Patent Publication Number: US-2010126980-A1

Title: Direct vessel heating for dissolution testing

Description:
FIELD OF THE INVENTION 
     The present invention relates generally to dissolution testing of analyte-containing media. More particularly, the invention relates to heating and monitoring the temperature of media contained in test vessels of a dissolution test apparatus by utilizing a direct vessel heating technique, and to test vessels that integrally include direct vessel heating components. 
     BACKGROUND OF THE INVENTION 
     Dissolution testing is often performed as part of preparing and evaluating soluble materials, particularly pharmaceutical dosage forms (e.g., tablets, capsules, and the like) consisting of a therapeutically effective amount of active drug carried by an excipient material. Typically, dosage forms are dropped into test vessels that contain dissolution media of a predetermined volume and chemical composition. For instance, the composition may have a pH factor that emulates a gastro-intestinal environment. Dissolution testing can be useful, for example, in studying the drug release characteristics of the dosage form or in evaluating the quality control of the process used in forming the dose. To ensure validation of the data generated from dissolution-related procedures, dissolution testing is often carried out according to guidelines approved or specified by certain entities such as United States Pharmacopoeia (USP), in which case the testing must be conducted within various parametric ranges. The parameters may include dissolution media temperature, the amount of allowable evaporation-related loss, and the use, position and speed of agitation devices, dosage-retention devices, and other instruments operating in the test vessel. 
     As a dosage form is dissolving in the test vessel of a dissolution system, optics-based measurements of samples of the solution may be taken at predetermined time intervals through the operation of analytical equipment such as a spectrophotometer. The analytical equipment may determine analyte (e.g. active drug) concentration and/or other properties. The dissolution profile for the dosage form under evaluation—i.e., the percentage of analytes dissolved in the test media at a certain point in time or over a certain period of time—can be calculated from the measurement of analyte concentration in the sample taken. In one specific method employing a spectrophotometer, sometimes referred to as the sipper method, dissolution media samples are pumped from the test vessel(s) to a sample cell contained within the spectrophotometer, scanned while residing in the sample cell, and in some procedures then returned to the test vessel(s). In another more recently developed method, sometimes referred to as the in situ method, a fiber-optic “dip probe” is inserted directly in a test vessel. The dip probe includes one or more optical fibers that communicate with the spectrophotometer. In the in situ technique, the spectrophotometer thus does not require a sample cell as the dip probe serves a similar function. Measurements are taken directly in the test vessel and thus optical signals rather than liquid samples are transported between the test vessel and the spectrophotometer via optical fibers. 
     During the course of dissolution testing, it is desirable and often required to heat the media residing in the vessels of the dissolution test apparatus, and control the temperature of this media at a constant level or according to a predetermined temperature profile. For instance, when operating in accordance with certain USP guidelines, the media must be maintained at 37±0.5° C. One way to control the temperature of the media is to provide a water bath with the dissolution test apparatus. The dissolution test vessels are supported by the dissolution test apparatus such that the vessels are at least partially immersed in the water bath. Heated water is circulated through the water bath and thus into thermal contact with each vessel, whereby heat is transferred from the water bath to the media contained in the vessels. Another way to control media temperature is by way of Direct Vessel Heating (DVH™) technology developed by Varian, Inc., Palo Alto, Calif. In this latter case, a heating element is attached to each vessel. The heating element is a multi-layered structure that includes resistive heating elements and temperature-sensing elements sandwiched between polymeric layers. Accordingly, the heating of each vessel of the dissolution system is independently controllable and the need for a water bath and associated components (water heater, pump, plumbing, etc.) is eliminated. Examples of vessels provided with this type of heating element are described in U.S. Pat. Nos. 6,303,909 and 6,727,480, assigned to the assignee of the present disclosure and incorporated herein by reference in their entireties. 
     While vessels provided with heating elements of the type noted above generally perform well, there is a need for further improvements in the direct heating of vessels. The known heating elements require several layers of material, and must first be fabricated as a complete article and then applied to the vessels. Typically, the as-constructed heating elements are manually applied with the use of adhesives, which may result in variations in performance from one vessel to another. Moreover, the various materials required and fabrication process are costly. Therefore, there is a need for providing directly heated vessels that are fabricated more consistently, function more precisely, and are less costly. 
     SUMMARY OF THE INVENTION 
     To address the foregoing problems, in whole or in part, and/or other problems that may have been observed by persons skilled in the art, the present disclosure provides methods, processes, systems, apparatus, instruments, and/or devices, as described by way of example in implementations set forth below. 
     According to one implementation, a dissolution test vessel configured for direct vessel heating is provided. The dissolution test vessel includes a lateral wall, a resistive heating element, and a temperature-sensing element. The lateral wall is disposed about a longitudinal axis of the vessel and includes an upper end, a lower end axially spaced from the upper end, and an outside surface extending from the upper end to the lower end. The resistive heating element is bonded directly to the outside surface and includes a first heating element end, a second heating element end, and a heating element section contiguously running from the first heating element end, over a heating zone of the lateral wall and to the second heating element end. The heating element section runs along at least two different directions. The temperature-sensing element is bonded directly to the outside surface and includes a first sensing element end, a second sensing element end, and a sensing element section contiguously running from the first sensing element end, over a temperature sensing zone of the lateral wall and to the second sensing element end. The sensing element section runs along at least two different directions. 
     According to another implementation, a dissolution test apparatus configured for direct vessel heating is provided. The dissolution test apparatus includes a vessel support member having an aperture, a heater control system, and a vessel mounted at the vessel support member. The vessel includes a resistive heating element bonded directly an outside surface of the vessel, and a temperature-sensing element bonded directly to the outside surface. The resistive heating element and the temperature-sensing element communicate with the heater control system. 
     According to another implementation, a method is provided for fabricating a dissolution test vessel. The method includes depositing a first flowable material directly on an outside surface of a lateral wall of a vessel to form a resistive heating element. A second flowable material is deposited directly on the outside surface to form a temperature-sensing element. A contact block is attached to the vessel and placed in communication with the resistive heating element and the temperature-sensing element. A clear film may be applied directly to the outside surface wherein the film covers at least a portion of the resistive heating element and the temperature-sensing element. 
     Other devices, apparatus, systems, methods, features and advantages of the invention will be or will become apparent to one with skill in the art upon examination of the following figures and detailed description. It is intended that all such additional systems, methods, features and advantages be included within this description, be within the scope of the invention, and be protected by the accompanying claims. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       The invention can be better understood by referring 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 figures, like reference numerals designate corresponding parts throughout the different views. 
         FIG. 1  is a perspective view of an example of a vessel provided in accordance with the teachings of the present disclosure. 
         FIG. 2  is an elevation view of the vessel illustrated in  FIG. 1 . 
         FIG. 3  is another elevation view of the vessel illustrated in  FIG. 1 . 
         FIG. 4  is a detailed view of the region designated “A” in  FIG. 2 . 
         FIG. 5  is a cross-sectional elevation view of a portion of the vessel illustrated in  FIGS. 1 to 3 . 
         FIG. 6  is an elevation view of the vessel illustrated in  FIGS. 1 to 3  mounted to a vessel support member and communicating with a vessel heating control system. 
         FIG. 7  is a schematic view of an example of a vessel heating control system according to the teachings of the present disclosure. 
         FIG. 8  is a schematic view of a vessel being fabricated according to an example taught in the present disclosure. 
         FIG. 9  is a perspective view of an example of a dissolution test apparatus at which one or more vessels taught in the present disclosure may be operated. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     An example of a vessel with integral direct vessel heating capability will now be described with reference to  FIGS. 1-6 . 
       FIG. 1  is a perspective view and  FIGS. 2 and 3  are elevation views of an example of a vessel  100  according to the present teachings. Typically, the vessel  100  has a cylindrical shape relative to a central or longitudinal axis  202  ( FIG. 2 ) of the vessel, but more generally the vessel  100  may have any shape suitable for containing dissolution media and receiving a stirring device and/or other types of in situ operative components. The vessel  100  generally includes a lateral wall or section  104  generally parallel with the central axis  202 . The lateral wall  104  terminates at an upper end  108 , which is open to the interior of the vessel  100  unless a vessel cover (not shown) is provided. Opposite to the upper end  108 , the lateral wall  104  includes a lower end at which a bottom section  112  of the vessel  100  adjoins the lateral wall  104 . The bottom section  112  may be hemispherical or rounded as illustrated or may have any other suitable shape. Typically, the bottom end  112  is completely closed but in other implementations may include an opening and an accompanying closure device, valve, or the like. 
     The vessel  100  may include a flanged section  116  (e.g., rim, flange, etc.), the outermost diameter of which is greater than the outermost diameter of the lateral wall  104 . The flanged section  116  facilitates the mounting of the vessel  100  at a vessel support member such as may be provided with a dissolution test apparatus. Typically, the vessel support member is provided in the form of a plate that has a plurality of apertures serving as vessel mounting sites supporting a plurality of respective vessels. The flanged section  116  may also be configured to facilitate centering of the vessel  100  within the aperture of the vessel support member. For this purpose, the flanged section  116  may be a separate component in the form of a collar or ring that is attached to the lateral wall  104  at the upper end  108 . As an example, the flanged section  116  may include a gap  120  ( FIG. 1 ) and one or more bores  324  ( FIG. 3 ) leading to the gap  120 . A screw or other fastener, tangentially oriented relative to the curvature of the vessel  100 , may be inserted through the bore(s)  324  and across the gap  120  to secure the flanged section  116  to the lateral wall  104 . The flanged section  116  may be similar to the TruCenter™ vessel commercially available from Varian, Inc., Palo Alto, Calif., or to embodiments disclosed in U.S. Pat. Nos. 6,562,301 and 6,673,319, assigned to the assignee of the present disclosure. As an alternative to the illustrated two-piece design of the vessel  100 , the flanged section  116  may be a rim integrally formed with the lateral wall  104 . 
     The vessel  100  may further include a contact block (or contact element)  128 . The contact block  128  may be attached to or form a part of the flanged section  116 , as described further below. In the illustrated example, the contact block  128  is removably attached to the flanged section  116  by way of screws  132 . The contact block  128  may include a first set of contacts (not shown) located at the underside of the contact block  128 , and a second set of contacts  136  located at an outer surface of the contact block  128 . As illustrated in  FIGS. 1  and  3 , the contact block  128  may protrude radially outward from the flanged section  116  relative to the central axis  202  ( FIG. 2 ). The function of the contact block  128  is described below. 
     The vessel  100  includes a direct vessel heating area  140 . The direct vessel heating area  140  may be fabricated over a large portion of the outside surface of the lateral wall  104 . For instance, the direct vessel heating area  140  may span over a large portion of the axial length of the lateral wall  104  (i.e., in the direction of the central axis  202 ), and fully circumscribe the lateral wall  104  to ensure uniform heating and temperature control of the media contents of the vessel  100 . 
     Referring to  FIG. 1 , the direct vessel heating area  140  may include a continuous, first resistive heating element  144  configured to provide heat over a first heating zone  146  of the direct vessel heating area  140 . By “resistive” is meant that the material of the first heating element  144  is electrically resistive and thus dissipates heat in response to electrical current. 
     Referring to  FIG. 2 , to provide heat throughout the first heating zone  146 , the first resistive heating element  144  includes a first heating element end  248 , a first main heating element section  250 , and a second heating element end  252 . The material constituting the first resistive heating element  144  is contiguous from the first heating element end  248 , to the first main heating element section  250 , and to the second heating element end  252 . Hence, establishing an electrical current from the first heating element end  248 , through the first main heating element section  250 , and to the second heating element end  252  generates heat. A majority of the heat is generated from first main heating element section  250  and thus in the first heating zone  146  defined thereby. For this purpose, the first main heating element section  250  may be configured or arranged in any suitable pattern. Generally, the first main heating element section  250  includes portions that run in at least two directions to provide sufficient heating coverage over the first heating zone  146 . In the illustrated example, the first main heating element section  250  includes horizontal portions  254  and vertical portions  256 . Moreover, again as an example, more than one horizontal portion  254  and/or vertical portion  256  may branch off of the first heating element end  248  and/or the second heating element end  252 . Alternative patterns may include, as examples, a sawtooth pattern, a square wave pattern, a trapezoidal pattern, a sinusoidal pattern, other serpentine patterns, and combinations of the foregoing. The first main heating element section  250  may also include fuse links  258 , which by example are illustrated as short sinusoidal portions. 
     Referring to  FIG. 1 , in the present example, the direct vessel heating area  140  also includes a continuous, second resistive heating element  164  configured to provide heat over a second heating zone  166  of the direct vessel heating area  140 . 
     Referring to  FIG. 2 , to provide heat over the second heating zone  166 , the second resistive heating element  164  includes a third heating element end  268 , a second main heating element section  270 , and a fourth heating element end. In the illustrated example, the fourth heating element end and the second heating element end  252  (associated with the first resistive heating element  144 ) are one and the same, i.e., a single termination common to both the first resistive heating element  144  and the second resistive heating element  164  is provided. The configuration, patterning or arrangement, and operation of the second resistive heating element  164  may be the same or similar as described above regarding the first resistive heating element  144 . 
     The dual-zone heating design of the illustrated vessel  100  is useful for accommodating the operation of the vessel  100  when utilizing different levels of media during different tests. The dual-zone heating design is illustrated as an example. In other implementations, the direct vessel heating area  140  may include a single resistive heating element and corresponding single heating zone, or may include more than two resistive heating elements and correspondingly distinct heating zones. 
     The direct vessel heating area  140  may further include a continuous temperature-sensing element  174  configured to measure media temperature. In the illustrated example, the temperature-sensing element  174  runs over a temperature sensing zone that may be located within the second heating zone  166 . The second heating zone  166  is the lower of the two heating zones  146  and  166  and media is most likely to be filled at least to an elevation level coextensive with the second heating zone  166 . Alternatively, the temperature-sensing element  174  may be located within the upper or first heating zone  146 , or in both heating zones  146  and  166 , or two temperature-sensing elements may be located in the respective heating zones  146  and  166 . Also in the illustrated example, the temperature-sensing element  174  is located “within” the second heating zone  166  so as to facilitate fabrication of both the second resistive heating element  164  and the temperature-sensing element  174 . Alternatively, the temperature-sensing element  174  may overlap into both heating zones  146  and  166 . To provide an accurate measurement of media temperature, the temperature-sensing element  174  may cover a large portion of the direct vessel heating area  140 . In the illustrated example, the temperature-sensing element  174  covers a large portion of the second heating zone  166 . 
     Referring to  FIG. 2 , the temperature-sensing element  174  includes a first sensing element end  278 , a main sensing element section  280 , and a second sensing element end  282 . The material constituting the temperature-sensing element  174  is contiguous from the first sensing element end  278 , to the main sensing element section  280 , and to the second sensing element end  282 . In this example, the resistivity of the material constituting the temperature-sensing element  174  varies with temperature and thus the temperature of the media, which is in thermal contact with the temperature-sensing element  174  across the lateral wall  104  of the vessel  100 , may be measured by sensing a change in the electrical current through the temperature-sensing element  174  or in the voltage across the temperature-sensing element  174 . The main sensing element section  280  may be configured or arranged in any suitable pattern. Generally, as in the case of the resistive heating elements  144  and  164 , the main sensing element section  280  includes portions that run in at least two directions to provide sufficient temperature-measurement coverage over the second heating zone  166 . In the illustrated example, the main sensing element section  280  includes horizontal portions and vertical portions arranged in a sinusoidal or serpentine pattern. Alternative patterns may be utilized, as noted above in the case of the resistive heating elements. 
       FIG. 4  is a detailed view of the region designated “A” in  FIG. 3 . As best shown in  FIG. 4 , the heating element ends  248 ,  252 ,  268  and the sensing element ends  278  and  282  may be located proximate to each other and to the contact block  128 . By this configuration, relatively short jumper wires or other types of electrical interconnections (e.g., a flexible ribbon cable) may be provided to electrically interconnect the heating element ends  248 ,  252 ,  268  and the sensing element ends  278  and  282  respectively to the first set of contacts (not shown) located at the underside of the contact block  128 , and thus to the second set of contacts  136  located at an outer surface of the contact block  128 . To facilitate making the electrical contact with jumper wires or the like, each of the heating element ends and the sensing element ends may terminate at a respective bond pad  486 . 
     All portions of the resistive heating element(s)  144  and  164  and the temperature-sensing element(s)  174 , including their respective ends  248 ,  252 ,  268 ,  278 ,  282 , main sections  250 ,  270 ,  280 , and bond pads  486 , are directly bonded to the outer surface of the lateral wall  104  of the vessel  100 . That is, no intervening layers of material exist between the resistive heating element(s)  144  and  164  and the temperature-sensing element(s)  174  and the lateral wall  104 . Accordingly, these components comprising the direct vessel heating area  140  of the vessel  100  are formed integrally with the vessel  100 , as opposed to comprising a separate, multi-layered article that must be applied to the vessel  100  through the use of adhesives or other means. The resistive heating element(s)  144  and  164  and the temperature-sensing element(s)  174  are not removable from the lateral wall  104 ; all of these components are part of the same unitary structure (i.e., the vessel  100 ) as an end product ready for use. Moreover, the various components of the resistive heating element(s)  144  and  164  and the temperature-sensing element(s)  174  may all be formed on the lateral wall  104  at the same radial distance relative to the central axis  202 , thus forming a single level of circuitry. That is, for instance, the resistive heating element(s)  144  and  164  do not need to be located at a different radial distance from the temperature-sensing element(s)  174 . Moreover, the resistive heating element(s)  144  and  164  and the temperature-sensing element(s)  174  do not need to be sandwiched between different layers of material. The resistive heating element(s)  144  and  164  and the temperature-sensing element(s)  174  may be formed as part of the vessel  100  by any suitable technique. In some implementations, the resistive heating element(s)  144  and  164  and the temperature-sensing element(s)  174  are formed by dispensing a liquid or paste of an electrically conductive material onto the lateral wall  104  according to a desired pattern. Examples of dispensing include, but are not limited to, ink printing, pad printing, and silk screening. The compositions of the resistive heating element(s)  144  and  164  and the temperature-sensing element(s)  174  may depend on the fabrication technique utilized, but generally will be materials exhibiting an amount of electrical resistivity or conductivity suitable for transferring heat to the vessel  100  or sensing temperature. Examples of compositions of the resistive heating element(s)  144  and  164  and the temperature-sensing element(s)  174  include, but are not limited to, conductive or resistive inks, epoxies, or the like, and generally any material that may be applied to the lateral wall  104  according to a desired pattern or arrangement and yield a desired electrical conductivity or resistivity. The composition may include a metal or a conductive polymer. A specific example is a silver-containing ink such as the product designated  118 . 41  commercially available from Creative Materials, Tyngsboro, Mass. The lateral wall  104  may have any composition suitable for dissolution testing and compatible with the direct bonding of the resistive heating element(s)  144  and  164  and the temperature-sensing element(s)  174 , examples including various glasses and polymers. 
     The only other material that may be desired to be added as part of the direct vessel heating area  140  is a protective layer  190 , the boundaries of which are indicated by dashed lines in  FIGS. 1-4 . The protective layer  190  is likewise bonded directly to the components of the resistive heating element(s)  144  and  164  and the temperature-sensing element(s)  174 , and to the regions of the outer surface of the lateral wall  104  between these components. The protective layer  190  may cover all or a portion of the direct vessel heating area  140 . The protective layer  190  may be composed of any material that provides desired types of protections for these components (e.g., electrical insulation, thermal insulation, protection from oxidation, etc.). Examples of materials suitable for the protective layer  190  include, but are not limited to, clear dielectric coatings, clear PVC coatings such as may be employed as adhesives for medical devices, or the like. A specific example is the product designated 1-20323 commercially available from Dymax Corporation, Torrington, Conn. 
       FIG. 5  is a cross-sectional elevation view of a portion of the vessel  100 . Representative sections of the resistive heating element  144  (or  164 ) and the temperature-sensing element  174  are bonded directly to the lateral wall  104  of the vessel  100 , at the same radial distance from the lateral wall  104 . A representative section of the protective layer  190  is bonded directly to the resistive heating element  144 , the temperature-sensing element  174  and the lateral wall  104 . Accordingly, the direct vessel heating area  140  is a single-layer device that forms an integral part of the vessel  100 , with the protective layer  190  optionally added. 
       FIG. 6  is an elevation view of the vessel  100  mounted in the aperture of a vessel support member  602  that is typically provided as part of a dissolution test apparatus. The vessel support member  602  typically includes a plurality of apertures  604  so that a like number of vessels  100  may be mounted and operated during a given dissolution test. The illustrated vessel support member  602  includes a recess  606  or like feature that receives the contact block  128  that extends from the flanged section  116  of the vessel  100 . The vessel support member  602  may include a set of contacts  608 , such as for example pins, which are configured for connection to the second set of contacts  136  of the contact block  128  during installation of the vessel  100 . By way of this interconnection and a wired or wireless communication link  610 , the electrical components of the vessel  100  may communicate with a vessel heating control system  612  that may be provided with the dissolution test apparatus. The use of the contact block  128  and corresponding features of the vessel support member  602  also ensure that the vessel  100  is precisely installed on the vessel support member  602  in the same location from one dissolution test to another, thereby ensuring consistency and validation of data acquisition. 
       FIG. 7  is a general schematic diagram of an example of vessel heating control system  700  that may be provided with a dissolution test apparatus such as described above to interface with one or more vessels  100  with integral direct vessel heating capability as described above, and optionally also with temperature probes  704  insertable into the vessels  100 . The vessel heating control system  700  generally includes an electronic controller  708  that communicates with various other components via suitable electrical lines or other types of communication links. That is, in the present schematic context, the illustrated communication lines represent wires or other physical types of electrical conduits or, alternatively, wireless transmissions of electromagnetic signals. Each vessel  100  includes one or more resistive heating element(s)  744  and temperature-sensing element(s)  774  as described above. The vessel heating control system  700  may include circuitry for presenting readouts of media temperature values based on measurement signals received from the temperature-sensing elements  774  of each vessel  100  and/or temperature probes  704  inserted in respective vessels  100  if temperature probes  704  are also provided. The vessel heating control system  700  may also include vessel heating control circuitry that communicates with or is part of the electronic controller  708 . As appreciated by persons skilled in the art, the electronic controller  708  may be processor-based and include analog and/or digital attributes as well as hardware, firmware and/or software attributes. The vessel heating control system  700  may also communicate with main control circuitry  712  of the dissolution testing apparatus over a dedicated communication link and hence can be housed within a suitable control unit of the dissolution testing apparatus such a head assembly. 
     The electronic controller  708  communicates the resistive heating elements  744  of the respective vessels  100  to heat the media contained in the vessels  100  by controlling the power supplied thereto. The electronic controller  708  is thus able to independently control the heating of each vessel  100 . The electronic controller  708  also communicates with each temperature-sensing element  774 , and each temperature probe  704  if provided, associated with each vessel  100 , and thus is able to monitor the temperatures of the respective volumes of media contained in each vessel  100  at any given instance of time based on measurement signals received from the temperature-sensing elements  774  and/or temperature probes  704 . The electronic controller  708  may be configured to continuously monitor media temperatures in real time, thus providing temperature readouts and heater control on a real-time basis or any other temporal or event-driven basis desired by the user. The temperature probe  704  may be utilized to provide feedback of temperature data for purposes complementary to the temperature-sensing elements  774 . As an example, the temperature probe  704  may be utilized to monitor start-up conditions. Once the set-point temperature in the vessel  100  has been reached and the system is stabilized, the temperature probe  704  may be removed from the vessel  100  and all further temperature monitoring handled by the temperature-sensing element  774  of the vessel  100 . The temperature probe  704  may also be utilized on an as-needed basis to verify that the temperature-sensing element(s)  774  and/or resistive heating element(s)  744  of a given vessel  100  are operating properly. Each temperature probe  704  may be inserted into and subsequently removed from the respective vessel  100  manually or by automated means provided by the dissolution test apparatus. In other implementations, the temperature-sensing elements  774  of the vessels  100  provide all temperature-monitoring tasks and separate temperature probes  704  are not utilized. 
     In the illustrated example, the electronic controller  708  also communicates with a peripheral readout or display device  716  such as an LCD screen or the like that is configured to display temperature readings taken from the vessels  100 , and may also display other information pertinent to the vessel heating process. The electronic controller  708  may also communicate with a peripheral input device  720  such as a keypad for enabling user input of vessel media set-point temperature, a variable or incremental temperature curve, and other appropriate system parameters for each vessel  100 . 
     In operation during a dissolution test, the user may operate the peripheral input device  720  to enter a set point temperature value, or a programmed temperature profile, according to which the media temperature in the vessels  100  installed at the dissolution test apparatus is to be maintained. The user has the additional option of setting different operating temperatures for each vessel  100  or each defined group of vessels  100 . The electronic controller  708  controls the operation of the heating elements  744  to ensure that an appropriate amount of power is being provided to maintain media temperature at the predetermined value. The temperature-sensing elements  774  measure and monitor media temperature in the vessels  100  by generating measurement signals periodically, continuously, or according to some other user-defined temporal or event-driven basis as described above, and transmit the measurement signals to the electronic controller  708 . In this manner, the electronic controller  708  is able to monitor the rise in media temperature in each vessel  100 , determine whether the media temperature in a given vessel  100  has stabilized at the previously inputted set point, and determine whether the media temperature has deviated from the set point or predetermined varying profile by greater than some predetermined error tolerance (e.g., ±0.05° C.) over some predetermined period of time (e.g., 10 seconds). When vessel media temperature needs to be adjusted to correct for a deviation, or needs to vary according to a predetermined profile, the electronic controller  708  transmits appropriate control signals to the heating elements  744  so that an appropriate amount of heat energy is transferred to the media. The electronic controller  708  may also utilize the measurement signals received from the temperature-sensing elements  774  and/or temperature probes  704  to determine whether a heating element  744  has malfunctioned, such as by failing to heat the vessel  100  or heating the vessel  100  in an excessive or uncontrolled manner. If such alert conditions are detected, the electronic controller  708  may operated to shut the heating system  700  down. 
       FIG. 8  illustrates an example of a method for fabricating a vessel  800  with direct vessel heating capability according to one implementation of the present disclosure. The vessel  800  is mounted to a lathe  804  capable of moving the vessel  800  in two or more directions. For example, the lathe  804  may translate the vessel  800  linearly in a direction  806  along the axis of the vessel  800  and rotate the vessel  800  in a direction  810  about the axis. A printing or drawing system  814  is utilized in this example. The printing system  814  may include a supply and transport device  818  (e.g., pump, reservoir, etc.) that fluidly communicates with a dispensing device  822  (e.g., a pen, hollow stylus, nozzle, etc.) to supply a flowable medium (electrical conductive ink or paste, etc.) to the hollow tip of the dispensing device  822 . The vessel  800  is positioned such that the tip of the dispensing device  822  is proximate to the outer surface of the vessel  800 . Flow of the flowable medium is established and the lathe  804  is operated to move the vessel  800  along two or more directions. Movement of the lathe  804  is programmed such that the dispensing device  822  prints a resistive heating element or temperature-sensing element  826  onto the vessel  800  in a desired pattern. In alternative implementation, the dispensing device  822  is also movable in two or more dimensions, or the dispensing device  822  is movable while the lathe  804  or other means for mounting the vessel  800  remains stationary during the printing process. 
       FIG. 9  is a perspective view of an example of a dissolution test apparatus  900  according to an implementation of the present disclosure. The dissolution test apparatus  900  may include a frame assembly  902  supporting various components such as a main housing, control unit or head assembly  904 , and a vessel support member (e.g., a plate, rack, etc.)  906  below the head assembly  904 . The vessel support member  906  supports a plurality of vessels  100  arranged in a desired array at a plurality of vessel mounting sites  912 . Each vessel  100  includes a direct vessel heating area  140  that forms an integral part of the vessel  100  and is configured as described above.  FIG. 1  illustrates eight vessels  100  by example, but it will be understood that more or less vessels  100  may be provided. The vessels  100  may be locked and centered in place on the vessel support member  906  by means such as ring lock devices or clamps (not shown). Alternatively, the vessels  100  themselves may be configured to have centering capability as noted above. Vessel covers (not shown) may be provided to prevent loss of media from the vessels  100  due to evaporation, volatility, etc. 
     The head assembly  904  may include mechanisms for operating or controlling various components that operate in the vessels  100  (in situ operative components). For example, the head assembly  904  typically supports stirring elements  914  that include respective motor-driven spindles and paddles operating in each vessel  100 . Individual clutches  916  may be provided to alternately engage and disengage power to each stirring element  914  by manual, programmed or automated means. The head assembly  904  also includes mechanisms for driving the rotation of the stirring elements  914 . The head assembly  904  may also include various other in situ operative components, two such operative components  918  and  920  being illustrated by example, and mechanisms for operating or controlling these operative components  918  and  920 . As examples, the operative components  918  and  920  may include, for any given vessel  100 , an optional temperature probe as described above, a fiber-optic probe for measuring analyte concentration in the media, media transport cannulas for dispensing and/or aspirating media to and from the vessel  100 , a pH detector, a dosage form holder (e.g., USP-type apparatus such as a basket, net, cylinder, disk, etc.), a video camera, etc. A dosage delivery module  926  may be utilized to preload and drop dosage units (e.g., tablets, capsules, or the like) into selected vessels  100  at prescribed times and media temperatures. Additional examples of mechanisms for operating or controlling various in situ operative components are disclosed for example in above-referenced U.S. Pat. No. 6,962,674, assigned to the assignee of the present disclosure. 
     The head assembly  904  may include a programmable systems control module for controlling the operations of various components of the dissolution test apparatus  900  such as those described above. As also noted above in conjunction with  FIG. 7 , the head assembly  904  may also include a vessel heating control system (module, circuitry, etc.) that interfaces with the components of the direct vessel heating area  140  of each vessel  100  as well as with a temperature probe if provided. Peripheral elements may be located on the head assembly  904  such as an LCD display  932  for providing menus, status and other information; a keypad  934  for providing user-inputted operation and control of spindle speed, temperature, test start time, test duration and the like; and readouts  936  for displaying information such as RPM, temperature, elapsed run time, vessel weight and/or volume, or the like. 
     The dissolution test apparatus  900  may further include one or more movable components for lowering operative components  914 ,  918 ,  920  into the vessels  100  and raising operative components  914 ,  918 ,  920  out from the vessels  100 . The head assembly  904  may itself serve as this movable component. That is, the entire head assembly  904  may be actuated into vertical movement toward and away from the vessel support member  906  by manual, automated or semi-automated means. Alternatively or additionally, other movable components  938  such as a driven platform may be provided to support one or more of the operative components  914 ,  918 ,  920  and lower and raise the components  914 ,  918 ,  920  relative to the vessels  100  at desired times. 
     In a typical operation, each vessel  100  is filled with a predetermined volume of dissolution media by pumping media to the media dispensing cannulas from a suitable media reservoir or other source (not shown). One of the vessels  100  may be utilized as a blank vessel and another as a standard vessel in accordance with known dissolution testing procedures. Dosage units are dropped either manually or automatically into one or more selected media-containing vessels  100 , and each stirring element  914  (or other agitation or USP-type device) is rotated within its vessel  100  at a predetermined rate and duration within the test solution as the dosage units dissolve. In other types of tests, a cylindrical basket or cylinder (not shown) loaded with a dosage unit is substituted for each stirring element  914  and rotates or reciprocates within the test solution. For any given vessel  100 , the temperature of the media may be maintained at a prescribed temperature (e.g., approximately 37±0.5° C.) if certain USP dissolution methods are being conducted or according to a predetermined temperature profile as described above. Media temperature is maintained by operating the components of the direct vessel heating area  140  of each vessel  100  as described above. The various operative components  914 ,  918 ,  920  provided may operate continuously in the vessels  100  during test runs. Alternatively, the operative components  914 ,  918 ,  920  may be lowered manually or by an automated assembly  904  or  938  into the corresponding vessels  100 , left to remain in the vessels  100  only while sample measurements are being taken at allotted times, and at all other times kept outside of the media contained in the vessels  100 . During a dissolution test, sample aliquots of media may be pumped from the vessels  100  via the media aspiration cannulas and conducted to an analyzing device (not shown) such as, for example, a spectrophotometer to measure analyte concentration from which dissolution rate data may be generated. In some procedures, the samples taken from the vessels  100  are then returned to the vessels  100  via the media dispensing cannulas (if provided) or separate media return conduits (if provided). Alternatively, sample concentration may be measured directly in the vessels  100  by providing fiber-optic probes as appreciated by persons skilled in the art. After a dissolution test is completed, the media contained in the vessels  100  may be removed via the media aspiration cannulas or separate media removal conduits. 
     In general, terms such as “communicate” and “in . . . communication with” (for example, a first component “communicates with” or “is in communication with” a second component) are used herein to indicate a structural, functional, mechanical, electrical, signal, optical, magnetic, electromagnetic, ionic or fluidic relationship between two or more components or elements. As such, the fact that one component is said to communicate with a second component is not intended to exclude the possibility that additional components may be present between, and/or operatively associated or engaged with, the first and second components. 
     It will be further understood that various aspects or details of the invention may be changed without departing from the scope of the invention. Furthermore, the foregoing description is for the purpose of illustration only, and not for the purpose of limitation—the invention being defined by the claims.