Powder compartment for high dosage drug delivery

Abstract

A dry powder inhaler for pulmonary or nasal use, comprising at least an inhaler body 801 and a cartridge 803 with at least one powder compartment 805 including one dose of a drug. The body has an opening 804 shaped for receiving the cartridge 803 and the means to allow a controlled sliding movement of the cartridge 803 relative to the body 801 after mounting. The cartridge powder compartment 805 comprises at least two inlets or slits 806, 809, at least one of which is a side inlet 809, for the admission of air, and a compartment outlet 807 to allow filling and fluid communication with an inhalation channel 808 provided in the body 801. In use, the patient slides the cartridge 803 relative to the body 801 from the storage position, where the inlets in the cartridge powder compartment 805 are blocked and sealed by walls comprised in the body 801, into the inhalation position, where the compartment inlets become available for the admission of air used in the dispersion of the particles there contained and the compartment outlet 807 becomes aligned with the inhalation channel 808 in the body 801 to allow the entrainment of the dose dispersed through the device and into the desired site of action during inhalation. The addition of one or more lateral vents 809 in the cartridge powder compartments induces a turbulent and swirling flow pattern that promotes improved dispersion and entrainment. The invention affords a very economical and simple device for the delivery of high dosages of inhaled medicines.

Claims

1. A dry powder inhaler suitable for pulmonary or nasal delivery, comprising an inhaler body and a cartridge; the inhaler comprising: (a) the inhaler body comprising a mouthpiece, a bottom channel inlet, an inhalation channel for providing fluid communication between the patient's mouth when engaged with the mouthpiece and the bottom channel inlet, at least one side inlet for allowing direct air admission from atmosphere into the inhalation channel; an inhaler body opening formed therein and defined between opposing top and bottom walls and opposing side walls, said inhaler body opening having at least one open end by means of which the cartridge is insertable into the opening and having at least one air inlet opening for admitting air into the inhaler body opening, means for guiding movement of the cartridge in the inhaler body opening relative to the body and control the cartridge travel from a storage position into an inhalation position; wherein the cartridge; (b) the cartridge being shaped for engagement in the inhaler body opening and having at least one substantially cylindrical powder compartment formed therein for carrying a powder-based medicament, and at least one air inlet vent; the powder compartment having an outlet which allows fluid communication with the body inhalation channel through the body bottom channel inlet and at least one pin for engaging with the body guiding movement means; wherein the cartridge is slidable within the body between the storage position in which the at least one air inlet vent of the cartridge is substantially sealed by the inhaler body such that there is no fluid communication to the cartridge, to the inhalation position, in which the or each air inlet vent of the cartridge is substantially aligned with an associated air inlet opening of the inhaler body such that there is fluid communication between the inlet opening of the inhaler body, the or each air inlet vent of the cartridge, the cartridge top outlet and the mouthpiece channel; wherein the cartridge having the at least one inlet vent includes at least two air inlet vents, at least one of which is a lateral air inlet vent and the inhaler body has an air inlet opening associated with each of the air inlet vents of the cartridge which allow admission of air from the atmosphere into the cartridge powder compartment when the cartridge is in the inhalation position; and the inhaler body bottom channel inlet further comprising at least one orifice which forms a sharp constriction in the fluid flow path from the cartridge powder compartment outlet into the inhalation channel when the powder cartridge is moved into the inhalation position.

2. The dry powder inhaler of claim 1, wherein the at least two air inlet vents of the cartridge includes a bottom inlet slit; and wherein the inhaler body includes a bottom opening which aligns with the bottom inlet slit when the cartridge is in the inhalation position.

3. The dry powder inhaler of claim 1, wherein the at least two air inlet vents of the cartridge includes at least one pair of lateral air vents formed in the side walls of the cartridge: and wherein the air inlet openings of the inhaler body include at least one pair of side openings formed in the side walls of the body opening, each side opening aligning with at least one associated lateral air vent of the cartridge when the cartridge is in the inhalation position.

4. The dry powder inhaler of claim 3, wherein the or each pair of lateral air vents are located on opposite sides of the compartment and the lateral air vents forming each pair are offset relative to each other so as to allow a non-tangential admission of air.

5. The dry powder inhaler of claim 1, wherein each cartridge powder compartment lateral vent has a width of between 0.1 and 2 mm.

6. The dry powder inhaler of claim 5, wherein each cartridge powder compartment lateral vent has a width of less than 1 mm.

7. The dry powder inhaler of claim 1, wherein each side opening in the inhaler body is associated with a plurality of lateral vents.

8. The dry powder inhaler of claim 1, wherein each cartridge powder compartment lateral vent tapers inwards towards the inner surface of the compartment so as to funnel the air as it passes through the vent into the compartment.

9. The dry powder inhaler of claim 1, wherein the inhaler body bottom channel inlet includes a plurality of orifices.

10. The dry powder inhaler of claim 9, wherein said plurality of orifices are arranged to form a structured grid.

11. The dry powder inhaler of claim 1, wherein cartridge powder compartment includes a lateral protrusion in the area of the or each air inlet opening that provides mechanical contact and inference with top, bottom and side walls of the body opening when the cartridge is in the storage position so as to seal each said air inlet opening.

12. The dry powder inhaler of claim 1, wherein the inhaler body inhalation channel bottom inlet provides a geometric constriction in the fluid channel passage area, the cross-sectional area of which constriction is between 30% and 99% of the powder compartment outlet cross section area.

13. The dry powder inhaler of claim 12, wherein the cross-sectional area of constriction is between 80% and 98% of the powder compartment outlet cross section area.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIGS. 1a to 1 c and 2a show a prior art inhaler;

(2) FIGS. 2b to 2g show perspective and side views of multiple embodiments of the powder compartment according to the invention;

(3) FIG. 3a shows a longitudinal sectional detailed view of the cartridge powder compartment outlet when the cartridge is moved into the inhalation position of and body inhalation channel bottom inlet according to the invention;

(4) FIG. 3b to 3d show top views of multiple embodiments of the body inhalation channel bottom inlet according to the invention;

(5) FIG. 4a to 4b show perspective views of the inhaler according to the invention when the powder cartridge is respectively in the storage and inhalation position;

(6) FIG. 5a shows a longitudinal sectional view of the inhaler according to the invention when the powder cartridge is in the storage position;

(7) FIG. 5b shows a longitudinal sectional detailed view of the powder cartridge bottom inlet according to the invention when the cartridge is in the storage position;

(8) FIG. 5c shows a transversal sectional view of the inhaler according to the invention when the powder cartridge is in the storage position;

(9) FIG. 6a shows a longitudinal sectional view of the inhaler according to the invention when the powder cartridge has been moved into the inhalation position;

(10) FIG. 6b shows a longitudinal sectional detailed view of the powder cartridge bottom inlet according to the invention when the cartridge has been moved into the inhalation position;

(11) FIG. 6c to 6d show transversal sectional detailed views of the inhaler according to the invention when the powder cartridge has been moved into the inhalation position;

DETAILED DESCRIPTION OF THE INVENTION

(12) Referring to the drawings, numbered sequentially after the word FIG., like numerals indicate like parts, and each of the embodiments is identified with series of numbers where the number of hundreds is the number of the embodiment (1xx to 8xx) and the equivalent feature in each of the embodiments has the same number xx.

(13) Referring to FIG. 2 which shows multiple embodiments of the powder compartment according to the invention, there is shown in FIG. 2a the first embodiment of the cartridge powder compartment 105 of tapered cylindrical or near-cylindrical shape comprising at least one bottom inlet slit 106. FIG. 2b shows a second embodiment of the cartridge powder compartment 205 of tapered cylindrical or near-cylindrical shape according to the invention comprising one bottom inlet slit 206 and at least one lateral vent 209. FIG. 2c shows a third embodiment of the cartridge powder compartment 305 according to the invention comprising one bottom inlet slit 306 and a pair of compartment lateral vent 309 included in opposite sides of the powder compartment 305. FIG. 2d shows a fourth embodiment of the cartridge powder compartment 406 according to the invention comprising one bottom inlet slit 406 and a pair of compartment lateral vent 409 included in opposite sides of the powder compartment 405 where each lateral vent 409 forming the pair is longitudinally offset relative to the other to allow a non-tangential admission of air into the powder compartment 405. FIG. 2e shows a fifth embodiment of the cartridge powder compartment 505 according to the invention comprising one bottom inlet slit 506 and a pair of compartment lateral vent 509 included in opposite sides of the powder compartment 505 where each lateral vent 509 forming the pair is longitudinally and vertically offset relative to the other to allow a diagonal and non-tangential admission of air into the powder compartment 505. FIG. 2f shows a sixth embodiment of the cartridge powder compartment 605 according to the invention comprising one bottom inlet slit 606 and multiple pairs of compartment lateral vent 609 included in opposite sides of the powder compartment 605 where each lateral vent 609 forming one of the pairs is longitudinally and vertically offset relative to the other to allow a diagonal and non-tangential admission of air into the powder compartment 605. FIG. 2g shows a seventh embodiment of the cartridge powder compartment 705 according to the invention comprising multiple pairs of compartment lateral vent 709 included in opposite sides of the powder compartment 705 where each lateral vent 709 forming one of the pairs is longitudinal and vertically offset relative to the other to allow a diagonal and non-tangential admission of air into the powder compartment 705.

(14) FIG. 3a shows a detailed longitudinal sectional view of the powder cartridge 203 including a powder compartment 205 according to the invention when the cartridge 203 is moved into the inhalation position and is aligned with a body inhalation channel 208 which allows the fluid communication between a powder compartment outlet 207 and a body inhalation channel bottom inlet 210 included in a top wall 211 of a body opening 204 for receiving the cartridge 203. There is also shown in FIG. 3a that the inhalation channel bottom inlet 210 comprises one or more orifices included in the top wall 211 of the body opening 204 that jointly provide a sudden geometric obstruction of the channel passage area in relation to the powder compartment outlet 207 cross sectional area. Moreover, FIGS. 3b to 3d show top views of additional embodiments of the inhalation channel bottom inlet 210, each similarly providing a sudden obstruction of passage area in relation to the powder compartment outlet 207 cross section area. FIG. 3b shows an embodiment of the inhalation channel bottom inlet 310 comprising a single circular orifice, while FIG. 3c shows an embodiment including an inhalation channel bottom inlet 410 formed of multiple circular orifices. FIG. 3d shows an embodiment of an inhalation channel bottom inlet 510 formed of multiple orifices with non-circular shape. FIG. 3e further depicts an embodiment of an inhalation channel bottom inlet 610 comprising multiple orifices forming a structured grid.

(15) Referring next to FIGS. 4, 5 and 6, there is shown an inhaler embodiment according to the invention in two different operational configurations. In FIG. 5a, a powder cartridge 803 is assembled into an opening 804 shaped for receiving it in the body component 801 and the cartridge 803 is the storage position. As shown in detail in FIGS. 5b and 5c, when the powder cartridge 803 is in it storage position, a compartment bottom inlet slit 806 is closed by smooth bottom walls 812 of the body opening 804 and a powder compartment lateral vent 809 is closed by the mechanical interference between compartment side protruding rims 813 and smooth side walls 814 of the body opening 804 so that the powder is blocked inside the compartment 805.

(16) In FIG. 6a, the powder cartridge 803 has been moved from the storage position shown in FIGS. 5a to 5c to the inhalation position allowing one of the powder compartments 805 to become aligned with the body inhalation channel 808. In this position. FIG. 6b details that air admission is allowed from atmospheric conditions through a body bottom opening 815 shaped in the body bottom walls 812 into the powder compartment 805 through the compartment bottom inlet slit 806. Also in this position, FIG. 6c shows in detail that supplementary air admission is also allowed from atmospheric conditions through the body side opening window 816 shaped in the body side walls 814 into the powder compartment 805 through the compartment lateral vent 809. Furthermore, FIG. 6a shows also that when one of the powder compartments 805 is moved into the inhalation position, fluid communication is established between a powder compartment outlet 807 and a body inhalation channel 808 through the body inhalation channel bottom inlet 810, which provides a sudden reduction of passage area relative to the powder compartment outlet 807 cross section area as depicted in FIG. 6a.

(17) When the powder cartridge 803 is in the inhalation position and the patient's mouth or nose is engaged with a body mouthpiece 802, the patient's inspiratory effort creates a suction that forces the air to travel through the body bottom inlet 815 and the powder compartment bottom inlet slit 806 inducing a bottom turbulent jet and simultaneously through the body side opening windows 816 and the powder compartment lateral vent 809 inducing a turbulent vortex confining the bottom turbulent jet, which generates a turbulent and swirling air flow pattern 817 shown in FIG. 6d through the powder compartment. This flow allows the drug particles to be dispersed while minimizing powder retention and travel through the powder compartment outlet 807 and into the bottom inhalation channel 810, where the sharp geometric constriction of fluid passage area allows further deagglomeration and break-up of the drug particle clusters, and finally into the body inhalation channel 808 and then into the mouth (or nose) and finally into the intended site of treatment such as the nasal cavity or the lung. Additional supplementary air flow is also provided to the body inhalation channel 808 through the body side inlets 818 to provide additional dispersive forces as well as a comfortable inhalation and to maximize the entrainment capability of the air.

EXAMPLE

(18) An inhaler embodiment according to the present invention has been tested in vitro to determine its aerodynamic profile as well as its powder dose delivery characteristics. The inhaler embodiment comprised a powder compartment according to the present invention that included one bottom inlet slit and four lateral vents with pairs of lateral vents in offset configuration as shown in FIG. 2f. The inhaler embodiment comprised a body inhalation channel bottom inlet, included in the top wall of the body opening, including multiple orifices arranged to form a structured grid that jointly provided a sudden obstruction of channel passage area where the obstruction area was approximately 0.85 of the compartment outlet cross section area.

(19) An experimental inhalation powder comprising inhalable amorphous spherical composite particles composed of 80% trehalose and 20% leucine was produced by spray drying. The composite particle spry dried powder was produced with a median particle size by volume (Dv50) of approximately 2 m leading to high cohesiveness and adhesiveness properties. The particle size, cohesive and adhesive properties of the powder were representative of powders produced by spray drying for applications of high dosage drug delivery to the lungs.

(20) The inhaler was hand filled with 80 mg of composite particle spray dried powder (40 mg per compartment), under controlled conditions of temperature and relative humidity (T<25 C. and % RH<30%), inside a glove box conditioned with nitrogen and using an appropriate analytical balance. The inhaler was then tested at a flow rate of 42 litres per minute and at a pressure drop of 4 kPa on an Andersen cascade impactor (Graseby Andersen. Smyrna, Ga.), actuated once to allow a volume of 4 litres of air to pass through the device, and the mass of powder deposited at each stage of the cascade impactor was quantified using gravimetric methods. From these data, the emitted mass and the fine particle mass were calculated, where the emitted mass was the sum of all masses collected from each of the impactor stages, including the inductor throat, and the fine particle mass was the mass of powder collected below the 5 m cut-off point. High dispersive and aerosolisation efficiency leads to a high emitted mass from the inhaler. In addition, the higher the fine particle mass, the higher the delivered lung dose is expected to be. The results are summarized in the following table:

(21) TABLE-US-00002 Delivery performance Emitted mass (EM) 73.4 mg Fine particle mass (FPM.sub.5m) 29.9 mg Fine particle fraction 40.7% (FPM.sub.5m/EM)

(22) This data indicates that the inhaler embodiment according to the present invention is capable of effectively dispersing and delivering large doses, in the range of 50 to 120 mg, of an inhalation powder, under inspiratory effort conditions which are compatible with the ability of patients.