Patent Application: US-39961606-A

Abstract:
a new dry powder inhaler is developed as a pulmonary medicine delivery device for dispersing precise tiny dosages of pure carrier - free ultra - fine powdered medicament into a patient &# 39 ; s lung . the powder is drawn from the blister cell and dispersed through an outlet tube assisted by two air streams . the first air stream goes through a the blister cell from its upstream side , to significantly fluidize the medicament in the dose to flow upward . the second one extracts the fluidized powder from downstream of the blister cell for further deagglomeration and dispersion of the medicament powder by shear force . the rotating multi - dose blister can hold up to 60 doses , which are pre - metered with pure ultra - fine powdered medicament . so that it has higher drug loading capability in small volumes , compared to most current dry powder inhalers , which usually use some excipient . the inhaler efficiently disperse the aerosolized medicament in the air stream to the deep interior of patient &# 39 ; s lung . the fine particle fraction is reported to reach as high as 80 % using this inhaler .

Description:
in the following description , like numerals in the different embodiments refer to the same or very similar parts . fig1 a and 1 b show an embodiment of a blister pack 10 that is used to hold multi - doses of a powdered medicament . the blister pack 10 contains a ( holding ) plate 12 with multiple powder pockets 14 extending through the plate in which the medicament is contained . the powder pockets 14 formed in the holding plate 12 which contain the powder medicament are also referred to as blisters or blister cells . powdered medicament is pre - charged into the blisters or blister cells 14 which is then put into an inhaler to be discussed hereinafter . by introducing a gas flow through the blisters 14 , the charged powder medicament will be blown out , to form a powder flow for the pulmonary drug delivery , as will be described in detail hereinafter . the blister cells 14 in the holding plate 12 are normally identical in size and have a fixed or pre - selected volume to store a pre - selected amount of powder therein . by changing the holding plates 12 with different pocket diameters and plate thickness , blister packs 10 of different volumes can be obtained . any number of powder pockets 14 can be arranged in any fashion in the plate 12 , but for easy use in the inhalers it is beneficial that powder pockets 14 are arranged along certain circles on the disk . in the illustrated blister pack of fig1 , the holding plate 12 is circular and the powder pockets 14 are arranged on the circumference of a circle . however , more powder pockets 14 may be arranged on multiple circles on the plate 12 . fig1 a and 17 b shows an embodiment of an alternative blister pack 610 that has a double circle arrangement of pockets . the blister pack 610 contains a holding plate 612 with an inner circle of multiple pockets 614 and an outer circle of pockets 624 arranged in two concentric circles . as before , the powder pockets 614 and 624 in the two circles formed in the holding plate 612 which contain the powder medicament are also referred to as blisters or blister cells . powdered medicament is pre - charged into the blisters or blister cells 614 and 624 after which the blister pack 610 is inserted into an inhaler . by introducing a gas flow through each of the blisters 614 and 624 , the charged powder medicament will be blown out , to form a powder flow for the pulmonary drug delivery , as will be described in detail hereinafter . the blister cells 614 and 624 in the holding plate 612 are normally identical in size and have a fixed or pre - selected volume to store a pre - selected amount of powder therein . by changing the holding plates 612 with different pocket diameters and plate thickness , blister packs 610 of different volumes can be obtained . any number of powder blisters 614 and 624 can be arranged in any fashion in the plate 612 , but for easy use in the inhalers it is beneficial that powder blisters 614 and 624 are preferably arranged in two concentric circles on the plate 612 . in the illustrated blister pack of fig1 , the holding plate 612 is circular and the blisters 614 and 624 are arranged on the circumferences of two concentric circles . the blister cells 14 in plate 12 in fig1 a and 1 b , and blister cells 614 and 624 in plate 612 in fig1 b , may be made of any shape , although a vertical cylindrical shape is preferred since it is the easiest to produce and to align with the powder outlet channel . for example , vertically tapered holes with increasing diameter towards the top surface of plate 12 and 612 would be beneficial for the easy charging and blowing - off of the powder . fig2 to 4 show different embodiments of inhalers constructed in accordance with the present invention . referring first to fig2 , an inhaler 20 includes a cylindrical housing 22 which holds a circular disc - shaped blister pack 10 ( fig1 ) which contains several individual blister cells 14 , each containing a known amount of powdered medicament , arranged in one or more circles on the blister pack 10 . housing 22 includes a gas flow inlet tube 34 which encloses a flow passageway 32 on the bottom of housing 22 and an air flow outlet tube 30 positioned above a blister cell 14 at the top of the blister pack 10 which encloses a flow passageway 36 . the blister pack 10 is sandwiched between , and held in place , by a top seal block 24 and a bottom seal block 26 . with a locking pin 42 , the blister pack 10 is tightly fixed with a ratchet wheel 28 , which can be rotated in steps to align in turn each of the individual pocket holes in the holding plate 12 with the flow passageways 32 and 36 . the ratchet wheel 28 is used to rotate the blister pack 10 and to align and hold in place each blister cell 14 aligned with the passageway 32 ( as well as 36 ) through which the powder is to be dispensed . from the top of air flow outlet tube 30 , and in the direction indicated by arrow 44 , a patient can suck the powder contained in the powder blister 14 adjacent to passageway 36 with a gas in passageway 32 . the gas flow inlet tube 34 which encloses the flow passageway 32 on the bottom of housing 22 may include an adjustable constriction means for adjusting gas flow in passageway 32 to allow adjustment of the gas flow rate . fig1 shows an inhaler arrangement 620 that is designed for holding the blister pack 610 ( fig1 a and 17 b ) with two concentric circles of blister pockets . the inhaler 620 includes a cylindrical housing 22 which holds a circular disc - shaped blister pack 610 which contains several individual blisters 614 and 624 ( 624 is not shown on the plane sectioned in fig1 ), each containing a known amount of powdered medicament , arranged in two circles on the blister pack 610 . housing 22 includes a gas flow inlet tube 34 which encloses a flow passageway 32 on the bottom of housing 22 and an air flow outlet tube 30 positioned above a blister cell 614 at the top of the blister pack 610 which encloses a flow passageway 36 . the blister pack 610 is sandwiched between , and held in place , by a top seal block 24 and a bottom seal block 26 . the top part of the bottom gas flow inlet tube 34 has a y shaped branching 632 extending into two directions each pointing to the positions of blisters in the inner and outer circles . likewise , the bottom part of the top air flow outlet tube 30 also has a y shaped branching 636 extending into two directions each pointing to the positions of blisters in the inner and outer circles . with a locking pin 42 , the blister pack 610 is tightly fixed with a ratchet wheel 28 , which can be rotated in steps to align in turn each of the individual pocket holes 614 and 624 in the holding plate 612 with the flow passageways 32 and 36 . the ratchet wheel 28 is used to rotate the blister pack 610 and to align and hold in place alternatively each blister cell 614 aligned with left branch of y shape 632 in the passageway 32 and each blister cell 624 aligned with right branch of y shape 632 in the passageway 32 . likewise , the left branch of the y shape 636 is aligned with blisters 614 and the right branch of the y shape 636 is aligned with blisters 624 , alternatively . through the gas passageway through either the left branches or the right branches , alternatively , the powder in the blisters on the inner circle or blisters on the outer circle is to be dispensed . for the inhalers 20 and 620 shown in fig2 and 18 , the powdered medicament can be drawn out by a negative pressure resulting from the patient &# 39 ; s suction from the top of the air flow outlet tube 30 or a positive pressure from the bottom of the gas flow inlet tube 34 . the latter can be provided by connecting a small compressed gas canister with an activation means or by the in - situ compression of a telescope section as shown in fig4 below . fig3 shows a cross sectional view of an alternative embodiment of an inhaler device at 40 . inhaler device 40 is very similar in structure to device 20 of fig2 but includes an additional small air flow inlet tube 46 , defining a flow passageway 48 , located just above the holding plate 12 of the blister pack 10 , which is positioned at 90 degrees to outlet tube 30 and which sweeps the top surface of the powder blister 14 adjacent to passageway 36 to entrain the powder out of the powder blister 14 aligned with outlet passageway 36 . with the assistance of this additional air flow through passageway 48 , the dispensing of the powder medicament is easier and more efficient than using the airflow from the inlet tube 32 alone . the relative ratio between the air flow through passageway 32 and the air flow through passageway 48 is determined by the relative flow resistance through the two passageways , mostly by the diameter and the length of the two passageways . a large diameter pipe for passageway 48 would increase the air flow rate which is used for sweeping gas across the top surface of the powder blister 14 and for entraining the powder out of the powder blister 14 . to further adjust the flow ratio , a small screw 49 is set through the top block 24 and ends at the wall of the air inlet tube 46 . to decrease the air flowrate through passageway 48 , the small screw can be advanced into the air inlet tube 46 , creating additional flow resistance inside passageway 48 . it will be understood that all embodiments of the inhalers disclosed herein having the two gas flow passageways may include this adjustable screw 49 to provide gas flow constriction , or any other type of gas flow constriction mechanism may be used . fig4 is a cross sectional view of another inhaler 60 which differs from inhaler 40 in that the housing 62 is constructed of a housing in two sections , an upper section 64 and a lower section 66 which move in telescoping relationship to each other for pressurizing the air entering passageway 32 located in the chamber defined by housing sections 64 and 66 . a spring 70 is located between the bottom of housing section 66 and the bottom surface of seal block 26 which acts to bias housing section 66 away from housing section 64 . housing section 64 includes a shoulder 68 around the periphery of the end portion located within housing section 66 with shoulder 68 extending outwardly to engage the inwardly protruding peripheral edge of section 66 in order to hold the two housing sections 64 and 66 together . at the bottom of housing section 66 , there is a threaded hole which is normally blocked off by a screw 72 . when needed , this screw 72 can be removed to allow airflow through the hole . the flow passageway 48 created by tube 46 as shown in fig4 is optional and its addition can further help the entrainment of powdered medicament . inhaler 60 as shown in fig4 provides for the production of a back pressure inside the chamber formed by housing sections 64 and 66 that can be used to disperse the powder from the blister cell aligned with passageway 36 . on the other hand , when the screw 72 is removed , inhaler 60 essentially becomes inhaler 40 of fig3 . when the screw 72 is threaded into the hole and sealed properly , as a patient squeezes housing sections 64 and 66 together the air in the interior chamber is pressurized thereby producing a compressed air flow up through passageway 32 flowing up through the bottom of the powder blister 14 and in through the small air passageway 48 which sweeps across the top of powder blister cell 14 aligned with passageway 36 . the compressed air flows up through passageway 32 and fluidizes the powder in the blister cell 14 of the blister pack 10 , then entrains and disperses the powder efficiently with the assistance air flow in passageway 48 . the blister pack 10 shown in fig1 a and 1 b may be charged with powdered medicament using the rotating fluidized bed disclosed in u . s . pat . no . 6 , 684 , 917 b2 or other suitable means that can dispense powder accurately into the blister cells . after dispensing powder into the blister cells 14 , the charged blister pack 10 may be covered on one or both sides with protection layers such as aluminum foils or other means , to prevent the powder from falling out and / or prevent moisture from getting into the packed cell with packed powder . before loading the blister pack 10 into the inhaler 60 , the protective films are removed . the blister pack 10 shown in fig1 a and 1 b is , however , only one embodiment and is likely the simplest embodiment . more complicated blister packs can be made that further ensure the accuracy of final pulmonary drug delivery . fig5 a , 5 b and 6 show another embodiment of a blister pack 310 that is used to hold multi - doses of a powdered medicament . fig6 shows an exploded view of the same blister pack 310 . the blister pack 310 includes a top plate ( the holding plate ) 312 with multiple blister or blister cells 314 extending through the plate in which the medicament is contained , and a bottom plate 316 with the same number of multiple air passage holes 317 as that of 314 extending through plate 316 , with a filter material 315 clamped in between the top plate 312 and bottom plate 316 . a set screw 318 is used , preferably going through the centre of plates 312 and 316 , to fix the two plates together and to align the pockets 314 in the top holding plate 312 with the holes 317 in the bottom plate 316 . powdered medicament is pre - charged into the blisters 314 and then the blister pack is put into an inhaler . by introducing a gas flow through the air passage holes 317 , either by inhalation ( suction ) from the top of the top plate 312 or by apply pressured air to the bottom of the bottom plate 316 , the charged powder medicament will be blown out , to form a powder flow for the pulmonary drug delivery . the main benefit of this embodiment over the blister pack 10 shown in fig1 is that the filter media supported by the bottom plate helps to hold the powdered medicament in place . if the bottom plate 316 and the filter media 315 are both removed after the powder charging and before the blister pack 310 is put into the inhaler , blister pack 310 shown in fig5 a , 5 b and 6 reduces to the blister pack 10 shown in fig1 . filter media 315 may be any inert porous material such as filter paper , fine mesh screens , membrane sheet , and porous solid materials such as porous teflon and porous ceramics , to mention just a few . it has a pore size to allow gas to flow through but blocks the medicament powder . after dispensing powder into the blister cells 314 , the charged blister pack 310 may be covered on one or both sides with protection layers such as aluminum foils or other protective films to prevent moisture from getting into the blister cells . the film on the top side also helps to hold the powder in the blister cells in place . before putting the blister pack into the inhaler , the protective films are removed . the blister cells 314 in the holding plate 312 are normally identical in size and have a fixed or pre - selected volume to store a pre - selected amount of powder therein . by changing the holding plates 312 with different pocket diameters and plate thickness , blister packs 310 of different volumes can be obtained . any number of blisters 314 can be arranged in any fashion in the plate 312 , but for easy use in the inhalers it is beneficial that blister cells 314 are arranged along certain circles on the disk . the bottom plate 316 is provided with air passage holes 317 designed to align with each of the blister cells 314 in plate 312 . in the illustrated blister pack of fig5 a and 6 , both top and bottom plates 312 and 316 are circular and the blisters 314 and holes 317 are arranged on the circumference of a circle in each plate of the same diameter . however , more blister cells 314 and holes 17 may be arranged on multiple circles on each plate . the blister cells 314 in plate 312 may be made of any shape , although a vertical cylindrical shape is preferred since it is the easiest to produce and to align with the powder outlet and air inlet channels . for example , vertically tapered holes with increasing diameter towards the top surface of plate 312 would be beneficial for the easy charging and blowing - off of the powder , but vertically tapered holes with decreasing diameter towards the top surface of plate 312 would be beneficial for holding the powder in position . the air passage holes 317 in the bottom plate 316 are preferably larger in diameter than the diameter of blister cells 314 , to ensure the complete blow - off of powdered medicament in the blister cells 314 by the gas flow through the bottom holes . as discussed above , in operation , the ratchet wheel 28 ( fig2 or 3 ) is used to rotate the blister pack 310 and to align and hold in place each blister cell 314 aligned with the passageway 32 ( as well as passageway 36 ) through which the powder is to be dispensed . holding plate 312 , filter 315 and bottom plate 316 are locked together and move together about the axis of rotation defined by screw 318 . another embodiment of the blister pack is shown generally at 320 in fig7 and with its exploded view shown in fig8 . in some cases , the packed powder may not be able to hold together tightly enough so that some particles may easily fall out of the blisters cells . in some other cases , the medicament particles become too sticky that some will stick onto the protective films when peeled before loading into the blisters . both cases would lead to loss of particles , affecting the accuracy of pulmonary delivery . the embodiment 320 shown in fig7 is useful in preventing the above problems . the blister pack 320 shown in fig7 has the lower parts ( 312 , 314 , 315 , 316 and 317 ) identical to the blister pack 310 , but with another top plate 326 on top of the holding plate 312 , with the same number of multiple air passage holes 327 as that of 314 extending through plate 326 , with a filter material 325 clamped in between the top plate 326 and the holding plate 312 . the same blister pack as 310 is first charged with powder medicament and then the top plate and filter media are put on to hold the particles in place . the set screw 328 , in this case , is longer than the screw 318 in fig5 a and can be advanced into the top plate 326 after powder loading , so as to fix all three plates together . the holes 327 in the top plate 326 should preferably be equal to , or larger than , the blister holes 314 in the holding plate 312 , for easier and more complete powder dispersing and inhalation . with such an arrangement , the powdered medicament is securely held inside the blister cells during transportation . if protection from moisture is also required , protective films can be sealed against the upper surface of the top plate 326 and the lower surface of the bottom plate 316 . because the protective films are not in direct contact with the medicament particles , there is no potential loss of medicament particles when the films are peeled off before inhalation and usually before loading into the inhalers . the above - mentioned blister pack 320 is then loaded into the inhaler , assuming the protective films , if any , have been peeled off . before inhalation , the top filter media 325 of the blister cell at the position in line with the air inlet passageway 32 and powder outlet passageway 36 must be pierced . this can be realized by a piercing device 322 being pushed into the passageway and onto the filter materials , as shown in fig9 . after such piercing operation , the air outlet passage way 36 is open and the blister contents are ready for inhalation . as discussed above , in operation , the ratchet wheel 28 ( fig2 or 3 ) is used to rotate the blister pack 320 and to align and hold in place each blister cell 314 aligned with the passageway 32 ( as well as passageway 36 ) through which the powder is to be dispensed . ratchet 28 turns the whole sandwiched assembly , including plate 312 / filters 315 and 325 / bottom plate 316 and top plate 326 which move together about the axis of rotation defined by screw 328 . in preferred embodiments of the blister discs the various holding plates and top and / or bottom plates are disc - shaped having an axis of rotation about which the ratchet rotates the blister pack . to further decrease the resistance to the air and powder flow during inhalation , it may be beneficial if the bottom filter media 315 is also pierced open . as shown in fig9 , a similar sharp object 324 to that 322 may be used for this purpose . when both the inlet and outlet passageways are open the flow resistance is minimized and the powdered medicament is more easily fluidized and entrained for more efficient pulmonary drug delivery . an alternative arrangement for reducing the flow resistance but avoiding the use of the piercing objective is shown in fig1 . the modified embodiment of blister pack 330 is essentially the same as the blister pack 320 ( both preferably being disc - shaped ), but the two filter media 315 and 325 each have a hole 335 and 336 respectively in them and one of the blister cells 334 on a modified holding plate 312 ′ is blocked completed ( or alternatively not drilled in the first place ). as in the case for blister pack 320 , the top plate and filter are not put on when loading the powdered medicament into the blister pack . at the loading stage , the open hole 335 in the lower filter media 315 and the blocked hole 334 on the holding plate are aligned together . after loading , the top plate 326 and top filter media 325 are assembled onto the lower portion , with the open hole 336 in the top filter media 325 aligned with the blocked hole 334 on the holding plate 312 ′. with such arrangement , the blank blister cell with the blocked hole is exposed to the two openings 336 and 335 on the upper and lower filter media 325 and 315 when the blister pack 330 is in storage and transfer , so that there will be no loss of particles . a preferred apparatus for filling the blister packs for use in the inhalers disclosed herein with the powder medicament is a volumetric metering fluidized bed such as disclosed in u . s . pat . no . 6 , 684 , 917 b2 , which is incorporated herein by reference in its entirety , which can be used to precisely dispense a pre - determined amount of pure powdered medicaments ( without any excepient ) into the powder pockets of the multi - dose blister pack forming part of the dry powder inhaler forming part of the present invention . the device disclosed in u . s . pat . no . 6 , 684 , 917 b2 can deliver a powder plume with approximately 90 % or more of the inhalable particles ( less than 5 μm in diameter or equivalent aerodynamic diameter ) in their primary particle form , that is , with less than 10 % particle agglomerates for the small inhalable particles . this ensures the accurate and uniform dispensing of the inhalable particles into the blister cells of the blister pack . thus , a preferred method of filling the powder pockets of the blister packs may include producing a fluidized bed in a housing defining an enclosure for containing fine powder medicament where the housing includes a fluid injection mechanism for injecting a fluid into the enclosure for fluidizing the fine powder medicament contained within the housing for forming a dilute phase alone or a dilute phase and a dense phase of fluidized powder medicament . the powder pocket of the blister pack is coupled into flow communication with the enclosure through an outlet passageway for withdrawing pre - selected amounts of the fine powder medicament from housing , and sealing the powder pockets for transporting the pre - filled blister pack . fig1 shows an embodiment of an inhaler at 340 which is similar to inhaler 40 , but designed to receive the thicker blister pack 330 shown in fig1 . in this case , the top plate 326 in fig1 , with the upper filter material 325 will be secured to the top seal block 24 and the bottom plate 316 with the lower filter material 315 will be secured to the bottom seal block 26 in inhaler 340 in fig1 so that the ratchet mechanism is configured to move only the holding plate 312 while the top plate 326 and the bottom plate 316 with filters 325 and 315 attached to each respectively remain in the same fixed position while the holding plate 312 ′ rotates . the holding plate 312 is , however , locked with the ratchet wheel 28 . at the initial position , the two openings 335 and 336 on the two filter materials 315 and 325 , and the blank blister 334 on the holding plate 312 are aligned together and also aligned with the inlet and outlet passageways 32 and 36 . before inhalation , the ratchet wheel 28 will advance the holding plate 312 ′ to its next position so that the next blister ( filled with powdered medicament ) will be exposed to the inlet and outlet passageways 32 and 36 . since the passageways are completely open without any filter material in the way , the flow efficiency is greatly increased and the probability for the powdered medicament to be stuck inside the blister is essentially zero . it will be understood that blister pack 330 may be made just using either the bottom plate 316 and filter 315 with the modified holding plate 312 ′ or a combination of both . it should be noted that other materials can also be used for the blister pack 330 . for example , the top and bottom plates 326 and 316 may be replaced with solid plates made from porous materials . this eliminates the need for drilling the very small holes in the plates . in addition , membrane sheets with proper pore size can be formed directly onto one surface of the above - mentioned two plates to act as the filter layers 315 and 325 . if the membranes are selected to bond well to the plates , there is no need to use other means to bond the filter layer to the plates . this is particularly useful to ensure membrane layers 315 and 325 stay bound with the top and bottom plates 326 and 316 when the holding plate 312 is rotating with the ratchet wheel 28 being rotated when loaded into the inhaler 340 . another alternative is to use partially porous media to make the top and bottom plates 326 and 316 , so that the areas marked as holes 327 and 317 are made porous while all the other areas are solid . this eliminates the needs for filter media 315 and 325 . referring now to fig1 a and 12 b , an alternative embodiment of an inhaler shown at 100 includes a housing 102 with two generally cylindrical telescoping sections 104 and 106 with a spring 108 bearing against section 106 . section 106 functions as a push bottom for activating the inhaler to pressurize the air on the interior of the housing for dispensing powder . the top seal block 24 and bottom seal block 26 serve the same function as in the inhalers 20 and 40 in fig2 and 3 for securing blister pack 310 between them . a mouthpiece 114 is mounted on the powder / air outlet passageway 36 . fig1 b is a cross - sectional top view at the a - a plane of the inhaler at 100 in fig1 a and shows the ratchet mechanism for rotating the blister pack 310 which includes a ratchet wheel 122 which is turned by handle 118 with the ratchet wheel 122 engaging a tongue 126 pivotally mounted on a block 124 for locking the blister pack 310 in place thereby controlling the position of the blister cells 314 in blister pack 310 . blister pack rotation handle 118 is connected to the blister pack 310 for rotating the pack into position for dispensing the powder from the different blister cell 314 . air compressed by pushing housing section 106 up into section 104 compresses the air in the chamber 111 defined by housing 104 and 106 which is forced into entrance 115 and up through passageway 32 into the blister cell 314 thereby forcing the powder to be expelled out through outlet passageway 36 and mouthpiece 114 . fig1 c shows an exploded perspective view of the ratchet mechanism for inhalers 100 and 120 shown in fig1 a and 13 a but it will be understood that the ratchet mechanisms for the other inhalers are similar . when the handle 118 and lever 121 connected thereto is advanced ( counter - clockwise ), it turns the ratchet wheel 122 counter - clockwise through a pivotal pin connection 119 . the handle 118 and lever 121 then turn clockwise back to its original position . since the ratchet wheel 122 is engaged with the tongue 126 pivotally mounted on block 124 , the ratchet wheel 122 cannot turn back but is locked in the position set by the tongue 126 and the block 124 . this locks the blister pack 310 in place thereby controlling the position of the blisters 314 . when the dose of powdered medicament in the air flow passageway is inhaled , the handle 118 is advanced again to turn the ratchet wheel 122 which then turns the blister pack 310 to the next position where the next blister cell is aligned for inhalation . it should be noted that although blister pack 310 is used to illustrate the utility of inhaler 100 in fig1 a , other blister packs such as 320 , 330 or 10 may also be used in combination with inhaler 100 . it should also be noted that inhaler 100 as shown in fig1 is a so - called active inhaler where compressed air is used to blow the powdered medicament out of the blister cells . however , inhaler 100 can be easily modified into a passive inhaler where the inhalation force of patient is the sole driving force to lift and then carry the medicament into the patient &# 39 ; s lung for pulmonary drug deposition . this can be done by removing the outer housing 106 and the spring 108 and then shorten the length of housing 104 . fig1 a shows another embodiment of an inhaler shown generally at 120 , fig1 b shows the a - a cross - section of the inhaler 120 and fig1 c is an exploded perspective view of the inhaler 120 . inhaler 120 is similar in structure to inhaler 100 of fig1 a but includes an additional secondary air flow passageway 132 . this secondary air flow is separated from the major air flow in passageway 32 and is directed into a hidden passageway inside the shaft 138 for the mechanism that turns the ratchet wheel 122 . a portion of the compressed air from the chamber 111 , other than the portion going through the main air channel 36 , passes through the hollow area of the fixed supporting block 134 and then into a passageway located in the shaft 138 ( the shaft is not solid , but hollow ), as shown by the arrow 136 . air comes out of the inner tube 138 then goes to the secondary air flow passageway 132 , as shown by the arrow 112 . eventually , this secondary air flow makes its way through the flow passageway 132 , to sweep across the top surface of the blister cell 314 aligned with the outlet passageway 32 . this helps to carry the powder out of the pocket into the mouthpiece 114 of the inhaler . the only difference between inhaler 100 and 120 is the presence of this secondary flow passageway 132 . fig1 b shows the mechanism for rotating the blister pack 310 which is essentially the same as the mechanism shown in fig1 b . also like inhaler 100 , inhaler 120 can also be modified to become a passive inhaler by removing the outer housing 106 and the spring 108 and then shortening the length of housing section 104 . fig1 a and 14 b show another alternate embodiment of an inhaler shown generally at 160 with fig1 c showing an exploded perspective view of the inhaler 160 . inhaler 160 differs from the previous embodiments of the inhaler in that the exit passageway 162 is perpendicular to the direction of the button 164 mounted in telescoping relationship with the housing section 166 . spring 168 returns the button 164 to its rest position . depressing button 164 acts to compress air within the housing which then enters passageway 170 and exits through exit passageway 162 and mouthpiece 174 . there is a secondary air - flow passageway 178 through top seal block 24 , which introduces air across the top of the blister cell 314 on blister pack 310 positioned adjacent to the exit passageway 162 . knob 118 and the lever 119 connected thereto is for rotating blister pack 310 to bring the dosages contained in the blisters 314 into alignment with the exit passageway 162 and works the same way as in inhaler 100 . fig1 b is the a - a cross - sectional view of the inhaler at 160 in fig1 a and shows the mechanism for rotating the blister pack 310 ( similar to fig1 b and 13 b ) which includes ratchet wheel 122 which is turned by handle 118 with the ratchet wheel 122 engaging a tongue 126 pivotally mounted on block 124 for locking the blister pack 310 in place thereby controlling the position of the blister cells 314 in blister pack 310 . again , inhaler 160 can also be modified to become a passive inhaler by removing the telescoping button 164 and the spring 168 and then leave some openings in place of the button to allow air inflow . for inhalers 100 , 120 and 160 , the blister pack 310 may be centered in the housings as shown for inhaler 160 ( see fig1 b ). however , for the inhalers 100 and 120 , since both have a vertical design , these inhalers have been constructed so that the position of the blister pack 310 is off - centre in the inhaler housing , in order to minimize the required radius while still accommodating the ratchet turning mechanism . for inhaler 160 , because it is of a horizontal design , minimizing the radius is less of a concern than minimizing the total vertical height , the latter being achieved by the positioning the exit passageway 162 perpendicular to the direction of the telescoping housing sections 164 and 166 . fig1 a shows another alternative embodiment of an inhaler shown at 190 which is similar to inhaler 160 of fig1 a . inhaler 190 differs from inhaler 160 in that the mouthpiece 194 has been moved to the bottom of the housing so that the main and secondary passageways are shorter with fewer turns . the primary or major air flow passageway 182 directs air to the hole 17 of the blister pack 310 , and into passageway 162 which is located in an elongated housing portion 194 forming the mouthpiece which is inserted into the user &# 39 ; s mouth , and the secondary air flow passes through a small tube 192 which introduces air across the top of the blister cell 314 on blister pack 310 positioned adjacent to the exit passageway 162 . fig1 b shows a view along the line a - a of the inhaler at 190 in fig1 a and shows the ratchet mechanism for rotating the blister pack 310 ( similar to that shown in fig1 b and 14 b ). fig1 c shows an exploded perspective view of inhaler 190 . inhaler 190 can also be modified to become a passive inhaler by removing the telescoping button 186 and the spring 180 and providing one or more air holes in the stationary housing to allow air inflow . fig1 shows another embodiment of an inhaler at 500 . inhaler 500 is similar in structure to inhaler 120 of fig1 a but has the blister pack 310 located concentrically within the housing 104 . all the internal parts in inhaler 500 have the same function as those in inhaler 120 , although their relative positions are adjusted and positioned to accommodate the blister pack being concentric within the housing section 104 . inhaler 500 can also be modified to become a passive inhaler by removing the section housing 106 and the spring 108 and then providing air vents so that when a user sucks on the mouthpiece 114 air can be drawn into housing 104 and through hole 116 in the blister pack and secondary passageway 132 so that powder within the blister cell aligned with outlet passageway 36 is drawn into the user &# 39 ; s mouth . optionally the length of housing 104 may be shorted when adapted for the passive mode of operation . as mentioned above , the inhaler of the present invention is most suitable for the delivery of very small dosages of pure powdered medicaments , giving the very high delivery efficiency . this is particularly useful for the delivery of very expensive medicaments such as peptide and protein drugs , for which the use of excipient will significantly reduce the delivery efficiency and therefore significantly increase the cost . it is also useful for the systemic delivery or localized delivery of any powdered medicament through the lungs . thus the present invention provides a method of pulmonary drug delivery of a powder medicament into a patient &# 39 ; s respiratory system , which includes filing the powder pockets of a blister pack with a fine powder medicament as discussed above . the fine powder medicament may for example be peptides or fragments thereof , proteins or fragments thereof , antibodies or fragments thereof , antibiotics , vaccines and any combination thereof . the blister pack is loaded into the powder inhaler and the blister pack is moved to bring a powder pocket into flow communication with an outlet flow passageway and a first gas flow inlet passageway , the first gas flow inlet passageway having an inlet in flow communication with a source of gas and an exit located on one side of the powder pocket , said outlet flow passageway having an inlet located on the other side of the powder pocket positioned in flow communication with the outlet flow passageway and an outlet on an exterior of the housing . the powder medicament in the powder pocket which is aligned with the first gas flow inlet and the outlet passageway is fluidized using a first flow of gas from the gas flow inlet passageway which flows into one side of the powder pocket to mobilize , fluidize and deagglomerate the powder medicament such that a mixture of powder medicament and gas flows out through the other side of said powder pocket and into said outlet flow passageway and out of the outlet through a mouthpiece inserted in a user &# 39 ; s mouth so that the medicament is expelled out through the mouthpiece and directly into the user &# 39 ; s respiratory system . the user can repeat this for as many powder pockets as needed . this method is very advantageous because the powder medicament does not need to contain any excipient powder particles , but a small amount may be included if desired . as used herein , the terms “ comprises ”, “ comprising ”, “ including ” and “ includes ” are to be construed as being inclusive and open ended , and not exclusive . specifically , when used in this specification including claims , the terms “ comprises ”, “ comprising ”, “ including ” and “ includes ” and variations thereof mean the specified features , steps or components are included . these terms are not to be interpreted to exclude the presence of other features , steps or components . the foregoing description of the preferred embodiments of the invention has been presented to illustrate the principles of the invention and not to limit the invention to the particular embodiment illustrated . it is intended that the scope of the invention be defined by all of the embodiments encompassed within the following claims and their equivalents . 6 , 546 , 929 april 2003 burr , et al . 6 , 325 , 061 december 2001 dagsland 6 , 257 , 732 july 2001 andersson , et al 6 , 209 , 538 april 2001 casper , et al . 6 , 116 , 239 september 2000 volgyesi 6 , 089 , 228 july 2000 smith 6 , 055 , 980 may 2000 mecikalski 6 , 012 , 454 january 2000 hodson , et al . 6 , 006 , 747 december1999 eisele , et al . 5 , 975 , 076 november 1999 yianneskis 5 , 921 , 237 july 1999 eisele , et al . 5 , 785 , 049 june 1998 smith 5 , 740 , 794 april 1998 smith 5 , 673 , 685 october 1997 heide , et al 4 , 627 , 432 december 1986 newel , et al . 1 . a . j . hickey , inhalation aerosols : physical and biological basis for therapy , new york , ( 1996 ). 2 . guidance for industry : metered dose inhaler ( mdi ) and dry powder inhaler ( dpi ) drug product , u . s . department of health and human services , 1998 . 3 . d . geldart , types of gas fluidization 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