranged at the top end of the stirring female shaft, protrusions of the cross-shaped protruding rod are matched with cross-shaped grooves, an internal thread connecting hole is formed in the lower portion of the stirring female shaft, the upper portion of the stirring shaft is in threaded connection with the lower portion of the stirring female shaft, an external thread column is in threaded connection with an internal thread top cap, the supporting structure is cylindrical and comprises a hollow steel column body and a plastic outer cover, the rear end of the supporting plate is fixedly embedded into the middle inner cavity of the hollow steel column body, the stepping motor is located the inner cavity of the hollow steel column body, a driving belt penetrates through an outer wall opening of the steel column body and is connected with the rotating shaft sleeve in a rotating mode, the driving belt and the rotating shaft sleeve body are covered by the plastic outer cover, the hollow steel column body vertically penetrates through a water tank top plate, an extending portion is formed in a horizontal mode, 3-9 extending portion threaded through holes are formed in the extending portion, 3-9 base threaded through holes are formed in the base of the rear box body, and the hollow steel column body is fixed through the supporting structure the extension part threaded through hole and the base threaded through hole are in threaded connection with the base of the rear box body; the base support structure comprises an integrated square column, a supporting seat, a water tank supporting column, a lower iron plate of the water tank, a rear box base, a water heater, The water circulator and the water circulation pipeline, 4 supporting seat screw holes are formed in four corners of the bottom of the integrated square column, the supporting seat screw columns are fixedly connected to the upper portion of each supporting seat, the supporting seat screw columns are in threaded connection with the supporting seat screw holes, 4-6 water tank support columns are fixedly connected to the front section of the upper portion of the integrated square column, the water tank is arranged on the water tank support columns through a lower iron plate of the water tank, the rear box is arranged on a rear box base, the rear box base is arranged on the rear section of the upper portion of the integrated square column, the water heater is fixed on 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 of a three-head structure, and one end of the water circulation pipeline is opened on the upper portion of one side of the water tank, the control structure comprises a PLC touch screen, a water tank temperature probe and a mobile temperature probe, a probe hole for inserting the water tank temperature probe is formed in a top plate of the water tank, a mirror is arranged on the front wall of the rear box body, a driving structure socket, a power switch and a total power socket are respectively arranged on the side wall of the rear box body, the driving structure socket is connected with a stepping motor through a wire, the total power socket is connected with a 220V indoor power supply and the power switch through wires, and the power switch is connected with a power supply through a lower PCB circuit board, The water heater and the water circulator, the power supply provides 24V direct current voltage and 10A rated current, and is connected with the stepping motor, the motor driver, the timer, the water tank temperature probe, the movable temperature probe, the PLC touch screen and the PLC controller through a lower PCB circuit board, the PLC touch screen is electrically connected with the PLC controller through an upper PCB circuit board, the PLC controller is connected with the lower PCB circuit board through an upper PCB circuit board, and regulates and controls signals of the timer, the water heater, the water circulator, the stepping motor, the motor driver, the water tank temperature probe and the movable temperature probe, and the release cup cover is respectively provided with a camera, a camera, Moving a temperature probe, a stirring mother shaft, a stirring shaft and an insertion hole for inserting a sampling needle; the middle top plate cover of the water tank top plate is 40-300 mm long and 100-400 mm wide, the two sides of the left top plate cover and the right top plate cover are 80-300 mm long horizontally and 100-400 mm wide longitudinally, and the distance between the supporting plate and the water tank top plate is 90-250 mm;

The solid preparation release tester is also provided with a female shaft fixing half ring which is movably clamped between the cross-shaped groove and the top end of the cross-shaped protruding rod, at least one positioning sleeve ring is fixedly adhered in the rotating shaft sleeve, and the positioning sleeve ring is made of wear-resistant hard polyoxymethylene plastic;

The driving structure and the supporting structure are respectively provided with 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 with a stepping motor in a left driving structure through a wire, the right driving structure socket is connected with the stepping motor in a right driving structure through a wire, 2 positioning lantern rings are fixedly adhered in the rotating shaft sleeve, and the positioning lantern rings are positioned at the upper end and the lower end of an inner cavity of the rotating shaft sleeve;

the method comprises the following steps:

M1, connecting a left driving structure socket and/or a right driving structure socket with a corresponding driving structure by using a lead, connecting a household alternating current power supply with a main power socket, switching on a power switch, setting the temperature of a water tank and the rotating speed for test, and starting a water heater and a water circulator;

The first stainless steel net is screwed with the annular vertical glass bottom through the skirt screw and the skirt internal thread through hole, the release cup transversely slides to the release cup mounting hole through the water tank top plate mounting hole, the left top plate cover and/or the right top plate cover are inserted between the upper surface square protruding part and the lower surface protruding part, the left top plate cover is moved left or/and the right top plate cover is moved right to be in contact with the release cup, the middle top plate cover is clamped between the left top plate cover and the right top plate cover, and a release medium is added into the release cup;

The stirring shaft of the ball type stirring structure penetrates through a round hole in the center of the cup cover of the release cup, is screwed to the stirring female shaft upwards through threads, a cross-shaped protruding rod at the top of the stirring female shaft is clamped into a cross-shaped groove at the top of the rotating shaft sleeve, an internal thread top cap of the driving structure is screwed, the cup cover of the release cup is lifted, glass balls are poured into the cup cover of the release cup, the cup cover of the release cup is covered, a clamping block of the cup cover of the release cup is inserted into a bayonet of a fixing block of the release cup, and a long screw penetrates through a lug through hole of the cup cover of the release cup, the lug through hole of the release cup and a threaded through hole in a top plate of a water tank to screw down and fix the release cup;

inserting a movable temperature probe into a release cup, putting a solid preparation to be tested into the release cup through a camera insertion hole of a cup cover of the release cup after the temperature of a release medium in the release cup reaches the requirement, immediately starting a stepping motor, observing the external release behavior of the solid preparation, and inserting a liquid taking needle into a corresponding insertion hole on the cup cover of the release cup to extract a liquid sample during liquid taking detection;

2. The method for detecting the in-vitro release behavior of a solid preparation according to claim 12, wherein the rigid ball in the step M1 is a glass ball with a diameter of 1-5 mm, the first stainless steel mesh in the step M1 has a mesh size of 18, 20, 24, 30, 40 and 50 meshes, the pH of the release medium in the step M1 is 1.0-8.0, the rotation speed of the stirring structure is 10-100 rpm, and the medium temperature is 20-45 ℃.