Pressurized metered dose inhalers (pMDI) may be used for delivering medication in the form of aerosols to patients. The route of delivery of the medicament using such inhalers may be oral or nasal.

Such an inhaler commonly comprises a canister containing the medicament aerosol formulation, and an actuator with a delivery passage. The canister contains the aerosol formulation, either as a solution or suspension, in the form of one or more drugs and propellant, and optionally excipients, selected from co-solvents, surfactants, stabilizing substances (for chemical or physical stability) and flavourings. The canister also comprises a metering valve arranged to deliver a metered dose of the medicament on actuation of the inhaler.

The actuator typically comprises a housing, generally made of a plastic material, within which the canister is located. A portion of the canister will usually project above the actuator housing.

In oral inhalers the actuator has a delivery passage in the form of a mouthpiece that is placed in the patient's mouth and through which the medicament passes on being dispensed. The patient places the mouthpiece in their mouth and breathes in, creating an air flow from the actuator through the mouthpiece and into the mouth and lungs. At the same time the patient actuates dispensation of the medicament from the canister. Actuation may occur as a result of inhalation by the patient or the patient may manually actuate the inhaler, for example, by depressing the projecting portion of the canister further into the housing. Nasal actuators operate in a similar fashion, but instead of a mouthpiece the actuator is provided with a nosepiece for delivery of the medicament to the nasal passages. In the case of nasal medicament delivery, there is not a need for the concurrent inhalation of air, however.

WO-A-98/031411 discloses an aerosol inhalation device that is manually operated and comprises a holding part for receiving an aerosol container with a valve and outlet tip, an inspiratory part and a member for passage of aerosol. US-A-2003/0089368 discloses nozzles for aerosol propellant systems, and more particularly aerosolization spray nozzles for metered dose inhalers.

US-B- 3,361,306 discloses an aerosol device for dispensing a liquid containing a medically active ingredient dissolved or suspended therein.

WO-A-99/25407 discloses an actuator for an inhaler for administering medicament by inhalation.

GB-A-2, 143,283 discloses applicators for dispensing medicaments from a pressurised dispensing container.

GB-A-2, 170,430 discloses improvements relating to spray nozzles, particularly of the kind that are used to dispense a fine spray of liquid.

GB-A- 1,021,739 discloses a device for use in inhalation therapy with aerosols.

GB-A-2, 366,519 discloses a dispensing apparatus for use with pressurised dispensing containers and, in particular, an apparatus for dispensing orally inhaled medicinal products in aerosol form.

GB-A-2, 415, 388 discloses a delivery device for products, such as medicaments, and particularly a device for transferring to the portal regions of the respiratory tract of a patient a metered dose of a product contained in a pressurised dispensing container.

Known actuators do not, however, take account of the need to accommodate various designs of canister valve. Actuators in the documents listed above do not take account of the need to provide devices to improve the assurance for patients in their use of inhalers, for example, dose indicators. Furthermore, it may be complex and costly to manufacture actuators to the required tolerances and quality.

In a first aspect, the present invention accordingly provides an actuator for an inhaler, the actuator comprising a body comprising a canister opening for insertion of a canister for supplying a medicament, the canister having a valve stem, a stem socket adapted for receiving the valve stem of a canister, a (fixable) base insertion portion, an orifice for

discharging a medicament (preferably to a delivery passage) and fixing means for fixing the base insertion portion in the body, wherein the base insertion portion is adapted and the body is adapted so that when the base insertion portion is inserted in the base of the body the base insertion portion and body cooperate to define a transition chamber in fluid connection with the orifice.

Arranging the base insertion portion and body to define a transition chamber is advantageous because it facilitates manufacture of an actuator with a relatively longer orifice and/or with a relatively longer, optional, expansion chamber. The possibility of having a longer orifice allows selection of appropriate characteristics of the spray exiting from the orifice. It is important to optimise the spray characteristics for medicament delivery, and for patient comfort particularly in nasal drug delivery applications. The longer, optional, expansion chamber allows more space to incorporate other components in the actuator (e.g. a dose counter). The longer orifice and/or the longer, optional, expansion chamber are of particular benefit when the spray is directed at an upward angle for intranasal administration.

Preferably, the stem socket is comprised in a stem post.

Generally, the transition chamber may be situated between the stem socket and a delivery passage (for delivery of the medicament to the patient), preferably between the stem socket and the orifice. Thus, the transition chamber is preferably in fluid communication with the stem socket and the delivery passage. The transition chamber is preferably in fluid communication between the stem socket and the orifice.

Preferably, the base insertion portion is inserted in the base of the body at a position remote from the delivery passage. Thus, the base insertion portion preferably does not form part of, nor is it inserted in, the delivery passage.

Preferably, the orifice and the expansion chamber are the only communicating ports in the transition chamber.

The base insertion portion may be adapted to be fixable solely by the action of insertion. In some embodiments additional fixing means such as clips, adhesives and/or welding portions may also be used to fix the base insertion portion and the body. Welding may be heat, ultrasonic and/or laser welding.

Preferably, intake of air for patient inhalation is provided through the canister opening.

Preferably, the body comprises a first transition region, preferably situated between the stem socket and the orifice.

Preferably, the stem post comprises an expansion chamber for receiving at least a portion of a metered dose of the medicament from the canister. Usually, the expansion chamber will be situated between the stem socket and first transition region and is preferably in fluid

communication with the stem socket and first transition region.

Preferably, the base insertion portion comprises a second transition region. Thus, in a preferred embodiment, the first transition region and the second transition region define (preferably cooperate to define) the transition chamber when the base insertion portion is fixed in the body.

The orifice, preferably, comprises a jet portion of predetermined width and predetermined length that preferably extends from the transition chamber to the orifice outlet. The predetermined width may be in the range 0.1 mm to 1.5 mm. The predetermined length may be in the range 0.05 mm to 5 mm, preferably 0.4 mm to 3 mm. The orifice may be generally of any cross sectional shape (e.g. oval, rectangular) but is preferably generally circular.

The orifice may be formed in the body (preferably the stem post portion of the body) or in the base insertion portion, or may be formed by interaction between parts of the body and base insertion portion.

The fixing means may advantageously use a flexible material for the base insertion portion so that part of it may be designed to interference fit like a bung into the stem post portion. Close to cylindrical surfaces of the interference fit may incorporate a draft angle to aid assembly.

Alternatively, the fixing means may comprise at least one press fit seal which may be a ring and groove press fit seal. The ring portion of a ring and groove press fit seal may be on the base insertion portion, with the groove situated in the actuator body. Alternatively, the ring may be on the body with the groove on the base insertion portion. The press fit seal preferably forms an interference fit seal when engaged.

The fixing means may comprise an adhesive portion (where an adhesive has been used to fix the base insertion portion and body) and/or a welded portion (where a welding process has been used to fix the base insertion portion and body). The welded portion may be an ultrasonic, laser and/or heat welded portion.

The fixing means may additionally comprise at least one clip.

The fixing means is preferably tamper -proof, or advantageously at least tamper-evident to discourage a patient from separating the base insertion portion from the actuator body.

Preferably, the body and/or base insertion portion may further comprise alignment features, for example asymmetric lugs, keying features, cradles, clips or flat surfaces that in combination with other alignment features define a position of alignment and engagement.

The base insertion portion may be a unitary moulding (i.e. the base insertion portion may be or is produced by moulding in one piece). This is particularly advantageous because it leads to manufacturing efficiency. Previously, it has been difficult to consistently mould an actuator in one piece, at least partly because of the need for tight tolerances and particularly minimal moulding flash. This has previously been a particular problem in the case of nasal inhalers where there is an acute angle between the stem socket/expansion chamber and delivery passage of the actuator. In the present invention, this problem is addressed by the use of a separate but fixable base insertion portion (usually of a smaller size than the assembled actuator), which enables higher tolerances to be achieved in the mould with a significant reduction in flash.

It is advantageous if the body is a unitary moulding (i.e. the body may be or is produced by moulding in one piece).

In a preferred embodiment, the actuator may be a nasal actuator. Consequently, the delivery passage may comprise a nose piece adapted for nasal delivery of the medicament. The nosepiece is preferably angled upwardly at an acute angle with respect to the long axis of the body, preferably at 85° or less, more preferably at 75° or less or 70° or less, most preferably at about 66°.

The body (or in an alternative embodiment the base insertion portion) may further comprise a window, preferably an indicator viewing window. The indicator viewing window is particularly useful for display of a dose indication or a dose count if the actuator further comprises a dose indicator or a dose counter.

The base insertion portion may further comprise supporting means (i.e. first supporting means) for supporting a dose indicator or a dose counter. Such supporting means may be, for example wing portions on the base insertion portion. The body may alternatively or additionally comprise second supporting means for supporting a dose indicator or dose counter.

In a second aspect, there is provided an inhaler comprising an actuator as discussed in relation to the first aspect, and a canister.

In a preferred aspect, the actuator may be produced by moulding, preferably injection moulding.

In a third aspect the present invention provides a method of assembling an actuator for an inhaler, the method comprising providing a body comprising a canister opening for insertion of a canister for supplying a medicament, the canister having a valve stem, a stem socket adapted for receiving the valve stem of a canister, a base insertion portion, an orifice for discharging a medicament and, fixing means for fixing the base insertion portion in the body, wherein the base insertion portion is adapted and the body is adapted so that when the insertion portion is inserted in the base of the body the base insertion portion and body cooperate to define a transition chamber in fluid connection with the orifice, and inserting the base insertion portion in the body.

Throughout this specification, the word "inhaler" means a device for delivery of a medicament in fluid (or powder) form either orally or nasally and does not imply that the device requires inhalation on the part of the patient during delivery. It is known that a medicament may be delivered successfully to the nasal passages by an inhaler without the need for the patient to inhale.

So that the present specification may be more completely understood, reference is made, by way of example only, to the accompanying drawings in which:

Figure 1 is a perspective front view of an embodiment of an inhaler.

Figure 2 is a rear view of the inhaler of Figure 1.

Figure 3 illustrates a vertical section through the inhaler of Figure 1 and Figure 2.

Figure 4 is a perspective view of the actuator of the inhaler of Figures 1 to 3.

Figure 5 is a vertical section through the lower part of an actuator similar to that of Figure 4, showing the base insertion portion.

Figure 1 illustrates, in perspective view, a pressurised metered dose inhaler 5 comprising a canister 20 and an actuator 10. The canister 20 is pressurised and holds medicament for delivery via the actuator 10. The actuator 10 has a generally elongate actuator body 15 that acts as a housing for the canister 20. The canister 20 is inserted into the canister opening 11 at the top portion of the actuator 10. The inhaler 5 is a nasal inhaler, having a nose piece (see Figure 4) covered by a cap 16.

Figure 2 shows, in a rear view, the actuator body 15, the actuator cap 16, and the canister 20. The body 15 has a cap track 17 arranged to guide the cap 16 from a closed position in which the cap 16 covers the nose piece (the position as shown in Figures 1 and 2) to an open position (not shown) in which the nose piece 30 is uncovered. The body 15 has a viewing window 47 through which the display of a dose indicator 42 is visible.

Figure 3 shows a vertical section through the inhaler 5. The actuator 10 comprises the body 15 having a stem post 75. The stem post 75 has a stem socket 100 for receiving the canister valve stem 22 of the canister metering valve 21. A base insertion portion 94 is engaged with the stem post 75, whereby a press fit sealing ring 140 is caused to contact a post support 68, with which it is a tight fit. Any interference between the sealing ring 140 and the post support 68 causes the press fit sealing ring 140 to splay slightly. Upon further insertion, the press fit sealing ring 140 engages the lead-in portion at the inside top portion of a sealing rim 66 that forms part of the post support 68. Any interference causes a return deformation of the press fit sealing ring 140, and provides a sealing engagement between the stem post 75 and the base insertion portion 94 which prevents leakage of formulation or other formulation components that, in use, need to be contained within the transition chamber 70 formed between the actuator body 15 and the body insertion portion 94 to avoid any loss of dose. Preferably, the base insertion portion 94 is engaged such that its top surface fits flush with the top of a stem post transition region. Preferably the base insertion portion and/or the actuator body 15 is provided with alignment features, e.g. clips to hold the two parts together, to ensure that the orifice is correctly aligned with a delivery passage 25 to reduce deposition of spray on surfaces within the actuator 10. In use, the patient would displace cap 16 from the nose piece 30, insert the nose piece 30 into a nostril and exert pressure on the top of the canister 20. This moves the canister 20 into the body 15 of the actuator and presses the canister valve stem 22 against the stem post 75, resulting in the canister metering valve 21 opening and releasing a metered dose of medicament into an expansion chamber 105 within the stem post 75. The expansion chamber 105 is in fluid communication with a delivery passage 25 in the body 15 so the medicament is delivered through the delivery passage 25 and out of the nose piece 30 into the patient's nostril. A dose indicator 42 is situated at the lower rear portion of the body 15 so that its indicia are visible through the indicator window 47. The dose indicator 42 is so arranged that movement of the canister 20 in use indexes the dose indicator 42.

Figure 4 shows the actuator 10 with the cap 16 and canister 20 removed. The nose piece

30 is angled upwardly at an acute angle with respect to the long axis of the body 15 for convenient insertion into the nostril of a patient. The nose piece 30 has a delivery passage 25 through which the medicament is delivered.

Figure 5 shows a vertical section through the lower part of an actuator 210 that is similar to that illustrated in Figures 1 to 4. In Figure 5, the dose indicator 42 and canister 20 (shown in

Figure 3) are not shown, although the indicator window 247 for a dose indicator is shown. Figure 5 shows ribs 245 that locate the canister (not shown in Figure 5) in the correct position in the body 215 of the actuator 210. The delivery passage 225 in the nose piece 230 is arranged to receive doses of medicament from the canister through an orifice outlet 285. The orifice outlet 285 is in fluid communication through a jet portion 290 with a transition chamber 270. The jet portion 290 is of predetermined width and predetermined length and may be in the form of a cylindrical tube of diameter 0.1 to 1.5 mm and of length 0.05 to 5 mm, the length usually being 0.4 mm to 3 mm. The transition chamber 270 is formed by parts of the stem post 275 and the base insertion portion 294, in particular, by cooperation between a first (body/stem post) transition region together with a second (base insertion portion) transition region. The stem post 275 is moulded in one piece with the body 215. The base insertion portion 294 is produced as a separate piece that is fixable in the body 215 by means of a press fit sealing ring (not shown) on the base insertion portion 294 in a press fit sealing groove (not shown) on the body 215. In use, the stem socket 300 accepts the tip of a valve stem of the canister (not shown in Figure 5), the end of the valve stem of the canister being supported on a stem ledge 310.

Preferably, the stem ledge is circumferential, and the expansion chamber cylindrical. A metered dose of medicament is delivered from the valve of the canister through the expansion chamber 305 of the stem post 275, into the transition chamber 270 formed by the interaction/cooperation of the base insertion portion transition region and a stem post transition region, and out of the orifice outlet 285 via the jet portion 290. From the orifice outlet 285, the dose is delivered through the delivery passage 225 to the patient.

It is to be understood that the specification is not limited to the embodiments described above and that various modifications can be made without departing from the principles or concepts of the specification. For example, the transition region of the base insertion portion may in an alternative embodiment be flat or relatively small in volume and the transition region of the actuator body or its stem post may be relatively larger.

Actuators and inhalers according to the specification may include any feature described herein separately or in combination with any other feature(s), if necessary with appropriate modification of other features, as would be readily apparent to the skilled person.