Nasal delivery devices

A nasal delivery device for and method of delivering particulate substance to the nasal airway of a subject, the delivery device comprising: a body assembly (3) including a mouthpiece unit (9) which includes a mouthpiece through which the subject in use exhales, and a substance-supply unit which is fluidly connected to the mouthpiece unit and actuatable to provide particulate substance for delivery to the nasal airway of the subject; wherein the body assembly is configured to receive a replaceable nosepiece unit (5) which includes a nosepiece and contains a container containing particulate substance.

The present invention relates to a nasal delivery device for and method of delivering particulate substance, in particular a powdered substance, to the nasal airway of a subject, and a container for use with the same.

There is an increasing interest in the nasal delivery of substances, typically pharmaceutical drugs, both as powders and liquids, for topical and systemic delivery.

Current delivery systems are not suited to the delivery of substances to the upper posterior region of the nasal airway, in particular targeted delivery to the olfactory region and the sinus ostia.

U.S. Pat. No. 4,013,075 and U.S. Pat. No. 4,889,114 disclose examples of prior art inhalation devices, which provide for the inhalation of a powdered substance from a capsule.

WO-A-00/051672, the content of which is herein incorporated by reference, discloses a delivery device for delivering a substance, in particular a medicament, in a bi-directional flow through the nasal cavities, that is, an air flow which passes into one nostril, around the posterior margin of the nasal septum and in the opposite direction out of the other nostril. A particular feature of this bi-directional mode of delivery is the ability to target defined regions in the nasal airway, for both topical and systemic delivery, in particular the upper posterior region which cannot be targeted with existing systems.

The present inventors have recognized that the delivery of powdered substances using the exhalation breath of a subject still presents a significant challenge.

It is an aim of the present invention to provide a delivery device which allows for delivery of powdered substances from containers, typically capsules or blisters, which contain a pre-metered dose of substance with the appropriate particle size distribution and surface properties, where using the exhalation breath of the subject.

In one aspect the present invention provides a nasal delivery device for delivering particulate substance to the nasal airway of a subject, the delivery device comprising: a body assembly including a mouthpiece unit which includes a mouthpiece through which the subject in use exhales, and a substance-supply unit which is fluidly connected to the mouthpiece unit and configured to receive a replaceable nosepiece unit which includes a nosepiece and contains a container containing particulate substance, wherein the substance-supply unit is actuatable to provide particulate substance for delivery to the nasal airway of the subject.

In one embodiment the delivery device further comprises: a replaceable nosepiece unit which includes a nosepiece for fitting to a nostril of a subject, and a container chamber which contains a container containing particulate substance.

In one embodiment the delivery device is configured to prevent operation until a nosepiece unit is fitted to the body assembly.

In one embodiment the body assembly includes an actuation mechanism which is manually actuatable by the subject to open the container, and the delivery device is configured to prevent actuation of the actuation mechanism until the nosepiece unit is fitted to the body assembly.

In one embodiment the substance-supply unit includes an interlock mechanism which adopts a first, locking configuration when a nosepiece unit is not fitted to the body assembly, in which the actuation mechanism is not actuatable, and a second, released configuration when a nosepiece unit is fitted to the body assembly, in which the actuation mechanism is actuatable.

In one embodiment the interlock mechanism comprises an interlock member which is movably disposed between locking and released positions and normally biased to the locking position.

In one embodiment the substance-supply unit includes a valve unit which is operable between a first, closed configuration in which a fluid communication path with the mouthpiece is closed, and a second, open configuration in which the fluid communication path is open.

In one embodiment the interlock mechanism is configured to lock the valve unit in the closed configuration when the interlock mechanism is in the locking configuration and allow operation of the valve unit when the interlock mechanism is in the released configuration.

In one embodiment the valve unit includes a locking element which is engaged by the interlock mechanism when the interlock mechanism is in the locking configuration to prevent operation of the valve unit.

In another aspect the present invention provides a nasal delivery device for delivering particulate substance to the nasal airway of a subject, the delivery device comprising: a mouthpiece unit which includes a mouthpiece through which the subject in use exhales; a nosepiece unit which includes a nosepiece for fitting to a nostril of the subject; and a substance-supply unit which is configured to receive a container containing particulate substance and operable to provide a metered amount of substance in fluid communication with the mouthpiece and nosepiece units, such that an exhalation air flow delivered through the substance-supply unit entrains the substance.

In one embodiment the container comprises first and second parts which together define an enclosed chamber and are movable between a first, closed configuration in which the container is closed and a second, open configuration in which the container is open, and the substance-supply unit is operable to move the first and second parts of the container to the open configuration.

In one embodiment the first and second parts of the container are slideably disposed relative to one another and each include at least one aperture, which are closed with the first and second parts in the closed configuration and opened by sliding of the first and second parts to the open configuration.

In one embodiment the substance-supply unit comprises a support member, and a body section which is movable relative to the support member between a first, container-receiving position for receiving a container in the closed configuration, and a second, operative position in which the container is opened and disposed in fluid communication with the mouthpiece and nosepiece units.

In one embodiment the body section is rotatably disposed to the support member.

In one embodiment the body section includes a container-receiving aperture, which allows for introduction of a container thereinto when the body section is in the container-receiving position and is closed when the body section is in the operative position.

In one embodiment one of the support member and the body section includes an inlet aperture which is fluidly isolated from the mouthpiece unit when the body section is in the container-receiving position and fluidly connected to the mouthpiece unit when the body section is in the operative position.

In one embodiment the support member and the body section each include an engagement feature for engaging respective ones of the first and second parts of the container, and the support member and the body section are axially movable relative to one another, such that, on movement of the body section from the container-receiving position to the operative position, the first and second parts of the container are moved to the open configuration.

In one embodiment the support member and the body section are coupled by a cam mechanism, which provides that the engagement features thereof are moved between a first spacing in which the container is received therebetween, a second, closer spacing in which the first and second parts of the container are moved to the open configuration, and a third spacing in which the container is moveable axially between the engagement features.

In one embodiment the delivery device further comprises: a housing which supports the mouthpiece unit, the nosepiece unit and the substance-supply unit.

In one embodiment the substance-supply unit includes a container-receiving member which is movably disposed to the housing between an open position for enabling loading of a container thereinto, and a closed position in which the container is contained within the housing.

In one embodiment the container-receiving member includes a cavity which defines an air flow channel between the mouthpiece and nosepiece units, such that an air flow is delivered therethrough on exhalation by the subject through the mouthpiece, and a support section for supporting the container in the cavity.

In one embodiment the container comprises, a main body part and first and second bearing support parts at the respective ends of the body part, and the support section includes first and second container supports for rotatably supporting the respective support parts of the container.

In one embodiment the support parts of the container comprise part-spherical projections and the container supports comprise part-spherical recesses.

In one embodiment the substance-supply unit includes a locking mechanism for locking the container-receiving member in the closed position.

In a further aspect the present invention provides a nasal delivery device for delivering particulate substance to the nasal airway of a subject, the delivery device comprising: a body assembly including a mouthpiece unit which includes a mouthpiece through which the subject in use exhales, and a substance-supply unit which is fluidly connected to the mouthpiece unit and actuatable to provide particulate substance for delivery to the nasal airway of the subject; wherein the body assembly is configured to receive a replaceable nosepiece unit which includes a nosepiece and contains a container containing particulate substance.

In one embodiment the delivery device further comprises: a replaceable nosepiece unit which includes a nosepiece for fitting to a nostril of a subject, and a container chamber which contains a container containing particulate substance.

In one embodiment the delivery device is configured to prevent operation until a nosepiece unit is fitted to the body assembly.

In one embodiment the body assembly includes an actuation mechanism which is manually actuatable by the subject to open the container, and the delivery device is configured to prevent actuation of the actuation mechanism until the nosepiece unit is fitted to the body assembly.

In one embodiment the actuation mechanism is locked in a locked configuration when a nosepiece unit is not fitted to the body assembly, such as to prevent operation of the actuation mechanism.

In one embodiment the nosepiece unit includes a release member for releasing the actuation mechanism from the locked configuration on fitting the nosepiece unit to the body assembly.

In one embodiment the actuation mechanism includes an actuation member which is latched in a locked position in the locked configuration of the actuation mechanism, and the release member of the nosepiece unit is operative to release the latched actuation member on fitting the nosepiece unit to the body assembly.

In one embodiment the nosepiece unit is fitted to the body assembly in one, fitting sense and removed from the body assembly in the opposite, removal sense, and the release member includes a support element, an engagement element for engaging the actuation mechanism and a frangible connection element which connects the support element to the engagement element, wherein the engagement element presents a substantially rigid structure when the nosepiece unit is fitted in a first instance to the body assembly and is operative to release the actuation mechanism from the locked configuration, and is deformed on removing the nosepiece unit from the body assembly.

In one embodiment the body assembly further comprises a locking mechanism for locking the actuation mechanism from further operation following a predeterminable number of operations of the actuation mechanism.

In one embodiment the locking mechanism comprises a rotatable element which is indexed with each actuation of the actuation mechanism and locks the actuation mechanism to prevent further operation thereof following a predeterminable number of operations of the actuation mechanism.

In a yet further aspect the present invention provides a container comprising first and second body parts which together define an enclosed chamber and are movable between a first, closed configuration in which the container is closed and a second, open configuration in which the container is open.

In one embodiment the first and second body parts are slideably disposed relative to one another and each include at least one aperture, which are closed with the first and second body parts in the closed configuration and opened by sliding of the first and second body parts to the open configuration.

In one embodiment the first and second body parts include inter-engaging guides which provide for axial sliding of the first and second body parts without substantially any rotation thereof.

In one embodiment the container is an elongate container.

In one embodiment the container is a capsule.

In one embodiment the container is for containing particulate substance.

In a still further aspect the present invention provides a container comprising a main body part and first and second bearing support parts at the respective ends of the main body part which provide bearing supports about which the container is rotatable.

In one embodiment the support parts comprise part-spherical projections, and preferably substantially hemi-spherical projections.

In one embodiment the container is an elongate container.

In one embodiment the container is a capsule.

In one embodiment the container is for containing particulate substance.

FIGS. 1 to 6illustrate a delivery device in accordance with a first embodiment of the present invention.

The delivery device comprises a main, body assembly3and a nosepiece unit5, which contains a container C containing substance to be delivered to the nasal cavity of a subject and is removably fitted to the body assembly3, such as to allow for re-use of the body assembly3, as will be described in more detail hereinbelow.

In this embodiment the container C comprises a capsule, but could have any form which contains a metered dose of substance, such as a blister.

The body assembly3comprises a housing7, a mouthpiece unit9and a substance-supply unit11which is fluidly connected to the mouthpiece unit9and to which the nosepiece unit5is fitted.

The mouthpiece unit9comprises a mouthpiece15which in use is gripped in the lips of a subject, and an air flow channel17which is fluidly connected to the substance-supply unit11.

In this embodiment the housing7and the mouthpiece unit9are integrally formed, typically from a plastics material.

The substance-supply unit11comprises a body section21which receives the nosepiece unit5, a rupturing mechanism23which is operable to rupture the container C as contained by the nosepiece unit5, and an interlock member25which is operative to prevent operation of the rupturing mechanism23without the nosepiece unit5being fitted, or at least being fitted properly, to the body section21.

The body section21comprises a body member29which includes a cavity31, in this embodiment cylindrical in shape, an inlet33which is in fluid communication with the cavity31and fluidly connected to the air flow channel17of the mouthpiece unit9, and an outlet35which is in fluid communication with the cavity31and fluidly connected to the nosepiece unit5when fitted to the body section21. With this configuration, an exhalation air flow, as delivered through the mouthpiece unit9, is delivered through the cavity31of the body section21and from the nosepiece unit5.

The body section21further comprises a first guide41, in this embodiment comprising a pair of laterally-extending slots43on opposed sides of the body member29, which act to guide the rupturing mechanism23laterally to the body member29in rupturing the contained container C.

The body section21further comprises a second guide45, in this embodiment comprising a first pair of longitudinally-extending slots47on opposed sides of the body member29, which act to guide the interlock member25longitudinally to the body member29, and a third longitudinally-extending slot49, which slideably contains a contact element87of the interlock member25and receives a contact element97on the nosepiece unit5in providing for release of the interlock member25, as will be described in more detail hereinbelow.

The substance-supply unit11further comprises a valve51which is disposed at the inlet33of the body member29and operable between a first, closed position, as illustrated inFIG. 4, which substantially prevents an air flow through the cavity31of the body member29, and a second, open position, as illustrated inFIG. 6, which allows for a flow through the cavity31of the body member29.

In this embodiment the valve51is a pressure-sensitive valve which is such as to prevent an air flow through the cavity31until a predetermined pressure has been developed upstream thereof.

In this embodiment the valve51comprises a flap member57which is hingeable about a pivot59and normally biased to a closed, sealing position by a resilient element61, here a spring, such that a predetermined pressure is required to overcome the biasing force of the resilient element61.

In this embodiment the flap member57includes a locking element63, here in the form of an arm, which is operably coupled to the interlock member25, such that the flap member57is locked in the closed position when the nosepiece unit5is not fitted to the substance-supply unit11and is free to be moved to the open position when the nosepiece unit5is fitted to the substance-supply unit11, as will be described in more detail hereinbelow.

In this embodiment the rupturing mechanism23comprises an actuating member73, here in the form of a button, which is configured to be depressed by the subject, a piercing element75, here including two pins, which is supported by the actuating member73and operable to pierce the container C, and thereby provide for release of the contained powdered substance on the generation of a flow through the cavity31of the body section21, and a biasing element76, here a resilient element, such as a compression spring, for biasing the actuating member73to an inoperative position.

The actuating member73includes at least one guide element77, here a pair of guide elements77in the form of arms, which are slideably disposed in the slots43of the first guide41of the body section21. In this embodiment the at least one guide element77includes a detent79, which retains the actuating member73captive in the first guide41.

The interlock mechanism25comprises an interlock member81which is slideably disposed to the body section21, in this embodiment longitudinally along the length thereof, and a biasing element83, here a resilient element, such as a compression spring, for normally biasing the interlock member81to a locking position, as illustrated inFIG. 3, such as to prevent operation of the actuation mechanism23when the nosepiece unit5is not fitted to the substance-supply unit11.

In this embodiment the interlock member81comprises at least one guide element85, here a pair of guide elements85in the form of arms, which are slideably disposed in the slots47of the second guide45of the body section21, a contact element87, here an elongate element, which is slideably disposed in the slot49of the second guide45of the body section21, and a locking element89, here defined by an aperture, which is operative to engage with the locking element63on the flap member57.

With this configuration, the interlock member81, when biased to the locking position, as illustrated inFIG. 3, acts to lock the flap member57in the closed position by engagement of the locking element89of the interlock member81and the locking element63of the flap member57, and the guide elements85of the interlock member81are located such as to prevent movement of the guide elements77of the actuating member73, and thereby prevent actuation of the same, and, when the nosepiece unit5is fitted to the substance-supply unit11, as will be described in more detail hereinbelow, the interlock member81is moved against the bias of the biasing element83to a released position, in which the locking element89of the interlock member81is disengaged from the locking element63of the flap member57, such as to allow for the flap member57to be moved and opened on exhalation by the subject through the mouthpiece unit9at a predetermined flow rate, and the guide elements85of the interlock member81are moved clear of the guide elements77of the actuating member73, such as to allow for actuation of the actuating member73.

In one embodiment the mouthpiece unit9could include a heat exchanger which is in fluid communication with the mouthpiece15and acts to draw heat from the exhaled air flow as delivered through the mouthpiece15, thus decreasing the temperature of the air flow as delivered to the cavity31. By decreasing the temperature of the air flow, the humidity of the air flow is reduced, with the water vapor condensing in the heat exchanger, and the impact of condensation is significantly reduced, thus allowing for successive doses of powdered substance to be delivered without affecting the release of powdered substance from the containers C.

The nosepiece unit5comprises a nosepiece91, in this embodiment a frusto-conical section, which is inserted into a nostril of the subject, in this embodiment to provide a sealing fit therewith, and a container chamber93which is in fluid communication with the nosepiece91and contains a container C containing a powdered substance for delivery to the nasal cavity of the subject.

In this embodiment the nosepiece unit5further comprises a grid, here a gauze, which is disposed between the nosepiece91and the container chamber93, such as to prevent the container C or any parts thereof, such as resulting from rupturing of the container C, from passing through the nosepiece91and entering the nasal cavity of the subject.

In this embodiment the container chamber93and the grid, as components which contact the container C and the contained powder, are fabricated from a material having a low moisture sensitivity, here a plastics material, such as to reduce any tendency to become tacky in the presence of moisture, and therefore reduce the tendency for the container C and the powdered substance as contained thereby to adhere to the wall of the container chamber93or the grid.

In this embodiment the nosepiece91, as a component which contacts the powdered substance, is fabricated from a material having a low moisture sensitivity, here a plastics material, such as to reduce any tendency to become tacky in the presence of moisture, and therefore reduce the tendency for the powdered substance to adhere to the wall of the nosepiece91.

In one embodiment the container C is a gelatine capsule.

In another embodiment the container C can be manufactured from a material which has a reduced tendency to become tacky in the presence of moisture, as occurs with gelatine capsules, and therefore reduce the tendency for the container C to adhere to the wall of the container chamber93or the grid.

In one embodiment the container C is formed of a cellulose derivative, such as hydroxypropyl methylcellulose (HPMC), hydroxypropylcellulose, methylcellulose, ethylcellulose and carboxymethylcellulose.

In another embodiment the container C can comprise a plastics material, preferably a water insoluble material, such as a polycarbonate.

In one embodiment the container C can be manufactured from a lightweight material, such as thin-wall section polymeric materials, which reduces the energy required to move the container C, typically by one or both of vibration and rotation, and thereby allow the delivery device to be operated at reduced flow rates, which is particularly advantageous for nasal delivery.

In an alternative embodiment the container C can include an outer coating of a material, such as parylene, which has a reduced tendency to become tacky in the presence of moisture, as occurs with gelatine capsules, and therefore reduce the tendency for the container C to adhere to the wall of the container chamber93or the grid.

In this embodiment, the container C is cylindrical in shape with hemispherical ends.

In other embodiments the container C could have other geometric forms, such as spherical, which allows for efficient powder release at low flow rates.

The nosepiece unit5further comprises a contact element97, in this embodiment an axially-extending element, which is configured to be a sliding fit in the third slot49of the second guide45of the body section21of the substance-supply unit11, such that, on inserting the nosepiece unit5into the body section21, the contact element97engages the contact element87of the interlock member81, in this embodiment the distal end thereof, such as to move the interlock member81to the released position.

Operation of the delivery device will now be described hereinbelow.

A subject first inserts a nosepiece unit5into the body section21of the substance-supply unit11. On inserting the nosepiece unit5into the body section21, the contact element97thereof engages the contact element87of the interlock member81, such as to move the interlock member81to the released position when the nosepiece unit5is fully inserted into the substance-supply unit11. With the interlock member81in the released position, the flap member57is disengaged from the locking element89of the interlock member81and free to be moved by an exhalation air flow, and the actuating member73of the rupturing mechanism23is operable by the subject.

The subject then operates the rupturing mechanism23to rupture the container C as contained in the container chamber93of the nosepiece unit5.

The subject then inserts the nosepiece91into one of his/her nostrils, grips the mouthpiece15in his/her mouth, and exhales through the mouthpiece15.

The exhaled air flow, where having a sufficient flow rate, is then driven through the cavity31of the body section21and the container chamber93, which acts to move the container C, in this embodiment by vibration and rotation, and entrain the powdered substance as contained by the container C.

The exhaled air flow, as then entraining the powdered substance, is delivered though the nosepiece91into one nasal cavity of the subject.

In this embodiment the exhaled air flow is such as to pass around the posterior region of the nasal septum, and into the other nasal cavity, thereby achieving a bi-directional air flow as described in the applicants' earlier WO-A-00/051672.

Following use, the nosepiece unit5is then removed and the above-described procedure can be repeated with another nosepiece unit5.

FIGS. 7 to 13illustrate a delivery device in accordance with a second embodiment of the present invention.

The delivery device comprises a housing103, a nosepiece unit105, a mouthpiece unit109and a substance-supply unit111which is fluidly connected to the nosepiece and mouthpiece units105,109. As will be described in more detail hereinbelow, the delivery device is a re-usable device, to which containers C, in this embodiment capsules, containing substance to be delivered to the nasal cavity of a subject are removably loaded.

As illustrated inFIGS. 12 and 13, the containers C comprise first and second body parts115,117, which together define an enclosed chamber119and are movably disposed, here slideably disposed relative to one another. The body parts115,117each include at least one aperture121,123, in this embodiment a plurality of apertures121,123, which are closed with the body parts115,117in a first, closed configuration and are opened by sliding of the body parts115,117to a second, open configuration in which the apertures121,123in the body parts115,117are aligned.

In this embodiment the body parts115,117include inter-engaging guides125,127, which provide for axial sliding of the body parts115,117without any rotation thereof, thereby ensuring alignment of the apertures121,123.

In this embodiment the housing103comprises a body135to which the nosepiece unit105, the mouthpiece unit109and the substance-supply unit111are disposed, and a cover137, here a hinged lid, which is operable between a closed position in which the nosepiece and mouthpiece units105,109are enclosed and an open position in which the nosepiece and mouthpiece units105,109are exposed for use.

The body135includes a container aperture139, in this embodiment an elongate aperture, through which a container C is loaded and removed from the substance-supply unit111, as will be described in more detail hereinbelow.

The nosepiece unit105comprises a nosepiece141, in this embodiment a frusto-conical section, which is inserted into a nostril of the subject, here to provide a sealing fit therewith, and a flow channel143which is fluidly connected to the nosepiece141and includes a grid145, in this embodiment a gauze, at one, lower end thereof.

The mouthpiece unit109comprises a mouthpiece147which in use is gripped in the lips of a subject, and a one-way, non-return valve149which is fluidly connected to the mouthpiece147and is operative to prevent inhalation by the subject through the mouthpiece147.

The substance-supply unit111comprises a support member151which is fixed to the body135of the housing103, and a body section153which is movably disposed, in this embodiment rotatably disposed, to the support member151.

The support member151includes a cam member161which includes a cam track163which extends between first and second positions165,167and includes stops169at the respective ends thereof, in this embodiment at angular positions of 180 degrees. In this embodiment the cam track163includes a first cam section, corresponding to a first phase of rotation, which is inclined from a first, lower position165to the second, higher position167and a second cam section, corresponding to a second phase of rotation, which is inclined from the second, higher position167to the first, lower position165.

The body section153comprises a body member171, in this embodiment a tubular member, which defines a container chamber172and includes a first, container-receiving aperture173in the lateral wall thereof for receiving a container C, a second, inlet flow aperture175at one, the lower, end thereof, and a third, outlet flow aperture177at the other, upper, end thereof which receives the flow channel143of the nosepiece unit105and is slideably disposed thereto. As will be described in more detail hereinbelow, the body section153is rotatable between a first, closed position in which the container-receiving aperture173is closed by the enclosure member of the body135and the inlet aperture175is in fluid communication with the mouthpiece unit109, and a second, open position in which the container-receiving aperture173is open to the container aperture139in the body135and the inlet aperture175is closed.

The body section153further comprises a grid181, here a gauze, which is located within the body member171at a location intermediate the container-receiving aperture173and the inlet flow aperture175, which acts to support a container C when loaded into the body member171. As will be described in more detail hereinbelow, the grid181is configured to compress the container C against the grid145in the nosepiece unit105, such as to open the container C by aligning the apertures121,123thereof.

The body section153further comprises a cam follower179, in this embodiment in the form of a projection which projects laterally from the body member171, which is configured to ride on the cam track163of the cam member161and provide for axial displacement of the body section153relative to the support member151on rotation of the body section153.

In this embodiment the body section153is rotatable between a closed position, as illustrated inFIGS. 7 to 9, in which the cam follower179is located on the cam track163of the cam member161at the first, lower position165, through an intermediate position, as illustrated inFIG. 11, in which the cam follower179is located on the cam track163of the cam member161at the second, raised height167, and to an open position, as illustrated inFIG. 10, in which the cam follower179is located on the cam track163of the cam member161at the first height165. When the cam follower179is located on the cam track163of the cam member161at the first height165, the grid181of the body section153is spaced from the grid145of the nosepiece unit105, such as to allow for axial movement and rotation of a contained container C, and, when the cam follower179is located on the cam track163of the cam member161at the second height167, the grid181of the body section153is spaced more closely to the grid145of the nosepiece unit105, such as to cause the compression of the body parts115,117of the container C and thereby open the container C.

The body section153further comprises an actuating member183, in this embodiment in the form of a knob, which can be gripped by the subject and is connected to the body member171, in this embodiment at a lower end thereof, such as to provide for rotation of the body member171.

In one embodiment the mouthpiece unit109could include a heat exchanger which is in fluid communication with the mouthpiece147and acts to draw heat from the exhaled air flow as delivered through the mouthpiece147, thus decreasing the temperature of the delivered air flow. By decreasing the temperature of the air flow, the humidity of the air flow is reduced, with the water vapor condensing in the heat exchanger, and the impact of condensation is significantly reduced, thus allowing for successive doses of powdered substance to be delivered without affecting the release of powdered substance from the containers C.

In this embodiment the container chamber172and the grids145,181, as components which contact the container C and the contained powder, are fabricated from a material having a low moisture sensitivity, here a plastics material, such as to reduce any tendency to become tacky in the presence of moisture, and therefore reduce the tendency for the container C and the powdered substance as contained thereby to adhere to the wall of the container chamber172or the grids145,181.

In this embodiment the nosepiece141, as a component which contacts the powdered substance, is fabricated from a material having a low moisture sensitivity, here a plastics material, such as to reduce any tendency to become tacky in the presence of moisture, and therefore reduce the tendency for the powdered substance to adhere to the wall of the nosepiece141.

In one embodiment the container C is a gelatine capsule.

In another embodiment the container C can be manufactured from a material which has a reduced tendency to become tacky in the presence of moisture, as occurs with gelatine capsules, and therefore reduce the tendency for the container C to adhere to the wall of the container chamber172or the grids145,181.

In one embodiment the container C is formed of a cellulose derivative, such as hydroxypropyl methylcellulose (HPMC), hydroxypropylcellulose, methylcellulose, ethylcellulose and carboxymethylcellulose.

In another embodiment the container C can comprise a plastics material, preferably a water insoluble material, such as a polycarbonate.

In one embodiment the container C can be manufactured from a lightweight material, such as thin-wall section polymeric materials, which reduces the energy required to move the container C, typically by one or both of vibration and rotation, and thereby allow the delivery device to be operated at reduced flow rates, which is particularly advantageous for nasal delivery.

In an alternative embodiment the container C can include an outer coating of a material, such as parylene, which has a reduced tendency to become tacky in the presence of moisture, as occurs with gelatine capsules, and therefore reduce the tendency for the container C to adhere to the wall of the container chamber172or the grids145,181.

In this embodiment, the container C is cylindrical in shape with hemispherical ends.

In other embodiments the container C could have other geometric forms, such as spherical, which allows for efficient powder release at low flow rates.

Operation of the delivery device will now be described hereinbelow.

A subject first operates the actuating member183such as to rotate the body section153from the closed position, as illustrated inFIGS. 7 to 9, in this embodiment through 180 degrees, to the open position, as illustrated inFIG. 10, in which the container aperture173in the body member171is aligned with the container aperture139in the housing103, such as to allow a container C to be loaded into the container chamber172of the body member171.

The subject then again operates the actuating member183such as to return the body section153to the closed position. In so operating the actuating member183, the body section153is first moved from the open position in which the cam follower179on the body section153is located on the cam track163of the cam member161at the first, lower height165, through an intermediate position, as illustrated inFIG. 11, in which the cam follower179is located on the cam track163of the cam member161at the second, raised height167. In this intermediate position, the grid181of the body section153is spaced more closely to the grid145of the nosepiece unit105, such as to cause the compression of the body parts115,117of the container C and thereby open the container C. With continued operation of the actuating member183, the body section153is moved from the intermediate position to the closed position, as illustrated inFIGS. 7 to 9, in which the cam follower179is located on the cam track163of the cam member161at the first, lower height165and the grid181of the body section153is spaced further apart from the grid145of the nosepiece unit105, such as to allow for axial movement and rotation of a contained container C, the container aperture173in the body member171is closed by the enclosure member of the housing103and the inlet aperture175is in fluid communication with the mouthpiece unit109.

The subject then inserts the nosepiece141into one of his/her nostrils, grips the mouthpiece147in his/her mouth, and exhales through the mouthpiece147.

The exhaled air flow, where having a sufficient flow rate, is then driven through the container chamber172of the body member171of the body section153, which acts to move the container C, in this embodiment by vibration and rotation, and entrain the powdered substance as contained by the container C.

The exhaled air flow, as then entraining the powdered substance, is delivered though the nosepiece141into one nasal cavity of the subject.

In this embodiment the exhaled air flow has such a pressure as to pass around the posterior region of the nasal septum, and into the other nasal cavity, thereby achieving a bi-directional air flow as described in the applicants' earlier WO-A-00/051672.

Following use of the device, the actuating member183is first operated such as to rotate the body section153from the closed position, in this embodiment through 180 degrees, to the open position, in which the container aperture173in the body member171is aligned with the container aperture139in the housing103, such as to allow the used container C to be removed from the container chamber172of the body member171, and the actuating member183is subsequently operated such as to rotate the body section153from the open position, in this embodiment through 180 degrees, to the closed position, in which the container aperture173in the body member171is closed.

FIGS. 14 to 17illustrate a delivery device in accordance with a third embodiment of the present invention.

The delivery device comprises a housing203, a nosepiece unit205, a mouthpiece unit209and a substance-supply unit211which is fluidly connected to the nosepiece and mouthpiece units205,209. As will be described in more detail hereinbelow, the delivery device is a re-usable device, to which containers C, in this embodiment capsules, containing substance to be delivered to the nasal cavity of a subject are removably loaded.

As illustrated inFIGS. 14 and 15, the containers C comprise a main body part215, in this embodiment of cylindrical section, and first and second supports217at the respective ends of the body part215, which act as bearings about which the container C is rotated. In this embodiment the supports217comprise hemi-spherical structures, which are of smaller radial dimension than the body part215and located on the longitudinal axis of the body part215. In one embodiment the supports217could be offset relative to one another or eccentrically weighted, such as to promote the vibration of the container C on rotation.

In this embodiment the housing203comprises a body235to which the nosepiece unit205, the mouthpiece unit209and the substance-supply unit211are disposed.

The body235includes a container aperture239, through which a container C is loaded and removed from the substance-supply unit211, as will be described in more detail hereinbelow.

The nosepiece unit205comprises a nosepiece241, in this embodiment as defined by a tubular section, which is inserted into a nostril of the subject, here to provide a sealing fit therewith.

In one embodiment the nosepiece unit205can include a grid, such as a gauze, for preventing the container C or parts thereof from passing through the nosepiece241and into the nasal cavity of the subject.

The mouthpiece unit209comprises a mouthpiece247which in use is gripped in the lips of a subject, and a heat exchanger249which is in fluid communication with the mouthpiece247and acts to draw heat from the exhaled air flow as delivered through the mouthpiece247, thus decreasing the temperature of the delivered air flow. By decreasing the temperature of the air flow, the humidity of the air flow is reduced, with the water vapor condensing in the heat exchanger249, and the impact of condensation is significantly reduced, thus allowing for successive doses of powdered substance to be delivered without affecting the release of powdered substance from the containers C.

In this embodiment the heat exchanger comprises a plurality of parallel, elongate tubes.

The substance-supply unit211comprises a container-receiving member251, which is slideably disposed within the container aperture239in the housing203between an open position for enabling the loading of a container C thereinto, as illustrated inFIGS. 14 and 15, and a closed position, as illustrated inFIGS. 16 and 17, in which the container C is contained within the housing203.

In this embodiment the container-receiving member251comprises a cavity253which defines an air flow channel from the mouthpiece245to the nosepiece241and includes first and second supports255, in this embodiment part-spherical structures which act as bearings and are configured to receive the respective supports217of the container C, such that, on delivery of an exhalation air flow through the cavity253, the container C is rotated by the supports217thereof.

The substance-supply unit211further comprises a locking mechanism261which is operative to lock the substance-supply unit211in the closed position.

In this embodiment the locking mechanism261comprises at least one arm member263, in this embodiment a plurality of arm members263a,263b,which are deflectable, here inwardly, and each include a detent265which is engageable with a surface of the housing203, such as to lock the substance-supply unit211in the closed position. In this embodiment the substance-supply unit211is located in the locked position by pushing the substance-supply unit211into the housing203, which causes the detents265on the arm members263a,263bto ride over the housing203and be locked behind a surface thereof, and withdrawn from the housing203by deflecting the arm members263a,263b, here by squeezing the arm members263a,263binwardly, such as to release the detents265from engagement with the respective surfaces of the housing203, and pulling the substance-supply unit211outwardly.

The substance-supply unit211further comprises a rupturing mechanism271which is operable to rupture the container C as contained by the nosepiece unit205.

In this embodiment the rupturing mechanism271comprises an actuating member273, here in the form of a button, which is configured to be depressed by the subject, as illustrated inFIG. 17, a piercing element275, here including two pins, which is supported by the actuating member273and operable to drive the piercing element275to pierce the container C, and thereby provide for release of the contained powdered substance on the generation of a flow through the cavity253in the container-receiving member251, and a resilient element277, here a compression spring, for returning the actuating member273to the rest position following piercing of the container C.

In this embodiment the container-receiving member251and the grid, as components which contact the container C and the contained powder, are fabricated from a material having a low moisture sensitivity, here a plastics material, such as to reduce any tendency to become tacky in the presence of moisture, and therefore reduce the tendency for the container C and the powdered substance as contained thereby to adhere to the container-receiving member251or the grid.

In this embodiment the nosepiece241, as a component which contacts the powdered substance, is fabricated from a material having a low moisture sensitivity, here a plastics material, such as to reduce any tendency to become tacky in the presence of moisture, and therefore reduce the tendency for the powdered substance to adhere to the wall of the nosepiece241.

In one embodiment the container C is a gelatine capsule.

In another embodiment the container C can be manufactured from a material which has a reduced tendency to become tacky in the presence of moisture, as occurs with gelatine capsules, and therefore reduce the tendency for the container C to adhere to the container-receiving member251or the grid.

In one embodiment the container C is formed of a cellulose derivative, such as hydroxypropyl methylcellulose (HPMC), hydroxypropylcellulose, methylcellulose, ethylcellulose and carboxymethylcellulose.

In another embodiment the container C can comprise a plastics material, preferably a water insoluble material, such as a polycarbonate.

In one embodiment the container C can be manufactured from a lightweight material, such as thin-wall section polymeric materials, which reduces the energy required to move the container C, typically by one or both of vibration and rotation, and thereby allow the delivery device to be operated at reduced flow rates, which is particularly advantageous for nasal delivery.

In an alternative embodiment the container C can include an outer coating of a material, such as parylene, which has a reduced tendency to become tacky in the presence of moisture, as occurs with gelatine capsules, and therefore reduce the tendency for the container C to adhere to the container-receiving member251or the grid.

Operation of the delivery device will now be described hereinbelow.

A subject first withdraws the substance-supply unit211by deflecting the arm members263a,263bof the locking mechanism261, here by squeezing the arm members263a,263binwardly, such as to release the detents265thereof from engagement with the respective surfaces of the housing203, and pulling the substance-supply unit211outwardly.

The subject then loads a container C into the cavity253in the container-receiving member251, such that the end parts217of the container C are located on the respective supports255of the cavity253. It will be appreciated that this design allows the containers C for different substances to be sized differently, such as to prevent the device from being used improperly with different substances.

The subject then closes the substance-supply unit211by pushing the substance-supply unit211into the housing203, which causes the detents265on the arm members263a,263bto ride over the housing203and be locked behind a surface thereof.

The subject then operates the rupturing mechanism271to rupture the container C, in this embodiment by depressing the actuating member273thereof, as illustrated inFIG. 17, following which the actuating member273is returned to the rest position by the biasing element277thereof.

The subject then inserts the nosepiece241into one of his/her nostrils, grips the mouthpiece247in his/her mouth, and exhales through the mouthpiece247.

The exhaled air flow, where having a sufficient flow rate, is then driven through the cavity253of the container-receiving member251, which acts to move the container C, in this embodiment by vibration and rotation, and entrain the powdered substance as contained by the container C.

The exhaled air flow, as then entraining the powdered substance, is delivered though the nosepiece241into one nasal cavity of the subject.

In this embodiment the exhaled air flow has such a pressure as to pass around the posterior region of the nasal septum, and into the other nasal cavity, thereby achieving a bi-directional air flow as described in the applicants' earlier WO-A-00/051672.

Following use of the device, the substance-supply unit211is opened by deflecting the arm members263a,263bof the locking mechanism261, here by squeezing the arm members263a,263binwardly, such as to release the detents265thereof from engagement with the respective surfaces of the housing203, and pulling the substance-supply unit211outwardly.

The subject then unloads the container C from the cavity253in the container-receiving member251, and closes the substance-supply unit211, in this embodiment by pushing the substance-supply unit211into the housing203, which causes the detents265on the arm members263a,263bto ride over the housing203and be locked behind respective surfaces thereof.

FIGS. 18 to 26illustrate a delivery device in accordance with a fourth embodiment of the present invention.

The delivery device comprises a main, body assembly303and a nosepiece unit305, which contains a container C, in this embodiment a capsule, containing substance to be delivered to the nasal cavity of a subject and is removably fitted to the body assembly303, such as to allow for the re-use of the device, as will be described in more detail hereinbelow.

The body assembly303comprises a housing307, a mouthpiece unit309, a rupturing mechanism315which is operable to rupture the container C as contained by the nosepiece unit305, and a locking mechanism317for preventing operation of the rupturing mechanism315without a nosepiece unit305being fitted to the housing307and also after a predetermined number of operations.

The housing307comprises a body319which defines a cavity321and includes a first, fitting aperture323in which the nosepiece unit305is fitted and a second, clearance aperture325through which extends an actuating member371of the rupturing mechanism315.

In this embodiment the body319includes at least one, here a plurality of projections327which are disposed about the fitting aperture323, such as to provide for the screw-fitting of the nosepiece unit305to the housing307.

The mouthpiece unit309comprises a mouthpiece331which in use is gripped in the lips of a subject, an air flow channel333which is fluidly connected to the cavity321of the housing307, and a one-way, non-return valve335for preventing inhalation through the mouthpiece331.

In this embodiment the housing307and the mouthpiece unit309are integrally formed, typically from a plastics material.

The nosepiece unit305comprises a body member341which is configured to fit in the fitting aperture323in the housing307, a nosepiece343, here as defined by a tubular section, which is supported by the body member341and is in use inserted into a nostril of the subject, here to provide a sealing fit therewith, and a container chamber345which is in fluid communication with the nosepiece343and contains a container C containing a powdered substance for delivery to the nasal cavity of the subject.

In this embodiment the body member341includes at least one, here a plurality of recesses351which are disposed thereabout in correspondence to the projections327which are disposed about the fitting aperture323of the housing307, such as to provide for the screw-fitting of the nosepiece unit305to the housing307. With this configuration, fitting of the nosepiece unit305to the housing307first requires insertion of the nosepiece unit305into the housing307and subsequently rotation of the nosepiece unit305in one sense, here in a counter-clockwise sense when viewed from above.

The nosepiece unit305further comprises a release member355which is configured to engage a counterpart latch member377on the actuating member371of the rupturing mechanism315, such as to release the actuating member371to an operative position following fitting of the nosepiece unit305, as will be described in more detail hereinbelow.

In this embodiment the release member355comprises a radially-directed arm, which comprises a support element359which is attached to the container chamber345, an engagement element361which is operative to engage the latch member377of the actuating member371of the rupturing mechanism315, and a frangible connection element363, here a flexible, deformable element, which connects the support element359to the engagement element361in such a manner that the engagement element361presents a rigid structure when rotated in the one, fitting sense in fitting the nosepiece unit305to the housing307and is deformed, here plastically deformed, when rotated in the other, removal sense in removing the nosepiece unit305from the housing307, as represented inFIGS. 20and21. In this embodiment the connection element363is bent, and permanently deformed, by engagement with the latch member377of the actuating member371of the rupturing mechanism315on removing the nosepiece unit305from the housing307, and this deformation prevents re-use of the nosepiece unit305, insofar as the release member355is no longer operative to release the actuating member371of the rupturing mechanism315to a release position. With this configuration, the possibility of using a used nosepiece unit305is avoided and the subject is thus ensured of receiving a dose of substance with each operation of the device.

In this embodiment the nosepiece unit305further comprises a grid363, here a gauze, which is disposed between the nosepiece341and the container chamber345, such as to prevent the container C or any parts thereof, such as resulting from rupturing of the container C, from passing through the nosepiece341and entering the nasal cavity of the subject.

In this embodiment the container chamber345and the grid363, as components which contact the container C and the contained powder, are fabricated from a material having a low moisture sensitivity, here a plastics material, such as to reduce any tendency to become tacky in the presence of moisture, and therefore reduce the tendency for the container C and the powdered substance as contained thereby to adhere to the wall of the container chamber345or the grid363.

In this embodiment the nosepiece341, as a component which contacts the powdered substance, is fabricated from a material having a low moisture sensitivity, here a plastics material, such as to reduce any tendency to become tacky in the presence of moisture, and therefore reduce the tendency for the powdered substance to adhere to the wall of the nosepiece341.

In one embodiment the container C is a gelatine capsule.

In another embodiment the container C can be manufactured from a material which has a reduced tendency to become tacky in the presence of moisture, as occurs with gelatine capsules, and therefore reduce the tendency for the container C to adhere to the wall of the container chamber345or the grid363.

In one embodiment the container C is formed of a cellulose derivative, such as hydroxypropyl methylcellulose (HPMC), hydroxypropylcellulose, methylcellulose, ethylcellulose and carboxymethylcellulose.

In another embodiment the container C can comprise a plastics material, preferably a water insoluble material, such as a polycarbonate.

In one embodiment the container C can be manufactured from a lightweight material, such as thin-wall section polymeric materials, which reduces the energy required to move the container C, typically by one or both of vibration and rotation, and thereby allow the delivery device to be operated at reduced flow rates, which is particularly advantageous for nasal delivery.

In an alternative embodiment the container C can include an outer coating of a material, such as parylene, which has a reduced tendency to become tacky in the presence of moisture, as occurs with gelatine capsules, and therefore reduce the tendency for the container C to adhere to the wall of the container chamber345or the grid363.

In this embodiment, the container C is cylindrical in shape with hemispherical ends.

In other embodiments the container C could have other geometric forms, such as spherical, which allows for efficient powder release at low flow rates.

In this embodiment the rupturing mechanism315comprises an actuating member371, here in the form of a button, which extends through the clearance aperture325in the housing307and is configured to be depressed by the subject, a piercing element375, here including two pins, which is supported by the actuating member371and operable to drive the piercing element375to pierce the container C, and thereby provide for release of the contained powdered substance on the generation of a flow through the container chamber345of the nosepiece unit305, and a biasing element376, here a compression spring, for normally biasing the actuating member371outwardly of the housing307, such as to withdraw the piercing element375.

The actuating member371includes a latch member377which is operative to lock the actuating member371in an intermediate position, as illustrated inFIG. 26, in which the piercing elements375are withdrawn from the container chamber345, such as to allow for rotation of the contained container C, and first and second lug members379,381which are operative to operate the locking mechanism317and prevent further depression of the actuating member371from the intermediate position.

In this embodiment the latch member377comprises a resilient arm383and a detent385at one end of the arm383, which engages a surface of the housing307to latch the actuating member371in the intermediate position. In this embodiment the latch member377is released, here by deflection of the resilient arm383, by engagement with the release member355of the nosepiece unit305in fitting the nosepiece unit305to the housing307. As described hereinabove, the release member355of the nosepiece unit305is not operative to release the latch member377on removal of the nosepiece unit305from the housing307, as the release member355is deformed through engagement with the latch member377.

In this embodiment the locking mechanism317comprises a rotatable member391which includes a plurality of first engagement elements393, in this embodiment disposed on a first annulus centred about the rotation axis of the rotatable member391, and a plurality of second engagement elements395which are disposed on a second, larger annulus centred about the rotation axis of the rotatable member391.

The first engagement elements393each include an outwardly-facing, locking surface397which, when the actuating member371of the rupturing mechanism315is in the intermediate position, acts to engage an adjacent first lug379of the actuating member371, such as to prevent depression of the same.

The second engagement elements395each include an indexing surface399which is engaged by respective ones of the lugs379,381such as to index the rotatable member351, such that the actuating member371of the rupturing mechanism315can be depressed to rupture the contained container C following release of the actuating member371to the released position and prevent further depression of the actuating member371following release of the actuating member371to the intermediate position.

In one embodiment the mouthpiece unit309could include a heat exchanger which is in fluid communication with the mouthpiece331and acts to draw heat from the exhaled air flow as delivered through the mouthpiece331, thus decreasing the temperature of the air flow as delivered to and downstream of the container member345. By decreasing the temperature of the air flow, the humidity of the air flow is reduced, with the water vapor condensing in the heat exchanger, and the impact of condensation is significantly reduced, thus allowing for successive doses of powdered substance to be delivered without affecting the release of powdered substance from the containers C.

Operation of the delivery device will now be described hereinbelow.

A subject first takes a nosepiece unit305for fitting to the body assembly303, as illustrated inFIG. 22.

The subject then inserts a nosepiece unit305into the fitting aperture323in the housing307, as illustrated inFIG. 23.

The subject then rotates the nosepiece unit305, in this embodiment in the counter-clockwise sense from above, such as to lock the nosepiece unit305to the housing307, as illustrated inFIG. 24. This rotation of the nosepiece unit305causes the release member355thereof to engage the latch element377of the actuating member371, such as to release the same, here by deflection of the resilient arm383of the latch element377through engagement with the release member355.

The subject then operates the rupturing mechanism315to rupture the contained container C, as illustrated inFIG. 25, following which the subject releases the actuating member371, which returns to the intermediate position, as illustrated inFIG. 26.

The subject then inserts the nosepiece341into one of his/her nostrils, grips the mouthpiece331in his/her mouth, and exhales through the mouthpiece331.

The exhaled air flow, where having a sufficient flow rate, is then driven through the cavity321in the housing307and the container chamber345, which acts to move the container C, in this embodiment by vibration and rotation, and entrain the powdered substance as contained by the container C.

The exhaled air flow, as then entraining the powdered substance, is delivered though the nosepiece341into one nasal cavity of the subject.

In this embodiment the exhaled air flow has such a pressure as to pass around the posterior region of the nasal septum, and into the other nasal cavity, thereby achieving a bi-directional air flow as described in the applicants' earlier WO-A-00/051672.

Following use of the device, the nosepiece unit305is then removed from the device assembly303, in order to allow for the device to be re-used.

The nosepiece unit305is removed by rotating the nosepiece unit305relative to the housing307, in this embodiment in a clockwise sense when viewed from above, and withdrawing the nosepiece unit305from the fitting aperture323in the housing307.

On rotating the nosepiece unit305, the release arm355of the nosepiece unit305engages the latch member377of the actuating member371, in this embodiment through engagement with the engagement element361of the release member355, which causes the connection element363of the release member355to be bent, and permanently deformed. As described hereinabove, this deformation prevents re-use of the nosepiece unit305, insofar as the release member355is no longer operative to release the actuating member371of the rupturing mechanism315to the operative position.

Finally, it will be understood that the present invention has been described in its preferred embodiments and can be modified in many different ways without departing from the scope of the invention as defined by the appended claims.

In one embodiment the powdered substance can also be formulated, for example, by coating or blending, such as to reduce the hygroscopicity and transiently increase the dissolution time, and thus reduce any loss of powdered substance in the device due to interaction with condensation on the internal surfaces of the device.

Also, the delivery devices of the described embodiments have been described particularly in relation to the use of capsules. It is to be understood that the present invention has application with any kind of powder delivery system, including blisters, and can be configured as a single-use or multi-use device.