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CN-121986265-A - Dissolution testing device for open loop or closed loop configuration

CN121986265ACN 121986265 ACN121986265 ACN 121986265ACN-121986265-A

Abstract

The invention relates to a dissolution test apparatus for testing a dissolution substance dissolved in a dissolution medium, comprising at least one dissolution medium reservoir (15), at least one flow cell (4) for receiving the dissolution substance to be tested, and at least one pump device (60) for pumping the dissolution medium through the at least one flow cell (4). Furthermore, the dissolution test apparatus comprises at least two sampling vessels (8.1, 8.2) connectable to one flow cell (4) for sampling a substance solution, an inlet fluid manifold (100) for selectively connecting the flow cell (4) to one of the at least two sampling vessels (8.1, 8.2), an outlet fluid manifold (110) for selectively connecting one of the at least two sampling vessels (8.1, 8.2) to a drain line (140), at least one test device (70) for testing the substance solution of a selected sampling vessel (8.1; 8.2), and a switching valve system (150) for selectively connecting the drain line (140) to a cell inlet line (27) or an extraction line (160) of the flow cell (4).

Inventors

  • ROLF. BENZ
  • Ruyi Fraga
  • Michele. Maniye
  • Damian Kazmelchak
  • Stephen Hengji
  • Jill Karl Bergmann

Assignees

  • 索泰克斯股份有限公司

Dates

Publication Date
20260505
Application Date
20240920
Priority Date
20230922

Claims (17)

  1. 1. A dissolution test apparatus for testing a soluble substance dissolved in a dissolution medium, comprising: At least one dissolution medium reservoir (15), At least one flow cell (4) for receiving a soluble substance to be tested, said at least one flow cell (4) being connected to said dissolution medium reservoir (15), Sampling container (8.1, 8.2) for sampling a substance solution containing a dissolution medium and a dissolution substance, and At least one pump device (60) for pumping the dissolution medium through the at least one flow cell (4), The dissolution test device is characterized by further comprising: At least two sampling vessels (8.1, 8.2) connectable to one flow cell (4), An inlet fluid manifold (100) for selectively connecting the flow cell (4) to one of the at least two sampling vessels (8.1, 8.2), An outlet fluid manifold (110) for selectively connecting one of the at least two sampling vessels (8.1, 8.2) to a drain line (140), And -A switching valve system (150) for selectively connecting the drain line (140) to a cell inlet line (27) or an extraction line (160) of the flow cell (4).
  2. 2. The dissolution test apparatus according to claim 1, wherein the inlet fluid manifold (100), the outlet fluid manifold (110), and the switching valve system (150) are connected to a controller to control selective fluid connections.
  3. 3. The dissolution test apparatus according to claim 1 or 2, characterized in that a test device (70) is arranged at the discharge line and/or the at least one sampling vessel (8.1, 8.2) for testing a substance solution in the discharge line (140) and/or the sampling vessel (8.1, 8.2).
  4. 4. The dissolution test apparatus according to any one of the preceding claims, wherein the inlet fluid manifold (100) comprises an inlet end (101) in fluid communication with the substance solution conduit (7) of the flow cell (4) and an outlet end (102.1, 102.2) of each of the sampling vessels (8.1, 8.2), the outlet ends (102.1, 102.2) being in fluid communication with a sampling vessel inlet line (112.1, 112.2).
  5. 5. The dissolution test apparatus according to any one of the preceding claims, wherein the outlet fluid manifold (110) comprises an inlet end (111.1, 111.2) of each of the sampling vessels (8.1, 8.2) and an outlet end (113) in fluid communication with the drain line (140), the inlet ends (111.1, 111.2) being in fluid communication with sampling vessel outlet lines (112.1, 112.2) of the respective sampling vessels (8.1, 8.2).
  6. 6. The dissolution test apparatus according to any one of the preceding claims, wherein a stirring loop is provided at a sampling vessel outlet line (112.1,112.2), the stirring loop comprising a pump (117.1,117.2) to pump a substance solution through the stirring loop and back into the sampling vessel (8.1, 8.2).
  7. 7. The dissolution test apparatus according to any one of the preceding claims, wherein the outlet fluid manifold (110) comprises a stirring end (115.1, 115.2) to connect the at least one sampling vessel (8.1, 8.2) to the stirring loop.
  8. 8. The dissolution test apparatus according to any one of the preceding claims, wherein the outlet fluid manifold (110) comprises a waste end (141) to connect the at least one sampling vessel (8.1, 8.2) to a waste line (141).
  9. 9. The dissolution test apparatus according to any one of the preceding claims, wherein a washing system comprises a washing medium reservoir (170) external to the at least two sampling vessels (8.1, 8.2) and a nozzle (171) located in the sampling vessel (8.1, 8.2), wherein the washing system is connected to the inlet fluid manifold (100) to connect the washing system to the at least two sampling vessels (8.1, 8.2).
  10. 10. The dissolution test apparatus according to any one of the preceding claims, wherein the dissolution medium reservoir (15) is connectable to the flow cell (4) by the switching valve system (150).
  11. 11. The dissolution test apparatus according to any one of the preceding claims, wherein the dissolution medium reservoir (15) comprises a medium selector (80) and a medium manifold (81), the medium selector (80) providing a plurality of different solvents, and the medium manifold (81) being connectable to the flow cell (4) by the switching valve system (150).
  12. 12. Dissolution test method for testing a dissolved substance in a dissolution medium using a dissolution test apparatus according to any one of the preceding claims, characterized in that the inlet fluid manifold (100), the outlet fluid manifold (110) and/or the switching valve system (150) establish a selective connection such that: The apparatus operates in an open loop mode by connecting the drain line (140) to the extraction line (160), or in a closed loop mode by connecting the drain line (140) to the pool inlet line (27).
  13. 13. The dissolution test method according to claim 12, wherein the at least two sampling vessels (8.1, 8.2) are alternately connected to the flow cell (4) and the discharge line (140) such that a continuous stream of substance solution exits from the flow cell (4).
  14. 14. The dissolution test method according to any one of the preceding claims 12 to 13, characterized in that in the open loop mode the at least two sampling vessels (8.1, 8.2) are alternately connected to the flow cell (4) and the discharge line (140) such that one sampling vessel (8.1) is filled with a substance solution while the substance solution in the other sampling vessel (8.2) is tested and/or discharged.
  15. 15. The dissolution test method according to any one of the preceding claims 12 to 14, characterized in that in the open loop mode one sampling vessel (8.1) of the at least two sampling vessels (8.1, 8.2) which has been filled with a first portion of the substance solution is disconnected from the flow cell and the first portion is tested by the test apparatus while the other sampling vessel (8.2) of the at least two sampling vessels (8.1, 8.2) is connected to the flow cell (4) and filled with a second portion of the substance solution.
  16. 16. The dissolution test method according to any one of the preceding claims 12 to 15, characterized in that in closed loop mode the flow-through cell (4) is connected to one of the at least two sampling vessels (8.1) and the drain line (140) is connected to the cell inlet line (27) and a plurality of portions are continuously sampled in the one sampling vessel (8.1) and tested by the test device (70).
  17. 17. The dissolution test method according to any one of the preceding claims 12 to 16, wherein the portion is stirred in the stirring loop before being tested by the at least one test apparatus (70).

Description

Dissolution testing device for open loop or closed loop configuration Technical Field The present invention relates to a dissolution test apparatus for drug release tests and dissolution tests, and more particularly to a flow cell apparatus or device having an open or closed mode of operation module. The invention relates in particular to eluting and testing of soluble substances. Background The dissolution test is a pharmacopoeia in vitro test, for example for drug research and development, to characterize the release rate of an Active Pharmaceutical Ingredient (API) from a formulated dosage form that correlates with its in vivo performance under reproducible conditions. Once the innovative drug product profile has been approved by the target market regulatory agency, the dissolution test is used to evaluate the batch-to-batch consistency of the produced product according to its submitted specifications and general test conditions described by the regulatory agency. The dissolution rate is also used by the pharmaceutical-imitation companies to establish bioequivalence of their products without repeating the initial clinical study performed by the pharmaceutical-imitation companies, which they have obtained bio-exemptions. Pharmaceutical formulations include granules, tablets, capsules, gels, creams, ointments, suspensions, suppositories, patches, microspheres, implants and other long-acting injections, such as micro-suspensions and nano-suspensions, and the like. "dissolution test" is a term used for solid dosage forms and more generally the term "drug release test" is used for other dosage forms, including coated medical devices. Outside the pharmaceutical field, dissolution test apparatus are also used for other applications, such as release of nicotine from smokeless tobacco products, and for persistence tests of asbestos fibers in lung fluids. The primary advantage of a dissolution testing apparatus in the form of a flow-through cell dissolution instrument is its flexibility, as the cell and its internal arrangement can accommodate the formulation structure and challenges tested. The dissolution test mode of solid dosage forms and the devices involved are described in the general dissolution section (U.S. pharmacopoeia <711 >) unified among the European, U.S. and Japanese pharmacopoeias. Flow cell dissolution is also described in the chinese pharmacopoeia as method 6. Standardized methods use, for example, paddle devices to agitate the material in the container, as described in EP0746759A1, basket devices to hold the material in the basket, as described in US5816701a, or flow-through devices to flow the dissolution medium through a pool containing the material, as described in WO2013/003518 A1. The dimensions and tolerances of such devices are precisely specified. Key test parameters that must be monitored periodically during use include, for example, the volume and temperature of the dissolution medium, the rotational speed, and the flow rate of the medium. The circulation device is used for various objects to be tested. The flow-through cell dissolution principle is to flow a dissolution medium onto a cell containing a dosage form to be tested at a defined temperature and flow rate. The total volume of dissolution medium is based on the solubility of the active pharmaceutical ingredient (i.e. the corresponding substance) to be dissolved and the duration of the test is ideally related to the in vivo performance of the product tested. The dissolution test apparatus is typically composed of a plurality of channels to allow simultaneous testing of, for example, seven channels (six samples and one control). Thus, before using the device, seven channels must be validated in a document flow (installation validation, run validation) to prove that they allow equivalent tests to be performed on all channels, since the final samples will all be compared to the specifications, since they represent the whole production batch. Flow cell dissolution test apparatus include media reservoirs, multichannel pump systems, dissolution modules (including cells), and modules that allow on-line partial collection, sampling, or direct analysis of samples. The flow cell dissolution device may be used in two different configurations/modes. In the open mode, the channels simultaneously receive the dissolution medium from a single reservoir. The media is flowed into the flow cell by each pump channel, filtered, and each eluent (i.e., solution) is then collected or analyzed. The dosage form is immersed in a medium that is always updated in the cell at a rate defined by the pump flow rate setting. In current systems, a portion of the collected sample must be homogenized and a smaller volume of sample must be extracted from the portion to be analyzed. During the test, if a different reservoir has been connected to the media selector, the source of the media (for all pools) can be changed at defined times. Because the media used may