KR20100023963A - Apparatus and methods for automatic insertion, debubbling, cleaning and calibration of a spectral probe during dissolution testing - Google Patents

Abstract

A dissolution test apparatus includes an optical probe, an automated actuator. The probe takes an optics-based measurement in dissolution media contained in a test vessel and transmits the measurement to an analytical instrument situated remotely from the vessel. The optical probe is movable by the actuator into and out from the vessel. The dissolution test apparatus may include a bubble removal apparatus that communicates with the optical probe and is configured for transmitting a variable vibrating force to the probe, wherein bubbles are removed from a light path gap of the probe. In another dissolution test apparatus, the bubble removal apparatus rotates the probe to remove bubbles. Another dissolution test apparatus includes a movable cleaning mechanism, a movable calibration mechanism, or both mechanisms.

Description

Apparatus and methods for automatic insertion, debubbling, cleaning and calibration of a spectral probe during dissolution testing}

This application claims the benefit of US Provisional Application Serial No. 60 / 936,257, filed June 20, 2007.

The present invention generally relates to methods and apparatus for performing spectral analysis in drug and medical device manufacturing tests. In particular, the present invention detects and removes bubbles from the observation window or optical path gaps of probes when immersed in resolution media and cleans and calibrate probes before, after and / or between spectral measurements. To this end, the present invention relates to an automated apparatus and method for inserting and removing spectral probes into and out of a medium when performing a resolution test.

Under normal conditions, degradation testing is used to determine the rate at which a drug solid dosage form, usually a tablet, capsule or topical dosage form, degrades to a given medium over time. The medium is generally used as a substitute for a fluid in the gastrointestinal tract of a human or animal. The concentration of Active Pharmaceutical Ingredients (API) released from the dosage form into the medium is measured over time. Such release may be rapid for immediate release dosage forms (eg, within 10-15 minutes) or considerably longer for controlled / modified release formulations (eg, hours, weeks or months). Testing is often performed by physically removing a sample from the degradation medium, filtering the sample, and then using an analytical tool such as HPLC (High Performance Liquid Chromatography) to analyze the sample. Alternatively, the measurements may be carried out in essence by using an optical fiber probe immersed in the dissolution medium for a full dissolution test. Requirements for such a dissolution test apparatus are provided in USP Section 711, Disassembly 2000. Basic processes and apparatus for decomposition testing to carry out such testing are known in the art. See, for example, US Pat. No. 4,279,860; 4,335,438 and 6,948,389 and Dissolution Tests, Third Edition, R. Hanson and V. Gray of Dissolution Technologies, Inc. (2004), handbooks, all provide a general description of the techniques of dissolution testing. .

Conventionally configured devices for disintegration testing of drug preparations include a disintegration unit with several dissolution vessels each having a medium and a dosage to be tested disposed therein. After the dose to be tested is placed in the medium in the digestion vessel, the stirring element is rotated (or reciprocated) in the test solution at a certain rate for a certain period of time. An example of such a conventionally constructed dissolution apparatus is described in US Pat. No. 5,589,649. Analytical measurements are taken at specific time points in each vessel during the dissolution test. Each sample is measured individually with a spectrum analyzer attached to an optical fiber probe placed at the residue in the vessel at the beginning of the dissolution test. Test solutions are individually measured / analyzed using a spectral instrument that measures the concentration of API (active pharmacology) that indicates the degree of degradation at a given point in time. These decomposition systems incorporate both reflective and transmissive fiber optic probes to make the spectral crystals in the test solution as a function of time. Many drug APIs contain aromatic functional groups, but cosmetics generally lack functional groups with spectral properties in this area. UV measurements are convenient because they provide near simultaneous measurements.

As will be appreciated by those skilled in the art, a typical optical fiber probe may be an elongated shaft or body (waveguide or optical fibers) that accommodates an optical transmitter and an optical receiver in optical communication with a spectrum analyzer, one or more focusing. Lenses and sometimes one or more mirrors or prisms according to design or principle of operation. The optical transmitter provides an optical transmission path from a light source (often provided by an analysis instrument) to a liquid sampling region formed in the body of the probe that receives the decomposition medium from the test vessel into which the probe is inserted. The photoreceiver provides a light transmission path from the liquid sampling area to the detector of the analysis instrument. The liquid sampling area represents the observation window of the liquid path gap or probe.

Existing methods and apparatus used for spectral resolution testing are well known, but there are a number of disadvantages in the art that still need to be addressed. Special problems addressed by the present invention are 1) minimizing turbulent flow of laminar flow in test vessels due to persistent residual probes, 2) effective removal of air or gas bubbles from the spectral probe optical path gap or viewing area, 3) Automatic normalization and generalization of probes, 4) effective cleaning of spectral probes between test points.

Thus, there remains a need for improved fiber optic probes and related devices that generate accurate signals from liquid samples.

In order to address, in whole or in part, the foregoing and / or other problems that may be observed by one of ordinary skill in the art, the present invention provides methods, processes, systems, apparatus, Provides apparatuses and / or devices.

According to one embodiment, a dissolution test apparatus is provided. The dissolution test apparatus includes an optical probe and an automatic actuator. The optical probe is configured to make an optics-based measurement in the dissolution medium contained in the test vessel and to transmit the optical-based measurement to an analysis instrument located remotely from the test vessel. The optical probe includes a light path gap formed in the body to receive the body and the decomposition medium. The automatic actuator is coupled to the optical probe and is movable along at least one dimension, the optical probe being alternately movable into and out of the test vessel by the automatic actuator.

The optical probe may include an optical transmitter and an optical receiver disposed in the body, and the optical path gap is in optical communication with the optical transmitter and the optical receiver. When the optical probe is moved into the test vessel by an automatic actuator, the optical path gap is submerged in the decomposition medium. When the optical probe is moved from the test vessel by an automatic actuator, the optical path gap is removed from the decomposition medium. The optical probe can monitor the resolution medium between performing light based measurements.

According to another embodiment, the dissolution test apparatus further comprises a defoamer device in contact with the optical probe and configured to transmit a variable vibration force to the probe, wherein bubbles are removed from the optical path gap.

According to another embodiment, the dissolution test apparatus further comprises an elastomeric coupling attached to the probe and configured to return the probe to the set / matched position after the defoamer is inactive.

According to another embodiment, the defoaming device is configured to transmit to the probe a vibration force having a variable frequency, a variable amplitude or having both a variable frequency and a variable amplitude.

According to another embodiment, the defoamer is further configured to rotate the probe at an angle to the nominal axis of the probe.

According to yet another embodiment, the defoaming device is adapted to change the angle at which the probe rotates about the nominal axis, to change the speed at which the probe rotates, or to change both the angle and the speed. It is composed.

According to another embodiment, the dissolution test apparatus further comprises an automatic cleaning mechanism with a bath to contain the cleaning solution. The self-cleaning mechanism is movable into and out of the position below the optical probe, the optical probe being movable into and out of the tank by the automatic actuator.

According to another embodiment, the dissolution test apparatus further comprises an automatic calibration mechanism with calibration calibration for holding calibration media. The autocalibration mechanism is moveable to and from the position below the optical probe, the optical probe being movable into and out of the bath by the auto actuator.

According to another embodiment, a dissolution test apparatus is provided. The dissolution test apparatus includes an optical probe, an automatic actuator and an automatic cleaning mechanism. The optical probe is configured to make light-based measurements in the dissolution medium contained in the test vessel and to deliver the light-based measurement to an analysis instrument located remotely from the test vessel. The optical probe includes a light path gap formed in the body for receiving the body and the decomposition medium. An automatic actuator is coupled to the optical probe and is movable along at least one dimension, the optical probe being movable into and out of the test vessel by the automatic actuator. The automatic cleaning mechanism includes a cleaning bath for containing the cleaning solution. The self-cleaning mechanism is moveable to and from the position below the light probe, the light probe being movable into and out of the cleaning bath by the automatic actuator.

According to another embodiment, a dissolution test apparatus is provided. The dissolution test apparatus includes an optical probe, an automatic actuator, and an automatic calibration mechanism. The optical probe is configured to make light-based measurements in the dissolution medium contained in the test vessel and to deliver the light-based measurement to an analysis instrument located remotely from the test vessel. The optical probe includes a light path gap formed in the body for receiving the body and the decomposition medium. An automatic actuator is coupled to the optical probe and is movable along at least one dimension, the optical probe being movable into and out of the test vessel by the automatic actuator. The automatic calibration mechanism includes a calibration calibration for containing calibration media. The autocalibration mechanism is moveable to and from the position beneath the optical probe, the optical probe being movable into and out of the calibrator by the auto actuator.

According to another embodiment, a dissolution test apparatus is provided that includes both an automatic cleaning mechanism and an automatic calibration mechanism. In one example, the cleaning mechanism and the calibration mechanism are integrated into the optical probe and into a single or integral mechanism that can move.

According to another embodiment, a method of operating an optical probe in a test vessel of a dissolution test apparatus is provided. The optical probe is inserted into the test vessel along the nominal axis of the optical probe by an automatic actuator until the optical path gap of the optical probe is submerged in the dissolution medium contained in the test vessel. Any bubbles remaining in the optical path gap are removed by vibrating the optical probe about the nominal axis.

According to another embodiment, the optical probe automatically returns the optical probe to a set / registered position by using an elastomeric coupling attached to the optical probe.

According to another embodiment, the bubbles are removed by vibrating the optical probe at variable frequency, variable amplitude or at both variable frequency and variable amplitude.

According to another embodiment, the method further comprises removing any bubbles by rotating the optical probe at an angle to the nominal axis of the optical probe.

According to another embodiment, the bubbles about the nominal axis are removed by rotating the optical probe at a variable angle, variable speed or at both the variable angle and the variable speed.

According to another embodiment, the method includes cleaning the optical probe by moving a cleaning mechanism to a position below the optical probe, and inserting the optical probe into the cleaning bath of the cleaning mechanism containing the cleaning solution. It further includes.

According to yet another embodiment, the method includes calibrating the optical probe by moving the calibration mechanism to a position below the optical probe, and calibrating the calibration mechanism containing the calibrant. And inserting the optical probe into it.

According to another embodiment, the method includes operating the probe to perform light-based measurement of the dissolution medium remaining in the optical path gap, and removing the optical probe from the test vessel by operating an automatic actuator. It further includes.

According to another embodiment, the method further comprises adjusting the actuator to adjust the height of the optical probe relative to the test vessel such that the optical probe is correctly positioned at the desired test position of the probe on which light-based measurement of the dissolution medium is performed. Activating.

According to another embodiment, the method includes automatically detecting the presence and / or absence of bubbles in the lightpath gap. In one example, software is used for the detection.

According to another embodiment, a method of operating an optical probe in a test vessel of a dissolution test apparatus is provided. The optical probe is cleaned by moving the cleaning mechanism to a position below the optical probe and inserting the optical probe into the cleaning bath of the cleaning mechanism containing the cleaning solution. The optical probe is then inserted into the test vessel.

According to another embodiment, a method of operating an optical probe in a test vessel of a dissolution test apparatus is provided. The optical probe is calibrated by moving the calibration mechanism to a position below the optical probe and inserting the optical probe into the calibration tank of the calibration mechanism containing the calibrant or blank medium. The optical probe is then inserted into the test vessel.

According to another embodiment, a method of operating an optical probe in a test vessel of a dissolution test apparatus is provided. The optical probe is inserted into the test vessel until the optical path gap of the optical probe is immersed in the dissolution medium contained in the test vessel. The optical probe is operative to perform light-based measurements of the resolution medium remaining in the optical path gap. After performing the light-based measurement and before performing another light-based measurement, the optical probe is removed from the test vessel by operating an automatic actuator.

According to yet another embodiment, the method comprises the steps of (a) removing any bubbles remaining in the optical path gap by vibrating the optical probe prior to performing the optical substrate measurement; (B) cleaning the optical probe and inserting the optical probe into the cleaning bath of the cleaning mechanism by moving the cleaning mechanism to a position below the optical probe while the optical probe is outside of the decomposition medium. ; While the optical probe is outside of the resolution medium, calibrating the optical probe by moving the calibration mechanism to a position below the optical probe and inserting the optical probe into the calibration tank of the calibration mechanism. Step (c); And executing a step selected from the group consisting of two or more combination steps (d) of said steps.

According to various implementations, the cleaning step, calibration step, or cleaning step and calibration step all perform light-based measurements before the initial test run and after completion of the test run and / or during the course of the test run. Can be performed between each repetition.

Other devices, devices, systems, methods, forms, and advantages of the present invention will become apparent to those skilled in the art upon examination of the following figures and detailed description. All such additional systems, methods, forms and advantages are intended to be included within the scope of this disclosure, the present invention and the invention is protected by the appended claims.

The invention can be better understood by reference to the following figures. The components in the figures are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention. In the drawings, like reference numerals designate corresponding parts throughout the different views.
1 is a schematic elevation view showing an example of an decomposition test apparatus that includes an optical probe and a mechanism for vibrating the optical probe;
FIG. 2 is an elevation view schematically illustrating an example of a dissolution test apparatus that includes an optical probe and a mechanism for cleaning, rinsing, calibrating, and / or normalizing the optical probe. FIG.

The present invention addresses issues and problems in the prior art of optical fiber (spectral) decomposition tests. In the prior art, the probes remain as residues in the test vessels during the dissolution test to generate unwanted fluid turbulence within the test vessels. Sustained disruption of the mixed fluid motion generated by the residual probe can have a significant impact on the degradation profile of the drug formulation. For example, it was reported that a 3 to 5% increase in degradation rate was observed when residual load probes were used compared to manual sampling methods. In prior art systems, the spectral probes remain as residues in the test solution for the entire test, thereby potentially accelerating or altering the degradation rate of the API. The reason for residual probes in prior art systems is that the rise and fall of probes in and out of the medium is at risk of trapping bubbles within the spectral window, which rather hinders accurate measurement of the sample. In addition, the material remains dry in the spectral observation window to prevent probes from interfering with absorption measurements.

In prior art systems, probes need to be calibrated off-line prior to commencing the experiment and generally need to be recalibrated (offline) between dissolution proceedings or between samples. In addition, the probes need to be cleaned offline between the progress of decomposition or after sampling to remove cross contamination between samples and to clean the probe observation window and optics in preparation for the next measurement. Regardless of the geometry of the probe, it has been found that insoluble particulate material often collects on the probe observation window, which obstructs the optical path and prevents proper spectroscopic measurements. Thus, there is a need to adjust the shortcomings of the prior art to integrate fiber optic probes with automatic decomposition testers, automatic probe insertion and removal devices, automatic bubble removal devices, automatic online probe cleaning devices and automatic online calibration devices.

According to one embodiment of the present invention, the system has an automatic mechanism for temporarily inserting spectral probes into and out of the test vessel at a suitable point in time, which in turn reduces any disruption of fluid motion within the vessel due to the probe. Let's do it. Temporary insertion of optical fiber probes can be compared to the use of conventional cannula which only disturbs the fluid motion of the vessel for a short time [concept of optical fiber in decomposition test, Schatz et al., 8 (2); 1-5 (2001); Shaft Sampling and Decomposition Techniques in Fiber Optics, such as Schatz, 7 (1): 20-21 (2000)].

According to another example of the invention, the system is a mechanism designed to apply vibrational force at variable amplitudes and frequencies, apply rotational motion at variable angles and speeds, and remove gas or air bubbles from the spectral probe lightpath gap or viewing area. Integrate. The bubbles may be trapped when the probe is inserted into the container medium or during the time the probe remains in the container medium. The device can also incorporate self-centering, elastomeric or adaptive mechanical couplings that allow the probe body to move and rotate during the defoaming process and allow the probe to return to the setting / matching position after defoaming has been removed. This defoamer can be combined with software to check and determine if a bubble is present and when the bubble is present and when the bubble is removed. Prior art systems do not have means to automatically detect and remove bubbles from the spectral probe lightpath, which often results in indeterminate or ambiguous results due to the interference of bubbles in the spectral transmission.

According to another example of the invention, the system incorporates an automatic on-line means for effectively cleaning spectral probes between test points or experiments. The new system incorporates one or more static and / or recycling baths for each probe. Static and / or recirculation baths are one or a series of cleanings to remove any debris, insoluble or hydrophobic materials, etc., collected in the spectral probe lightpath gap or observation area during the time period immersed in the digestion vessel or calibration standard. And rinse fluids. Also, the jaws are used to clean the outer surface of the probes, thereby reducing or eliminating any carryover and cross contamination. This cleaning process ensures that the data for the dissolution profiles collected indicate the sample tested.

According to another example of the invention, the system incorporates an automatic on-line means to calibrate the fiber optic probes to a known reference standard. The system integrates one or more static and / or recycling baths for each probe. The baths contain known concentrations of API and / or blank media used to calibrate the probe and associated spectral instruments. The probes are automatically inserted into the calibration bath (s) (bubbles are removed by the defoamer when necessary as described above) and the spectra are collected to calibrate the probe. The automated method is the ability to automatically calibrate on-line between each test run, allowing multiple dissolution tests to be run in series.

Thus, there is a need for an automatic spectral decomposition test apparatus that overcomes the above-mentioned disadvantages associated with the prior art. There is also a need for an automatic dissolution test apparatus, which automatically 1) minimizes turbulence of laminar fluid flow in test vessels by automatically inserting spectral probes only when test measurements are needed, and 2) spectra. Effectively removes air or gas bubbles from probe lightpath gaps or viewing areas, 3) performs automatic cleaning of spectral probes between test points, and 4) automatically provides standardization and generalization of probes.

In accordance with the present invention, several novel devices and methods are provided for implementation in a dissolution test apparatus. Several implementations of the invention include: 1) an automatic mechanism for lowering and elevating the spectral probes into and out of the test vessel, 2) automatic means for removing air or gas bubbles from the spectral probe optical path gap or viewing area, and 3) spectral Automatic mechanism including a rack to hold the plurality of static or recycle baths for cleaning of the probes, and / or 4) a rack to hold the plurality of static or recycle baths for standardization and generalization of the spectra and associated analytical instruments. It may include an automatic mechanism.

1 shows an example of a dissolution test apparatus 100 according to one or more implementations described herein. The resolution test apparatus 100 generally includes a spectral probe (eg, an optical fiber probe or an optical probe) 104, which may be configured as described above. The probe 104 may descend into and rise from the dissolution test vessel 108 containing the dissolution medium 112. The stirring device or other USP-type device 116 may operate in the decomposition medium 112 in a manner that can be understood by those skilled in the art. The automatic actuator 120 is a test location in the disassembly medium 112 when the test is conducted and above the disassembly medium 112 and at a location outside the disassembly medium 112. Like), coupled to the probe 104 to allow the probe 104 to move vertically. 1 specifically shows the probe 104 in a test position. The probe 104 includes an optical path gap or observation window 124, typically located near the distal end of the probe 104, as described above. The optical path gap 124 is immersed in the dissolution medium 112 at the test position of the probe 104 to enable light-based measurements. As described above, the actuator 120 operates to remove the probe 104 from the degradation medium 112 after the measurement point is obtained, such that the probe 104 remains in the degradation medium 112 only during the test. Therefore, the probe 104 may be removed from the fluid 112 when not used for testing to remove any fluid turbulence in the vessel 108. In the test position, the probe 104 is located along the nominal longitudinal axis (ie, the vertical axis) 128. The height of the probe 104 and other positional coordinates of the probe 104 relative to the test vessel 108 may be described by guidelines such as the USP described above. Actuator 120 may be operated to adjust the position (especially the height) of probe 104 to facilitate adaptation to the position condition.

As further shown in FIG. 1, the dissolution test apparatus 100 may further include an antifoaming device 132 that may be installed in the actuator 120 or any other suitable structure of the dissolution test apparatus 100. Can be. The defoaming device 132 may include, for example, a vibration source or a vibration generator 136 in communication with the probe 104 via any suitable interlock 140. By way of example, the vibration mechanism 136 of the defoamer 132 may be a solenoid type device. By way of example, the vibration source 136 may be fixed in place and the linkage 140 is movable relative to the vibration source 136. The interlock 140 transmits vibration energy to the probe 104 through contact with the probe 104. The pendulum (oscillation) of the interlock device 140 is indicated by arrow "144" in FIG. 1 and the pendulum motion or vibration of the probe 104 is indicated by arrow "148". Contact with the probe 104 may be performed by any suitable means. As one example, the interlock 140 intermittently contacts the probe 104, such as by "tapping" the probe 104, whereby the probe 104 is impacted by the interlock 140. In response to displacement. As another example, the interlock 140 may generally remain coupled to the probe 104 such that the probe 104 moves directly in response to movement by the interlock 140. In one embodiment, the vibration of the probe 104 is characterized by the forward and backward movement of the probe 104 through an angle with respect to the pivot point 152 of the probe 104. The pivot point 152 may be realized through the coupling of the probe 104 to any suitable structure of the dissolution test apparatus 100, such as the actuator 120. In one embodiment, the probe 104 is maintained with self centering, adaptive or elastomeric coupling 156, as shown in FIG. 1. The coupling 156 allows the probe 104 to move in parallel motion in response to a stimulus by the vibration mechanism 136 of the defoaming device 132. Upon deactivation of the defoamer 132 (ie, after the end of the defoamer procedure), the coupling 156 returns to its setting / matching position where the probe 104 is collinear with the nominal axis 128. Make it possible.

In addition to periodic translation along one dimension, such as side by side movement indicated by the arrows in FIG. Likewise, the probe 104 may be configured to activate the probe 104 in a motion along another dimension. Additionally or alternatively, the vibration mechanism 136 may be configured to drive the probe 104 in a rotational or pivotal motion at an angle with respect to the nominal axis 128 and with respect to the pivot point 152 of the probe 104. Can be. The elastomeric coupling 156 may be configured to receive the other type of movement of the probe 104 and return the probe 104 to its setting / matching position upon vibration stop, as described above. Displacement of the probe 104 along one or more dimensions or axes and / or rotation or pivoting of the probe at an angle with respect to the nominal axis 128 of the probe 104 may be performed by any suitable means. In one example, the linkage 140 may be positioned at an angle with respect to the probe 104, ie, at any angle of another horizontal orientation of the linkage 140 specifically illustrated in FIG. 1. In another example, the linkage 140 can pivot and / or rotate via a connection to the vibration generating component 136 of the defoamer 132, which movement is associated with the linkage 140 relative to the probe 104. ) Is delivered to the probe 104 via a coupling (eg, yoke, ring, etc.). In another example, the defoaming device 132 may include one or more vibration generating components 136 and associated linkages 140. For example, one vibration generating component 136 and associated linkage 140 may be arranged / orientated, as shown in FIG. 1, while the other vibration generating component 136 and associated linkage 140 may be It can be arranged or oriented orthogonally to add the forward and backward motion to the side-by-side motion shown.

In some embodiments, the vibration mechanism 132 is configured to exert a variable amplitude and / or frequency vibration force, which may be programmable and sufficiently adjusted to accommodate other probe geometries and fluids. In an embodiment that provides a rotational motion, the vibration mechanism 132 alters the angle at which the probe 104 pivots or rotates about the nominal axis 128 and / or the rotation of the probe 104 about the nominal axis 128. It may be further configured to change the rotation or swing speed.

2 illustrates another example of a dissolution testing apparatus 200 in accordance with one or more embodiments described herein. The dissolution test apparatus 200 includes similar shapes or components as shown in FIG. 1 and like reference numerals designate similar shapes. The dissolution test apparatus 200 includes a mechanism 260 for cleaning or rinsing the probe 204. By way of example, the illustrated mechanism 260 includes a rack 264 that holds one or more jaws 268, 272 containing cleaning or rinsing fluids. As noted above, the jaw (s) 268, 272 can be static or recycled (not shown to perform the cycling operations). As indicated by arrow “276”, mechanism 260 may be moved to a position above test vessel 208 and below probe 204 by a suitable actuator (not shown). Actuator 220 coupled to probe 204 may then be operated to lower probe 204 into a selected jaw 268 or 272 of mechanism 260. By this configuration, the probe 204 can be cleaned between test points or sample readings (ie, between performing light-based measurements) if desired. Thus, the probe 204 can be lowered into the decomposition medium 212 by the actuator 220 and lifted from the decomposition medium 212 after the measurement is performed. The probe 204 may be raised up sufficiently to provide clearance for the cleaning mechanism 260. Subsequently, the cleaning mechanism 260 moves to a position below the probe 204 and the probe 204 can be lowered into one of the jaws 268 or 272 for cleaning / rinsing. The cleaning mechanism 260 can then move out of the vertical movement path of the probe 204, and the probe 204 can be lowered back into the dissolution medium 212 to obtain the next test point. This process can be repeated one or more times depending on the desired test procedure. The cleaning step may also be performed before the beginning of the decomposition process (after a series of data points are generated to generate a decomposition rate curve) and after the completion of the decomposition process.

2 illustrates an embodiment where mechanism 260 is a calibration or standardization mechanism. In this case, the static or recirculating jaws 268, 272 of the rack 264 may contain a calibrant or blank medium. In one example, one jaw 268 may contain calibration media and another jaw 272 may contain blank media. In the case of cleaning / rinsing, the mechanism 260 and related components of the dissolution test apparatus 200 may operate to perform calibration / standardization of the probe 204 (and spectrum analyzer) between test points if desired. . The cleaning step may also be performed before the beginning of the decomposition process (after a series of data points are generated to generate a decomposition rate curve) and after the completion of the decomposition process.

In all such cases, it can be seen that the dissolution test apparatus 200 allows procedures such as cleaning, rinsing, calibration, etc. to be performed online, while conventional apparatus and methods require the procedures to be performed offline. .

In one embodiment, the dissolution test apparatus 200 includes a mechanism for cleaning the probe 204 and a second mechanism for calibrating the probe 204. In other embodiments, the same mechanism 260 can be used for both cleaning and calibration, in which case different jaws 268 and 272 can contain respective cleaning and calibration fluids.

As further shown in FIG. 2, the dissolution test apparatus 200 may include the defoamer device 232 described above in connection with FIG. 1. Therefore, the defoamer device 232 can be activated before each measurement iteration, if desired. The timing, duration and order of the respective operations of the defoamer 232, the cleaning and / or calibration mechanism 260, the actuator 220 and related components may be determined or programmed in any manner desired by the user. have.

1 and 2, the dissolution test apparatus 100,200 is schematically shown to include a single assembly (e.g., probe, actuator, defoamer, cleaning / calibration mechanism, etc.) operating in a single test vessel 108,208. Although shown, one of ordinary skill in the art will appreciate that the dissolution test apparatus 100,200 typically includes an array of test vessels 108,208. Accordingly, it will be further understood that the dissolution test apparatus 100, 200 shown in FIGS. 1 and 2 may include a plurality of assemblies associated with a similar number of test vessels 108, 208. Further modifications can also be readily expected. For example, in the case of a multiple vessel dissolution test apparatus, a single cleaning / calibration mechanism 260 or a pair of cleaning and calibration mechanisms 260 may move continuously from one probe 204 to another.

In general, terms such as "communicate" and "in communication with" (eg, the first component is in "communication" or "communicating with the second component") are herein referred to as two or more components or elements. It is used to indicate structural, functional, mechanical, electrical, signal, optical, magnetic, electromagnetic, ionic or fluidic relationships between them. As such, the fact that one component is described as communicating with a second component It is not intended to exclude the possibility that the first and second components may be provided and / or operatively related or combined.

It will be understood that various forms or details of the invention may vary within the scope of the invention. In addition, the foregoing description is for illustrative purposes only, and not for purposes of limitation, the invention is defined by the claims.

Claims (20)

As the decomposition test device,
Configured to perform optics-based measurements on the dissolution medium contained in the test vessel and to transmit the light-based measurement to an analysis instrument located remotely from the test vessel, the body and an optical path gap formed in the body An optical probe; And
An automatic actuator coupled to the optical probe and movable along at least one dimension,
Wherein the optical probe is alternately moveable into and out of the test vessel by the automatic actuator. The method of claim 1,
And an antifoam device configured to communicate with the optical probe and to transmit a variable vibration force to the probe, wherein the bubbles are removed from the optical path gap. The method of claim 2,
And an elastomeric coupling attached to the probe and configured to return the probe to a setting position after the anti-foaming device is deactivated. The method of claim 3, wherein
The auto actuator is connected to the elastomer coupling. The method of claim 2,
Wherein the defoaming device is configured to transmit a vibration force having a variable frequency, a variable amplitude or having both a variable frequency and a variable amplitude to the probe. The method of claim 2,
Wherein the defoamer device is further configured to rotate the probe at an angle with respect to the nominal axis of the probe. The method of claim 6,
Wherein the defoamer is configured to change the angle at which the probe rotates, the speed at which the probe rotates about the nominal axis, or to change both the angle and the speed. The method of claim 1,
And further comprising an automatic cleaning mechanism having a bath for containing the cleaning solution, wherein the automatic cleaning mechanism is movable to and from the position below the optical probe, the optical probe being moved into the tank by the automatic actuator. And a disassembly test apparatus movable from the tank. The method of claim 8,
The tank is a recycle join, decomposition test device. The method of claim 1,
And further comprising an autocalibration mechanism with a jaw to hold the calibration medium, the autocalibration mechanism being movable to and from a position below the optical probe, the optical probe being moved by the automatic actuator. Disassembly test apparatus movable into and out of the bath. The method of claim 1,
Further comprising an automatic cleaning mechanism having a cleaning bath for containing a cleaning solution and movable to a position below and from said optical probe, and an automatic calibration mechanism for calibrating the calibration medium; The self-cleaning mechanism and the auto-calibration mechanism are movable to and from a position below the optical probe, the optical probe being moved into the cleaning bath and the calibration tank by the automatic actuator and to the cleaning bath and the Disassembly test apparatus, movable from the calibration tank. A method of operating an optical probe in a test vessel of a dissolution test apparatus,
Inserting the optical probe into the test vessel along the nominal axis of the optical probe by operating an automatic actuator until the optical path gap of the optical probe is submerged in the dissolution medium contained in the test vessel; And
Oscillating the optical probe about the nominal axis, thereby removing any bubbles remaining in the optical path gap. The method of claim 12,
After vibrating the optical probe, further comprising automatically returning the optical probe to a setting position by using an elastomer coupling attached to the optical probe. The method of claim 12,
Removing the random bubbles comprises oscillating the optical probe at a variable frequency, a variable amplitude or at both a variable frequency and a variable amplitude. The method of claim 12,
Removing the optional bubbles further comprises rotating the optical probe at an angle to the nominal axis of the optical probe. The method of claim 15,
The removing of any bubbles comprises rotating the optical probe at a variable angle, at a variable speed about the nominal axis, or at both the variable angle and the variable speed. The method of claim 12,
Cleaning the optical probe by moving the cleaning mechanism to a position below the optical probe, and further including inserting the optical probe into the cleaning bath of the cleaning mechanism containing the cleaning solution. Way. The method of claim 12,
Calibrating the optical probe by moving the calibration mechanism to a position below the optical probe, and inserting the optical probe into the calibration tank of the calibration mechanism containing the calibrant. Included as, the operation method of the optical probe. A method of operating an optical probe in a test vessel of a dissolution test apparatus,
Inserting the optical probe into the test vessel until the optical path gap of the optical probe is submerged in the dissolution medium contained in the test vessel;
Operating the probe to perform a light-based measurement of the decomposition medium remaining in the optical path gap; And
After performing the light-based measurement and before performing another light-based measurement, removing the optical probe from the test vessel by operating an automatic actuator. The method of claim 19,
(A) removing any bubbles remaining in the optical path gap by vibrating the optical probe prior to performing the optical substrate measurement; (B) cleaning the optical probe and inserting the optical probe into the cleaning bath of the cleaning mechanism by moving the cleaning mechanism to a position below the optical probe while the optical probe is outside of the decomposition medium. ; While the optical probe is outside of the resolution medium, calibrating the optical probe by moving the calibration mechanism to a position below the optical probe and inserting the optical probe into the calibration tank of the calibration mechanism. Step (c); And executing a step selected from the group consisting of two or more combination steps (d) of said steps.

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