UNIT FOR THE MICRONIZATION AND DOSAGE OF SOLID ACTIVE AGENTS

Abstract

A micronization unit for a solid active agent, such as a salt, preferably table salt (NaCl), for inhalation, is described.

The micronization unit includes a closed rotary drum containing a solid active agent having a grain size, preferably 0.1-4 millimeters (mm). Wall surfaces of the micronization unit are made at least in part of a material having a filtering capacity of 0.1-1000 micrometers (m). The material preferably is a mesh-like or microperforated material. The rotary drum dispenses particles of reduced size as it rotates.

Claims

1. A micronization unit for reducing particle size of particulate solid active agent having an average grain size no greater than 4 millimeters which comprises a closed rotary drum having an axis of rotation and a defining a micronization chamber containing said particulate solid agent, and a motor rotatably associated with the closed rotary drum; the closed rotary drum being adapted for positioning in an air flow path so that said axis of rotation is aligned with said air flow path, having a wall portion permeable to said active agent particles having a reduced particle size, and adapted to dispense only said particles having a reduced particle size into the air flow path while the closed rotary drum rotates about said axis of rotation.

2. A micronization unit according to claim 1, wherein the closed rotary drum contains a predetermined amount of a particulate solid active agent and is permanently sealed.

3. The micronization unit according to claim 1, wherein the particulate solid active agent is table salt (NaCl).

4. The micronization unit according to claim 1, wherein a wall portion of the rotary drum is made of a material having a filtering capacity of 0.1-100 m.

5. The micronization unit according to claim 1, wherein a wall portion of the rotary drum is made of a material having a filtering capacity of 0.1-20 m.

6. The micronization unit according to claim 1, wherein the rotary drum is driven by a constant rotational speed motor.

7. The micronization unit according to claim 1, wherein the rotary drum is capable of being spun up by the motor in a cyclical manner, undergoing an accelerating rotary motion with an angular acceleration of 25 radians/second.sup.2.

8. The micronization unit according to claim 1, wherein a heating element is included under the rotary drum.

9. The micronization unit according to claim 1, wherein a heating element is located in the air flow path upstream of the rotary drum.

10. The micronization unit according to claim 1, wherein the unit is disposed in an accumulation and dosing chamber fitted with flap valves.

11. The micronization unit according to claim 1, wherein the unit further comprises control electronics, a the control unit of the control electronics being fitted with an electronic device adapted for blocking operation of the unit based on parameter values specified in advance and measured operating data.

12. The micronization unit according to claim 1, further including a fan located in the air flow path.

13. The micronization unit according to claim 1, further including a housing surrounding the closed rotary drum and a mouthpiece downstream from the closed rotary drum, and in flow communication with the housing.

14. A micronization unit for reducing particle size of particulate solid active agent having an average grain size no greater than 4 millimeters which comprises a housing defining an air flow path therethrough; a frame positioned in the housing; a motor mounted to the frame; and a closed rotary drum in the housing, positioned in the air flow path, and operably associated with the motor for rotation about an axis of rotation.

15. The micronization unit according to claim 14, wherein a fan driven by the motor is positioned in the air flow path upstream from the closed rotary drum.

16. The micronization unit according to claim 14, wherein the closed rotary drum and the fan have a common axis of rotation.

17. The micronization unit according to claim 14, wherein the closed rotary drum is removably positioned in the housing, contains a predetermined amount of said particulate solid active agent, and is permanently sealed.

18. A micronization unit comprising a housing defining an air flow path, a motor in the housing and provided with a rotatable shaft, a rotary block of a first active agent mounted to the shaft, a friction block of a second active agent in a friction relationship with the rotary block, and a clamping device pressing the friction block against the rotary block.

19. The micronization unit according to claim 18 wherein the first active agent and the second active agent are the same.

20. The micronization unit according to claim 18 wherein the first active agent and the second active agent are different.

Description

BRIEF DESCRIPTION OF DRAWINGS

[0044] Preferred embodiments of the unit according to the present invention will be described in detail below, referring to the attached drawings, where

[0045] FIG. 1 is the schematic drawing of the first preferred embodiment of the unit according to the invention,

[0046] FIG. 2 is the schematic drawing of the second preferred embodiment of the unit according to the invention,

[0047] FIG. 3 is an exemplary arrangement for building the unit according to the invention into an indirect inhaler device,

[0048] FIG. 4 is an exemplary arrangement for building the unit according to FIG. 2 into a direct inhaler device,

[0049] FIG. 5 shows the block diagram of an exemplary control unit of the unit according to the invention,

[0050] FIG. 6 is an exploded perspective view of a preferred embodiment of the invention, and

[0051] FIG. 7 is a schematic drawing of yet another preferred embodiment of the unit according to the invention that does not include a rotary drum.

MODES FOR CARRYING OUT THE INVENTION

[0052] Referring to FIG. 1, micronization unit 1 comprises two major parts, a rotary drum 2 and a motor 3 driving rotary drum 2. Cylindrical surface of rotary drum 2, at least in the material part, is made of a material preferably having a filtering capacity of 0.1 to 100 m. Preferably the material is a closely woven metal mesh or a microperforated sheet. Drum 2 is expediently formed as a cylinder with a surface having an overall filtering capacity in the range of 0.1 to 1000 m, but the drum may also have a different, e.g. a spherical shape. The filter material has a typical filtering capacity of 0.1 to 20 m or 0.1 to 100 m depending on end use. The reduced particle size required for therapy can be different, however. It may be as large as 100 m for application primarily in the upper respiratory tract.

[0053] Since there is no officially established upper limit for the particle size of inhalable dust particles floating for a limited time (according to the WHO the particle size ranges from under 1 m to above 100 m, with no specific upper limit), the upper limit of the particle size range let through by the filter has been specified as 1000 m, which allows an appropriate leeway. On the other hand, with regard to the fact that the presently applied method of micronization generates extremely fine particles, having even sub-micron particle size, thenwhile although the most expedient maximum particle size would be e.g. 0.1 to 20 m but different maximum particle size values are not harmful eitherdriven, for example, by economic considerations, the use of materials having coarser filtering capacity may also be allowed, which results in an active agent with a particle size primarily appropriate for the application, and also in a micronized active agent having coarser particles that settle in the environment and in the upper respiratory tract. The filtering capacity range of 0.1 to 1000 m has been specified based on this.

[0054] A predetermined amount of active agent grains having the same grain size as table salt (NaCl), typically 0.1 to 4 millimeters (mm), are placed in the rotary drum 2 in such a manner that the material does not take up the entire volume of the rotary drum 2, preferably about one-half of the interior volume of rotary drum 2. During the operation of the unit, fine particles of the active agent separate from the grains loaded in the rotary drum 2. The unit 1 optionally includes fan 4. In this exemplary embodiment, fan 4 and the rotary drum 2 have a common shaft 6 driven by a motor 3. Also, in this embodiment reducing gear 5 is disposed between motor 3 and rotary drum 2. The reducing gear can also be omitted, as desired. It should be noted that rotary drum 2 and fan 4 may be driven independently of each other as well.

[0055] An optional heating element 7, adapted for keeping the active agent grains contained in rotary drum 2 sufficiently dry to avoid sticking to one another during operation, is disposed below rotary drum 2.

[0056] Heating element 7 may also be omitted, if desired.

[0057] Depending on the intended use, the unit 1 can be fitted with control electronics 13, the functionality whereof will be described in detail later.

[0058] FIG. 2 illustrates an embodiment of the unit 1 shown in FIG. 1 that also defines an accumulation and dosing chamber 8 provided with flap valves 9 and/or electromechanical or mechanical blocking valves 10 at input and output. For the sake of simplicity, both solutions have been included herein. The accumulation and dosing chamber 8 according to FIG. 2 may at the same time be the housing of an inhaler device. The unit 1 may also be fitted with control electronics 13. The arrow 14 indicates the direction of the air flow through the accumulation and dosing chamber 8.

[0059] FIG. 3 shows another exemplary embodiment of the unit 1 illustrated in FIG. 1, a simple apparatus comprising a fan. The unit 1 according to the invention and the control electronics 13 thereof are disposed inside the housing 11 of the apparatus. Again, the arrow 14 indicates the direction of the air flow.

[0060] As it is seen in FIG. 3, in this particular embodiment there is no reducing gear between rotary drum 2 and fan 4. Thus fan 4 and rotary drum 2 are operating at the same rotational speed. The embodiment described above can be utilized as a simple, tabletop indirect inhaler apparatus that includes a fan.

[0061] FIG. 4 illustrates another exemplary embodiment of the unit shown in FIG. 2.

[0062] In unit 1 no reducing gear is disposed between rotary drum 2 and fan 4. Thereby rotary drum 2 and fan 4 are driven at the same rotational speed by motor 3. Unit 1 is also equipped with control electronics 13. Unit 1 is implemented as a handheld device adapted for inhalation. A flap valve 9 is disposed at both ends of the housing 11 that receives the unit 1. By means of the flap valves 9 the prepared dose can be prevented from escaping from the housing before suction is applied to adapter 12 connected to one end of the housing. Moisture can also be prevented from reentering the device through the adapter (which the users doing the inhalation place in their mouth).

[0063] The unit illustrated in FIGS. 1 and 2 can be built into any inhaler or air treatment device/apparatus, but it is imperative that the unit 1 is located in, or is accessible to, the air flow path of the inhaler device/apparatus.

[0064] The rotary drum 2 of the unit 1 illustrated in FIGS. 1 to 4 can be operated either at a constant rotational speed mode or in a cyclical mode with rapid rotational speed changes.

[0065] The constant rotational speed mode is typically applied with the solution comprising a horizontal-axis gear, while the mode based on rapid rotational speed changes is typically utilized with the configuration wherein the longitudinal axis of the drum is set at an arbitrary acute angle relative to the horizontal axis of the unit.

[0066] During the operation of the constant rotational speed, preferably horizontal-axis rotary drum 2 of unit 1, the active agent grains, by way of example, salt crystals, preferably NaCl crystals, are contained in the rotary drum 2but only partially fill the rotary drum 2. The active agent grains rotated about a horizontal axis 6 or an axis set at an angle of at most 75 relative to the horizontal at such a speed that the crystals are pulled downwards by the gravitational force just before they could reach the top dead point. This means that during rotation, the gravitational force exerted on the crystals exceeds the centrifugal force (as calculated for a horizontal axis):

[0067] The gravitational force is: F=m*g

[0068] The centrifugal force is: F=m*(r*4*pi.sup.2)/T.sup.2

[0069] Hence g=r*4*pi.sup.2/T.sup.2.sub.min

[0070] 1/T.sup.2.sub.min=g/(r*4*pi.sup.2)

[0071] T.sub.min={square root over (r*4*pi2/g)}. Considering that pi.sup.2/g1, the approximate formula is T.sub.min2*{square root over (r)}.

[0072] This implies that the rotation cycle time should be longer than that, where g refers to gravitational acceleration, and r denotes a value equaling the inside radius of the rotary drum minus the radius of the smallest grain. In practice, it is expedient to allow an appropriate leeway.

[0073] As an example, a preferred embodiment has a rotary drum 2 with a diameter of 3.1 cm, and the rotary drum 2 is rotated at a maximum speed of n=244 rev/min during the phase when micronizing is carried out applying the above principle. As indicated by practical experience, the angle of the axis 6 of rotation may be varied in a relatively wide range, about 15, without significantly degrading the efficiency of the apparatus.

[0074] The rotary drum 2 is rotated at a constant speed. The active agent grains contained therein are turned over as a result, colliding and rubbing against one another. Thus a micronized active agent is produced that leaves the rotary drum and enters the accumulation chamber through its surface filtering material having a filtering capacity of 0.1 to 1000 micrometers (m). In addition to gravity, expelling the micronized active agent from the rotating drum is also assisted by the centrifugal forces occurring upon rotation of the drum, the optionally included fan 4 and/or by the suction effect of the air flow generated by the inhaler or air treatment device/apparatus in which the unit 1 is disposed. A sufficiently low rotational speed of the rotary drum 2 can also be provided by the reducing gear 5.

[0075] The unit 1 according to the invention can also be operated without a reducing gear (see FIG. 3).

[0076] The unit 1 may also be operated (with an arbitrary angle of axis) by spinning up the rotary drum 2 by means of the motor 3 in the same direction, or in alternating directions. By spinning up it is meant that the rotary drum 2 is rotated with varying speed, i.e. the rotary drum 2 is rotated such that it has a relatively high angular acceleration, which is followed by braking it either actively or by taking advantage of mechanical losses, thereby providing that, in addition to the micronizing action described above, the active agent grains are also subjected to a rubbing and turning action generated by the relatively high initial acceleration and fast braking of the rotary drum 2. In this case, in a resting state the active agent grains inside the rotary drum 2 take a position determined by gravity. During the spin-up phasedue to their inertiathe grains only gradually reach the rotational speed of the rotary drum 2, meanwhile being rubbed against the wall of the rotary drum 2 and turned over and rubbed against one another, and spreading all over the cylindrical surface of the rotary drum 2, thereby producing a micronized active agent that leaves the drum in a filtered manner through the 0.1 to 1000 micrometers (m) filtering-capacity walls of the rotary drum 2. A similar phenomenon occurs during hard braking. The expelling of the micronized active agent is assisted by the centrifugal forces occurring upon rotation of the drum, the optionally included fan 4 and/or by the suction effect of the air flow generated by the inhaler or air treatment device/apparatus in which the unit 1 is disposed, and, depending on the angle of the principal axis, also by gravity. Applying such a mode of operation with the dimensions exemplified above, the spin-up duration can be 1.5 seconds (sec.), the braking duration 3.5 sec., and the length of the rest period can be 2 sec. If a half filled-up rotary drum 2 having a 3.1 cm-long horizontal axis is spun up from resting state, the angular acceleration of the rotary drum 2 is preferably about 25 radians/second.sup.2. Rest periods are expediently included because of the variability of the duration of the deceleration/braking phase.

[0077] It is important to note that by the term motor an electric motor is primarily meant but it can also refer to a functionally equivalent rotating mechanism with a different operating principle. The above described modes of operation can be partly realized by mechanisms operated exclusively by the input of mechanical energy (by way of example, by pressing a button connected to a ratchet and gear mechanism, or by winding up a coil spring). These mechanisms can mostly be utilized when built into portable inhalers, by way of example in such a manner that the user spins up the rotary drum as many times and with a frequency as specified in the user's manual. The implementation of the mechanical rotating mechanism is not included in the invention since it can be realized by a skilled person in a number of known ways. The functionality of the motor may also be performed by the motor or fan of the apparatus containing the unit according to the invention.

[0078] It is of common knowledge that when a hygroscopic material is heated to a higher-than ambient temperature, its moisture content will drop. Taking into account that a major part of solid active agents to be micronized, for example NaCl, is hygroscopic, and therefore prone to clumping, it is expedient to heat it in order to keep it drier. This can be achieved by heating the rotary drum 2 and thereby the active agent contained therein applying a heating element 7. The heating element 7 is disposed below the rotary drum 2 (considering the typical operating position of the rotary drum 2). For a rotary drum 2 with a diameter of 3.1 cm and a length of 3 cm, containing 6 grams of NaCl crystals the required heating power of the heating element is 1-2 Watts, in case the air flow is applied intermittently (corresponding to the spin-up phases). It should be noted here that the heating element may also be disposed upstream of the rotary drum.

[0079] In FIG. 2 a variant of the unit 1 according to the invention further comprising an accumulation and dosing chamber 8 is shown, wherein the accumulation and dosing chamber 8 essentially corresponds to the housing that contains the unit's mechanism. Due to the action of the flap valves and blocking valves the particles leaving the rotary drum will be kept inside the accumulation and dosing chamber 8 while a dose is being prepared, and until the produced micronized active agent is used up. A dose of the active agent can leave the accumulation and dosing chamber 8 on the one hand when the user inhales the prepared micronized active agent by means of an oral or nasal adapter 12 (see FIG. 4) such that due to the suction action the flap valves 9 free up the path of the air flow (and thereby, the path of the active agent). At the same time, the flap valves prevent moist and contaminated exhaled airresulting from user errorfrom reentering the accumulation and dosing chamber 8 of the unit 1. Alternatively (by way of example, with a larger-sized inhaler unit) the active agent can also be fed to the air flow of the inhaler device containing the unit expediently by opening the electromechanical or mechanical blocking valves 10 and making the air flow through them. The optionally included fan 4 facilitates the expelling of the micronized active agent from the rotary drum 2, and also allows for circulating the micronized active agent in a floating state in the accumulation and dosing chamber 8 until it is used, preventing the micronized agent from settling.

[0080] The application of the accumulation and dosing chamber is justified if either the user cannot be expected to inhale low doses for a prolonged period of time (for example, with a pocketable handheld electronic inhaler), or if a single, higher dose is preferred for other reasons. Then, the duration of dose preparation (performed expediently in a closed chamber) is relatively long.

[0081] FIG. 5 shows the flow diagram of the control electronics 13 applicable with the unit 1 according to the invention. The control electronics can be operated by a switch 15, and has a control unit 16 and a power electronics unit.

[0082] A storage unit 17, adapted to store all the operating data that have been gathered since the unit 1 was first switched on, is connected to the control unit 16. Such data are the operating parameters of the motor 3, the count of operating cycles, and the data supplied by an ammeter 18 that may also be fed directly to the control unit 16. Control of the apparatus is performed by the control unit 16 utilizing current ammeter 18 data and data acquired earlier from the ammeter 18, further data stored in the storage unit 17, and also the data retrieved from a storage unit 19.

[0083] The storage unit 19 is applied for storing lab-measured decrease characteristics of the applied agent, the date of expiry, the maximum cycle count, and other factory-set parameters required for process control and for blocking the operation of the apparatus.

[0084] The control unit 16 also comprises a built-in clock 20. The control unit also comprises a signaling unit 21 adapted to provide light and/or sound signaling to indicate the on-off switching of the apparatus and for instance the expiry of the contained agent.

[0085] The control electronics 13 may also comprise a separate power source 22 (battery). By controlling the micronizer utilizing an embodiment or a combination of more than one embodiments of the unit 1 according to the invention in an appropriate manner it can be provided with a sufficient accuracy that the desired amount of micronized active agent is produced during each operating cycle.

[0086] In order to do that, the momentarily available (remaining) quantity of the active agent has to be determined applying one of the following methods: [0087] Under laboratory conditions the active agent release (per time unit) characteristics of the unit, dependent on certain parameters, such as the operating voltage, the mode of operation, the amount of remaining active agent, are determined and permanently stored in the memory of the unit at the factory. Based on these characteristics, and also on the stored operating data of former operating cycles and the starting amount the remaining amount of active agent can be calculated. [0088] Considering that in case of the mode of operation based on rapid change of rotational speed the spin-up characteristics will change as a function of the remaining amount of active agent (spinning up a lower mass requires a lower initial current), the remaining amount of active agent can also be inferred from the initial current.

[0089] Knowing the remaining amount of active agent the cycle time and optionally other parameters, by way of example the operating voltage of the motor, are automatically adjusted by the control unit 16.

[0090] The solutions operating as described above can be combined with a solution whereinunder certain conditionsthe control unit 16 blocks the further operation of the unit.

[0091] This solution is based on that the conditions under which the amount of delivered agent falls below the desired minimum within a fixed operation period are known from lab measurements, or under which a dose cannot be prepared within a comfortable period or with a sufficient safety margin even with the application of the operating parameters adjusted by the control electronics. In that case, and also upon the expiry of the active agent or at the end of a pre-programmed therapy session, the operation of the unit is blocked by the control electronics.

[0092] In the mode of operation of the unit according to the invention that is based on rapid changes of rotational speed the duration of the operating cycles (detectable by listening)the cycles consisting of a spin-up phase, a total or partial braking phase, and optionally, a resting phaseis expediently adjusted to the cycle time of relaxed breathing, i.e., approximately 6 seconds, which according to the literature can be utilized for practicing relaxed breathing in order to achieve proper air exchange and a lower blood pressure.

[0093] Yet another embodiment of the present invention is illustrated in FIG. 6. In particular, a battery-powered motor having a central drive shaft (not shown) is mounted in frame 30 and situated in housing 36 which has an open air intake end 38 and an open air exhaust end 40. Closed rotary drum 32 and fan 34, also situated in housing 36, are carried by the motor's drive shaft, and are rotated in unison when the motor is energized. Drum 32 and fan 34 preferably have a common axis of rotation. Slotted grille 44 provides closure for air exhaust end 40 of housing 36. If desired, a similar slotted grille may be provided for air intake end 38 as well.

[0094] Rotary drum 32 defines a micronization chamber and includes base portion 46, cylindrical midportion 48 and closure cap 50. Cylindrical midportion 48 is a superfine sieve having a desired filtration capacity for the active agent particles of reduced size which are dispensed through the sieve from drum 32 as drum 32 is rotated while the rest of the particulate agent is retained within drum 32.

[0095] Housing 36 also defines an air flow path therethrough into which the reduced size particles dispensed from rotary drum 32 are introduced.

[0096] The closed and permanently sealed rotary drum 32, containing a predetermined amount of the particulate solid active agent can be removably mounted to the driveshaft of the motor. In this manner, a permanently sealed rotary drum can serve as a readily replaceable sealed cartridge, for example, when the particulate solid active agent contained therein has irreversibly coagulated due to use of storage under extremely humid circumstances.

[0097] FIG. 7 schematically illustrates a further embodiment of the unit according to the invention that does not include a rotary drum. The unit 1 has four major parts: motor 3, rotary block 23preferably a disc or a ringfriction block 24 adapted to be in a friction relationship with rotary block 23, and a clamping device 25 adapted for pressing the friction block 24 against the rotary block 23. The friction relationship of friction block 24 relative to rotary block 23 means that contacting surfaces of blocks 24 and 23 are movable relative to one another during operation. Preferably, the contacting surfaces are relatively smooth and polished because it has been found that polished contacting surfaces generate more finely divided particles than abrasive surfaces. The unit 1 is disposed in an accumulation and dosing chamber 8 that can be fitted with flap valves 9 and blocking valves 10.

[0098] The unit is preferably incorporated in a housing 11, the input and output portions of the housing 11 being covered by a material having a filtering capacity of 0.1 to 1000 micrometers (m), preferably a closely woven filter 26, preferably a metallic mesh or microperforated plate adapted for filtering the air flowing through the unit 1.

[0099] The rotary block 23a disc or ringis disposed on the shaft 6 of the fan 4 driven by the motor 3. Thereby the rotary block 23 is driven by the motor 3 together with the fan.

[0100] A heating element 7 may be disposed below the rotary block 23. The motor 3 may also have control electronics 13.

[0101] The rotary block 23 and the friction block 24 can be made of identical or different materials.

[0102] If the rotary block 23 and the friction block 24 are made of the same material, then the material is, by way of example, table salt (NaCl). In case they are made of different materials, the rotary block 23 can be made, by way of example, of NaCl, while the material of the friction block 24 can be, by way of example, salbutamol.

[0103] The functionality of the heating element 7, the control electronics 13, the accumulation and dosing chamber 8, the flap valve 9 and the blocking valve 10 is essentially the same as was explained in relation to the unit comprising a rotary drum.

[0104] The operation of the unit 1 shown in FIG. 7 is described as follows:

[0105] By switching on the motor 3 the fan 4 and the rotary block 23disc or ringare brought into operation. During the rotation of the disc or ring 23 the friction block 24, being in frictional relation with the disc or ring 23, separates particles therefrom. The particles are expelled through the perforations of the filter 26 constituting the closing wallings of the housing 11 into the surrounding environment by the air flow produced by the fan 4, where its beneficial effect is produced upon inhaling them by the user.

[0106] Due to the frictional relation of the rotary block 23disc or ringand the friction block 24 fine particles separate from both objects.

[0107] The micronization capacity of the unit 1 is fundamentally dependent on rotational speed.

[0108] It should be noted that particle separation may also be accomplished applying a mechanism different from the friction block 24.

[0109] The unit according to the invention has the following advantages: [0110] it has simple structural arrangement, [0111] it can be adapted to suit different user needs.

[0112] The foregoing description and Figures are intended to be illustrative of the present invention and are not to be taken as limiting. Still other variants and rearrangements of parts within the spirit and scope of this invention are possible and will readily present themselves to the skilled artisan.