Abstract:
A method of cleaning a metered dose spray device, and a cleaning composition for such cleaning, to prevent the device from becoming clogged with medication. The method includes removing the aerosol can containing the medication from the actuator, placing an aerosol can containing a cleaning composition in the actuator, and dispensing the cleaning solution through the actuator. The residual medication is thereby removed from the actuator. A sufficiently small quantity of cleaning composition remains in the actuator so that the cleaning composition itself will not clog the actuator. Additionally, the cleaning composition is non-toxic, so that residual cleaning composition remaining in the actuator will not harm the user when a subsequent dose of medication is dispensed.

Description:
RELATED APPLICATION  
       [0001]     This application is a Divisional of U.S. application Ser. No. 10/320,045, filed Dec. 16, 2002. 
     
    
       [0002]     The entire teachings of the above application are incorporated herein by reference.  
       FIELD OF THE INVENTION  
       [0003]     The present invention relates to a method of cleaning actuators or metered dose dispensers used to dispense pharmaceutical compositions. The invention also relates to a composition to be used in cleaning actuators of metered dose dispensers.  
       DESCRIPTION OF THE RELATED ART  
       [0004]     Metered dose spray devices are presently used to administer many different medications to the mouth and lungs, for example, asthma medication and nitroglycerin for treatment of heart disease. A typical metered dose spray device includes a container, for example, a can, for containing a solution or suspension of medication, a metering valve, and an actuator. The can will contain the medication to be dispensed, possibly a solvent for the medication, and a propellant. The propellant is a substance having a low boiling point and high vapor pressure, so that as liquid is dispensed from the container the propellant evaporates, thereby maintaining a constant pressure within the can. Actuation of the metering valve causes the metering chamber within the valve to close with respect too the can&#39;s interior, and open with respect to the mouthpiece (the structure of the actuator to be positioned in communication with the user&#39;s mouth). Propellant within the metering chamber will evaporate due to the sudden decrease in pressure then the valve is actuated, propelling the medication into the user&#39;s mouth.  
         [0005]     After repeated use, the actuator can become clogged with the medication being dispensed. This can interfere with proper dosing and delivery of the medication. It is desirable, therefore, to provide a method of cleaning the actuator on a regular basis to resist clogging and assure delivery of the desired amount of medication.  
       SUMMARY OF THE INVENTION  
       [0006]     The present invention provides a method of cleaning an actuator of a metered dose dispenser containing a pharmaceutical product, and also provides a chemical composition for performing this cleaning.  
         [0007]     Generally, the metered dose spray device consists of three major components: an aerosol container (which in many preferred embodiments will be a can) containing medication in liquified propellant gas; a metering valve, which when depressed dispenses a known quantity of the medication; and a buccal spray actuator which when combined with the stem of the metering valve comprises an expansion chamber, also called a sump, and a nozzle, often called a spray orifice. The actuator itself is comprised of an actuator bot, stem block, sump, spray orifice and mouthpiece. The actuator boot keep the aerosol can fixed in place. The stem block is dimensioned and configured to receive the stem of the metering valve, which is fixed to the aerosol can, and whose purpose is to carry the medication from the metering valve to the actuator sump, specially designed to act as an expansion chamber and to redirect the aerosol through the spray orifice.  
         [0008]     In the rest position, the metering chamber of the valve is connected directly to the aerosol can containing the medication, permitting free flow from the metering chamber to the container. The vapor pressure of the propellant therefore ensures that the metering chamber remains full of the medication/propellant mixture, and the capillary action of the passage from the container to the metering chamber prevents fluid in the metering chamber from exiting back into the container. Upon depression of the can towards the actuator, the valve stem is pushed into the can. The connection between the aerosol container and metering chamber is thereby closed and the metered discharge process begins. The metered dose is ejected from the metering chamber under the pressure of the flashing liquid propellant. The medication then passes through the valve stem orifice into the actuator sump where it undergoes further boiling as it attempts to fill the chamber and displace the air. Finally, a high-quality spray, particularly suited to buccal delivery, emerges from the spray orifice and mouthpiece of the actuator.  
         [0009]     Cleaning is performed by first removing the aerosol can containing the medication, and replacing it with an aerosol container or can containing a cleaning composition. The cleaning composition&#39;s can is then depressed towards the actuator to force the valve stem into the container and discharge the cleaning composition through the actuator&#39;s sump and orifice. Residue of the pharmaceutical product present in the actuator is substantially removed by the discharge of the cleaning composition therethrough, by the force of the flowing cleaning composition and/or by being dissolved in a solvent within the cleaning composition.  
         [0010]     A cleaning composition, to be used in the above method, is also provided in the present invention. The cleaning composition is itself non-toxic and leaves little or no residue in the actuator, and thus does not interfere with subsequent delivery of the pharmaceutical product. The cleaning composition is preferably comprised of silicone and a propellant, and optionally, an organic solvent.  
         [0011]     It is therefore an object of the present invention to provide a method of cleaning an actuator of a metered dose spray device used in delivery of pharmaceutical agents.  
         [0012]     It is another object of the present invention to provide a cleaning composition for preventing clogs within the actuator of a metered dose spray device.  
         [0013]     It is a further object of the present invention to provide an efficient and economical method of cleaning a metered dose spray device.  
         [0014]     It is another object of the present invention to provide an apparatus for cleaning a metered dose spray device that is easy to use.  
         [0015]     It is a further object of the present invention to provide a safe cleaning composition for use with metered dose spray devices.  
         [0016]     These and other objects of the present invention will become more apparent through the following description and drawings. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0017]     The foregoing and other objects, features and advantages of the invention will be apparent from the following more particular description of preferred embodiments of the invention, as illustrated in the accompanying drawings in which like reference characters refer to the same parts throughout the different views. The drawings are not necessarily to scale, emphasis instead being placed upon illustrating the principles of the invention.  
         [0018]      FIG. 1  is a front isometric view of a metered dose spray device.  
         [0019]      FIG. 2  is a side view of a can and metering valve assembly for a metered dose spray device.  
         [0020]      FIG. 3  is a cross-sectional side view of an actuator, can and metering valve for a metered dose spray device showing the metering valve closed.  
         [0021]      FIG. 4  is a side cross-sectional view of an actuator, can and metering valve for a metered dose spray device showing the metering valve open.  
         [0022]      FIG. 5  is a cross-sectional view of a can and valve assembly, taken along the lines  5 - 5  in  FIG. 3 . 
     
    
       [0023]     Like reference numbers denote like elements throughout the drawings.  
       DETAILED DESCRIPTION OF THE INVENTION  
       [0024]     A description of preferred embodiments of the invention follows.  
         [0025]     The present invention provides a method of cleaning a metered dose spray device, and a chemical composition for performing this cleaning.  
         [0026]     Referring to the figures, the metered dose spray device  10  includes an actuator  12 , an aerosol can  14 , and a metering valve  16 .  
         [0027]     The aerosol can  14  is best illustrated in  FIGS. 2-4 . The aerosol can  14  is preferably cylindrical having an open end  18 . The open end  18  is dimensioned and configures to mate with the ferrule (described below) of the metering valve  16 . A preferred material for the can  14  is aluminum, but stainless steel or other suitable materials can also be used.  
         [0028]     Referring to  FIGS. 3-4 , the metering valve  16  includes a housing  20 , having a plurality of slots  21  ( FIG. 5 ) with a stem  22  slidably contained therein. A preferred material for the 3-slot housing and stem is polyester, but acetyl resins or other suitable materials can be used as well. The metering valve  16  also includes a ferrule  24 , dimensioned and configured to fit around the outside of the open end  18  of the aerosol can  14 , being crimped around the end  18  to secure the metering valve  16  to the can  14 . A preferred material for the ferrule is aluminum. A sealing gasket  26  provides a seal between the can&#39;s open end  18  and the ferrule  24 . A preferred material for the sealing gasket  26  is nitrile (buna) rubber. A metering chamber  28  within the 3-slot housing  20  is defined between the upper annular stem gasket  30  and the lower annular stem gasket  32 . A preferred material for the first and second stem gaskets  30 ,  32  is nitrile (buna) rubber. The stem  22  includes an upper stem and a lower stem, with the lower stem having a U-shaped retention channel  34  having ends  36  and  38 , and an upper stem having a channel  40  having ends  42  and  44 . The principle of retention lies in the particular geometry at the base of the stem  22 , which allows the passage of the fluid under the differential pressure from the aerosol can  14  to valve metering chamber  28  after actuation, but resists the return (due to gravity) of the fluid to the aerosol can  14  by the capillary action of the retention channel  34 .  
         [0029]     The stem  22  moves between the rest (closed) position and an open position. Within the rest position, shown in  FIG. 3 , the inlet end  36  of the retention channel  34  is above the first stem gasket  30 , so that the contents of the aerosol can  14  may enter the retention channel  34 . The outlet end  38  of the retention channel  34  is below the first stem gasket  30  and within the metering chamber  28 . Both the inlet end  42  and outlet end  44  of the channel  40  are outside the metering chamber  28 , thereby resisting passage of fluid from the metering chamber  28  to the channel  40 . In the open position, shown in  FIG. 4 , both the inlet end  36  and outlet end  38  of the retention channel  34  are above the first stem gasket  30  of the metering chamber  28 , thereby resisting any fluid flow from the aerosol can  14  to the metering chamber  28 . At the same time, the inlet end  42  of the channel  40  is above the second stem gasket  32  and inside the metering chamber  28 , thereby permitting passage of fluid from the metering chamber  28  through the passage  40 . The stem  22  is biased by the spring  46  into the rest position of  FIG. 3 .  
         [0030]     The actuator  12  is best illustrated in  FIGS. 1, 3  and  4 . The actuator  12  includes mouthpiece  50 , a stem block  48  and an actuator sump  52 . The actuator sump  52 , which is located in the stem block  48 , includes an inlet end  54 , dimensioned and configured to receive the lower end  56  of the valve stem  22 , and an outlet end  58 , called a spray orifice. The spray orifice  58  of the actuator sump  52  is dimensioned and configured to direct medication towards the back of the throat. The spray orifice  58  may have a generally round configuration. The sump volume is preferably sufficient to generate a high-pressure stream of fluid upon actuation of the metered dose spray device.  
         [0031]     The actuator  12  may also include a cap  60 , surrounding the actuator  12  and aerosol can  14 . The cap  60  is preferably slidably and removably secured to the actuator  12 . One method of slidably and removably securing the cap  60  to the actuator  12  is by friction, thereby permitting removal or reattachment of the cap  60  and actuator  12  by merely pulling upward on the cap  60 . The actuator  12  may also include a dust cover  68 , dimensioned and configured to cover the mouthpiece  50 .  
         [0032]     The cleaning composition of the present invention includes a mixture of silicone and an appropriate propellant, and may optionally include an organic solvent. Preferably, silicone is about 1-10 wt./wt. % of the total cleaning composition, and propellant is about 90-99 wt./wt. % of the cleaning composition.  
         [0033]     Propellants commonly used in conjunction with drug delivery via metered dose spray devices are also appropriate for use with the present cleaning composition. Such propellants include tetrafluoroethane, heptafluoroethane, dimethylfluoropropane, tetrafluoropropane, butane, isobutane, dimethyl ether and other non-CFC and CFC propellants. The preferred propellants are hydrogen-containing chlorofluorocarbons, hydrogen-containing fluorocarbons, dimethyl ether and diethyl ether. Even more preferred is HFA-134a (1,1,1,2-tetrafluoroethane).  
         [0034]     Suitable organic solvents for use with the cleaning composition of the present invention include alcohol solutions, such as ethanol.  
         [0035]     Use of the metered dose spray device  10  begins with the valve  16  in its rest position. When the valve  16  is in its rest position as shown in  FIG. 4 , medication within the aerosol can  14  is free to move through the slots  21  within the metering valve&#39;s housing  20 , through the U-shaped retention channel  34 , and into the metering chamber  28 . The propellant, specifically selected for its high vapor pressure, evaporates to the maximum extent permitted by the volume of the aerosol can  145 . The medication within the aerosol can  14  is thereby forced through the retention channel  34  until the metering chamber  28  is full. The elongated and curved shape of the retention channel  34  keeps the medication in the metering channel  28  from traveling back into the aerosol can  14 . The location of the channel  40  below the second stem gasket  32  resists medication from exiting the metering chamber  28  prematurely.  
         [0036]     To use the metered dose spray device  10 , the lower end  56  of the stem  22  is first inserted into the inlet end  54  of the actuator sump  52 , located in the stem block  48  of the actuator  12 . The cap  60  may also be secured to the actuator  12 , thereby completely concealing the aerosol can  14 . The dust cover  68  is removed from the mouthpiece  50 . The mouthpiece  50  is inserted into the user&#39;s mouth and the aerosol can  14  (possibly along with the cap  60 ) is depressed towards the actuator  12 . This action causes the metering valve  16  to move from its rest position of  FIG. 3  to its open position of  FIG. 4 . When the stem  22  is moved from the rest position of  FIG. 3  to the open position shown in  FIG. 4 , the outlet opening  38  of the retention channel  34  is moved above the first stem gasket  30 , thereby resisting medicine from moving from the aerosol can  14  to the metering chamber  28 . At the same time, the inlet end  42  of the channel  40  is brought above the second stem gasket  32 , thereby providing a path from the metering chamber  28 , through the channel  40  and actuator sump  52 , spray orifice  58 , through the mouthpiece  50 , and into the user&#39;s mouth. Opening the metering valve  16  also decreases the pressure within the metering chamber  28 , causing the propellant in the metering chamber  28  to evaporate, thereby pushing the medication out through the channel  40  into the actuator sump  52 , where it undergoes further evaporation as it attempts to fill the chamber and displace the air, and finally through spray orifice  58  and out the mouthpiece  50 . Releasing downward pressure on the aerosol can  14  causes the metering valve  16  to return to its rest position under pressure from the spring  46 , thereby permitting a new dosage of medication to enter the metering chamber through the retention channel  34 , under pressure from the evaporated propellant within the aerosol can  14 .  
         [0037]     To clean the actuator  12  of the metered dose spray device  10 , the cap  60  is first removed. The can  14  containing the medication is then removed, and is replaced with another can  14  containing the cleaning composition. As before, the lower end  56  of the stem  22  is inserted into the inlet end  54  of the actuator sump  52 , located in the stem block  48  of the actuator  12 . The dust cover  68  should remain removed from the mouthpiece  50 . The aerosol can  14  containing the cleaning composition is depressed towards the actuator  12 . This action causes the metering valve  16  to move from its rest position of  FIG. 3  to its open position of  FIG. 4 . When the stem  22  is moved from the rest position of  FIG. 3  to the open position shown in  FIG. 4 , the outlet opening  38  of the retention channel  34  is moved above the first stem gasket  30 , thereby resisting cleaning composition from moving from the aerosol can  14  to the metering chamber  28 . At the same time, the inlet end  42  of the channel  40  is brought above the second stem gasket  32 , thereby providing a path from the metering chamber  28 , through the channel  40  and actuator sump  52 , spray orifice  58 , and through the mouthpiece  50 . Opening the metering valve  16  also decreases the pressure within the metering chamber  28 , causing the propellant in the metering chamber  28  to evaporate, thereby pushing the cleaning composition out through the cannel  40  into the actuator sump  52 , where it undergoes further evaporation as it attempts to fill the chamber and displace the air, and finally through the spray orifice  58  and out the mouthpiece  50 . As the cleaning composition passes through the various portions of the actuator  12 , it carries with it any remaining medication within the actuator  12 , thereby preventing any clogs within the actuator sump  52 . Releasing downward pressure on the aerosol can  14  causes the metering valve  16  to return to its rest position under pressure from the spring  46 , thereby permitting a new supply of cleaning composition to enter the metering chamber through the retention channel  34 , under pressure from the evaporated propellants within the aerosol can  14 . Upon completion of cleaning, the aerosol can  14  containing the cleaning composition should immediately be replaced with the aerosol can  14  containing the medication. The cap  60  may again be place on the actuator  12 , so that the metered dose spray device  10  is ready to administer the next dose of medication.  
         [0038]     While a specific embodiment of the invention has been described in detail, it will be appreciated by those skilled in the art that various modifications and alternatives to those details could be developed in light of the overall teachings of the disclosure. Accordingly, the particular arrangements disclosed are meant to be illustrative only and not limiting as to the scope of the invention which is to be given the full breadth of the appended claims and any and all equivalents thereof.