WO2001078817A1

WO2001078817A1 - Dosing system for a dry powder inhaler

Info

Publication number: WO2001078817A1
Application number: PCT/US2001/005797
Authority: WO
Inventors: Charles F. Ganem; Andrew W. Gieschen
Original assignee: Dura Pharmaceuticals, Inc.
Priority date: 2000-02-25
Filing date: 2001-02-21
Publication date: 2001-10-25
Also published as: AU2001241697A1

Abstract

A dry powder inhaler has a powder cartridge (50) installed in a cartridge slot in an inhaler housing. The powder cartridge has a tapered lower end terminating at a fill hole (80). A shaft (72) with a dose cup (74) is pivotable from a first position where the dose cup faces the fill hole to a second position where the dose cup faces downwardly. The tapered lower end of the cartridge housing forms a leveling angle of 30-80 degrees with the shaft for increased dosage uniformity.

Description

DESCRIP TION

DOSING SYSTEM FOR A DRY POWDER INHALER

BACKGROUND OF 1 HE INVENTION The field of the invention is dry powder inhalers. Dry powder inhalers are used to deliver a pharmaceutical, typically in a finely powdered form, to the lungs of a patient. The active pharmaceutical powder is typically mixed with an excipient, such as lactose, to better facilitate handling and delivery. The dry powder mixture is generally contained in sealed blisters, or similar containers, or it may be stored within a bulk powder reservoir within the inhaler.

A long-standing challenge in the design of dry powder inhalers having bulk powder storage is maintaining the particle size, flow and dosing characteristics of the bulk powder. Many pharmaceutical powders have a tendency to absorb moisture from the environment. The moisture can cause the powder to clump or cake up, or change the particle size distribution within the powder, resulting in inconsistent doses. Unlike blisters or other single use containers, a bulk pharmaceutical powder storage container in a dry powder inhaler must be repeatedly opened, so that individual doses may be metered out for inhalation. Moisture may penetrate into the powder, each time the bulk powder storage container is opened. Consequently, over time, dose consistency can be degraded, especially in humid environments.

Accordingly, it is an object of the invention to provide a dry powder inhaler having an improved dose delivery system.

BRIEF STATEMENT OF THE INVENTION In a first aspect of the invention, a dry powder inhaler has an inhaler housing including a cartridge slot above a mixing chamber. A removable powder cartridge containing a pharmaceutical powder is installed within the cartridge slot in the inhaler housing. The powder cartridge includes a cartridge housing having a tapered lower end terminating at a fill hole. A pivotable shaft has a dose cup aligned under the fill hole. The shaft is pivotable from a first position where the dose cup faces the fill hole, to a second ">

position where the dose cup faces the mixing chamber. The powder cartridge can advantageously be removed from the inhaler, and replaced with a new powder cartridge. The bulk pharmaceutical powder within the powder cartridge is metered out in uniform doses by pivoting the shaft. In a second and separate aspect of the invention, the tapered lower end of the cartridge housing has conical lower end walls terminating in a round fill hole. The lower end walls form a leveling angle with the shaft of from about 30-80 degrees. As a result, dose delivery precision is improved.

In a third and separate aspect of the invention, a powder storage chamber is provided in an inhaler housing or in a powder cartridge. A spring in the powder storage chamber has a lower end extending into the dose cup. The pivoting movement of the shaft which occurs with the delivery of each individual dose causes the spring to shift positions within the powder storage chamber, to agitate the powder and better facilitate powder flow.

BRIEF DESCRIPTION OF THE DRAWINGS In the drawings, wherein the same reference number denotes the same element throughout the several views:

Fig. 1 is a perspective view of a first embodiment of the present inhaler; Fig. 2 is a side section view thereof;

Fig. 3 is a front section view thereof;

Fig. 4 is a perspective view of the powder cartridge shown in Figs. 2 and 3; Fig. 5 is a perspective view of the mouthpiece shown in Figs. 1 and 2; Fig. 6 is a side view of an alternative powder cartridge embodiment; Fig. 7 is a front section view thereof;

Fig. 8 is a front view of the cap and spring shown in Fig. 7; Fig. 9 is an enlarged front view of the cartridge housing shown in Fig. 6; Fig. 10 is a side view of the dosator shown in Fig. 6; Fig. 11 is a section view taken along line 11-11 of Fig. 10; Fig. 12 is a schematic illustration of an alternative powder cartridge or reservoir geometry; Fig. 13 is a schematic illustration of the powder cartridge or reservoir geometry shown in Figs. 2 and 6;

Fig. 14 is a schematic illustration of yet another powder cartridge or reservoir geometry; and Fig. 15 is a schematic illustration of the measurement of leveling angles.

DETAILED DESCRIPTION OF THE INVENTION Turning now in detail to the drawings, as shown in Fig. 1, an inhaler 20 has a lid 24 attached to a housing 22. A mouthpiece 26 is movable between a retracted position, to an extended position (shown in Fig. 1) via finger movement of a slide button 92.

As shown in Figs. 2 and 3, a circuit board 30, batteries 32, and a motor 34 are contained within the housing 22. A propeller 36 attached to the motor 34 spins within a mixing chamber 38. as described e.g., in U.S. Patent No. 5,577,497.

A powder cartridge 50 is installed within a cartridge slot 40 in the inhaler housing 22, as shown in Fig. 2. Referring to Figs. 2 and 4, a powder cartridge 50 has a cartridge housing 52 including an upper cylindrical section 54, a conical lower section 56, and a shaft section 58. The upper cylindrical section 54 and conical lower section 56 define a powder storage chamber 60 for storing powder. A lid 62 closes off the upper end of the upper cylindrical section 54. A desiccant 64 is optionally provided on the lid or another location in the cartridge 50..

The conical lower section 56 of the cartridge housing 52 terminates in a fill hole 80, which provides a passageway from the powder storage chamber 60 into a shaft bore 78 extending through the shaft section 58. A drop hole 66 aligned with the fill hole 80 extends out through the bottom of the bore 78 and into the mixing chamber 38. A dosator 70 is installed within the cartridge housing 52, as shown in Figs. 3 and 4

(with an alternative dosator 104 shown in Figs. 6 and 10). The dosator includes a shaft 72 extending through the bore 78. A dose cup 74 is formed on or in the shaft 72. The dose cup 74 is aligned with the fill hole 80 and the drop hole 66. In the embodiment shown in Fig. 4, a spur gear 76 is attached at one end of the shaft 72. Referring to Figs. 1 and 5, the mouthpiece 26 has a tube 84 attached to spaced apart legs 86. One of the legs 86 has a rack gear 88 having teeth 90, adapted to mesh with the spur gear 76. The slide button 92 is attached to, or formed with, the leg 86 having the rack gear 88.

In use, the powder cartridge 50 is filled with a pharmaceutical powder composition. Preferably, the powder cartridge 50 is sealed within a pouch or other enclosure, until ready for use. The powder cartridge 50 is then removed from its package, the lid 24 of the housing 22 is opened, and the powder cartridge 50 is installed in the cartridge slot 40. The cartridge slot 40 locates the powder cartridge 50 so that the fill hole 80 and drop hole 66 align over the mixing chamber 38. The lid 24 is closed. The slide button 92 is moved out (from right to left in Fig. 1 ) via the patient's thumb or fingers As this occurs, the rack gear 88 turns the spur gear 76, causing the shaft 72 to rotate 180 degrees. Consequently, the dose cup 74, which initially is facing upwardly towards the powder storage chamber 66, and is filled with powder, moves to a downward facing position, in alignment with the drop hole 66. As the shaft 72 turns, the powder in the dose cup 74 is leveled as the cup moves away from the drop hole 66 and into the bore 78. The pharmaceutical powder in the dose cup 74 then drops into the mixing chamber 36. The motor 34 is then turned on when the patient inhales, as described in U.S. Patent No. 5,577,497.

The storage chamber 60 is preferably large enough to store at least 1.6 grams of powder, which is about the equivalent of 200 doses, of a unit dose of 8 mg. The size of the dose cup 74, which controls the volume of powder dispensed, can be varied to suit different pharmaceutical preparations. The diameter of the dose cup 74 is greater than the depth of the dose cup, so that all of the powder will tend to fall into the drop hole 66, with little or no powder remaining the upside down dose cup. The fill hole 80 is larger in diameter than the dose cup 74, so that the dose cup 75 is completely filled with powder when facing the fill hole 80. The drop hole 66 is larger in diameter than the dose cup 74 to avoid the hold up or accumulation of powder above the drop hole 66.

The shaft 72 is provided within an interference fit in the bore 78, i.e., with the shaft diameter preferably about .02-.3 mm larger than the bore diameter. The shaft 72 is preferably hollow, allowing it compress within the bore 78, and creating an outward spring force, to assist in sealing the shaft in the bore 78. The interference fit between the shaft 72 and the bore 78 minimizes powder leakage through the bore 78, and also minimizes moisture penetration into the storage chamber 60. For us with powder formulations which are not largely affected by ingress of moisture, less of an interference fit may be used.

The dosator 70 and cartridge housing 52 are preferably made of two different plastic materials, to avoid binding between the shaft 72 and bore 78. For example, the shaft 72 may be made of polypropylene, while the cartridge housing 52 is Delrin or Nylon.

Referring to Figs. 6-11, an alternate powder cartridge embodiment 100 is the same in design and operation as the powder cartridge 50 described above, with the following differences. The dosator 104 in the powder cartridge 100 has a knob 106 attached to shaft

108 having a dose cup 100. The dosator 104 is pivotably installed at the lower end the cartridge housing 102 of the powder cartridge 100. The upper end of the cartridge housing

102 is closed off, or sealed, with a cap 112. A spring 1 14 is attached to the cap 1 12 and extends down through the powder storage chamber 128 within the cartridge housing 102.

The bottom end or tip 1 16 of the spring 114 projects into the dose cup 110.

The cartridge housing 102 has a fill hole 122 above a shaft bore 120, and a drop hole 124, aligned with the fill hole 122, below the shaft bore 120, similar to the arrange of the fill hole 80, drop hole 66, and shaft bore 78 shown in Figs. 2 and 3.

The lower end of the cartridge housing 102 includes a conical section 126 terminating in a round fill hole 122. The powder cartridge 100 operates in a manner similar to the powder cartridge 50, except that the dosator is manually operated by turning the knob 106, in contrast to the automatic operation of the dosator 70 with movement of the slide button 92, in the inhaler shown in Fig. 1. In addition, as the shaft 108 turns, the spring member moves within the storage chamber 128, to agitate the powder and better facilitate free flow of powder into the cup 112.

Figs. 12-14 illustrate alternative cartridge housing or storage chamber geometries. As shown in Fig. 12, in an alternative chamber embodiment 140, the sidewalls of the chamber are straight, and meet the circumference of the shaft 72 perpendicularly to a horizontal line H passing through the shaft.

Fig. 13 shows the embodiments of Figs. 2 and 6, in a simplified form, for better comparison to the embodiments in Figs. 12 and 14. Fig. 14 shows an alternative storage chamber embodiment 150 having a cylindrical upper section 152, a conical section 154, and a smaller diameter cylindrical section 156 engaging the shaft 72, also with straight walls, as in Fig. 12 but with a reduced diameter. Table 1 below shows data from testing run on the designs shown in Figs. 12-14. As shown, the "straight walls to funner embodiment of I ig. 1 provides the best precision in dose delivery.

Table 1

In addition to the wall configuration shown in Figs. 12-14, another parameter affecting dosator performance is leveling angle. Referring to Fig. 15, the leveling angle is the angle formed by the walls W of the powder storage chamber engaging the shaft, and a tangent T to the circumference of the shaft, at the point that the walls W intersect the shaft (forming the angle LA in Fig. 15).

Data collected from testing on powder storage chambers having different leveling angles is shown in Table 2 below. As is apparent, leveling angles of from about 30-80 degrees, and more preferably from about 50-70 degrees, provide improved dose delivery precision.

Table 2

Turning to Fig. 16, in another alternative dosator embodiment 170, a knob or gear 172 is attached to a shaft 175. A cup 176 is provided in a cylindrical central cup section 174 on the shaft 175. The central cup section 174 is spaced apart from shoulders 178 by gaps 180. The shoulders 178 have narrow seal surfaces 182, of width W, which allows the dosator 170 to be installed within a bore of a storage chamber, with greater interference fit, for improved sealing. The width W of the seal surfaces 182 on the shoulders 178 is substantially less than the length S of the central cup section 174. A central bore 184 ma\ optionally be provided through the shaft 175, so that the shaft 175 can be more easiK compressed to provide an interference fit when installed in a storage chamber

Claims

1. A dry powder inhaler comprising: an inhaler housing: a cartridge slot in the inhaler housing; a mixing chamber in the inhaler housing, underneath the cartridge slot; a powder cartridge, removable from the inhaler housing, in the cartridge slot , the powder cartridge including a cartridge housing having a tapered lower end terminating at a fill hole, a shaft opening in the cartridge housing, a shaft in the shaft opening, and a dose cup on the shaft and aligned under the fill hole, the shaft pivotable from a first position wherein the dose cup is facing the fill hole, to a second position wherein the dose cup is facing the mixing chamber.

2. The inhaler of claim 1 wherein the first position is from 150 to 210 degrees from the second position.

3. The inhaler of claim 1 further comprising a finger actuated element on the outside of the inhaler housing linked to the shaft, for moving the shaft between the first and second positions.

4. The inhaler of claim 3 further comprising a mouthpiece attached to the finger actuated element.

5. The inhaler of claim 1 wherein the shaft has a single round blind dose cup having a diameter greater than its depth.

6. A dry powder inhaler comprising: an inhaler housing; a mixing chamber in the inhaler housing; a powder storage chamber having conical lower end walls terminating at a round fill hole; a shaft having a dose cup aligned under the fill hole, the shaft pivotable from a first position wherein the dose cup is facing the fill hole, to a second position wherein the dose cup is tacing the mixing chamber, and the lower end walls forming a leveling angle with the shaft of from about 30-80 degrees

7 The dry powder inhaler of claim 6 wherein the leveling angle is from about

50-70 degrees

8 A dry powder inhaler comprising an inhaler housing, a mixing chamber in the inhaler housing, a powder storage chamber having lower end walls terminating at a fill hole, a shaft having a dose cup aligned under the fill hole, the shaft pivotable from a first position wherein the dose cup is facing the fill hole, to a second position wherein the dose cup is facing the mixing chamber, and a spring in the powder storage chamber having an end tip extending into the dose cup

9 The inhaler of claim 8 further comprising a cap closing off a top end of the powder storage chamber, and with the spπng attached to the cap

10 A powder cartridge for use in a dry powder inhaler, comprising a cartridge housing having lower end walls terminating at a fill hole, a shaft having a dose cup aligned under the fill hole, the shaft pivotable from a first position wherein the dose cup is facing the fill hole, to a second position wherein the dose cup is facing away from the fill hole, and the lower end walls forming a levehng angle with the shaft of from about

30-80 degrees

11 The powder cartridge of claim 9 wherein the lower end walls are conical

12 The powder cartridge of claim 10 wherein the fill hole is round

13 T he powder cartridge of claim 9 further comprising a gear attached to the shaft and adapted to engage an actuator on an inhaler.

14. The inhaler of claim 1 further comprising a dessicant in the cartridge housing.

15. The inhaler of claim 14 wherein the cartridge housing has a sealed upper end. and the dessicant is attached to the upper end of the cartridge housing.