RELEASE TEST SYSTEM FOR SIMULATING THE CHANGE IN STATE OF MEDICAL ACTIVE INGREDIENTS

Abstract

The invention relates to a release test system (10) for simulating the change in state of medical active ingredients in the region of a human or animal organ, comprising at least: a main body (12) of a release test vessel (16); a lid (14) of the release test vessel (16); technical control means (18) for influencing simulation conditions prevailing within the release test vessel (16), wherein the technical control means (18) comprise at least one stirring mechanism (20) and one temperature control device (22); and further comprising a sampling device (26).

Provision is made for the lid (14) and at least the stirring mechanism (20) to be permanently connected to one another and for a nondetachable connection to be producible or to exist between the main body (12) and the lid (14).

Claims

1. A release test system for simulating the change in state of medical active ingredients in the region of a human or animal organ, comprising at least: a main body of a release test vessel; a lid of the release test vessel; technical control means for influencing simulation conditions prevailing within the release test vessel, wherein the technical control means comprise at least one stirring mechanism and one temperature control device; and furthermore a sampling device; wherein the lid and at least the stirring mechanism are permanently connected to one another and a nondetachable connection is producible or exists between the main body and the lid.

2. The release test system according to claim 1, wherein the lid is form-lockingly and/or force-lockingly connectable or connected and/or is materially bondable or bonded to the main body.

3. The release test system according to claim 1, wherein the lid is hermetically sealed or sealable relative to the main body.

4. The release test system according to claim 1, wherein the stirring mechanism has a drive interface, which is accessible from outside the release test vessel.

5. The release test system according claim 1, wherein the sampling device comprises at least one sampling tube or additionally a sample return tube, these each being arrangeable or arranged in a complementary receptacle in the lid.

6. The release test system according to claim 1, wherein one or more of the following features are incorporated structurally into the stirring mechanism: a feed path for liquid and/or gaseous substances; technical means for measuring pH; technical means for measuring temperature.

7. The release test system according to claim 1, wherein a resilient flask is arranged or arrangeable inside the release test vessel and can be supplied with a pressure medium.

8. The release test system according to claim 1, wherein an auxiliary substance for transferring mechanical stirring energy to a test liquid is introduced or introducible into the release test vessel.

9. The release test system according to claim 1, wherein the lid has one or more predetermined breaking points for producing interfaces in the release test vessel, wherein in the region of the interfaces sealing elements or receptacles are provided for this purpose.

10. The release test system according to claim 1, wherein the release test system additionally comprises one or more of the following features: a drive for the stirring mechanism; a pump for delivering test liquid from and/or into the release test vessel; an analyzer for analyzing the test liquid; one or more stoppers for closing interfaces of the lid.

Description

[0051] The invention is described in greater detail below with reference to exemplary embodiments and associated figures, in which:

[0052] FIG. 1 shows a preferred embodiment of a release test system according to the invention, in an exploded view;

[0053] FIG. 2 shows the release test system of FIG. 1 in a cross-sectional view, a plan view and an isometric view;

[0054] FIG. 3 shows a further preferred embodiment of a release test system according to the invention;

[0055] FIG. 4 shows a further preferred embodiment of a release test system according to the invention;

[0056] FIG. 5 shows a further preferred embodiment of a release test system according to the invention;

[0057] FIG. 6 shows a further preferred embodiment of a release test system according to the invention; and

[0058] FIG. 7 shows a simulation procedure using a preferred embodiment of a release test system according to the invention.

[0059] FIG. 1 shows a preferred embodiment of a release test system 10 according to the invention. The release test system 10 is shown in exploded view. The release test system 10 comprises a main body 12 and a lid 14. The main body 12 and the lid 14 are assemblable into a release test vessel 16 (cf. FIG. 2). The release test system 10 further comprises technical control means 18 for influencing simulation conditions prevailing inside the release test vessel 16. The technical control means 18 comprise at least one stirring mechanism 20 and one temperature control device 22. The temperature control device 22 is shown here purely by way of example as a heating coil 24 on the outside of the main body 12. It may however just as possibly be incorporated into the release test vessel 16 or implemented in another known manner. The release test system 10 further comprises a sampling device 26. The sampling device 26 is implemented in FIG. 1 merely in the form of interfaces 28 which are configured to receive a sampling tube 30 and a sample return tube 32 (cf. in each case FIGS. 3 to 7).

[0060] The lid 14 shown in FIG. 1 is connectable with the main body 12 in such a way that the lid 14 and the main body 12 are no longer non-destructively detachable from one another once the connection has been produced. To this end, the lid 14 and the main body 12 have regions for producing a snap-in connection 34, i.e. depending on structural configuration, a form- or additionally force-locking connection. These regions for producing a snap-in connection 34 are shown in yet more detail in FIG. 2. They are configured in such a way that, after assembly of the lid 14 and the main body 12, they can no longer be accessed and the connection can no longer be undone from outside.

[0061] The stirring mechanism 20 is incorporated structurally into the lid 14 and thus permanently connected therewith. This mechanism comprises in the present case a paddle stirrer 36, a stirring shaft 38, a bearing portion 40 and a sealing ring 42 arrangeable on the bearing portion 40 and in the lid 14. The bearing portion 40 likewise has in an upper region one of the regions for producing a snap-in connection 34 (cf. FIG. 2). In the present case, the stirring mechanism 20 may thus be simply snapped into the lid 14 and sealed relative thereto with the sealing ring 42.

[0062] For hermetic sealing of the lid 14 relative to the main body 12 and of the release test vessel 16 relative to the environment, a flat seal 44 is provided in the region of the snap-in connection. Furthermore, the sealing ring 42 described participates in the hermetic sealing. The interfaces 28 are sealed materially impermeably, provided no sampling device 26 or other required additional technical elements are arranged there. In this case, predetermined breaking points 46 are merely provided in the material of the lid 14. If the interfaces 28 are not needed, the lid 14 is thus itself hermetically impermeable. The seal in the case of use of the interfaces 28 is described further below.

[0063] FIG. 2 shows the release test system 10 of FIG. 1 in an assembled state. The release test vessel 16 is shown top left in FIG. 2 in a cross-sectional view A-A with lid 14 mounted on the main body 12. The associated section line A is shown in the lower left-hand part of FIG. 2, in which the release test system 10 is shown in plan view. In the lower right-hand part of FIG. 2, the assembled release test system 10 is shown in an isometric view.

[0064] In FIG. 2 the lid 14 and the main body 12 are inseparably connected to one another. A drive interface 48, which projects from the lid 14 and is thus readily accessible from outside, is readily apparent. Likewise easily visible is the arrangement of the flat seal 44 between lid 14 and main body 12. This is shown in detail B. Detail C shows the arrangement of the sealing ring 42 between bearing portion 40 and lid 14. In cross-sectional view A-A the stirring shaft 38 is visible. This is configured in the present case as a hollow shaft. Additional structural space is thus available in which, where needed, technical control means 18 or indeed measuring means may be incorporated (cf. FIG. 6).

[0065] FIG. 3 shows a further preferred embodiment of the release test system 10. Indicated therein is how the sampling device 26 with the sampling tube 30 and the sample return tube 32 projects through the lid 14 into the release test vessel 16. The sampling tube 30 in this case projects as far as into a test liquid 50 located in the release test vessel 16. The interfaces 28 known from FIGS. 1 and 2 are here in each case further developed into complementary receptacles 52 in relation to the sampling tube 30 or the sample return tube 32. To this end, for example, the predetermined breaking points 46 in question may have been opened. Different variants are conceivable as to how the exposed interfaces 28 may be further developed into the complementary receptacles 52. For example, sealing elements or receptacles may be provided to this end from the outset under the predetermined breaking points 46. Plain bearings may also be provided in the lid, for example in the form of regions of resilient material which at the same time function as a sealing element. Further development into the complementary receptacles 52 may for example proceed through resilient deformation. A plurality of sealing rings arranged one behind the other may for example be arranged which are expanded when the sampling tube 30 or sample return tube 32 is passed through. It is however also possible to penetrate the resilient regions. It is likewise possible to insert the plain bearings, for example resilient elements, only subsequently.

[0066] FIG. 1 shows that a dosage form 54 of a medical active ingredient has been introduced into the test liquid 50. This is by way of example a tablet or capsule.

[0067] Through rotation of the stirring mechanism 20, simulation conditions may be mechanically influenced in the release test vessel 16. The temperature control device 22, which is not illustrated here but which may be arranged in or on the release test vessel 16 or indeed separately therefrom, allows the temperature of the test liquid 50 to be adjusted before and/or during and optionally after the simulation.

[0068] The sampling device 26 allows simple sampling and recirculation. To this end, either the sample may be taken using the sampling tube 30 and air or another medium added using the sample return tube 32 or indeed the sample taken may be recirculated via the sample return tube 32.

[0069] FIG. 4 shows a further preferred embodiment of the release test system 10. Here, an auxiliary substance 56 for transferring mechanical stirring energy to the test liquid 50 and thus the dosage form 54 is additionally introduced into the test liquid 50. The auxiliary substance 56 is by way of example polystyrene pellets.

[0070] FIG. 5 shows a further preferred embodiment of the release test system 10. Here a resilient flask 58 is arranged inside the release test vessel 16. Via a feed path 60, which is embodied by way of an appropriately adapted interface of the interfaces 28, the resilient flask 58 may be supplied with a pressure medium 62. The resilient flask 58 is arranged in a sample chamber 64 arranged inside the release test vessel 16, wherein the sample chamber 64 is connected fluidically with the remaining volume located inside the release test vessel 16. The dosage form 54 is arranged in the sample chamber and is thus surrounded by the test liquid 50. This embodiment makes it possible for the dosage form 54 to be exposed purposefully to a pressure or pressure profile characteristic of the relevant human or animal organ. The pressure may be transferred to the dosage form 54 as a pressure wave through the test liquid 50 or through contact with the resilient flask 58.

[0071] FIG. 6 shows a further preferred embodiment of the release test system 10. In this embodiment the feed path 60 is incorporated directly into the stirring mechanism 20. The feed path 60 may be configured to guide substances 66 into the release test vessel 16 or to remove them in a controlled manner. The feed path is a further example of a technical control means 18, as is the auxiliary substance 56 of FIG. 4 and the resilient flask 58 of FIG. 5. The substances 66 may be liquid, solid, gaseous or a mixture. Titrimetric substances, carbon dioxide or nitrogen may for example be supplied. Technical means for measuring pH 68 or technical means for measuring temperature 70 may also be incorporated into the stirring mechanism 20. In the present case, for example, an integral pH/temperature sensor 72 is incorporated into the stirring shaft 38.

[0072] Finally, FIG. 7 shows by way of example how the release test system 10 according to the invention is in principle to be used. In a step I the release test vessel 16 is provided. The lid 14 and the main body 12 may be delivered, as shown in step I.sub.a, already in the preassembled state or, as shown in step I.sub.b, in the unassembled state. The unassembled state makes filling of the main body 12 with test liquid 50 simpler, while the preassembled state simplifies sterile transport. If, on the other hand, the main body 12 is preassembled with the lid 14, the release test vessel 16 may be filled via the interfaces 28. These may then be securely closed for example with one or more stoppers 74.

[0073] In step II at the latest, filling with test liquid 50 proceeds, and placement of the dosage form, then, at the latest, fitting of the lid 14 onto the main body 12, followed by adjustment of the temperature of the test liquid 50.

[0074] In step III at the latest, stirring 76 proceeds with the stirring mechanism 20. To this end, a corresponding drive 78 is connected to the stirring mechanism 20. A sample is further taken with the sampling device 26 via a pump 80, for example, and the sample is analyzed using an analyzer 82. As indicated, recirculation of the sample may optionally take place, to perform a continuous test.

[0075] Step IV involves disposal of the release test vessel 16 including stirring mechanism 20, sampling and return tubes and the test liquid 50 and the dosage form 54. In this way, all contaminated elements, which are complex and risky to clean, are directly disposed of. The contaminated test liquid 50 in this case remains safely contained inside the release test vessel 16.

REFERENCE SIGNS

[0076] 10 Release test system [0077] 12 Main body [0078] 14 Lid [0079] 16 Release test vessel [0080] 18 Technical control means [0081] 20 Stirring mechanism [0082] 22 Temperature control device [0083] 24 Heating coil [0084] 26 Sampling device [0085] 28 Interfaces [0086] 30 Sampling tube [0087] 32 Sample return tube [0088] 34 Regions for producing a snap-in connection [0089] 36 Paddle stirrer [0090] 38 Stirring shaft [0091] 40 Bearing portion [0092] 42 Sealing ring [0093] 44 Flat seal [0094] 46 Predetermined breaking points [0095] 48 Drive interface [0096] 50 Test liquid [0097] 52 Complementary receptacles [0098] 54 Dosage form [0099] 56 Auxiliary substance [0100] 58 Feed path [0101] 60 Resilient flask [0102] 62 Pressure medium [0103] 64 Sample chamber [0104] 66 Substances [0105] 68 Technical means for measuring pH [0106] 70 Technical means for measuring temperature [0107] 72 Integral pH/temperature sensor [0108] 74 Stopper [0109] 76 Stirring [0110] 78 Drive [0111] 80 Pump [0112] 82 Analyzer