WO1997006842A1

WO1997006842A1 - Spray applicator

Info

Publication number: WO1997006842A1
Application number: PCT/GB1996/002011
Authority: WO
Inventors: Nicholas Richard James Opperman
Original assignee: Pharmasol Limited
Priority date: 1995-08-18
Filing date: 1996-08-16
Publication date: 1997-02-27
Also published as: EP0846011A1; AU6750396A; AU707525B2; JPH11514254A; CN1193283A; CA2229666A1

Abstract

A multi-dose spray applicator is disclosed for dispensing a pharmaceutical from a sealed container, said applicator comprising means for holding the container, a manually operable metering pump for delivering said pharmaceutical as a nasal spray and a hollow needle associated with said pump for penetrating a membrane sealing said container and dispensing the pharmaceutical through the pump, said container having a movable wall or plug which is movable to displace liquid from the container as it is dispensed by the pump.

Description

SPRAY APPLICATOR

This invention relates to spray applicators, particularly for dispensing pharmaceutical substances. One established method of dispensing pharmaceuticals is by spray e.g. as a nasal or oral spray. This method has the advantage as compared with sub-cutaneous or intravenal injection that it is easier for a patient with poor co-ordination or muscular weakness to administer the pharmaceutical himself. In the past, containers fitted with a pump or aerosol packaged products have been employed. However, these methods have proved to be unsatisfactory for packaging pharmaceuticals which are sensitive to substances in the atmosphere, such as compounds which degrade by contact with water or oxygen.

It is. therefore, one object of the present invention to provide an applicator for dispensing pharmaceuticals in the form of a spray, which minimises contact with atmospheric components until the product is dispensed.

According to one aspect of the present invention. there is provided a spray applicator for dispensing a pharmaceutical from a sealed container, said applicator comprising means for holding said sealed container, a manually operable pump for delivering said pharmaceutical as a nasal spray and a hollow needle associated with said pump for penetrating a membrane sealing the container and dispensing the pharmaceutical through the pump.

The applicator of the present invention is particularly designed for dispensing pharmaceuticals which are sensitive to oxygen or water. One example of such a compound is apomorphine hydrochloride (or other pharmaceutically acceptable salt) which is widely used in the treatment of Parkinson's disease. For such use. apomorphine is conveniently applied as a nasal spray and is rapidly absorbed through the nasal membrane. The spray applicator may, however, be adapted for other purposes, e.g. for applying a spray to the mouth and for dispensing other pharmaceuticals via the mouth or nose, particularly for treating the mouth, nose and lungs.

The pump component of the applicator may be constructed as a metering pump so that on actuation of the pump, a metered dose of the pharmaceutical is sprayed into the patient's nose or mouth.

Preferably, the applicator includes means for moving the needle towards the membrane automatically on actuation or just prior to actuation ofthe pump. For example, depression of the pump system may cause the needle to move towards and penetrate a membrane sealing the container in which the pharmaceutical is packaged.

In order to prevent the device from being actuated unintentionally, the applicator may include a removable device such as a clip, ring or tag which prevents the needle penetrating the membrane or prevents, respectively, means carrying the needle and sealed container from coming together until the applicator is intended to be used.

When the needle penetrates the membrane over the end of the vial, the contents remain substantially sealed with respect to the atmosphere so that air cannot enter the vial.

In order to allow the hquid within the pharmaceutical container to be displaced without the need to introduce air or other gas into the sealed vial, the pharmaceutical container preferably has a wall or plug which is movable to displace Uquid as it is pumped out of the container by the pump device. Such moveable wall or plug may be urged inwardly by a spring or other mechanical device so as to assist priming the pump, although the spring is not essential. The container may be constructed as a collapsible container, such as a tube, by making the walls from a flexible material such as a plastics sheet material.

One pharmaceutical apphcation of the spray apphcator is for dispensing compounds for controlling Parkinson's Disease. Patients suffering from Parkinson's Disease often have difficulty in manipulating devices for administering their medication. A further feature of the apphcator of the invention is to provide a dispensing cap in which the outlet from the pump is angled obhquely, thus providing a platform on the cap of the apphcator which enables the patient to operate the pump conveniently with his thumb.

Two embodiments of the present invention will now be described with reference to the accompanying drawings, which are partly schematic.

In the accompanying drawings:-

Figure 1 is a longitudinal section through the apphcator in assembled condition.

Figure 2 is a perspective view of a clip for preventing the needle penetrating the sealed container.

Figure 3 shows the components of the apphcator in a disassembled state.

Figure 4 is a schematic view showing an alternative method of actuating the pump.

Figure 5 is a longitudinal view in section of a second embodiment ofthe apphcator in its "use" position;

Figure 6 is a similar seαion through the apphcator shown in Figure 5, but in its "rest" position: Figures 7 shows the disassembled components of the apphcator shown in Figures 5 and 6: and

Figures 8A and 8B are two perspective views of a modified dispenser.

Referring to Figures 1 to 4 of the accompanying drawings, the nasal apphcator comprises a container (1) shaped to receive a sealed vial (2) into which the pharmaceutical is packaged. Vial (2) is of a type which is currently used in the pharmaceutical industry for packaging injectable materials. The vial comprises a glass or plastics tube (3) having a lower end which is closed with a rubber or plastic bung or plug (4). The upper end of the vial has membrane (5) which is designed to be penetrated by a hypodermic needle for removing the contents. After penetration of the membrane the membrane is sufficiently elastic to close around the needle and seal self against inadvertent escape of hquid or escape under the pressure arising during pumping of doses of hquid from the container. The membrane is preferably a rubber or rubbery plastics material. Vial (2) is designed to be a multi-dose container so that as Uquid is removed from the vial (2), plug (4) moves upwardly to displace the Uquid so removed. A spring (6) may be employed to assist this action and/or priming of the pump but is not essential. At its upper end, container (1) is threaded to receive a cap (7) and a pump holder (8) is mounted for axial sUding movement on the neck (9) of the contamer (1). Crimped onto the neck (10) of the pump holder (8) is a pump (11) and mounted on the upper end of the pump is a nasal actuator and overcap (12) and (13) respectively. Pump (11) is of the kind conventionally used for pumping pharmaceuticals from closed containers. The pump may be an airless mechanical pump with or without a dosing device such as those manufactured by Perfect- Valois or their parent company Valois Step under model No. 'VT 7'. An example of a metering pump of this kind is also described in WO 95/09054.

The lower end of the pump (11) has a tubular portion (14) to which a hollow needle (15) is attached either internally or externally, e.g. by means of a luer-type conneαion.

The apphcator works in the foUowing manner. Cap (13) which is a press fit of actuator (12) is removed and the actuator pressed down by placing the fingers on ledges (16). This causes pump holder (8) to move downwardly until needle (15) penetrates the membrane (5) and enters the hquid contained in vial (2). Continuing downward pressure causes the pump to take in a dose of the pharmaceutical and to spray the dose through the nasal actuator (12). On release of such finger pressure, needle (15) remains in the vial with the membrane sealing around the needle to prevent escape of hquid between the outer surface ofthe needle and the membrane. This is because the underside 26 ofthe cap engages with the recess 25 ofthe cap 8 or the annular projeαion 27 engages in the groove 21. The piston (not shown) within pump 11 is returned to its initial position by a return spring within the pump housing 11. This aspirates Uquid into the pump ready for dispensing the next dose from the vial. Further doses of Uquid can be pumped from the vial by the patient as required by pressing on the ledges 16.

In order to prevent the apphcator from being inadvertently actuated, a removable cUp (20) may be fitted into a groove (21) in the neck (9) of container (1). The cUp (20) may be manufaαured from a springy plastics material so that it is readily removed by pulling the tag or ring which is attached to it. When the chp (20) is in place, however, its thickness or an abutment protruding from it, prevents the pump holder moving down the neck (9) sufficiently far to aUow the hollow needle to penetrate the membrane (5).

Figure 4 shows an altemative way of depressing the actuator (12) for patients who have very poor co-ordination or muscular power. In this modification, the container (1) may be gripped by a holder (30) having a lever (31) mounted thereon. Lever (31) has an arm (32) which is shaped to press onto shoulders (16) of the nasal actuator (12). By operating lever arm (33). the patient is able to actuate the apphcator with mmimπm mechanical force.

It will be appreciated that various modifications can be made to the apphcator in accordance with the invention. For example, the holder may be formed with a threaded, removable base for introducing the vial and the neck (7) may be formed integraUy with the body (1). The pump unit may be crimped downwardly onto the neck of the holder and be arranged to be movable downwardly to permit the needle to enter the membrane (5).

Conveniently, most of the components of the apphcator may be manufactured from plastic materials. The holder (1) may, for example, be made from a clear plastics material so that the patient can see whether the vial is empty. In the case of apomorphine, the pharmaceutical turns green after exposure to atmospheric oxygen. Once the contents of the vial are observed to have changed to a green colour which is sufficiently deep (as indicated by a shade chart on the apphcator or packaging), to indicate that the pharmaceutical is no longer effeαive. An important aspeα ofthe apphcation of this invention is that the pharmaceutical in the vial remains sealed from the atmosphere until the patient uses the apphcator for the first time. Figures 5, 6, 7, 8 A & 8B show modified apphcators which include a number of modifications but work in a similar fashion to the apphcator shown in Figures 1 to 4.

Referring to Figures 5, 6 and 7, the modified dispenser comprises an outer hoUow component (101) forming one part of a container, preferably moulded from plastics material. In the embodiment shown in these Figures, the pump (105) is the same kind of metering pump as already described in connection with Figures 1 to 4. Also, the vial (111) is essentially as described in relation to the embodiments of Figures 1 to 4. The differences concern the container for the vial and the nozzle through which the product is dispensed. Component (101) is open at one end (102) and at its other end (103) is formed with a mouth and throat (104) for receiving a dosing pump (105). Pump (105) is preferably crimped into the mouth (104) of component (101). e.g. with an aluminium closure ferrule. A hollow needle ( 106) is fitted to the pump (105).

A second component (107) of the container is shdably received in the tubular hoUow part of component (101). Again, the second component is conveniently moulded from plastics material. Component (107) is formed with two longitudinaUy spaced grooves (108) and (109) and the inside of the component (101) is formed with a corresponding annular ring or projeαion (110).

Component (107) is formed with a tubular cavity for receiving a vial (111) and has a closed base (112) and a neck (113). Vial (111) is rαained within the component (107) by a threaded cap (114) which engages with corresponding threads on the inside of the neck of the component (107). Altematively, the cap (114) may be a friαion fit in the neck of component (107) or one of the components may have lug(s) which engage with groove(s) or recesses. In use, the shoulder of the vial (111) will abut against the cap (114) or the neck will abut against a ledge (115). However, for clarity a sUght gap is shown in the drawing. Vial (111) is a tube open at its lower end but includes a sealing plug (1 16) (preferably of elastomeric material). Plug (116) is preferably in contact with a spring (117) tending to urge the plug towards the neck ofthe vial.

As shown in Figure 6. the cap (114) is formed with a slot (118) into which a guard strip (119) slides. Guard strip (119) passes through slots (118A & 1 18B) in components (101 & 107) which are ahgned with slots (118) in cap (114). The width and toughness of strip (119) is such that it would be difficult for needle (106) to penetrate it and reach the membrane across the neck of vial (111).

Pump (105) has an outlet tube (120) depression of which causes the pump to operate. Tube (120) is received within a nasal spray head (121) which has a dispensing nozzle (122) conneαed to the tube (120). Nozzle (122) extends obhquely to the centre Une of the dispenser so as to provide a convenient ledge (123) for the patient to apply finger pressure to operate the device.

The dispenser shown in Figures 5, 6 and 7 works in the following manner. In the position shown in Figure 6, the projection (110) engages in groove (108) and releasably retains the inner component in relation to the outer component (101) in the position shown in Figure 6.

When it is desired to use the dispenser, the guard strip (119) is pulled out by pulling on the ring (120). The dispenser can then be operated by pressing the base (112) on a flat surface and pressing, e.g. with the thumb on the ledge (123). This causes the inner component to be pressed into the outer component (101) and the needle to penetrate the membrane (124) across the neck ofthe vial. At the same time, the annular projeαion (110) engages in the groove (109) thus retaining the component (107) within the component (101). For this purpose, projeαion (110) can be made to be a better fit in groove (109) than in groove (108) so that it is easier to dislodge projection (110) from groove (108) than groove (109).

It has been found that a needle which has a very shght or no taper at aU is best employed. This is because needles with a long taper tend to allow the contents of the vial to spray out as the needle begins to penetrate the membrane. However, conventional needles may be employed.

The walls ofthe components (101,107) may be transparent or include a window. This arrangement enables the contents ofthe vial to be checked, e.g. to see if the vial contains sufficient Uquid for one more treatment or, in the case of some medicaments, to check the appearance of the contents since this can undergo a colour change which may indicate it is no longer effeαive.

Instead of having a spring such as the spring (6) shown in the embodiments of Figures 1 to 3, a projection is moulded on the base (108). This projeαion bears on the plug (112) so that when the apphcator is mitiaUy aαivated, the plug is urged upwardly and primes the pump.

Figures 8A and 8B show external perspeαive views of a modified dispenser. In this embodiment, the vial (not visible) is contained within a body 400 which may be formed from inner and outer components similar to components ( 101 , 107) in Figures 5 and 6. A guard strip (401 ) is received in a slot (402) and prevents the dispenser being actuated inadvertently. A spray head (403) is fitted to the discharge tube of the pump and provides a platform

(404) for applying finger or thumb pressure to operate the pump. Nozzle

(405) terminates in a discharge outlet which may incorporate various outlet designs to vary the spray pattem. A closure cap (405) may be fitted over the nozzle to proteα the nozzle for storage and transport.

Claims

CLAIMS: -

1. A multi-dose spray apphcator for dispensing a pharmaceutical from a sealed container, said apphcator comprising means for holding the container, a manuahy operable metering pump for deUvering said pharmaceutical as a nasal spray and a hoUow needle associated with said pump for penetrating a membrane sealing said container and dispensing the pharmaceutical through the pump, said container having a movable waU or plug which is movable to displace hquid from the container as it is dispensed by the pump.

2. An apphcator as claimed in claim 1, which includes means for moving the needle towards the membrane on initial actuation ofthe pump.

3. An apphcator as claimed in claim 2 which includes a removable device to prevent the needle penetrating the membrane until the apphcator is intended to be used.

4. An appUcator as claimed in claim 3 in which the safety device comprises a shield located between the membrane and the needle, said shield being movable to an inoperative position when the apphcator is intended to be used.

5. An apphcator as claimed in claim 3 in which the safety device comprises a locking means which in its operative position prevents a component carrying the pump towards the container to an extent that the needle penetrates the membrane.

6. An appUcator as claimed in any one of the preceding claims wherein the plug is movable into the container under the influence of a spring.

7. An apphcator as claimed in any one of the preceding claims in which the pump is primed by movement ofthe needle into the container.

8. An appUcator as claimed in any one of the preceding claims wherein the means for holding the container comprises a housing, said housing comprising a base part for holding said container and a top part for holding the pump, the top and base parts being relatively movable to aUow the needle to penetrate the membrane.

9. An apphcator as claimed in claim 8 wherein the base part is shdable within the top part and the two parts include co-operating means for holding them together with the end of the needle within the container and the membrane forming a seal around the needle.

10. An apphcator as claimed in claim 9 wherein the co-operating means include at least one resihent finger on one part which is engageable in a recess in the other part.