Patent Publication Number: US-2018029041-A1

Title: Improved Apparatus for Disintegration of a Solid and Method

Description:
CROSS REFERENCE TO RELATED APPLICATIONS 
     The present invention is related to the following patent applications, the disclosures of which are incorporated herein by cross reference.
     AU 2013204792 entitled APPARATUS METHOD AND SYSTEM FOR DISINTEGRATION OF A SOLID   PCT/AU2013/001147 entitled APPARATUS METHOD AND SYSTEM FOR DISINTEGRATION OF A SOLID   

     FIELD OF THE INVENTION 
     The present invention relates to improved apparatus for disintegration or dispersion of a solid in liquid using ultrasound energy and/or a method for the same. It relates particularly but not exclusively to disintegration of a solid being a pharmaceutical composition or medication in the form of a tablet, pill, capsule, caplet or the like for dissolving, dispersing, suspending, emulsifying and/or otherwise working into a fluid for consumption by drinking. 
     BACKGROUND TO THE INVENTION 
     A preferred method for administering medication orally is by consumption of a solid form of medication such as a tablet, pill, capsule, caplet or the like. Providing medication in tablet form utilises inexpensive production techniques, cheaper packaging and provides a relatively long shelf life for the medication. A further advantage is that each tablet may contain a known dosage of the medication which may be dispensed in unitary fashion from a bottle, blister pack or other packaging immediately prior to consumption. Where tablets are contained in a blister pack, unitary dispensing of each tablet dosage may prevent oxidation and/or contamination of the remaining dosages. In contrast, liquid formulations may have a relatively short shelf life and each dose may require individual measuring. 
     There are, however, problems associated with administering medication in tablet form. A large proportion of the population experiences difficulty swallowing tablets. This syndrome is known as dysphagia and is associated with taking certain forms of oral medication, particularly tablets. In some cases, tablets may be particularly large and difficult to swallow. For many patients, swallowing tablets may elicit a gag reflex. Other patients such as the mentally ill, the elderly and small children may be unable to swallow solid medication. This problem may also be experienced by patients who are unconscious and/or patients who use a feeding tube. 
     Historically, problems associated with swallowing whole tablets have been addressed by mechanical crushing of a solid medication. There are various ways to perform mechanical crushing of medication in solid form. One approach may involve use of a mortar and pestle to break up the tablet for dissolution or suspension in a liquid. Other approaches may involve placing the tablet inside a plastic envelope or sheath and hammering the sheath to break the tablet into small particles. These particles are then collected and worked into jam or other food to be consumed by the patient. 
     Drawbacks of these methods include inconsistent particle size and a risk of cross-contamination between medications. Although the devices may be cleaned between uses, this may add considerably to the time required to prepare and administer the medication and there may be a risk that cleaning may not be performed as regularly or as thoroughly as needed. Furthermore, there may be a risk that a recipient may receive a medication dosage which is less than an entire tablet, since residual tablet particles may be left behind in a crushing device. In addition, nurses and carers operating mechanical crushing devices may become exposed to the medication when in powdered form by inhaling or physical contact which may have health implications. 
     In view of these drawbacks, it would be desirable to provide an alternate approach for disintegrating medication in solid form for consumption, e.g. in a liquid. 
     A reference herein to a patent document or other matter which is given as prior art is not to be taken as an admission that that document or matter was known or that the information it contains was part of the common general knowledge as at the priority date of any of the claims. 
     Throughout the description and claims of the specification, the word “comprise” and variations of the word, such as “comprising” and “comprises”, is not intended to exclude other additives, components, integers or steps. 
     SUMMARY OF THE INVENTION 
     Viewed from one aspect, the present invention provides an apparatus for disintegration of a solid in a vessel containing liquid, the apparatus comprising: a control unit; an ultrasound transducer for generating ultrasonic energy under control of the control unit; a coupling medium in communication with the ultrasound transducer and adapted to receive the vessel and through which ultrasonic energy is transferred to the contents of the vessel such that in use the ultrasonic energy causes disintegration of the solid into the liquid contained in the vessel; and an agitating mechanism adapted to agitate the disintegrated solid in the liquid contained in the vessel. 
     The agitating mechanism may include a paddle having a coating of a flavouring material. The coating material may include neutral gelatine, flavouring concentrate and/or artificial sweetener. 
     The apparatus may include a cover member for closing an opening in the vessel, wherein the cover member includes the agitating mechanism. The cover member may include a force actuator adapted to apply a force to the vessel to enhance coupling between the vessel and the coupling medium. The cover member may be operable from an open configuration to a closed configuration in two or more stages to maintain alignment with the vessel. 
     The apparatus may include means to detect dissolution of the paddle coating material. The means to detect dissolution of the paddle coating material may include at least one of an optical means, an electrical conductivity means and a fudicial marker. 
     The apparatus may include means to detect presence of the paddle in the agitating mechanism. The means to detect presence of the paddle may include at least one of a micro-switch associated with the agitating mechanism, means for monitoring current drawn by an associated drive motor and means for monitoring a break in an optical beam. 
     The coupling medium may include a water bath. The apparatus may include means for maintaining a predetermined level of the coupling medium. The ultrasound transducer may communicate ultrasonic power to the coupling medium by way of an ultrasound waveguide or the like. 
     The control unit may control the ultrasound transducer to operate in a swept frequency mode in which ultrasonic energy frequency fluctuates between a resonant frequency and a first non-resonant frequency and optionally, a second non-resonant frequency. 
     The resonant frequency may be substantially  42  kHz and the first and second non-resonant frequencies may be substantially ± 2  kHz relative to the resonant frequency. 
     The swept frequency mode may be one or more of: cyclical; random; and dynamically controlled by the control unit based one or more sensor inputs. The apparatus may include cooling means for maintaining temperature of the apparatus and/or the contents of the vessel in an acceptable range during operation of the apparatus. The vessel may include a marking to indicate a fill level for a liquid added to the vessel. 
     Another aspect of the invention provides a method for disintegrating a solid in a vessel including the steps of providing a volume of liquid together with the solid in the vessel; providing an ultrasound transducer for generating ultrasonic energy; loading the vessel containing the solid and liquid into a coupling medium in communication with the ultrasound transducer; transferring the ultrasonic energy to the contents of the vessel to cause disintegration of the solid into the liquid contained in the vessel; and agitating the disintegrated solid in the liquid contained in the vessel. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Preferred embodiments of the present invention will now be described with reference to the accompanying drawings. It is to be understood that the embodiments illustrated are provided by way of example only. The particularity of these embodiments does not supersede the generality of the preceding parts of the description. In the drawings: 
         FIG. 1  shows apparatus according to one embodiment of the present invention; 
         FIG. 2  shows a graph of an ultrasonic energy signal in swept mode, according to one embodiment of the invention; 
         FIG. 3 a    shows a flow diagram including steps of a method of disintegrating a solid form of medication according to one embodiment of the present invention; 
         FIG. 3 b    shows a flow diagram including steps of a method of disintegrating a solid form of medication according to another embodiment of the invention; 
         FIG. 3 c    shows a flow diagram including further steps which may precede the method steps outlined in  FIGS. 3 a    and  3   b;    
         FIGS. 4 a    shows a side view of a receptacle securing device; 
         FIGS. 4 b  and 4 c    show side and perspective views of a receptacle securing device with mechanical stirrer; 
         FIG. 5  shows apparatus according to another embodiment of the present invention including a mechanical stirring mechanism; 
         FIG. 6  shows detection of dissolution of a drug tablet; 
         FIG. 7  shows detection of dissolution of a flavouring paddle coating by means of electrical conductivity; 
         FIG. 8  shows a fudicial marker applied to a paddle; 
         FIG. 9  shows detection of dissolution of a paddle coating by optical means; and 
         FIG. 10  shows a method of regulating level of a water bath. 
     
    
    
     DETAILED DESCRIPTION 
     Throughout this description, the terms “tablet” and “drug tablet” will be used to describe any solid form of medication or pharmaceutical preparation provided in tablet, pill, capsule, caplet or other such like form which is amenable to disintegration. Although some such tablets have coatings or layered formulations for slow release of active constituents, the method and apparatus of the present invention may still be useful for disintegration of the tablet into a form which can be dispersed, suspended, dissolved, emulsified or otherwise combined into a liquid for oral consumption. 
     Although the apparatus and method are described herein in the context of disintegration of a solid form of medicament, it is to be understood that the present invention and the claims appended hereto are not so limited. The present invention has applicability to disintegration of non-medicament solids and/or mixing of liquids and or solids/particles in a liquid. 
     Referring to  FIG. 1  there is shown apparatus  100  for disintegration of a solid, such as solid medication in the form of a tablet, according to an embodiment of the present invention. Apparatus  100  includes housing  102  which is preferably manufactured from durable plastics or other material which can be wiped with a cloth and which can be manufactured and shipped in a cost effective manner. Although housing  102  has little involvement with functionality of apparatus  100  (other than a cover member as discussed below), it is desirable that housing  102  be designed with usability in mind. Thus it may be desirable that housing  102  has attractive appearance akin to a household appliance, rather than a device used in a medical setting. 
     Housing  102  includes opening  122  into which drug vessel  120  containing a tablet and liquid may be received. A cover member  116  is provided to close opening  122  during use so that drug vessel  120  is not inadvertently removed before disintegration is completed and/or to avoid accidental spillage or contamination. Drug vessel  120  may be fitted with a sealing lid prior to being inserted into apparatus  100  to limit risk of liquid being spilled from inside drug vessel  120  and concomitant loss of medication. After the tablet has been disintegrated, drug vessel  120  may be removed from apparatus  100 , the sealing lid may be removed from drug vessel  120  and the contents, which include the disintegrated drug tablet, may be consumed by drinking. 
     Housing  102  includes power supply  104  and control unit  106 . Power supply  104  may be coupled to an external AC power source and may regulate power to provide voltage as needed to control unit  106 , ultrasonic transducer  108 , display  114  and other powered components in apparatus  100 . Preferably, power supply  104  includes an auto-regulating supply to minimize power required to maintain ultrasonic vibrations generated by transducer  108  at an amplitude specified by control unit  106 . 
     Control unit  106  is operably coupled to ultrasound transducer  108  and other components such as display  114  and actuator  124  for cover member  116 , each of which may be controlled by an electronic signal. Control unit  106  comprises control electronics preferably embodied in firmware written to read only memory (ROM) or programmable ROM (PROM) of a microprocessor as is known in the art, although it is to be understood that control electronics may alternatively be provided on a standalone computer or other memory-processor device operably connected to apparatus  100  and its components. 
     Ultrasound transducer  108  generates ultrasonic energy under control of control unit  106  and is coupled to coupling element or sonotrode  112  via amplifier  110 . Amplifier  110  amplifies the ultrasound signal from transducer  108  to an intensity sufficient to cause disintegration of a tablet in drug vessel  120  within a reasonable time frame. 
     Amplification may be by a factor of e.g. 10 or more where a low intensity ultrasound signal is emitted from transducer  108 . Preferably, acousto-mechanical amplification required may be less than ×10, and more preferably, less than x  5  so that amplifier  110 , whose geometry may be dictated by the amount of amplification, may be accommodated in apparatus  100  for use on a bench top or trolley. For a standard 50 W transducer, an amplification factor of about 3 has been found sufficient as this may give rise to disintegration times of less than about 6 minutes for a range of different tablet types. Preferably, the time required to achieve disintegration is less than 10 minutes and more preferably less than 6 minutes. A disintegration time of about 3 to 6 minutes may be acceptable in many settings although a disintegration time of one minute or less may be desirable e.g. for high throughput apparatus. Shorter disintegration times may be achieved by using a higher intensity/higher amplitude ultrasound signal. 
     Ultrasound transducer  108  may be of any suitable type although a piezoelectric transducer is preferred, having a resonant frequency greater than 20 kHz which is accepted to be an upper limit of human hearing. In one embodiment, ultrasound transducer  108  may have a resonant frequency of about 40 kHz although such frequency is not to be taken as prescriptive and transducers having different operational ranges may be utilised while the design of other components such as amplifier  110  and sonotrode  112  may be modified to achieve tablet disintegration in a desired time. 
     Resonant frequencies in a range 20-45 kHz may be used. However, as resonant frequency approaches a lower limit of this range, likelihood of human awareness of the ultrasonic signal may increase. Thus, use of apparatus  100  at lower frequencies may cause irritation to persons in the vicinity of apparatus  100  when in use. In addition, in a preferred embodiment sonotrode  112  may have a circumference equivalent to about one wavelength of energy generated by ultrasound transducer  108  at resonance. Since wavelength is inversely proportional to frequency, decreasing resonant frequency may increase the diameter of sonotrode  112  for a given sonotrode material. 
     Sonotrode  112  may be configured to receive drug vessel  120  containing the solid to be disintegrated. Ultrasonic energy may be coupled, through sonotrode  112  and wall of drug vessel  120 , to the contents. Since drug vessel  120  may sit inside sonotrode  112  to achieve this coupling, a relatively large sonotrode diameter may require a drug vessel  120  such as a cup that may be too large for many users to handle. Moreover, an overly large sonotrode  112  may in turn require an unacceptably large apparatus  100  which may limit appeal to end users. 
     Conversely, increasing ultrasound frequency may produce a decrease in diameter of sonotrode  112  which may, in turn, require a decrease in diameter of drug vessel  120  at least at a region which fits into and couples with sonotrode  112 . This may have implications for receptacle usability eg. (a cup which is too small can be just as difficult to handle and drink from as a cup which is too large) and also for receiving an acceptable volume of liquid. Thus, embodiments of the present invention may adopt a trade-off wherein a readily available ultrasound transducer able to produce a resonant frequency of about  42  kHz may be selected. 
     Alternatively or additionally, ultrasound transducer  108  may be amenable to operating at a range of frequencies, and the operating frequency may be controlled by control unit  106 , based on resonant frequency of apparatus  100  including drug vessel  120  and its contents when placed in sonotrode  112 . Control unit  106  may determine automatically an optimal frequency for disintegration of a solid within drug vessel  120 , and may control ultrasound transducer  108  to generate ultrasonic energy at an optimal frequency. Such an arrangement may include feedback control electronics which may monitor e.g. current being drawn as an indicator of whether or not apparatus  100  is operating at resonance. Other methods for determining resonance of apparatus  100  and/or matching operating frequency of ultrasound transducer  108  may be utilised, as may be understood by persons of ordinary skill in the art. 
     In one embodiment, ultrasound transducer  108  may operates in a simple mode, generating energy at about a resonant frequency. The ultrasonic signal may be coupled, through amplifier  110  and sonotrode  112 , to drug vessel  120  and its contents comprising one or more medication tablets together with a liquid such as water. Unless the particles in the drug tablet are held together very firmly they will tend to separate due the immense accelerations generated by high pressure changes caused by ultrasonic vibrations. 
     During testing of the apparatus of the present invention, it has been discovered that particulate matter which forms as the drug tablet disintegrates may group together inside the drug vessel  120 , most notably in the crease where the wall of vessel  120  meets the floor. This is undesirable since reflective and diffractive losses may occur thereby limiting efficiency of continued ultrasonic treatment by apparatus  100 . Furthermore, when the disintegration process is complete it can become difficult to dislodge particles from the drug vessel  120  when the contents are consumed orally. 
     To address this problem, it may desirable to agitate the contents of drug vessel  120  such that they become properly dispersed within the liquid or at least removed from the crease area. Agitation may be provided in any suitable manner and by any suitable means. In one embodiment a mechanical agitator may be associated with cover member  116 . The mechanical agitator may include a steel hook driven via a stepper motor as shown in  FIGS. 4 b  and 6 c    and/or a stirring mechanism as shown in  FIG. 5 . 
     In another embodiment, agitation of contents of drug vessel  120  may be achieved by operating ultrasound transducer  108  in a swept frequency mode.  FIG. 2  shows a graph representing a driving signal as may be applied to ultrasound transducer  108  in swept frequency mode, according to an embodiment of the present invention. In swept frequency mode the signal driving ultrasound transducer  108  and hence the ultrasonic energy emitted from transducer  108 , fluctuates between a resonant frequency and a non-resonant frequency. In one embodiment, swept frequency mode operation may involve fluctuations between the resonant frequency and a non-resonant frequency either side of the resonant frequency. The non-resonant resonant frequency may be e.g. ±0.1%, ±0.5%, ±1%, ±2%, ±3%, ±5% or even ±10% of the resonant frequency. Experimental data suggests that for a transducer resonant frequency of about 42 kHz, the non-resonant end point frequencies employed in swept frequency mode may be approximately 5% or 2 kHz either side of the resonant frequency such that the ultrasonic frequency signal emitted by transducer  108  oscillates between about 40 kHz and 44 kHz. 
     During swept frequency operation, control unit  106  controls the frequency applied to ultrasound transducer  108  to increase and decrease around the resonant frequency. Sweeping of frequencies may occur at any rate. In one embodiment, the sweep cycle may be approximately 0.3 to 2 Hz such that frequency sweeps between resonance and a predetermined non-resonant frequency every 0.5 seconds to every 2 or 3 seconds, although longer or shorter sweep cycles may be implemented. Frequency sweeping may be cyclical or random, and/or may be adjusted dynamically and preferably automatically by control unit  106  according sensor inputs providing feedback to control unit  106  indicating the extent to which particles disintegrated from a solid may require further agitation within drug vessel  120 . 
     As the drive signal frequency approaches the resonant frequency, the amplitude of ultrasound vibrations may increase. At the resonant frequency, apparatus  100  may apply maximum amplitude ultrasonic vibrations to drug vessel  120 . As the drive signal frequency is further increased, apparatus  100  may move past its resonance point and the amplitude of ultrasound vibrations may decrease. 
     Control unit  106  may be configured with a predetermined upper limit (e.g. the maximum frequency) for a drive signal. Once the frequency of the drive signal reaches a predetermined upper limit, control unit  106  may begin to decrease the frequency. As the decreasing frequency approaches the resonant frequency the amplitude of ultrasound vibrations will again increase until apparatus  100  is operating in resonance mode. 
     Preferably, control unit  106  further decreases the frequency of the drive signal. As the frequency of the drive signal is decreased below resonance, the amplitude of ultrasound vibrations may decrease again. Control unit  106  may be configured with a predetermined lower limit (i.e. minimum operational frequency) for a drive signal. Once the frequency of the drive signal reaches a predetermined lower limit control unit  106  may begin to increase the frequency. As the increasing frequency approaches the resonant frequency, the amplitude of ultrasound vibrations may again increase until apparatus  100  is operating in resonance mode. Sweeping the frequencies between resonance and one or more predefined non-resonance frequencies may continue. 
     Operating apparatus  100  in swept frequency mode may agitate the contents of drug vessel  120  and decreases the extent to which disintegrated particles group together in the drug vessel. This may improve efficiency with which the solid is disintegrated. 
     Preferably, apparatus  100  includes a force actuator  126  which applies force to drug vessel  120  when loaded in sonotrode  112  to enhance coupling between sonotrode  112  and a wall of drug vessel  120 . This may maximise transference of ultrasonic energy to the contents of drug vessel  120 . In the embodiment illustrated in  FIG. 1 , force actuator  124  is contained within cover member  116  for closing opening  122  in housing  102  although any actuator suitable for applying a coupling force between drug vessel  120  and sonotrode  112  may be utilised. 
     In the illustrated arrangement, force actuator  124  may include an internally sprung membrane suitable for applying a downward force of approximately 800 to 1,000 grams through vessel  120  when cover member  116  is in a closed position. Force actuator  124  may limit the extent to which vessel  120  hovers or moves within sonotrode  112  during operation. Applying a greater downward force into sonotrode  112  may improve coupling (i.e. energy transfer into vessel  120 ) until damping occurs. A downward force greater than 1,000 g may be used to improve coupling although this may negatively impact overall design. For example, in the case of downward forces greater than about 1000 grams in embodiments where a mechanical (e.g. spring loaded) actuator is used to release cover member  116 , design and operation may become complex. 
     Preferably, cover member  116  including force actuator  124  may be operable from an open configuration ( FIG. 1 ) to a closed configuration (not shown) in two stages to maintain alignment of vessel  120  within sonotrode  112  particularly during application of a coupling force. In one embodiment, cover member  116  may utilise a two-stage actuator  124  during closure. In one stage, cover member  116  may pivot around hinge  124   a ; in another stage, cover member  116  may be lowered into opening  122  via vertical actuator  124   b . Vertical actuator  124   b  may be provided by resilient, pneumatic, hydraulic, electronic and/or other means and may operate manually via mechanical means or automatically, under control of control unit  106  to open and close cover member  116 . 
     It is to be understood that a range of different closure arrangements may be provided which facilitate closure of opening  122  while maintaining alignment of vessel  120  within sonotrode  112 . One arrangement may include a securing device for vessel  120  as shown in  FIG. 4 a    including a flared body adapted to be received in the mouth of vessel  120 . The flared body may provide better lateral alignment of vessel  120  within sonotrode  112 . The flared body may also include springs as shown in  FIGS. 4 a  and 4 b    to provide additional downward force to vessel  120 . Another arrangement may involve a sliding closure in combination with vertical actuator  124   b.    
     Display  114  may be provided to convey information to a user of apparatus  100 . Display  114  may include a simple LED or LED array configured to illuminate in a particular colour scheme or pattern to indicate when apparatus  100  is in use and/or when disintegration process is complete i.e. the tablet has been disintegrated into the liquid in vessel  120  and is ready for oral consumption. In a more sophisticated embodiment, display  114  may incorporate an LED or LCD screen controlled by control unit  106  to present a user with information such as time remaining until disintegration is complete and control unit  106  may be pre-programmed with personalised medication data, to present a user with information pertaining to relevant dosage regimes, the time and date and other useful information. 
     Where apparatus  100  is intended for use in the home, control unit  106  may be connected with a remote monitoring station via a local area network (LAN) or wide area network (WAN), telephone line, wireless network or the like. Such connection may be used to communicate compliance information to a remote station as may be located e.g. with a general medical practitioner, nurse or monitoring service, to supervise a user&#39;s compliance with prescribed medication regimes. 
     Apparatus  100  may also be fitted with loudspeaker  130  operated under control of control unit  106  to give audible alerts to a user to indicate when the disintegration process is complete. Loudspeaker  130  may be operable to provide an audible alert to indicate when a medication dosage is due. The audible alert may be in the form of an alarm, beep, chime or synthesised or pre-recorded voice message. 
     In a preferred embodiment apparatus  100  may also include inputs  132  operable by a user to input data to control unit  106 . Inputs  132  may be in a form of buttons, a keypad or a touch-screen incorporated into display  114 . Inputs  132  may also include a USB or memory card slot so that control unit  106  may receive personalised medication regime information and/or software and system upgrades. 
     Cooling unit  128  may be provided to maintain an acceptable temperature within vessel  120 . This may be particularly useful where high intensity ultrasonic energy is applied to minimise disintegration time, or where disintegration times are long and cause the contents of vessel  120  to approach a limit of acceptable heating. Cooling unit  128  may also cool apparatus  100  e.g. by way of a fan. Cooling unit  128  may be thermostatically controlled or may operate according to signals from control unit  106 . 
     Referring to  FIG. 3 a   , a flowchart illustrates steps in a method of disintegrating a solid medication or pharmaceutical substance in the form of a tablet according to an embodiment of the present invention. In step  302  a drug vessel ( 120 ) is provided containing volume of liquid and a tablet to be disintegrated. A volume of around 40 ml is useful for disintegration of most tablet types although initial testing indicates that a larger liquid volume (e.g. 60 ml) may be required as more tablets are placed inside the vessel for disintegration. 
     More than one tablet may be disintegrated in the drug vessel simultaneously, although this may require higher intensity treatment and/or longer sonication times (and larger liquid volumes as discussed above) to achieve adequate disintegration of the tablets. In step  304  the drug vessel containing the liquid and the tablet is loaded into the sonotrode ( 112 ) inside the apparatus and in step  308 , ultrasonic energy generated by ultrasound transducer  108  is applied through the wall of the drug vessel to its contents. The ultrasonic vibrations distort the sonotrode causing pressure changes inside the vessel and disintegration of the tablet into particles (step  312 ). The disintegration process concludes (step  314 ) when the ultrasound transducer ceases operation. 
       FIG. 3 b    is a flow chart illustrating the method of  FIG. 3 a    with additional steps that may be performed in another embodiment of the present invention. Here, in a step  306  a coupling force is applied to the vessel, urging the vessel into the sonotrode to minimise movement during operation thereby maximising ultrasonic energy transference to the contents of the vessel. The coupling force may be about 800 to 1,000 grams downward force and may be applied by a sprung interior membrane of a cover member which covers the vessel when loaded in the apparatus. Preferably, the drug vessel is sealed closed with a removable lid prior to being loaded into the sonotrode. Thus, the coupling force may be applied through the lid and/or through the rim of the opening of the vessel. In a preferred embodiment, control unit  106  may control operation of ultrasound transducer  108  to operate in swept frequency mode (step  310 ) to minimise likelihood of disintegrated particles grouping together inside the vessel. 
     
       
         
           
               
               
             
               
                   
                 TABLE 1 
               
             
            
               
                   
                   
               
               
                   
                 Cycle Time 
               
            
           
           
               
               
               
               
            
               
                 Product 
                 3.5 minutes 
                 4.5 minutes 
                 6.5 minutes 
               
               
                   
               
               
                 Diabex Tablet 500 mg 
                 Dispersed 
                   
                   
               
               
                 Losec Tablet 20 mg 
                 Dispersed 
               
               
                 Panadeine Forte Tablet 
                 50% Dispersed 
                 60% Dispersed 
                 Dispersed 
               
               
                 Valium Tablet 5 mg 
                 Dispersed 
               
               
                 Coversyl Plus Tablet 
                 Dispersed 
               
               
                 5.1.25 mg 
               
               
                 Maxolon Tablet 10 mg 
                 Dispersed 
               
               
                 Stemetil Tablet 5 mg 
                 Dispersed 
               
               
                 Zocor Tablet 40 mg 
                 60% Dispersed 
                 Dispersed 
               
               
                 Tenormin Tablet 50 mg 
                 Dispersed 
               
               
                 Motilium Tablet 10 mg 
                 Dispersed 
               
               
                 Karvezide Tablet 300/ 
                 50% Dispersed 
                 80% Dispersed 
                 Dispersed 
               
               
                 12.5 mg 
               
               
                 Rulide Tablet 150 mg 
                 Dispersed 
               
               
                 Plavix Tablets 75 mg 
                 60% Dispersed 
                 Dispersed 
               
               
                 Panamax Tablets 500 
                 Dispersed 
               
               
                 mg x 2 
               
               
                 Nurofen Caplets 200 mg 
                 Dispersed 
               
               
                 Lipitor Tablet 20 mg 
                 Dispersed 
               
               
                   
               
            
           
         
       
     
     Table 1 above provides results from use of apparatus  100 , according to an embodiment of the invention, for disintegration of a variety of solid medications types in a liquid volume of 40 ml. Disintegration and satisfactory dispersion of disintegrated medication within the liquid was achieved in around 3.5 minutes for most medications. All of the medication types tested were disintegrated and dispersed within the liquid in less than 6.5 minutes. 
     In some embodiments, it may be desirable to use water as the liquid into which the solid is disintegrated and becomes dispersed, dissolved or emulsified. However, many forms of solid medication have a taste which is unpleasant. Accordingly, it may be desirable to use a flavoured liquid as the dispersion medium in order to mask or at least improve the taste of the liquid. 
     In a particularly preferred embodiment a mechanical agitating mechanism may be employed as shown in  FIG. 5  including a paddle coated with a flavouring material. Alternatively, a flavouring powder, liquid or other form of additive may be added to the vessel ( 120 ,  53 ) to mask the unpleasant taste of some medications. Where a flavouring pellet is used, this may be placed in the vessel, along with the solid medication to be disintegrated, prior to sonication. This may ensure that the flavouring pellet is adequately dissolved or dispersed into the liquid, together with the medication. 
     Ultrasound transducer  108  may be operated under control of control unit  106  which may be pre-programmed to operate transducer  108  for a fixed duration. This duration may be set in firmware according to the type of tablet to be disintegrated. In one embodiment, control unit  106  may be pre-programmed with a range of disintegration times required for disintegration of various tablet types. A user may use inputs  132  to select the tablet type to be disintegrated before loading vessel  120  containing the tablet into sonotrode  112  and closing cover member  116 . Control unit  106  may then control ultrasound transducer  108  to deliver ultrasonic energy for a pre-programmed duration required for that tablet. 
     Alternatively, control unit  106  may determine automatically the time required to disintegrate a tablet in vessel  120 . Control unit  106  may also determine automatically an optimal frequency for disintegration of the tablet and optionally, cause transducer  108  to operate in a swept frequency mode. 
     In a preferred embodiment, apparatus  100  may include one or more optical sensors, accelerometers or the like for detecting the condition of the contents of vessel  120  and specifically, the degree to which the solid has been disintegrated and/or dispersed. The sensors may provide a feedback signal to control unit  106  which in turn may be used to control operation of ultrasound transducer  108 . When the sensor signals indicate that the contents of vessel  120  are sufficiently disintegrated (e.g. to a particle size able to be passed through a No.  10  mesh sieve), then control unit  106  may automatically stop operation of ultrasound transducer  108 . 
     Alternatively and/or additionally the sensors may provide a feedback signal to control unit  106  which indicate the extent to which particles in vessel  120  have been mixed. When the sensor signals indicate that the contents of vessel  120  require further mixing (e.g. the suspension is inconsistent) control unit  106  may operate ultrasound transducer  108  in swept frequency mode for further agitation of the contents of vessel  120  and/or may activate a mechanical agitator. When the sensor signals indicate that there has been adequate mixing, control unit  106  may automatically stop operation of ultrasound transducer  108  in swept frequency mode and/or the mechanical agitator and may stop operation of ultrasound transducer  108  altogether. 
     In a preferred embodiment, when disintegration of the tablet is complete (step  314 ) control unit  106  may operates loudspeaker  130  to provide an audible alert to a user (step  316 ) to indicate that the tablet has been disintegrated and is ready for oral consumption by drinking the liquid contents of the vessel. The audible alert may be in the form of an alarm, beep, chime or synthesised or pre-recorded voice message. Alternatively or additionally, control unit  106  may operate display  114  to provide a visible cue at completion of the disintegration process. 
     In one embodiment, the method steps of  FIGS. 3 a  and 3 b    may be preceded by the steps of  FIG. 3 c    controlled by control unit  106  which has been pre-programmed with personalised medication data including patient dosage regimes. In this embodiment, control unit  106  may include a clock and may continuously poll to determine whether a medication dosage is due (step  300 ). If a dosage is due, control unit  106  may actuate cover member  116  to open apparatus  100  in step  301  a and in step  301   b  may provide an audible alarm through loudspeaker  130  to indicate that medication is due. The user may respond by providing a vessel  120  containing liquid and one or more tablets to be disintegrated (step  302 ) and may load the vessel  120  into sonotrode  112  (step  304 ) according to the method of  FIG. 3 a    or  3   b.    
       FIG. 4 a    shows a side view of a securing device  40  for a vessel  120  that may provide an alternative to cover member  116  and/or force actuator  126  shown in  FIG. 1 . Vessel securing device  40  includes a flared body  41  adapted to be received in the mouth of vessel  120 . The purpose of flared body  41  is to provide better lateral location or alignment for vessel  120  inside housing  102 . Approximate location or alignment of vessel  120  may be provided by opening  122  in housing  102 . 
     Vessel securing device  40  includes a plurality of springs  42  -  44  adapted to interface with cover member  116 . The purpose of spring  42 - 44  is to provide additional downward force onto vessel  120  as this may help to ensure good coupling of ultrasonic energy between the floor of vessel  120  and sonotrode  112 . 
       FIGS. 4 b  and 4 c    are side and perspective views of a vessel securing device  45  that adds a mechanical agitator  46  to securing device  40  of  FIG. 4 a   . Mechanical agitator  46  comprises a stainless steel hook adapted to agitate or stir dissolved contents in vessel  120 . Agitator  46  is driven via direct coupled stepper motor  47  shown inside a hub or pocket of body  41 . Agitator  46  may be actuated to more thoroughly disperse or dissolve disintegrated contents such as medication in vessel  120  and/or minimize aggregation of disintegrated contents. 
       FIG. 5  shows apparatus according to another embodiment of the present invention including a mechanical stirring mechanism.  FIG. 5  shows apparatus  50  including ultrasonic receptacle  51 , partially filled with water bath  52  and/or another acoustically conductive medium. A drug vessel  53  is placed in water bath  52  with drug tablet(s)  54  placed within drug vessel  53  and water/liquid  55  added to drug vessel  53 . Drug vessel  53  may have one or more drug tablets  54  placed in it. 
     Apparatus  50  includes a vessel securing device having stirrer boss  56  with cover member  57  or similar to help secure and apply downward pressure or force on drug vessel  53  and/or to ensure contact with ultrasonic receptacle  51 . Boss  56 / lid  57  may include an over-return spring or a magnetic means (not shown) to apply downward pressure or force. Ultrasonic power may be delivered to receptacle  51  from an ultrasonic transducer (not shown) via waveguide  58 . Boss  56  may include a mechanical stirring mechanism including paddle  59 . Paddle  59  may be user replaceable. 
     Referring to  FIG. 6 , detection of dissolution of drug tablet  54  may be achieved via attenuation of transmitted light, and/or back-scatter, side-scatter or reflection of light. In one form light emitted from optical emitter  61  such as an LED may pass through water/liquid  55  in drug vessel  53  and may scatter ( 62 ) when it strikes particles  63  of a dissolved drug tablet  54 . The scattered light  62  may be detected by way of detectors  64 ,  65 ,  66  respectively. 
     Paddle  59  may include a coating of flavouring material  70  as shown in  FIG. 7 . Flavouring material  70  may be dissolvable in water/liquid  55  contained in drug vessel  53 . Flavouring material  70  may be arranged to have a dissolve time that is commensurate with that of drug tablet  54  that is to be dissolved. Detection of dissolution of paddle coating material  70  may be by optical means and/or electrical conductivity means. 
     Electrical conductivity means may include two metalized strips  71  placed on the surface of paddle  59  before a coating of flavouring material  70  is applied. This may enable detection of dissolution of flavouring material  70  in water/liquid  55  by utilizing insulating properties of flavouring material  70  to impede electrical conduction. Upon dissolution of flavouring material  70 , electrical conductivity between strips  71  will increase due to contact with water/liquid  55  which is more conductive than material  70 . The increase in conductivity or reduced resistance between strips  71  may be detected in any suitable manner and by any suitable means known in the art. 
     Alternatively an optical method may be used to detect dissolution of flavouring material  70  from paddle  59  including by way of fiducial marker  80  as shown in  FIG. 8  or similar. Fudicial marker  80  may be visible only when paddle material  70  has been substantially or fully dissolved. Fiducial marker  80  may include but is not limited to a laser etched pattern and/or text. 
     Alternatively fiducial marker  80  may be formed by or may include a highly reflective strip or coating  90  as shown in  FIG. 9 . Reflective strip or coating  90  may be exposed when paddle coating  70  has been dissolved. Exposure of strip or coating  90  may ensure that paddle  59  is not re-used after flavouring material  70  has been dissolved. In this implementation light emitted from source  91  such as an LED may be reflected from strip or coating  90  and may be detected by optical detector  92  when paddle  59  rotates in water/liquid  55  contained in drug vessel  53 . 
     Flavouring material  70  may be applied to paddle  59  in any suitable manner and by any suitable means. Paddle  59  may be made of plastics, wood and/or another material. Flavouring material  70  may be applied to paddle  59  by a process including spray painting, brush coating, dipping or drying the flavouring material  70  in a mould or by press/forging or otherwise forming flavouring material  70  onto paddle  59 . 
     One method of coating flavouring material  70  onto paddle  59  may include producing a batch of slurry of flavouring material with ingredients including neutral flavoured gelatine, flavouring concentrate such as peppermint essence and/or artificial sweetener. Paddle  59  may be dipped into this slurry of flavouring material and then removed and allowed to dry by natural convection, forced air or heated forced air convection. 
     Presence of paddle  59  in stirrer boss  56  may be detected in any suitable manner and by any suitable means. The latter may include a micro-switch (not shown) located in boss  56  and/or or by measuring drag applied to an associated drive motor. Drag may be detected by measuring magnitude of current supplied to the drive motor, and/or by detecting a break in an optical beam as it momentarily passes, not unlike the arrangement shown in  FIG. 9  for detecting dissolution of flavouring coating material  70 . 
     The level of water bath  52  used to couple ultrasonic energy into drug vessel  53  may be regulated in any suitable manner or by any suitable means. Referring to  FIG. 10  a float valve  90  or a larger external reservoir  91  may be employed. If the volume of reservoir  91  is sufficiently large then the effect on level of water bath  52  by placement of drug vessel  53  in ultrasonic receptacle  51  may be minimised. Also a reduction of level of water bath  52  from natural or induced vaporisation may be reduced by presence of a greater volume of water in reservoir  91 . Level of water bath  52  may be maintained at a substantially constant level by way of tube  92  and may be viewed by way of indicator  93 . 
     Vessel  120 / 53  containing a tablet may be loaded into apparatus  100 / 50  manually. Alternatively, apparatus  100 / 50  may be fully automated, automatically loading vessel  120 / 53  into the sonotrode  112 / receptacle  51  and filling with the required volume of liquid. The apparatus may additionally be fitted with a secure container holding tablets or other medication units to be loaded into vessel  120 / 53  automatically e.g. according to a personalised medication regime pre-programmed into control unit  106 , or upon receiving input from a user via inputs  132 . 
     In one embodiment, apparatus  100 / 50  may be suitable for use in the home, e.g. on a kitchen or bathroom bench. Apparatus  100 / 50  may be powered from a mains power outlet or it may be embodied in a mobile unit operated by battery. A battery powered unit may be suitable for use in environments where mobility is desirable and in such arrangement it is preferred that the battery is rechargeable by connecting apparatus  100 / 50  to mains power when it is not in use although replaceable or interchangeable, rechargeable batteries may be employed. 
     Because the disintegration process involves application of ultrasonic energy having known characteristics, tablets may be disintegrated in a controlled and predictable manner. Thus, there may be consistency in the size of the particles which result from the disintegration process. This is typically not the case for mechanical tablet crushing systems which adopt manual force to break up the tablet. The arrangement of the coupling element (sonotrode) or medium and cup vessel or design may also give rise to improved efficiency over existing tablet crushing methods. 
     It is to be understood that various modifications, additions and/or alterations may be made to the parts previously described without departing from the ambit of the present invention as defined in the claims appended hereto.