Spray applicator

A multi-dose spray applicator is disclosed for dispensing a pharmaceutical liquid 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 liquid through the pump, said container having a movable wall or plug which is movable to displace the liquid from the container as it is dispensed by the pump.

BACKGROUND OF THE INVENTION 
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. 
SUMMARY OF THE INVENTION 
WO 95/00195 discloses 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. In accordance with the present invention, 
such a spray applicator is characterised in that the container has a 
moveable wall or plug which is movable to displace liquid from the 
container as it is dispensed by the pump. An advantage of the invention is 
that liquid from within the container can be displaced without the need to 
introduce air or other gas into the sealed container. 
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 of the 
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. 
The moveable wall or plug may be urged inwardly by a spring or other 
mechanical. device so as to assist prig 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 application of the spray applicator is for dispensing 
compounds for controlling Parkinson's Disease. Patients suffering from 
Parkinson's Disease often have difficulty in manipulating deices for 
administering their medication. A further feature of the applicator of the 
invention is to provide a dispensing cap in which the outlet from the pump 
is angled obliquely, thus providing a platform on the cap of the 
applicator 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.

Referring to FIGS. 1 to 4 of the accompanying drawings, the nasal 
applicator 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 itself against inadvertent escape of liquid or escape under the 
pressure arising during pumping of doses of liquid 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 liquid is removed from 
the vial (2), plug (4) moves upwardly to displace the liquid 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 sliding 
movement on the neck (9) of the container (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. `VP 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 connection. 
The applicator works in the following 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 liquid 
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 liquid between the outer surface of the needle and the membrane. 
This is because the underside 26 of the cap engages with the recess 25 of 
the cap 8 or the annular projection 27 engages in the groove 21. The 
piston (not shown) within pump 11 is returned to its initial position by a 
return sprig within the pump housing 11. This aspirates liquid into the 
pump ready for dispensing the next dose from the vial. Further doses of 
liquid can be pumped from the vial by the patient as required by pressing 
on the ledges 16. 
In order to prevent the applicator from being inadvertently actuated, a 
removable clip (20) may be fitted into a groove (21) in the neck (9) of 
container (1). The clip (20) may be manufactured from a springy plastics 
material so that it is readily removed by puling the tag or ring which is 
attached to it. When the clip (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 allow the hollow needle to penetrate the 
membrane (5). 
FIG. 4 shows an alternative 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 applicator with minimum 
mechanical force. 
It will be appreciated that various modifications can be made to the 
applicator 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 integrally 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 applicator 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 components of the vial are 
observed to have changed to a green colour which is sufficiently deep (as 
indicated by a shade chart on the applicator or packaging), to indicate 
that the pharmaceutical is no longer effective. An important aspect of the 
application of this invention is that the pharmaceutical in the vial 
remains sealed from the atmosphere until the patient uses the applicator 
for the first time. 
FIGS. 5, 6, 7, 8A & 8B show modified applicators which include a number of 
modifications but work in a similar fashion to the applicator shown in 
FIGS. 1 to 4. 
Referring to FIGS. 5, 6 and 7, the modified dispenser comprises an outer 
hollow 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 FIGS. 1 to 4. Also, the vial (111) is essentially as described in 
relation to the embodiments of FIGS. 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 slidably received in the 
tubular hollow part of component (101). Again the second component is 
conveniently moulded from plastics material. Component (107) is formed 
with two longitudinally spaced grooves (108) and (109) and the inside of 
the component (101) is formed with a corresponding annular ring or 
projection (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 retained 
within the component (107) by a threaded cap (114) which engages with 
corresponding threads on the inside of the neck of the component (107). 
Alternatively, the cap (114) may be a friction 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 slight gap is shown in the drawing. Vial (111) is a 
tube open at its lower end but includes a sealing plug (116) (preferably 
of elastomeric material). Plug (116) is preferably in contact with a 
spring (117) tending to urge the plug towards the neck of the vial 
As shown in FIG. 6. the cap (114) is formed with a slot (118) into which a 
guard strip (119) slides. Guard strip (119) passes through slots (118A & 
118B) in components (101 & 107) which are aligned with slots (118) in cap 
(114). The width and toughness of sip (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) connected to the tube (120). Nozzle (122) 
extends obliquely to the centre line 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 FIGS. 5, 6 and 7 works in the following manner. In 
the position shown in FIG. 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 FIG. 6. 
When it is desired to use the dispenser, the guard strip (119) is pulled 
out by puling on the ring. 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 of the vial. At the same time, the annular projection (110) engages 
in the groove (109) thus retaining the component (107) within the 
component (101). For this purpose, projection (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 slight or no taper at all 
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 of the components (101,107) may be transparent or include a 
window. This arrangement enables the contents of the vial to be checked 
e.g. to see if the vial contains sufficient liquid 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 effective. 
Instead of having a sprig such as the spring (6) shown in the embodiments 
of FIGS. 1 to 3, a projection is moulded on the base (108). This 
projection bears on the plug (112) so that when the applicator is 
initially activated, the plug is urged upwardly and primes the pump. 
FIGS. 8A and 8B show external perspective 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 FIGS. 5 and 6. A guard sip (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 pattern. A closure cap (405) may be 
fitted over the nozzle to protect the nozzle for storage and transport.