Dissolution analysis device and method for monitoring or analyzing the dissolution of a substance into a liquid or liquid matrix

Abstract

A dissolution activity analyzer includes an integrating cavity with one or more reflective inner walls and configured to receive a cuvette containing a liquid sample. The integrating cavity includes an optical inlet port and an optical outlet port, the optical inlet port configured to receive light from a light source and the optical outlet port configured to provide light to a spectrometer. The dissolution activity analyzer is configured to operate in a diffuse reflectance mode, in which light from the light source travels an optical path from the inlet port to the integrating cavity, impinges on the one or more reflective inner walls, and is diffusely reflected so as to illuminate the liquid sample before being transmitted through the optical outlet port and received by the spectrometer to provide an absorbance spectrum of the liquid or liquid matrix contained in the liquid sample.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to European Patent Application EP22206532.8, filed November 10, 2022, the entire contents of which are incorporated herein by reference. FIELD OF THE INVENTION

[0002] The present invention relates to monitoring or analyzing dissolution of a substance into a part or element within a liquid or liquid matrix, and more particularly to a dissolution analysis device and method for monitoring or analyzing dissolution of a substance into a part or element within a liquid or liquid matrix.

[0003] Monitoring and quantifying the rate at which a substance, such as a tablet or pharmaceutical product, dissolves in a liquid is an important process in product development and manufacturing.

[0004] Monitoring the release of a substance into a liquid as it dissolves in the liquid is called dissolution testing. Applications of dissolution testing include monitoring the release profile of vitamins from tablets after they are placed in a liquid matrix for human consumption, and understanding the release profile of active pharmaceutical ingredients in the body.

[0005] In pharmaceutical applications, dissolution studies are a regulated step in the production and quality assurance of formulation development, and the developed product must comply with accepted release profile guidelines.

[0006] Absorption spectroscopy using an ultraviolet-visible (UV-Vis) spectrophotometer is a common tool used to monitor and quantify the dissolution of a substance into a liquid. Typically, a spectral region is selected in which the active ingredient being monitored absorbs light. As the product dissolves, the active ingredient is released into the dissolution liquid matrix, and the UV-Vis spectrum of the solution is measured. The intensity of the absorbance in the region of interest is determined and can be related to the concentration of the active ingredient currently present in the liquid. As dissolution continues, sequential sampling of the solution over time and measuring the absorbance spectrum can determine the concentration of the active ingredient released into the solution as a function of time, thus generating what is known as a dissolution curve.

[0007] However, to obtain accurate absorbance measurements, samples must undergo elution-related processing steps, including, for example, filtration, centrifugation, precipitation, or degassing, before being analyzed by a UV-Vis spectrophotometer. These elution-related processing steps not only significantly increase sample throughput, but also mandate the use of consumables such as pipette tips, filters, and sample containers, which have a negative impact on the environment.

[0008] This adds additional cost to the measurement. The additional elution-related processing steps may also introduce undesirable errors and inaccuracies into the resulting absorbance measures.

[0009] One solution to these inconveniences is to envision measurement methods that do not involve such dissolution-related processing steps, but a drawback of such methods is that conventional spectrophotometers inaccurately measure the absorbance of a sample when there is background turbidity in the liquid sample. The background turbidity of the sample, caused by light scattering from suspended particles or air bubbles introduced into the liquid during dissolution activity, contributes to or saturates the absorbance measurement, thus preventing accurate measurement of the component concentration in the liquid.

[0010] In many cases of dissolution, such as the dissolution of tablets or effervescent tablets into liquid, the sample will have a high level of turbidity caused by undissolved tablets, large clumps or particles of excipient material, or from air bubbles generated by the dissolution process. Therefore, to obtain accurate absorbance measurements to determine accurate dissolution profiles, the sample must be subjected to the processing steps described above, including, for example, filtration, centrifugation, sedimentation, or degassing, before analysis by UV-Vis spectrophotometer.

[0011] If the above processing steps to remove turbidity are not performed, the dissolution curve will be highly susceptible to sample scattering and therefore provide erroneous information regarding the dissolution kinetics of the components.

[0012] Additionally, traditional ultraviolet-visible (UV-Vis)-based methods are also susceptible to errors due to sample settling, because the light beam only probes the sample at a fixed height. Any material that settles to the bottom of the sample container will not be included in the measurement, and the measured absorbance may give a value that is lower than the actual concentration of the material in the liquid. Similarly, the possibility of particles that cause turbidity settling to the bottom of the container will also affect the absorbance results obtained using traditional UV-Vis-based methods, resulting in further inaccuracies in material concentrations.

[0013] Accordingly, in one aspect, the present disclosure provides a dissolution activity analyzer, or dissolution analyzer, for measuring, monitoring, or analyzing the dissolution of a substance into a liquid or liquid matrix. The dissolution analyzer comprises: an integration cavity having one or more reflective inner walls, the integration cavity configured to receive a cuvette containing a liquid sample within the integration cavity; the integrating cavity comprises at least one optical entrance port and at least one optical exit port, the or each optical entrance port configured to receive light from at least one light source, and the or each optical exit port configured to provide light to a spectrometer; The dissolution analysis apparatus is configured to operate in a diffuse reflectance mode, in which light from the light source follows a light path from the or one of the inlet port(s) to the integrating cavity, impinges on one or more reflective inner walls of the integrating cavity, and is diffusely reflected within the integrating cavity so as to illuminate the liquid sample before the light from the light source is transmitted through the or one of the light exit port(s) and received by the spectrometer for wavelength analysis of the light providing an absorbance spectrum of the liquid or liquid matrix contained in the liquid sample.

[0014] The dissolution activity device or analyzer ensures that light scattering during dissolution activity is not lost, but is collected and measured to allow more accurate absorbances to be measured or determined, as well as more accurate dissolution profiles to be measured or determined.

[0015] Specific embodiments and other advantageous features of the dissolution analysis device are set out in the dependent claims.

[0016] In a further aspect, the present disclosure provides a dissolution analysis method for measuring, monitoring or analyzing at least one substance SB while it is dissolving in a liquid, liquid matrix or liquid sample, or for measuring, monitoring or analyzing at least one substance SB dissolving in a liquid, liquid matrix or liquid sample.

[0017] This method is providing a dissolution analyzer or dissolution activity analyzer as described herein; performing measurements using a dissolution analyzer or dissolution activity analyzer in a diffuse reflectance operating mode during the release of at least one substance from at least one substance carrier into at least one liquid or liquid matrix contained in a liquid sample; Includes.

[0018] The method may also include determining a plurality of absorbance spectra over a period of time during release of the at least one substance from the at least one substance carrier into the at least one liquid or liquid matrix.

[0019] The method may also include determining a substance release profile for the at least one substance based on the determined plurality of absorbance spectra.

[0020] Specific embodiments and other advantageous features of the dissolution analysis method are set out in the dependent claims.

[0021] The present invention overcomes the shortcomings of conventional UV-Vis-based methods for dissolution testing by employing an integrating cavity-based spectrophotometer to perform absorbance measurements. The use of an integrating cavity-based device eliminates the effects of scattering on the measured absorbance spectrum, thereby enabling the generation of a "pure absorbance" spectrum of the sample, which more accurately represents the concentration of the substance of interest without the need for the processing steps described above prior to measurement, i.e., without the need to filter or pre-treat the sample to remove turbidity-causing components.

[0022] This solution advantageously ensures that no centrifugation, filtration, precipitation, degassing, or other such elution-related processing steps are required prior to measurement. Eliminating the elution-related processing steps required to remove sample turbidity to obtain an absorbance spectrum, and therefore an elution curve, saves time and provides faster results. Importantly, the environmental impact is significantly reduced because the need for consumables such as filters and pipette tips in processing steps is eliminated. This elimination also has the added benefit of cost savings.

[0023] Additionally, accuracy can be improved since the sample is not processed and therefore the measurements are more representative of the sample in its current state.

[0024] Importantly, dissolution measurements and dissolution curves are not affected by sample scattering and therefore provide smoother and more accurate information about the dissolution kinetics of a substance into a liquid.

[0025] Furthermore, the integrating cavity approach probes the entire sample volume compared to standard transmission-based geometries that only probe specific regions of the sample, thereby reducing errors due to sample settling.

[0026] The solution provided by the present invention has never before been used, disclosed or suggested as a solution to the aforementioned problems of additional sample processing steps associated with obtaining dissolution measurements or dissolution measurements, and an integrating cavity has never before been used or suggested as a method for measuring and / or monitoring dissolution curves and eliminating the need for additional sample processing steps prior to measurement.

[0027] Indeed, the effect of turbidity on elution curves has not been studied before and is now shown for the first time in this disclosure by the inventors by using an integrating cavity to obtain the "true absorbance" of the sample and simultaneously comparing it with conventional UV-Vis-based results.

[0028] The inventors also show herein how attempting to remove background turbidity using background subtraction from UV-Vis-based results is insufficient to obtain a smooth elution curve that is not affected by sample turbidity.

[0029] Dissolution analyzers according to the present disclosure may be further configured to include a light path adjuster configured to selectively adjust the light path through the integrating cavity so that at least two different light paths are provided. When the light path adjuster is in a first configuration, the dissolution analyzer is in a transmission mode, in which light from the light source follows a first light path from the or one of the light entrance port(s) to the liquid sample such that light from the light source directly illuminates the liquid sample before light transmitted through the or one of the light exit port(s) is transmitted through the or one of the light exit port(s) and received by a spectrometer for wavelength analysis of the light to provide an extinction spectrum of the liquid sample. When the light path adjuster is in the second configuration, the dissolution analysis apparatus is in a diffuse reflectance mode, in which light from the light source follows a second optical path from the inlet port(s) or one of the inlet port(s) to the integrating cavity, impinges on one or more reflective inner walls of the integrating cavity, and is diffusely reflected within the integrating cavity so as to illuminate the liquid sample before the light from the light source is transmitted through the or one of the light exit port(s) and received by the spectrometer for wavelength analysis of the light to provide an absorbance spectrum of the liquid or liquid matrix contained in the liquid sample.

[0030] In particular, the dissolution analyzer can be used to obtain spectra that are the absorbance and extinction spectra of a sample, thereby obtaining an absorbance and extinction spectrum defined for a given path length through the sample using appropriate calibration procedures implemented by one or more electronic data processors.

[0031] By providing a dissolution analyzer that can be used in each of the above configurations, quantitative spectra can be obtained in each configuration with well-defined path lengths of light through the sample so that the data obtained in each configuration can be correlated.

[0032] When the dissolution analyzer is in the second configuration, light from the second optical path: a) directly from the inlet port to one or more walls of the integrating cavity, and / or b) from an inlet port, onto and through the sample and then directly onto one or more walls of the integrating cavity; It may be configured to be transparent.

[0033] Thus, when in the second configuration, the second optical path can be from the entrance port, initially through the sample, or transmitted directly through one or more cavity walls. In either variation, the device is configured so that the exit port used in the second configuration does not look into the entrance port. In other words, the exit port used in the second configuration "faces" the wall of the integrating cavity. For example, the exit port may be at 90° to the entrance port or at any other position on the integrating cavity. The relative positions of the entrance and exit ports used in the second configuration are such that the spectrometer does not collect incident light or light directly transmitted through the sample.

[0034] Preferably, an appropriate calibration procedure will result in absorbance and extinction spectra that are defined for a given path length through the sample.

[0035] A preferred implementation of the second configuration is to position the outlet port so that it faces directly toward an area of ​​the cavity wall that is not directly illuminated by light from the inlet port. In both configurations, and used with appropriate calibration procedures, the dissolution analyzer generates both extinction and absorbance spectra of the liquid sample; in both of the above configurations, the path length through the sample is well-defined, so that the resulting spectra provide the wavelength-dependent extinction and absorbance coefficients of the sample, respectively, over the range of wavelengths of light illuminating the sample.

[0036] The dissolution analyzer may include one or more integral light source(s), or the light source may be configured to connect to one or more separate light source(s).

[0037] The dissolution analyzer may further include an integral or remote controller configured to control the light path adjuster to selectively adjust the path of light through the dissolution analyzer. The controller is preferably configured to control the spectrometer, and in particular to process light received by the spectrometer for wavelength analysis of the light to provide an extinction spectrum and / or absorbance spectrum of the liquid sample contained in the cuvette. The spectrometer may be integral with the dissolution analyzer. The one or more controllers may: a) switching between a first configuration and a second configuration; b) obtaining a spectrum from an integrating cavity; c) selecting the operating conditions; d) displaying the spectrum on a display of the dissolution analyzer or controller or on a display in communication with the dissolution analyzer or controller; e) storing the data in a memory of the dissolution analyzer or controller or in communication with the dissolution analyzer or controller; f) a user interface of or in communication with the dissolution analysis device or controller that interacts with the dissolution analysis device and allows a user to control the position of the light path adjustment mechanism; The optical path adjuster may be configured to control one or more of: a first optical path adjuster configured to adjust a first position of the optical element relative to the integrating cavity, the first optical path adjuster configured to adjust the first optical path and the second optical path; a second optical path adjuster configured to adjust the first position of the optical element relative to the integrating cavity, the second position of the optical element relative to the integrating cavity, the first optical path adjuster configured to adjust the second optical path and the second optical path; a third optical path adjuster configured to adjust the second optical path and the first optical path; a fourth optical path adjuster configured to adjust the second optical path and the second optical path; a fifth optical path adjuster configured to adjust the second optical path and the first optical path; a fifth optical path adjuster configured to adjust the second optical path and the second optical path; a fifth optical path adjuster configured to adjust the second optical path and the second optical path; a fifth optical path adjuster configured to adjust the second optical path and the second optical path; a sixth ... first optical element relative to the integrating cavity, the sixth optical path adjuster configured to adjust the second optical path and the second optical path;

[0038] The integrating cavity has orthogonal longitudinal, vertical, and transverse axes and the following positional characteristics of the optical element: a) longitudinal position, b) vertical position; c) horizontal position; d) orientation, e) slope Any one or more of the axes can be adjusted relative to any one or more of the axes.

[0039] A plurality of movable optical elements may be provided. The movable optical elements preferably include: ·prism, ·lens, ·mirror, Diffraction gratings, Fiber optic cables, ·light source, ·shutter, is selected from any one or combination of:

[0040] The optical path adjuster may additionally or alternatively comprise at least one fixed optical element that is not adjustable relative to the integrating cavity. The fixed optical element may be configured to manipulate light from the light source before the light inlet port. The fixed optical element may be configured to manipulate light from the light outlet port.

[0041] The fixed optical element is a) prism, b) lenses, c) mirrors, d) diffraction grating, e) fiber optic cables; f) light source; may be selected from any one or combination of:

[0042] The light path adjuster may comprise at least one electronic controller operative to effect selective operation of one or more light sources to selectively provide the first light path and the second light path.

[0043] The dissolution analyzer may include at least a first light source and a second light source, and the controller is configured to independently control each light source. The light sources may be switched on and off in a flashing or continuous manner, such that in configuration 1, the first light source is on and in configuration 2, the second light source is on and the first light source is off. The light sources may be controlled so that both or all light sources can be turned off to obtain a dark spectrum.

[0044] The optical path adjuster is a) Between the light source and the light entrance port, and / or b) between the spectrometer and the optical exit port; can be placed in

[0045] Multiple optical path adjustment mechanisms may be provided. Multiple optical entry ports may be provided, with the optical path adjuster configured to provide a first optical path by directing light from the light source through a first optical entry port and to provide a second optical path by directing light from the light source through a second optical entry port. Multiple optical exit ports may be provided, with the first optical path directing light from the integrating cavity through the first optical exit port and the second optical path directing light from the integrating cavity through the second optical exit port.

[0046] The integral cavity is a) Diffusely reflecting spherical integrating cavity, b) cylindrical cavity, c) cubic or square cavity; It may include any one of the following:

[0047] It will be appreciated that the integrating cavity may be any other shape or combination of shapes.

[0048] The integral cavity is a) Specular reflectance, b) diffuse reflectance, c) reflectance in the UV light spectrum; d) reflectance in the visible light spectrum; e) reflectance in the infrared spectrum; The coating may include an internal coating configured to provide any one or more of:

[0049] The light source is a) a quartz halogen source; b) LED, c) laser, d) any polychromatic source; It may include any one or more of the following:

[0050] The shape of the cuvette is a) square; b) Plate-shaped, c) cylindrical, d) spherical; may be.

[0051] The dissolution analyzer may be a UV-VIS spectrometer dissolution analyzer.

[0052] The dissolution analyzer may further include a sample holder configured to hold a cuvette containing a liquid sample within the integration cavity.

[0053] The light source may include a first LED light source and a second LED light source, and the light path adjuster comprises a controller configured to control the first LED light source and the second LED light source such that, when in the first configuration, the first LED light source is controlled to provide light in the first light path, and when in the second configuration, the second LED light source is controlled to provide light in the second light path.

[0054] Light from each LED light source may be delivered to the integrating cavity via a respective fiber optic cable. Each LED light source may deliver light to a respective optical inlet port. Each optical path delivers light via a respective optical outlet port.

[0055] The first LED light source may be associated with a collimation lens disposed between the first LED light source and an optical inlet port associated with the first LED light source. The apparatus may further include a first exit port and a second exit port, and a beam splitter configured to selectively allow light from the first exit port and the second exit port to be transmitted to the spectrometer. [Brief explanation of the drawings]

[0056] The above and other objects, features, and advantages of the present invention, and the manner in which the same are accomplished, will become more apparent, and the invention itself will best be understood from a consideration of the following description taken in conjunction with the accompanying drawings, which illustrate certain preferred embodiments of the invention.

[0057] [Figure 1] 1 shows an exemplary substrate or carrier for an effervescent tablet of a berry-flavored vitamin B and vitamin C supplement placed in water, where dissolution of the tablet occurs. Exemplary measurements according to the present invention were performed using this exemplary substrate or carrier.

[0058] [Figure 2A] Figures 2A and 2B show the measured absorbance and extinction spectra measured during dissolution in water of the tablet of Figure 1. Figures 2A and 2B show the measured absorbance and extinction spectra measured over time during dissolution in water of a portion of the tablet, an exemplary "berry" flavor sample tablet. [Figure 2B] Figures 2A and 2B show the measured absorbance and extinction spectra measured during dissolution in water of the tablet of Figure 1. Figures 2A and 2B show the measured absorbance and extinction spectra measured over time during dissolution in water of a portion of the tablet, an exemplary "berry" flavor sample tablet. [Figure 2C]Figure 2C shows these absorbance and extinction spectral measurements at specific spectral regions or values ​​of interest that were selected based on the spectral profile of the substance being measured and monitored over time to determine the time dependence of substance dissolution. For the exemplary "berry" flavor sample investigated, a spectral value of interest of 469 nm was selected.

[0059] [Figure 3] FIG. 3 shows absorbance and extinction spectral measurements similar to those in FIG. 2C in a particular spectral region or value of interest selected based on the spectral profile of the substance being measured, an "orange" flavored tablet sample, the selected spectral value of interest being 448 nm.

[0060] [Figure 4A] 4A and 4B show the measured absorbance and extinction spectra measured over time during dissolution in water of another sample, a vitamin C supplement tablet. [Figure 4B] 4A and 4B show the measured absorbance and extinction spectra measured over time during dissolution in water of another sample, a vitamin C supplement tablet.

[0061] [Figure 5] FIG. 5 is a schematic diagram of exemplary components of a dissolution analysis apparatus according to the present disclosure.

[0062] [Figure 6A] 6A and 6B are schematic diagrams of a first embodiment of a dissolution analysis device according to the present disclosure in first and second configurations. [Figure 6B] 6A and 6B are schematic diagrams of a first embodiment of a dissolution analysis device according to the present disclosure in first and second configurations.

[0063] [Figure 7A]7A and 7B are schematic diagrams of a second embodiment of a dissolution analysis device according to the present disclosure in first and second configurations. [Figure 7B] 7A and 7B are schematic diagrams of a second embodiment of a dissolution analysis device according to the present disclosure in first and second configurations.

[0064] [Figure 8] FIG. 8 is a schematic diagram of a third embodiment of a dissolution analyzer according to the present disclosure, together showing the first and second configurations of the dissolution analyzer.

[0065] [Figure 9] FIG. 9 is a schematic diagram of a fourth embodiment of a dissolution analyzer according to the present disclosure, together showing first and second configurations of the dissolution analyzer.

[0066] [Figure 10] FIG. 10 is a schematic diagram of a fifth embodiment of a dissolution analyzer according to the present disclosure, together showing first and second configurations of the dissolution analyzer.

[0067] [Figure 11] FIG. 11 is a schematic diagram of a sixth embodiment of a dissolution analyzer according to the present disclosure, together showing first and second configurations of the dissolution analyzer. Detailed Description of Some Embodiments

[0068] In this specification, the same reference numbers are used wherever possible to designate identical elements common to the figures, and images have been simplified for illustrative purposes and may not be drawn to scale.

[0069] The accompanying drawings constitute a part of this specification, illustrate presently preferred embodiments of the invention, and together with the general description above and the detailed description below, serve to explain features of the invention.

[0070] 5-11 schematically illustrate an exemplary dissolution analysis apparatus 1 or dissolution device 1 of the present disclosure.

[0071] During the action or process of elution, the substance or item SB elutes into the liquid or liquid matrix LQ, out or away from the host or carrier CR in which the substance or item is contained, held or carried before coming into contact with or being placed in the liquid.

[0072] The dissolution analysis device 1 of the present disclosure is, for example, a dissolution activity analysis device 1 configured to monitor the dissolution activity of a substance into a liquid, or a dissolution kinetic process analysis device 1 configured to monitor the kinetic dissolution process of a substance into a liquid.

[0073] The dissolution analysis device 1 of the present disclosure may be, for example, a released substance analysis device 1, an eluted substance analysis device 1, or an eluted substance activity analysis device 1, in which the substance to be released or eluted is provided to a liquid or liquid matrix by a host or carrier in which the item or substance is contained, held, or carried before contacting or being placed in the liquid or liquid matrix, and the substance or item is eluted into the liquid or liquid matrix.

[0074] The dissolution analyzer 1 measures, analyzes or monitors dissolution behavior or dissolution activity in a liquid or liquid matrix during the release of at least one substance or item into the liquid or liquid matrix.

[0075] The substance or item SB is held, carried or contained in at least one (substance) carrier CR or at least one (substance) substrate CR. The substance or item SB is released from the carrier or substrate CR when the carrier or substrate CR or a part thereof is placed in a liquid or liquid matrix LQ.

[0076] The dissolution analyzer 1 measures, analyzes or monitors the dissolution kinetics of releasing substances or items, or measures, analyzes or monitors the dissolution rate or dissolution profile of a substance released into a liquid.

[0077] The dissolution analysis device 1 is, for example, an apparatus 1 for analyzing the dissolution of a substance into a liquid or an apparatus for analyzing the dissolution effect of a substance into a liquid. The dissolution analysis device 1 is, for example, an apparatus 1 for monitoring or analyzing the dissolution of a substance into a liquid, a liquid matrix, or a liquid sample.

[0078] During elution, at least one substance or item dissolves or diffuses into the liquid, liquid matrix, or liquid sample. The elution or diffusion causes light scattering by the substance or item dissolving or diffusing into the liquid, liquid matrix, or liquid sample. The elution or diffusion of the eluted substance or item produces a turbid liquid or a turbid liquid matrix.

[0079] At least one substance or item is incorporated into the liquid or liquid matrix.

[0080] For example, a substance may dissolve into a liquid to form a mixture, solution, suspension, or emulsion. A substance(s) or item(s) may diffuse into a liquid to form, for example, a mixture, solution, suspension, or emulsion.

[0081] The substance or item may be, for example, a solid substance or item, a gaseous substance or item, or a liquid substance or item.

[0082] The carrier or substrate may, for example, comprise or consist of a tablet, capsule, or powder or granules.

[0083] The carrier or substrate may, for example, contain and release a plurality of different items or substances into the liquid in addition to the substance or item of interest. The elution characteristics of only one of the plurality of items or substances, the substance or item of interest, may be measured, monitored, or analyzed. Several substances or items may be the substance or item of interest, and the elution characteristics of the plurality of items or substances may be measured, monitored, or analyzed. Alternatively, the elution characteristics of a subset of the plurality of items or substances may be measured, monitored, or analyzed.

[0084] The carrier or matrix may, for example, contain elements that aid in the elution process or in the diffusion of substances, such as sodium carbonate or sodium bicarbonate.

[0085] A monitored substance or item of interest is, for example, a target substance or active substance (or item) that is released or made available for use, utilization, or consumption by humans or animals.

[0086] The monitored dissolution characteristics of the target or active substance may be required to comply with certain dissolution standards or substance release conditions. Monitoring and measurement may, for example, make it possible to ensure consistent quality in the production of carriers that deliver such substances via dissolution release, or may, for example, ensure that such carriers provide a consistent release profile.

[0087] The substance or item being monitored can be any substance or item intended to be dissolved or released into a liquid or liquid matrix. Dissolution characteristics depend on many factors, such as surface area, temperature, and agitation. The dissolution analyzer 1 allows dissolution characteristics to be determined and verified for compliance with product requirements.

[0088] The substance or item may, for example, comprise or consist of nutrients such as vitamins or minerals, or may be an inorganic compound. The substance or item may, for example, be a drug, e.g., a pharmaceutical drug, where the elution of the drug, or the elution of the drug according to a particular release profile, may be important for the therapeutic effect.

[0089] The liquid or liquid matrix is, for example, water, but can be any liquid or liquid matrix in which the substance or item of interest is expected to dissolve. During measurement, the liquid or liquid matrix is ​​contained or held in a cuvette received in the dissolution analysis apparatus 1. The substance or item to be analyzed or monitored is introduced into the cuvette for measurement, for example, by introducing the carrier or a portion thereof into the cuvette and performing a dissolution measurement while the substance is released from the carrier into the liquid in the cuvette.

[0090] 5 shows an exemplary embodiment of the above-described analytical device 1 for measuring the spectrum of a liquid sample during dissolution of a substance, component or item into the liquid or liquid matrix of the liquid sample. The dissolution analysis device 1 is configured to measure several optical properties of the liquid sample, among which are the wavelength-dependent extinction coefficient and extinction coefficient of the liquid.

[0091] Dissolution analysis apparatus 1 may, for example, comprise an integrating cavity 3 with reflective inner walls 5 configured to hold a cuvette 7 containing a liquid or liquid matrix therein, and light from a light source 9 is provided to cavity 3 via different optical paths 15, 17 entering cavity 3, which are selectively adjustable by an optical path adjuster 13. Optical path adjuster 13 is used to provide light to cavity 3 through at least one inlet port P1, P2 along different paths depending on the configuration of optical path adjuster 13.

[0092] The dissolution analysis apparatus 1 further comprises at least one optical exit port P3, P4 configured to provide light to a spectrometer 11. In some embodiments, an output optical path adjuster 13B is provided to control the path of light from the integrating cavity 3 to the spectrometer 11.

[0093] In a first configuration, the dissolution analyzer 1 is in a transmission mode in which the input path conditioner 13 is positioned so that light from the light source 9 enters the cavity 3 through the inlet port P1 so as to directly illuminate the liquid contained in the cuvette 7, and the exit light path conditioner 13B is configured so that a portion of the light from the light source 9 illuminates the sample before being collected through the outlet port P3 and sent to the spectrometer 11 so that the light is directly transmitted through the sample. In this configuration, an extinction spectrum of the sample is obtained.

[0094] In a second configuration, dissolution analyzer 1 is in a diffuse reflectance mode, in which inlet light path conditioner 13 is positioned so that light from light source 9 entering cavity 3 through inlet port P2 can either directly illuminate the liquid contained in cuvette 7 or can impinge on cavity walls 5 and be diffusely reflected within cavity 3 before interacting with the liquid sample. Furthermore, in this second configuration, outlet light path conditioner 13B is configured so that light transmitted through and / or reflected by the sample and collected through outlet port P4 and sent to spectrometer 11 is reflected at least once from cavity walls 5 before entering outlet port P4. In this configuration, an absorption spectrum of the sample is obtained without the effects of scattering by the liquid sample.

[0095] The means for switching between configuration modes is provided, for example, by one or more electronic controllers which select the configuration of both the inlet optical path conditioner 13 and the outlet optical path conditioner 13B (if provided) to obtain either an extinction spectrum or an absorbance spectrum of the liquid sample depending on the selected configuration mode.

[0096] The dissolution analysis apparatus 1 and the method of using the dissolution analysis apparatus 1 allow a single device to be used to measure the extinction and absorbance spectra of a liquid sample, e.g., a liquid in which a substance, item, or component is released or eluted.

[0097] 6A and 6B, a first embodiment of a dissolution analyzer 1 for measuring the spectrum of a liquid sample comprises an integrating cavity 3 with reflective inner wall(s) 5 configured to hold a cuvette 7 containing the liquid sample within the integrating cavity 3. The integrating cavity 3 comprises at least one optical entrance port P1, P2 and at least one optical exit port P3, P4, where the optical entrance port(s) P1, P2 are configured to receive light from a light source 9 and the optical exit port(s) P3, P4 are configured to provide light to a spectrometer 11.

[0098] The dissolution analyzer 1 further comprises a light path adjuster 13 configured to selectively adjust the path of light through the integrating cavity 3 so that at least two different light paths 15, 17 are provided.

[0099] When the light path adjuster 13 is in the first configuration, the dissolution analysis apparatus 1 is in a transmission mode in which light from the light source 9 follows a direct light path 15 from either the light entrance port P1 or the light entrance port P2 to the liquid sample such that the light from the light source 9 is transmitted through the light exit port P3, P4 or either thereof and directly illuminates the liquid sample before being received by the spectrometer 11 for wavelength analysis of the light providing the extinction spectrum of the liquid sample in the cuvette 7.

[0100] When the light path adjuster 13 is in the second configuration, the dissolution analyzer 1 is in a diffuse reflectance mode, in which light from the light source 9 follows a light path 17 from the inlet port P1, P2, or either of them, to the integrating cavity 3; and a) the light from the light source 9 is directly incident on the reflective inner wall(s) 5 of the integrating cavity 3 and is diffusely reflected within the integrating cavity 3 so that the light indirectly illuminates the liquid sample; or b) light from the light source 9 directly illuminates the liquid sample, such that the light transmitted and / or reflected by the sample is diffusely reflected within the integrating cavity; It is incident directly on the liquid sample 7 (not shown).

[0101] The light is then transmitted through optical exit ports P3 and / or P4 and received by spectrometer 11 for wavelength analysis of the light which provides the absorbance spectrum of the liquid sample contained in cuvette 7.

[0102] The dissolution analysis apparatus 1 and its method of use allow for the measurement of extinction and absorbance spectra of a liquid sample using a single device. The method involves placing a liquid sample, which may be contained in, for example, a standard 1 cm square cuvette 7, in an integrating cavity 3 and providing light to the sample in either a transmission or diffuse reflection configuration. A carrier (or a portion thereof) containing at least one substance that is released into the liquid or liquid matrix can be inserted into the cuvette before placing the cuvette in the integrating cavity 3 or while the cuvette is already inside the integrating cavity 3. In the first configuration, light transmitted by the sample is sent to a spectrometer 11 to obtain an extinction spectrum, while in the second configuration, light is diffusely reflected within the cavity 3 and interacts with the sample, preventing the loss of light scattered by the sample.

[0103] In the second configuration, the light may initially interact with the sample in the cuvette or may be incident directly on the cavity walls. The spectrum collected by spectrometer 11 in the second configuration can be related to an absolute absorption spectrum using appropriate calibration and modeling.

[0104] Switching between measurement configurations is provided via one or more adjustable optical elements L1-L5, M1-M4 that are configured to manipulate light from the light source 9 before it enters the integrating cavity 3. Such optical elements may include one or more shutters and / or movable mirrors that control the light path through the integrating cavity 3, thus allowing a single apparatus 1 to be used to obtain both the extinction spectrum and the extinction spectrum of the light.

[0105] The dissolution analysis apparatus 1 suspends or supports the sample cuvette 7 within the integrating cavity 3, which in combination with one or more optical elements has a particular optical entrance / exit port configuration that allows two different optical paths to be provided through the integrating cavity 3 between the light source 9 and the spectrometer 11, and in particular the photodetector of or connected to such spectrometer.

[0106] The first and second optical paths through the integrating cavity 3 can be provided in a number of different ways, and can be provided by modifying at least one or more of the following: a. the number and / or location of inlet ports; b. the number and / or location of outlet ports; c. the number, location, and / or type of movable optical elements; d. The number, location, and / or type of any auxiliary fixed optical elements that may be used; e. The relative position of the integrating cavity with respect to the light source and / or spectrometer.

[0107] In practice, the use of the dissolution analyzer 1 provides one or more of the following advantages: How to perform standard UV-VIS measurements as in any other device using standard cuvettes available on the market. Ability to switch to absorbance mode to remove any effects of scattering. · Acquisition of both extinction and absorbance spectra instantly from the user's point of view. Measurement of absorbance and extinction spectra, as well as dissolution measurements, in a single instrument and without user intervention. Convenient sample exchange via cavity port, similar to exchange in standard UV-VIS instruments. Provides a means to determine absolute absorbance of turbid / scattering media. Different inlet ports

[0108] 6A and 6B, light is transmitted from the light source 9 through one of two optical entry ports P1, P2 along a first optical path 15 into the integrating cavity 3. When the device 1 is in the first configuration, light enters through the first optical entry port P1 and is incident directly on the liquid sample in the cuvette 7. Light transmitted by the liquid sample is collected via the first optical exit port P3 and processed by measuring the wavelength-dependent extinction spectrum of the sample to determine the wavelength-dependent extinction coefficient of the sample, in the same way that standard UV-VIS measurements are performed.

[0109] In the second configuration, light from the light source is sent along the second optical path 17 through P2 and is first incident directly on the reflective wall 5 of the cavity 3. The surfaces of the wall 5 of the cavity 3 are, for example, approximately perfect diffuse reflectors (Lambertian surfaces). Thus, the incident light spreads diffusely within the cavity 3, illuminating the sample and interacting with it. Although light may be absorbed by the sample, the light scattered by the sample is still part of the diffuse illumination present in the cavity 3.

[0110] In the second configuration, the light is then collected via a second optical exit port P4, which is specially positioned so that as little light as possible transmitted or reflected by the sample enters the exit port P4 before being reflected from the cavity wall 5, and is processed by the spectrometer 11, allowing the true absorbance spectrum of the sample to be determined without spectral light losses due to scattering. Switching between extinction mode and absorbance mode is done via a light path adjuster without the need to change the sample position or any other optics of the device.

[0111] Thus, the optical path adjuster 13 adjusts the light received by the integrating cavity 3 from the light source 9 to provide a first optical path 15 in which the light is incident directly on the liquid sample rather than on the walls 5 of the cavity 3, and a second optical path 17 in which the light is incident directly on the walls 5 of the cavity 3 but not on the liquid sample.

[0112] In the illustrated embodiment, the light path adjuster 13 comprises optical elements in the form of a set of two laterally spaced, angled entrance mirrors M1, M2 between the light source 9 and the cavity 3, and a corresponding pair of laterally spaced, angled exit mirrors M3, M4 between the cavity 3 and the spectrometer 11. In this embodiment, the cavity 3 comprises two laterally spaced optical entrance ports P1, P2 and two laterally spaced optical exit ports P3, P4. In this embodiment, a plurality of lenses L1-L5 are provided at different positions along the first and second optical paths 15, 17. The light path adjuster also comprises a movable shutter S1 configured to open and close the first exit port P3.

[0113] One entrance mirror M1 and one exit mirror M4 are both movable along the transverse axis of the cavity 3, while the second entrance mirror M2 and second exit mirror M3 are fixed and not movable. In a first configuration, both mirror sets are positioned so as not to obstruct the conceptual paths from the light source 9, the first entrance port P1, the liquid sample, and the first exit port P3. In this position, light from the light source 9 is transmitted along a direct optical path 15 and is directly incident on the liquid sample.

[0114] In parallel, when mirror M1 exits first optical path 15, shutter S1 is simultaneously open, allowing light transmitted by the sample to exit cavity 3 through attenuated light exit port P3. Movable exit mirror M4 is also simultaneously positioned outside first optical path 15, so that light exiting P3 can be focused directly into spectrometer 11 via lens L5.

[0115] In configuration 2, a movable entrance mirror M1 is placed in the optical path between the light source 9 and the first entrance port P1. The mirror M1 is, for example, positioned at a 45° angle to the optical path, so that the light is directed toward the fixed mirror M2. This allows the light to be focused into the absorption entrance port P2 via a focusing lens L2. In this configuration, the light is directly incident on the inner wall 5 of the cavity 3 and is diffusely reflected within the cavity 3. The light within the cavity 3 is then collected through the exit port P4 using a lens L4 and sent to the spectrometer. The light cannot exit the cavity 3 through the first exit port P3 because the first exit port P3 is closed by a movable shutter S1.

[0116] In practice, the use of the dissolution analysis apparatus 1 provides one or more of the above advantages.

[0117] The dissolution analysis apparatus 1 may comprise or be in communication with an electronic controller / software configured to perform the measurements, i.e., reference and sample the measurements, collection times, integration times, and display of the resulting extinction, absorbance, and scattering spectra. Same inlet port

[0118] 7A and 7B, a second embodiment of a dissolution analyzer 1 is provided, having like features designated with like reference symbols. In this example, the dissolution analyzer 1 is similar to that of FIG. 6, but a single optical inlet port P1 is provided. The optical path adjuster 13 comprises a combination pinhole-lens system comprising a pinhole PN1 and a focusing lens L2, positioned between the light source 9 and the inlet port P1, and a movable shutter S1 positioned after the outlet ports P3 and P4.

[0119] In the first configuration shown in Figure 7B, the optical path adjuster 13 is configured so that pinhole PN1 is aligned with the input optical path, such that light entering entrance port P1 is essentially collimated. In this position, light from light source 9 is transmitted along optical path 15 and directly incident on the liquid sample. In parallel, when pinhole PN1 is in the optical path, the shutter is simultaneously closed, allowing light transmitted by the sample to exit cavity 3 through attenuated optical exit port P3. Movable exit mirror M3 is also simultaneously positioned outside first optical path 15, so that light exiting P3 can be directly focused into spectrometer 11 via lens L5.

[0120] In configuration 2, the optical path adjuster 13 is positioned such that the input pinhole PN1 is outside the optical path, the focusing lens L2 is in the optical path, and the incident light from the light source 9 is focused at the entrance port P1 so that the light transmits along a direct optical path to the sample but diverges to illuminate the entire lateral width of the sample cuvette, since it is focused to a point at the entrance port position. Concurrently, when the focusing lens L2 is in the optical path, the shutter S2 simultaneously opens, covering the exit port P3 with a movable mirror M4 positioned, for example, at a 45° angle to the optical path. In this configuration, light scattered, transmitted, or reflected by the sample is diffusely reflected within the cavity 3, which allows the diffusely reflected light within the cavity 3 to exit the cavity 3 through the light-extracting exit port P4. This light is then collected via the exit port P4 using the lens L4 and sent to the spectrometer via the mirror M3 and the movable mirror M4. Shutter selection to avoid samples

[0121] Referring now to FIG. 8, a third embodiment of the dissolution analysis apparatus 1 is provided, having like features designated with like reference symbols. In this example, the movable entrance mirror M1 is replaced with an entrance shutter S2 and a second fixed entrance mirror M1. Exit mirrors M3 and M4 are laterally movable together from a position where the angled exit mirror M3 is in the optical path of exit port P3 to direct light from the first optical path 15 to the second exit mirror M4 and spectrometer 11. The exit shutter S1 includes a shutter opening that aligns with exit port P3 in this first configuration. The entrance shutter S2 includes a pair of laterally spaced shutter openings. In the first configuration, the shutter S2 is positioned such that one of the shutter openings is aligned with entrance port P1, but entrance port P2 is closed. The angled fixed entrance mirrors M1 and M2 direct light to entrance port P1. In the second configuration, entrance shutter S2 moves laterally so that entrance port P1 is closed and entrance port P2 is aligned with one of the openings in entrance shutter S2, allowing light from light source 9 to be transmitted directly to entrance port P2. Exit mirrors M3, M4 move laterally so that mirror M3 is not in the optical path between exit port P4 and spectrometer 11. Shutter selection directly through the sample

[0122] Referring to FIG. 9, a fourth embodiment of a dissolution analysis apparatus 1 is provided, with similar features designated by similar reference symbols. In this embodiment, the dissolution analysis apparatus 1 is similar to that of FIG. 8, except that no entrance mirror is provided. An entrance shutter S2 is provided adjacent to the entrance lens L6. Lateral adjustment of the position of the entrance shutter S2 aligns one or the other shutter opening with the entrance lens L6 and the light source. One entrance shutter opening is relatively small, while the other is relatively large. Adjusting the opening that aligns with the light source, in combination with lens L6, allows both light paths 15, 17 to be directly incident on the liquid sample, with the first light path passing through the sample and exiting the cavity 3 through exit port P3. The second light path also passes through the liquid sample, but when the exit shutter S1 closes the first exit port P3, it diffuses and contacts the wall 5 of the cavity 3 before exiting the cavity 3 through the second exit port P4.

[0123] Referring now to FIG. 10, a fifth embodiment of a dissolution analyzer 1 is provided, having similar features with similar reference symbols. In this example, the dissolution analyzer 1 is similar to that of FIGS. 7A and 7B, but manipulation of the optical path for the two different configurations is provided via off-axis parabolic (OAP) mirrors rather than lenses and plane mirrors. Furthermore, in this embodiment, two inlet ports P1 and P2 are provided. In this example, OAP M1 is located between the light source 9 and the first inlet port P1 and comprises a mirror with a hole centered parallel to the incident light path, while OAP M2 has no hole and redirects light between the light source 9 and the second inlet port P2, in this example at an angle of 60°. The light path adjuster comprises two movable shutters S1 and S2 at the inlet and outlet sides of the integrating cavity 3, which move in parallel and, depending on their position, block the light entering and exiting from ports P1 and P3 simultaneously, or from ports P2 and P4 simultaneously.

[0124] In the first configuration, the light path adjuster is positioned so that the focused light reflected from OAP M2 is blocked from entering cavity 3 through second entrance port P2, and thus only light passing through the hole in OAP M1 enters cavity 3 through first entrance port P1 and is transmitted along direct optical path 15. This light is directly incident on liquid sample 7. In parallel, on the exit side of cavity 3, shutter S2 of the light path adjuster is positioned so that second exit port P4 is closed, preventing light diffusely reflected within cavity 3 from reaching spectrometer 11. In parallel, first exit port P3 is opened, allowing light transmitted by sample 7 to exit first optical exit port P3, be transmitted parallel to the optical path through a hole drilled in OAP M3, and be directly focused onto spectrometer 11 via lens L5.

[0125] In the second configuration, the shutter S1 of the light path adjuster is positioned to block light passing through the hole in OAP M1 from entering cavity 3 via entrance port P1. Thus, divergent light reaching OAP M1 is collimated by OAP M1 and redirected 90° to OAP M2, from where it is focused and redirected 60° to a point at second entrance port P2. The light entering cavity 3 then diverges, thus illuminating the entire lateral width of the sample cuvette but not allowing direct transmission through first light entrance port P1. In parallel, on the exit side of cavity 3, the shutter S2 of the light path adjuster is positioned to close exit port P3 to prevent light directly transmitted by sample 7 from reaching spectrometer 11. In parallel, exit port P4 is opened to allow light scattered, transmitted, and reflected by sample 7 to be diffusely reflected within cavity 3 and then exit cavity 3 via second exit port P4. This divergent light is then collected via OAP M4, where it is collimated and redirected at 90° to OAP M3, from where it is redirected at 90° and focused directly to the spectrometer 11 by OAP M3.

[0126] 11, a sixth embodiment of a dissolution analysis apparatus 1 is provided, having like features with like reference symbols. In this example, operation of the optical pathways for two different configurations is provided via a pair of fiber optic cables 21, 23, each associated with a respective light source 25, 27 and a respective inlet port P1, P2. Each light source 25, 27 may include a respective LED source 25, 27 which, together with an associated LED electronic controller 29, constitutes a light regulator in this example, such that the delivery of light to inlet port P1 or P2 is controlled by appropriate activation and deactivation of the LED source 25, 27 by the controller 29.

[0127] In this embodiment, fiber optic cable 21 feeds light directly into first inlet port P1. Fiber optic cable 23 feeds light via collimation lens 30 into second inlet port P2.

[0128] An exit mirror 32 and a beam splitter 33 are provided between the exit ports P3, P4 and the spectrometer 11 and are configured to selectively allow light from the first exit port P3 and the second exit port P4 to reach the spectrometer 11 depending on the configuration in which the dissolution analysis apparatus is operating.

[0129] In a first configuration, the dissolution analyzer 1 is in a transmission mode, in which the light path conditioner, i.e., controller 29, is controlled so that light from the LED source 25 is supplied to the inlet port P1 via the first fiber optic cable 21. The light entering the cavity 3 through the inlet port P1 directly illuminates the liquid contained in the cuvette 7, and the exit light path conditioner, i.e., the exit mirror 31 and splitter 33, are configured so that the light collected through the outlet port P3 and sent to the spectrometer 11 includes a portion of the light from the first LED source 25 that was directly transmitted by the sample after illuminating it. In this configuration, an extinction spectrum of the sample is obtained.

[0130] In a second configuration, the dissolution analyzer 1 is in a diffuse reflectance mode, in which the controller 29 controls the second LED source 27 to provide light to the second inlet port P2 via the second fiber optic cable 23. Light from the LED source 25 that enters the cavity 3 through the inlet port P2 can either directly illuminate the liquid contained in the cuvette 7 or impinge on the cavity walls 5 and be diffusely reflected within the cavity 3 before interacting with the liquid sample. In this second configuration, the exit mirror 31 and / or splitter 33 are configured such that light transmitted through and / or reflected by the sample and collected through the second outlet port P4 and sent to the spectrometer 11 is reflected at least once from the cavity walls 5 before entering the outlet port P4. This configuration provides an absorbance spectrum of the sample without the effects of scattering by the liquid sample.

[0131] The use of independently controllable LED light sources, each feeding a specific inlet port P1, P2, can result in a somewhat simpler device that requires fewer separate movable and / or fixed optical elements to control the light entering the sphere 3 and enable the dissolution analysis apparatus to operate in the first and second configurations.

[0132] In this embodiment, entrance port P2 is not parallel to entrance port P1, and therefore light enters the cavity through entrance port P2 at an oblique angle relative to the major axis of the cavity. The position / angle of port P2 should be selected to minimize the possibility of any Fresnel reflections from cuvette 7 exiting through transmission ports P3 and P4 upon first reflection when light strikes cuvette 7. The angle of the light path through port P2 can be selected accordingly.

[0133] The movable and / or fixed optical elements in the dissolution analysis apparatus 1 can be selected from: A. Prism, b. Lens, C. Miller, d. diffraction grating, e. Fiber optic cable f.Light source Example components

[0134] Below is a non-limiting summary of example components that can be used with some embodiments of the dissolution analysis apparatus 1. Light Source 9: A tungsten halogen lamp purchased from ThorLabs that provides light for excitation from 350-900 nm. Movable mirror (M1, M4 in the examples of Figures 5 and 6): a standard optical mirror mounted at 45° to the optical path and translatable in and out of the beam path to select either the first or second configuration. Purchased from ThorLabs. Fixed mirror (M2, M4 in the examples of Figures 5 and 6): a standard optical mirror mounted at 45° to the optical path and translatable in and out of the beam path to select either the first or second configuration. Purchased from ThorLabs. Supply lens (L2 in the examples of Figures 5 and 6): a standard convex lens of defined focal length used in the second configuration to focus the incident light through entrance port P2 onto the cavity wall 5 for extinction measurements. Purchased from ThorLabs. Integrating Cavity 3: A spherical integrating cavity with an inner diameter of 50 mm and diffusely reflecting inner walls. The sphere has four ports (P1-P4) drilled into the walls for light supply and collection, and a custom-drilled sample port at the north pole for suspending a cuvette 7 in the center of cavity 3. Integrating Cavity 3 is purchased from Avian Technologies. The sphere shape may be custom-made for the application in which device 1 is used. Cavity 3 may be non-spherical and may be cylindrical or cubic. The coating on wall 5 may have different types of surface reflectance, including specular and diffuse reflectance in the UV, visible, or infrared regions, or a combination thereof. Sample holder / cuvette 7: The cuvette 7 is held in the device 1 via a holder that clamps around the cuvette 7 and also allows the cuvette 7 to be suspended in a fixed position within the cavity 3. The following cuvette shapes can be provided: standard (1 cm square), thin or plate-like (10 x 1 mm), cylindrical, spherical (combinations are also possible, e.g. cylindrical with flat areas). USB spectrometer 11: Analyzes the intensity of the light leaving the cavity 3 as a function of wavelength, allowing a spectrum to be obtained and displayed, for example, on a computer screen. This can be a standalone device powered via a USB connection and interfaced with a controller in the form of a laptop / computer. Light detection can be done as in a standard spectrometer with dispersive optics and detection via CMOS, CCD, diode array or scanning monochromator. Electronics: The movable mirror is driven by a stepper motor and controlled by a programmable microcontroller with a stepper motor driver board. Both the microcontroller and the USB spectrometer are attached to a controller, such as a minicomputer, inside the device 1. The minicomputer serves two purposes: i) to facilitate communication with the spectrometer 11 and the motor driver, and ii) to provide a web-based graphical user interface. This facilitates interaction with the device 1 in that users do not need to install special software and developers do not need to maintain custom operating system-dependent software. Light sources: standard UV-VIS (i.e. halogen, xenon, deuterium lamps), various LEDs, lasers, combinations of all of these, and any polychromatic source fitted with a monochromator for wavelength selection. · Supply optics: an assembly of standard optical components such as lenses, mirrors, shutters, diffraction gratings, optical fibers, or any combination thereof. Optical path switching: motorized linear stage(s) and / or shutter(s). Parameters / Variables

[0135] There are a number of physical and geometric parameters / variables that are factors in the design and operation of the above-described dissolution analyzer 1. These include one or more of the following: The cavity surface reflectance ρ is the ratio of reflected light to incident light. For the cavity to operate according to the dissolution analysis device 1, the reflectance must be close to 1, i.e., the walls 5 contain a highly reflective material. The device 1 further requires that the reflectance be strongly diffuse (Lambertian). The port ratio f is the ratio of the surface area of ​​all cavity ports P1-P4 to the total surface area of ​​the walls 5 of the cavity 3. Thus, a ray of light randomly traversing the cavity 3 has a probability f of leaking out. Enhancement factor M: Approximately encodes the number of diffuse cavity surface reflections a ray undergoes before being absorbed by the cavity walls or exiting through a port. In the ideal case of an empty spherical cavity, M=ρ / 1-ρ(1-f). · Probability of hitting the sample μ: This is a purely geometrical factor and indicates the probability that a ray diffusely reflected from the cavity surface will interact with the sample cuvette. The path length L is the average length of the path taken by the ray within the sample volume. The larger M and i are, the larger L is. Overview of equipment calibration, measurement and control

[0136] The following factors are fundamental for obtaining error-free spectra in the dissolution analyzer 1: Related to absorbance measurements: The controller determines the absolute extinction cross section of the sample inserted into the integrating cavity, which requires accurate calibration of the measurable intensity against known standards. Input port location for absorbance: There are two options for placing this port: i) Avoiding direct illumination of the sample improves measurement reproducibility by reducing sensitivity to the exact geometrical displacement of the sample cuvette. The drawback of this approach is that even for perfectly absorbing samples, some light (determined by μ) reaches the detector without interacting with the sample, limiting the range of measurable optical densities. ii) Alternatively, all incident light can be passed through the sample. This overcomes the problem of saturated absorbance and allows the measurement of highly absorbing samples. In this case, the detection port must collect from a section of the cavity wall that does not receive light from direct or reflected illumination. Detection port location for absorbance: The detection port's field of view should not intersect with the sample, and the detection port should collect light only from the cavity surface. This minimizes the dependence of the measurement on the scattering properties of the sample. Geometric optimization of the setup: The average path length L through the sample is determined by the ratio rV = V between the sample volume and the cavity volume. sample / V cavity , the average cord length in the cavity is c'=4V cavity / A cavity (where A cavity It can be approximated by multiplying rVc'M (where rV is the surface area of ​​the cavity) by the enhancement factor M. The approximate path length L = rVc'M governs the lower limit of detectable optical density. For example, for low-absorbance samples, it is desirable to maximize L: i) M is maximized as the cavity surface reflectance p → 1 and the cavity port ratio f → 0; ii) rV increases with the relative volume of the sample, approaching 1 as the sample completely fills the sphere; and iii) c' is maximized for spherical cavities. A spherical cavity completely filled with sample, with maximum surface reflectance and minimum number of ports, may be the optimal setup for detecting ultralow concentrations. Choosing a combination of parameters (cavity and sample geometry, port locations, numerical aperture, etc.) that meets the requirements for validity, reproducibility, and user convenience is not easy. Design choices may not be easy compromises. For example, the dissolution analyzer 1 described above is suitable for standard cuvettes, including cuvettes with short optical path lengths for highly absorbing liquids. Related to combined quenching and absorbance measurements: Extinction measurements are performed in an integrating cavity. This imposes a geometric constraint: the sample walls must be perpendicular to the incident beam, necessitating a square or flat-walled cuvette. Curved (e.g., cylindrical) cuvettes are also possible, but require special optics to deal with refraction effects. The available numerical apertures for both delivery and detection must be limited to avoid diffuse illumination of the sample and minimize detection of multiply scattered light. A combination of supply and detection optics that can switch between the absorption and extinction paths is required. The layout of these paths must be such that they do not affect each other. Equipment Calibration / Measurement / Control Example Details

[0137] Details of exemplary calibration methods that can be used to calibrate the dissolution analyzer described above are set forth in the appendix disclosed in WO 2018 / 070882, the entire contents of which are hereby fully incorporated by reference.

[0138] The dissolution analyzer may be configured to measure a spectrum of a liquid sample selected from one or more of the following: Water, b. Beverage, c. Edible liquid or partially liquid products; d. Seawater and other water e. solution, f. suspensions, f. Emulsion, g.Blood

[0139] In some embodiments, the dissolution analysis apparatus 1 does not include input optical path conditioner 13 and / or output optical path conditioner 13B. The dissolution analysis apparatus 1 does not include components that enable transmission mode operation, in which the liquid sample is directly illuminated to determine the wavelength-dependent extinction spectrum of the liquid sample. The dissolution analysis apparatus 1 includes components that enable only diffuse reflectance mode operation, in which the liquid sample's true wavelength-dependent absorbance spectrum is determined. Additionally, the integrating cavity may include only input port P2 and output port P4 configured for such absorbance measurements. This may provide a less complex dissolution analysis apparatus 1.

[0140] The present disclosure also relates to a dissolution analysis or monitoring method or a dissolution activity analysis or monitoring method for measuring, monitoring or analyzing at least one substance SB while it is dissolving in a liquid, liquid matrix or liquid sample, or for measuring, monitoring or analyzing at least one substance SB dissolving in a liquid, liquid matrix or liquid sample.

[0141] The method comprises providing a dissolution analysis device 1 or dissolution activity analysis device 1 as disclosed above and using the dissolution analysis device 1 to perform absorbance-related measurements in a diffuse reflectance mode of operation during release of at least one substance, item or component SB from at least one carrier CR into at least one liquid or liquid matrix LQ contained in a liquid sample.

[0142] For example, measurements may be taken multiple times in a diffuse reflectance mode of operation over a given or determined period of time. Such measurements may be provided to the spectrometer 11 and analyzed / processed to process the light received by the spectrometer for wavelength analysis of the light to provide or calculate at least one or more (absolute or actual) absorbance spectra of the liquid sample contained in the cuvette. An extinction spectrum may also be determined and provided.

[0143] At least one or more of the (absolute or actual) absorbance spectra are determined or provided over a given or determined period of time (see, e.g., Figures 2A and 4A), which preferably allows, for example, the complete dissolution or release process to be measured or a significant portion of the dissolution or release process to be measured or determined via absorbance spectra, thereby allowing the dissolution characteristics of the substance or item into the liquid or liquid matrix to be determined.

[0144] Each absorbance spectrum may be determined, for example, after a determined time interval. This time interval may be a fixed or constant value, or may vary depending on the evolutionary stage of the release. For example, the time interval may be smaller initially and increase to a larger value in later stages of the release or diffusion process.

[0145] The optical spectrum measurement is performed over a wide wavelength range, such as a wide UV-visible wavelength range, which may be, for example, from 300 nm to 900 nm, or from 300 nm to 700 nm.

[0146] This allows the spectral location of the emission behavior in a broad wavelength spectrum to be determined / identified spectrally, and then the characteristic emission or elution behavior can be analyzed at one or more specific wavelengths or in one or more (narrower) wavelength ranges.

[0147] In the present disclosure, the dissolution analysis apparatus 1 is operated in a diffuse reflectance mode as previously described. After activating the light source and passing diffused light through the cuvette 7 in the integrating cavity 3, wavelength analysis is performed on the light transmitted through the optical exit port to the spectrometer to provide one or more absorbance spectra of the liquid sample contained in the cuvette.

[0148] The dissolution analysis apparatus 1 operates in a diffuse reflectance mode in which light from the light source 9 follows an optical path from the inlet port(s) of the above inlet port(s) to the integrating cavity 3, strikes one or more reflective inner walls 5 of the integrating cavity 3 and is diffusely reflected within the integrating cavity 3 so as to illuminate the liquid sample before the light from the light source is transmitted through the optical exit port(s) of the above optical exit port(s) and received by the spectrometer 11 for wavelength analysis of the light and to provide an absorbance spectrum of the liquid or liquid matrix contained in the liquid sample.

[0149] A reference spectrum and a dark spectrum in which no eluting substance or carrier CR is present in the liquid or liquid matrix are used to determine the (real) absorbance spectrum, as described, for example, in the measurement procedure described in WO 2018 / 070882, the entire contents of which are incorporated herein by reference. The dissolution analyzer 1 is configured to calculate the absorbance spectrum by the following equation:

number

[0150] Next, as disclosed on pages 23 to 27 of WO 2018 / 070882, the following formula:

number

[0151] The integration cavity 3 is configured to receive and hold a cuvette 7 therein, the cuvette 7 containing a liquid or liquid matrix, and thus a liquid sample, within the integration cavity 3. A substance, item, or component SB is released into the liquid, liquid matrix, within the cuvette 7 while the cuvette 7 is held or received within the integration cavity 3.

[0152] The substance, item or component SB is held, carried or contained in at least one (substance) carrier or at least one (substance) substrate CR. The substance item or component CR is released from the carrier or substrate CR when the carrier or substrate CR or a part thereof is placed in a liquid or liquid matrix contained in a cuvette 7.

[0153] A carrier or substrate CR (or part thereof) comprising at least one substance, item or component SB to be released into the liquid or liquid matrix may be inserted into the cuvette 7, for example, before placing the cuvette 7 in the integration cavity 3 or while the cuvette 7 is already positioned inside the integration cavity 3, the cuvette preferably already containing the liquid or liquid matrix, although the liquid or liquid matrix may be added in addition to the carrier or substrate CR.

[0154] As previously mentioned, the release of the substance, item, or component SB causes turbidity or light scattering in the liquid, liquid matrix, or liquid sample.

[0155] The absorbance spectrum is an absolute absorbance spectrum or the true absorbance spectrum as previously described, and using the diffuse reflectance mode operation of the dissolution analysis apparatus 1, the wavelength-dependent true absorbance spectrum of the liquid sample from which the substance, item, or component SB is released is determined.

[0156] At least one substance, item, or component SB that dissolves in at least one liquid or liquid matrix is ​​inserted into at least one liquid or liquid matrix LQ, and multiple absorbance spectral related measurements are performed over time during elution into the at least one liquid or liquid matrix.

[0157] The substance, item, or component SB release profile or dissolution curve of at least one substance SB into at least one liquid or liquid matrix can be determined based on multiple absorbance spectra determined or provided over a measurement period during the release or dissolution of the substance SB into the liquid or liquid matrix. This can be done, for example, by identifying or determining the release or dissolution characteristics / behaviors at one or more dissolution behavior-specific wavelengths or at one or more dissolution behavior (narrower) wavelength ranges. For example, this can be the wavelength or wavelength range at which maximum optical absorption is measured, or wavelengths within ±5° or 10% of this maximum. However, it should be understood that other selection criteria may be used, which often depend on the substance. The wavelength or wavelength range is, for example, characteristic of the presence of the substance in the liquid or liquid matrix.

[0158] The evolution of the optical absorption values ​​over a period of time at this characteristic emission or dissolution wavelength or emission or dissolution wavelength range is determined (see, for example, FIG. 2C), which is one non-limiting exemplary method that allows determining the release profile or dissolution curve of a substance into a liquid or liquid matrix.

[0159] If multiple different substances, items, or components are being released, a release profile or elution curve for each can be determined based on the emission or elution characteristic wavelengths or emission or elution characteristic wavelength ranges determined and attributed to each substance, item, or component.

[0160] A comparison of the determined release profile or dissolution curve can be performed with respect to a target / standard release profile or target / standard dissolution curve that the dissolution / release process is expected to match or correspond to.

[0161] The compatibility of the determined release profile or dissolution curve with the target release profile or dissolution curve can then be determined or established, and a correspondence score can be determined based on the similarity between the measured release profile or dissolution curve and the target release profile or dissolution curve.

[0162] Dissolution testing was performed using the Dissolution Analyzer 1 having an integrating cavity-based spectrophotometer described herein.

[0163] The dissolution analyzer 1 can generate two spectra of a liquid sample measured simultaneously. The first spectrum is an "extinction spectrum," in which the sample is measured in transmission geometry, and as previously described, there is a drop in light intensity that is the result of sample absorbance and scattering. This is the equivalent spectrum generated by a conventional UV-Vis spectrophotometer. The second spectrum is an "extinction spectrum," in which the sample is measured in integrating cavity geometry, and the drop in light intensity is the result of sample absorbance alone.

[0164] In an exemplary approach to demonstrating the operation and advantages of a dissolution analyzer according to the present disclosure, the inventors studied the time evolution of the spectrum during the dissolution of an exemplary carrier CR, an effervescent tablet, into water. The tablet contains a berry-flavored vitamin B and C supplement that is dissolved or released into water. Figure 1 shows exemplary images illustrating the dissolution or release process of the carrier CR and the substance SB in water.

[0165] To measure or analyze the dissolution or release process, the inventors set the number of spectra determined to 100 in order to have sufficient time resolution to monitor the dissolution process.

[0166] The inventors then measured a 1 mL water reference (10 mm cuvette). A small amount (a few tablets) of tablets was then dropped into cuvette 7, the dissolution analyzer 1 tower was closed over cuvette 7, and the measurement was initiated, restarting immediately (approximately every 5.5 seconds) after the measurement was completed, and then more sparsely thereafter. For each experiment, the complete extinction and absorbance spectra were measured as a function of wavelength from 300 nanometers to 700 nanometers. Specific regions of interest based on the spectral profile of the substance were then selected to monitor the time dependence of the substance dissolution. 469 nm was selected for the berry-flavored sample, and 448 nm was selected for the orange-flavored sample.

[0167] 2A to 2C show the results for the berry-flavored sample, and FIG. 3 shows the results for the orange-flavored sample.

[0168] Air bubbles strongly influence the extinction results due to scattering. This is shown in the elution curve labeled "Ext." The presence of air bubbles in the extinction beam is random, which creates strong fluctuations. The results show that this cannot be corrected by simple baseline subtraction, as shown in the elution curve labeled "Ext-Ext(650nm)" (where the extinction value at 650nm is subtracted from the extinction value at 469nm).

[0169] Attempting to remove background turbidity using background subtraction from UV-Vis-based results is insufficient to obtain a smooth elution curve that is not affected by sample turbidity.

[0170] In contrast, as shown in the dissolution curve labeled "Abs," the absorbance values ​​increase smoothly and reflect much more reliably the increasing concentration of released active substance.

[0171] It is also noteworthy that the extinction is lower than the initial extinction because extinction only probes the central region traversed by the beam, whereas extinction is sensitive to the entire volume within the cell and is therefore not affected by inhomogeneities or particle settling in the sample.

[0172] The effect of turbidity on dissolution curves has not been studied before and is now shown for the first time in this disclosure by the inventors by using an integrating cavity to obtain the "true absorbance" of the sample and simultaneously comparing it with traditional UV-Vis-based results.

[0173] Figure 3 shows the results of the same experiment with an orange-flavored supplement, reaching similar conclusions.

[0174] Figures 4A and 4B show the spectrum of a vitamin C supplement, focusing here on the visible portion of the spectrum because the values ​​below 300 nm are very strong and saturation occurs.

[0175] This highlights another advantage of the disclosed dissolution analyzer and dissolution measurement method: increased sensitivity to low-absorbing samples, where the peak at 500 nm is barely distinguishable in extinction but is clearly observed in absorbance, despite its peak OD of approximately 0.01.

[0176] Unless the context clearly requires otherwise, throughout the description, the terms "comprises", "comprises", and the like, are to be interpreted in an inclusive sense, rather than an exclusive or exhaustive sense, i.e., "including, but not limited to".

[0177] Any discussion of prior art throughout the specification should in no way be considered as an admission that such prior art is widely known or forms part of the common general knowledge in the field.

[0178] Although the present invention has been disclosed with reference to certain preferred embodiments, numerous modifications, variations, and variations to the described embodiments and their equivalents are possible without departing from the scope and spirit of the present invention. Features of any one of the described embodiments may be included in any other of the described embodiments. The method steps need not be performed in the exact order presented above, and may be performed in a different order. Therefore, the present invention is not limited to the described embodiments, but is intended to be accorded the broadest reasonable interpretation in accordance with the language of the appended claims.

Claims

1. A dissolution activity analyzer (1) for measuring, monitoring or analyzing the dissolution of a substance into a liquid or liquid matrix, comprising: an integrating cavity (3) having one or more reflective inner walls (5), the integrating cavity (3) being configured to receive a cuvette (7) containing a liquid sample (LQ) within the integrating cavity (3); the integrating cavity (3) comprises at least one optical inlet port (P1, P2) and at least one optical outlet port (P3, P4), the or each optical inlet port (P1, P2) being configured to receive light from at least one light source (9), and the or each optical outlet port (P3, P4) being configured to provide light to a spectrometer (11); The dissolution activity analysis device (1) is configured to operate in a diffuse reflectance mode, in which light from the light source (9) follows an optical path from the or one of the inlet port(s) to the integrating cavity (3), impinges on the one or more reflective inner walls (5) of the integrating cavity (3) and is diffusely reflected within the integrating cavity (3) so as to illuminate the liquid sample before the light from the light source (9) is transmitted through the or one of the light outlet port(s) and received by the spectrometer (11) for wavelength analysis of the light providing an absorbance spectrum of the liquid or liquid matrix contained in the liquid sample.

2. further comprising an optical path adjuster (13, 13B) configured to selectively adjust an optical path through the integrating cavity (3) so as to provide at least two different optical paths; When the light path adjuster (13, 13A) is in a first configuration, the dissolution activity analysis device (1) is in a transmission mode, in which light from the light source (9) follows a first optical path from the or one of the light entrance port(s) to the liquid sample such that the light from the light source (9) directly illuminates the liquid sample before the light transmitted through the or one of the light exit port(s) is transmitted through the or one of the light exit port(s) and received by the spectrometer (11) for wavelength analysis of the light to provide an extinction spectrum of the liquid sample; 2. The elution activity analysis device (1) of claim 1, wherein when the optical path adjuster (13, 13B) is in a second configuration, the elution activity analysis device (1) is in the diffuse reflection mode, and in the diffuse reflection mode, light from the light source (9) follows a second optical path from the inlet port or one of the inlet port(s) to the integrating cavity (3), enters the one or more reflective inner walls (5) of the integrating cavity (3), and is diffusely reflected within the integrating cavity (3) so as to illuminate the liquid sample before the light from the light source (9) is transmitted through the or one of the optical exit port(s) and received by the spectrometer (11) for wavelength analysis of the light to provide an absorbance spectrum of the liquid or liquid matrix contained in the liquid sample.

3. a. from the inlet port directly to the wall or walls of the integral cavity (3), and / or b. from the inlet port, onto and through the sample and then directly onto the wall or walls of the integrating cavity (3); 3. A dissolution activity analysis device (1) according to claim 1 or 2, arranged so as to be transparent to light.

4. 3. A dissolution activity analysis device (1) according to claim 2, wherein the inlet port used in the first configuration is directly opposite the outlet port used in the first configuration, such that when in the first configuration, the first optical path extends directly across the integrating cavity (3).

5. Dissolution activity analysis device (1) according to any one of claims 1 to 4, further comprising said light source (9).

6. The dissolution activity analysis device (1) of any one of claims 2 to 5, further comprising a controller or a controller configured to control the light path adjuster (13, 13A) that selectively adjusts the path of light through the dissolution activity analysis device (1).

7. 7. The elution activity analyzer (1) of claim 6, wherein the controller is an integral part of the elution activity analyzer (1) and communicates directly with the elution activity analyzer (1).

8. 7. The elution activity analyzer (1) of claim 6, wherein the controller is remote from the elution activity analyzer (1) and configured to communicate wirelessly with a transceiver of the elution activity analyzer (1).

9. 9. The dissolution activity analysis device (1) according to any one of claims 6 to 8, wherein the controller is configured to control the spectrometer (11), in particular to process the light received by the spectrometer (11) for wavelength analysis of the light to provide an extinction spectrum and / or an absorbance spectrum of the liquid sample contained in the cuvette (7).

10. Dissolution activity analysis device (1) according to any one of claims 1 to 9, further comprising said spectrometer (11).

11. The controller: a. switching between the first configuration and the second configuration; b. Obtaining a spectrum from the integrating cavity (3); c. Selecting operating conditions; d. Displaying the spectrum on a display of the elution activity or the controller, or on a display in communication with the elution activity or the controller; e. storing data in a memory of the elution activity analysis device (1) or the controller, or in a memory in communication with the elution activity analysis device (1) or the controller; f) a user interface of the dissolution activity analysis device (1) or the controller, or a user interface in communication with the dissolution activity analysis device (1) or the controller, which interacts with the dissolution activity analysis device (1) and allows a user to control the position of the optical path adjustment mechanism; Dissolution activity analyzer (1) according to any one of claims 6 to 10, configured to control one or more of:

12. 12. The dissolution activity analysis device (1) of any one of claims 1 to 11, wherein the optical path adjuster comprises at least one movable optical element, the at least one movable optical element configured to manipulate light incident on the optical element from the light source (9), and the optical path adjuster configured to adjust the movable optical element to selectively provide the first optical path and the second optical path.

13. 13. The dissolution activity analysis device (1) of claim 12, wherein the optical element is adjustable by moving the optical element relative to the integrating cavity (3) from a first position in which the light travels along the first optical path and a second position in which the light travels along the second optical path.

14. The integrating cavity (3) has orthogonal longitudinal, vertical and transverse axes, and the optical element has the following positional characteristics: a. longitudinal position; b. vertical position, c. horizontal position, d. Orientation, e. slope, 14. Dissolution activity analyzer (1) according to claim 13, wherein any one or more of are adjustable relative to any one or more of said axes.

15. Dissolution activity analysis device (1) according to any one of claims 12 to 14, wherein a plurality of movable optical elements are provided.

16. The movable optical element is a. Prism, b. Lens, c. mirror, d. diffraction grating; e. Optical fiber cable f. the light source; 13. The dissolution activity analyzer (1) according to claim 12, selected from:

17. Dissolution activity analysis device (1) according to any one of claims 12 to 16, wherein the optical path adjuster comprises at least one fixed optical element that is not adjustable relative to the integrating cavity (3).

18. 18. Dissolution activity analysis device (1) according to claim 17, wherein the fixed optical element is configured to manipulate the light from the light source (9) before the light entry port.

19. 19. Dissolution activity analysis device (1) according to claim 17 or 18, wherein the fixed optical element is configured to manipulate the light from the light exit ports (P3, P4).

20. The fixed optical element is a. Prism, b. Lens, c. mirror, d. diffraction grating; e. Optical fiber cable f. the light source; The dissolution activity analyzer (1) according to any one of claims 17 to 19, selected from:

21. 21. A dissolution activity analysis device (1) according to any one of claims 1 to 20, wherein the light path adjuster comprises at least one electronic controller operative to effect selective operation of one or more light sources (9) to selectively provide the first light path and the second light path.

22. 22. A dissolution activity analyzer (1) according to claim 21, comprising at least a first light source (9) and a second light source (9), the controller being configured to control each light source independently.

23. Dissolution activity analysis device (1) according to any one of claims 1 to 22, wherein the optical path adjuster is arranged between the light source (9) and the optical inlet ports (P1, P2).

24. Dissolution activity analysis device (1) according to any one of claims 1 to 23, wherein the optical path adjuster is arranged between the spectrometer (11) and the optical outlet ports (P3, P4).

25. Dissolution activity analysis device (1) according to any one of claims 1 to 24, wherein a plurality of optical path adjustment mechanisms are provided.

26. 26. A dissolution activity analysis device (1) according to any one of claims 1 to 25, wherein a plurality of light entrance ports are provided, and the light path adjuster is configured to provide the first light path by directing light from the light source (9) through a first light entrance port, and to provide the second light path by directing light from the light source through a second light entrance port.

27. 27. A dissolution activity analysis device (1) according to any one of claims 1 to 26, wherein a plurality of optical exit ports are provided, the first optical path directing light from the integrating cavity (3) through a first optical exit port and the second optical path directing light from the integrating cavity through a second optical exit port.

28. The integral cavity (3) a. Diffusely reflecting spherical integrating cavity; b. a cylindrical cavity; c. cubic or square cavity; A dissolution activity analyzer (1) according to any one of the preceding claims, comprising any one of:

29. The integral cavity (3) a. specular reflectance, b. Diffuse reflectance; c. Reflectance in the ultraviolet spectrum; d. Reflectance in the visible light spectrum; e. Reflectance in the infrared spectrum; A dissolution activity analyzer (1) according to any one of the preceding claims, comprising an internal coating configured to provide any one or more of:

30. The light source (9) a. a quartz halogen source; b. Light emitting diodes; c. laser, d. any polychromatic source; A dissolution activity analyzer (1) according to any one of the preceding claims, comprising any one or more of:

31. The shape of the cuvette is a. square, b. Plate-shaped c. cylindrical; d. spherical, Dissolution activity analyzer (1) according to any one of claims 1 to 30, wherein the dissolution activity analyzer (1) is one or more of:

32. A dissolution activity analysis device (1) according to any one of claims 1 to 31, configured to perform UV-visible spectroscopy analysis.

33. Dissolution activity analyzer (1) according to any one of the preceding claims, further comprising a sample holder configured to hold a cuvette (7) containing a liquid sample in said integrating cavity (3).

34. 34. The dissolution activity analysis device (1) of any one of claims 2 to 33, wherein the light source (9) comprises a first light emitting diode light source and a second light emitting diode light source, and the light path adjuster comprises a controller, the controller being configured to control the first light emitting diode light source and the second light emitting diode light source such that, when in the first configuration, the first light emitting diode light source is controlled to provide light in the first light path, and when in the second configuration, the second light emitting diode light source is controlled to provide light in the second light path.

35. 35. A dissolution activity analysis device (1) according to claim 34, wherein light from each light emitting diode light source is supplied to the integrating cavity (3) via a respective fiber optic cable.

36. 36. A dissolution activity analyzer (1) according to claim 34 or 35, wherein each light emitting diode light source provides light to a respective light inlet port.

37. Dissolution activity analyzer (1) according to any one of claims 34 to 36, wherein each optical path supplies light through a respective optical exit port.

38. 38. A dissolution activity analysis device (1) according to any one of claims 34 to 37, wherein the first light emitting diode light source is associated with a collimation lens arranged between the first light emitting diode light source and the light entrance port associated with the first light emitting diode light source.

39. 39. The dissolution activity analysis device (1) of any one of claims 34 to 38, further comprising a first outlet port and a second outlet port, and a beam splitter configured to selectively allow light from the first outlet port and the second outlet port to be transmitted to the spectrometer (11).

40. 1. A dissolution analysis method for measuring, monitoring or analyzing at least one substance (SB) during its dissolution into at least one liquid or liquid matrix contained in a liquid sample, comprising: Providing a dissolution activity analysis device (1) according to any one of claims 1 to 39; performing measurements using the dissolution activity analyzer (1) in diffuse reflectance mode of operation during the release of the at least one substance (SB) into the at least one liquid or liquid matrix contained in the liquid sample; A dissolution analysis method comprising:

41. 41. The dissolution analysis method of claim 40, wherein said measurements are a plurality of absorbance spectral related measurements performed on said at least one liquid or liquid matrix during release of a substance.

42. 42. The dissolution analysis method of claim 40 or 41, wherein at least one substance carrier (CR) containing the at least one substance (SB) that dissolves in the at least one liquid or liquid matrix is ​​inserted into the at least one liquid or liquid matrix, and a plurality of absorbance spectrum-related measurements are performed in the diffuse reflectance operating mode over a period of time during the dissolution of the at least one substance (SB) into the at least one liquid or liquid matrix.

43. 43. A dissolution analysis method according to claim 42, wherein a plurality of absorbance spectra are determined over a period of time during the elution of said at least one substance (SB) into said at least one liquid or liquid matrix.

44. 44. The dissolution analysis method of claim 43, wherein a release profile or dissolution curve of said at least one substance (SB) into said at least one liquid or liquid matrix is ​​determined based on said plurality of absorbance spectra.

45. 45. The dissolution analysis method of claim 44, wherein the release profile or dissolution curve of the release of the at least one substance (SB) into the at least one liquid or matrix is ​​determined based on the evolution of absorbance values ​​of the determined absorbance spectrum at specific wavelengths or wavelength ranges characteristic of the presence of the at least one substance in the liquid or liquid matrix.

46. 46. ​​The dissolution analysis method of claim 44 or 45, wherein the release profile or dissolution curve is determined at one particular wavelength value or range.

47. 47. A method for dissolution analysis according to any one of claims 44 to 46, wherein the comparison of the determined release profile or dissolution curve is carried out against a target release profile or target dissolution curve.

48. A method for dissolution analysis according to any one of claims 44 to 47, wherein the compatibility of the determined release profile or dissolution curve with the target release profile or target dissolution curve is established.

49. 49. Dissolution analysis method according to any one of claims 40 to 48, wherein said at least one substance (SB) causes turbidity in said at least one liquid or liquid matrix.

50. a. activating the light source (9); b) performing wavelength analysis of the light transmitted through the optical outlet ports (P3, P4) via the spectrometer (11) for wavelength analysis of the light to provide one or more absorbance spectra of the substance (SB) dissolved in the liquid sample contained in the cuvette (7); The dissolution analysis method according to any one of claims 40 to 49, comprising:

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