GB2628633A

GB2628633A - Improvements relating to the filling and stoppering of containers

Info

Publication number: GB2628633A
Application number: GB2304786.3A
Authority: GB
Inventors: Gibbons Adam
Original assignee: Consort Medical Ltd
Current assignee: Consort Medical Ltd
Priority date: 2023-03-31
Filing date: 2023-03-31
Publication date: 2024-10-02
Also published as: GB202304786D0; WO2024200093A1

Abstract

A method of filling and stoppering a container body (10), comprising providing a container body that is open at a first end (11) and open at a second end (12); inserting a first stopper (21) into the container body and filling a fluid (23) into the container body through the first end. The first end of the container body is sealed with a second stopper (22) such that the fluid is retained in the container body between the first stopper and the second stopper. Wherein the second stopper comprises a flange portion (32) that in use is engaged against at least a portion of a rim (13) of the first end of the container body on sealing of the first end of the container body to prevent subsequent movement of the second stopper within the container body towards the second end of the container body. A corresponding container and method of dispensing fluid from the container is also provided.

Description

Improvements relating to the filling and stoppering of containers The present disclosure relates to methods of filling and stoppering a container body, containers for fluids and use of such containers in a dispensing apparatus. The container may, for example, be intended for use in a nasal dispensing apparatus.

Background to the Disclosure

It is known to provide a metered dose of medicament in a sealed container, such as a vial, to be dispensed from a dispensing apparatus. One example is described in EP 0 827 782 A2 in which a piercing element is provided on a piston that pierces a sealing member in the vial. The sealing member is then displaced into the vial forcing medicament out of the vial through the pierced opening in the sealing member. The medicament then passes through a channel formed in the piston and is expelled from the dispenser. Another example is described in EP 3 820 625 A2 wherein, according to its abstract, a device for dispensing a fluid product comprises a body, a reservoir containing one or two doses of a fluid product, said reservoir comprising a plug which closes off said reservoir in a sealed manner before actuation, a dispensing head provided with a dispensing orifice, and dispensing means for dispensing at least some of said fluid product through said dispensing orifice during an actuation, said device comprising a needle of which the tip is adapted to pierce said plug during the actuation, said reservoir being filled with said fluid product and plugged under vacuum with said plug such that the residual air volume present in said reservoir between said fluid product and said plug is substantially zero.

While sealed containers for fluids such as medicaments are available there remains a need to provide improved, or at least commercially acceptable, alternative containers and methods for their filling and stoppering.

Summary of the Disclosure

A first aspect of the present disclosure provides a method of filling and stoppering a container body, comprising the steps of: i) providing a container body that is open at a first end and open at a second end; ii) inserting a first stopper into the container body, optionally through the first end; iii) locating the first stopper within the container body, optionally by displacing the first stopper towards the second end; iv) filling a fluid into the container body through the first end; and v) sealing the first end of the container body with a second stopper such that the fluid is retained in the container body between the first stopper and the second stopper; wherein the second stopper comprises a flange portion that in use is engaged against at least a portion of a rim of the first end of the container body on sealing of the first end of the container body to prevent subsequent movement of the second stopper within the container body towards the second end of the container body.

For example, the second stopper may comprise a plug portion that projects into the first end of the container body and a flange portion that extends over at least a portion of a rim of the first end of the container body when the second stopper is in its sealed position. In use, the maximum radial extent of the flange portion is greater than the maximum radial extent of the plug portion.

Beneficially, the configuration of the container results in an arrangement where, on dispensation, the first stopper may slide within the container body until it makes contact with the second stopper. In this way, the volume reduction within the container body can be precisely controlled since the end-stop point is defined by the contact between the two stoppers. This may allow for better control of the ullage of the container, both in terms of the absolute volume of fluid remaining and in terms of consistency from container to container. For example, the mutually-contacting surfaces of the stoppers may have a partly-or fully-complementary shape to reduce the ullage void formed when the stoppers contact one another. This in turn may increase the predictability of the volume of fluid dispensed.

In addition, contact of the needle with a bottom of the container body (which may be formed of glass) can be prevented since the second stopper may function as a resilient receptor for the end of the needle, thereby preventing clash of the needle with the container body. This can reduce activation noise and vibration which may result in a better user experience and enhance user confidence in the apparatus. This also reduces the risk of the container body rupturing due to contact with the needle, in particular where large actuation forces are required to deliver the pharmaceutical.

In addition, the stopper-to-stopper contact at the end of the delivery stroke may function to provide a damped, soft stop which may also serve to further reduce activation noise and vibration.

In addition, the second stopper may, in use, be contacted or struck by a pusher component of the dispensing apparatus on activation of the dispensing apparatus at the point when a delivery force is first imparted to the container. Beneficially, the pusher component may strike or contact the second stopper, which may be formed of a relatively soft, resilient material. This may also serve to further reduce activation noise and vibration.

Beneficially, the method may avoid the need to apply a vacuum during filling of the fluid and/or sealing of the container body.

In an embodiment the first stopper is configured to be pierced during subsequent dispensation of the fluid from the container body. In an embodiment the second stopper is configured to remain axially stationary with respect to the container body during subsequent dispensation of the fluid from the container body.

The first stopper may be configured as a slidable stopper that can move axially along a length of the container body.

In some embodiments, prior to step v), the container body and fluid within the container body may be subjected to at least a partial vacuum to remove gas from a headspace of the container body situated between a free surface of the fluid and the first end of the container body. In such embodiments, step v) may be carried out under at least the partial vacuum.

In some other embodiments, the filling and stoppering may be carried out at atmospheric pressure. In such embodiments in step v), sealing the first end of the container body with the second stopper may also act to displace the fluid and the first stopper towards the second end. In an embodiment in step iv) the fluid is filled into the container body until the fluid fills, or substantially fills, the container body up to the level of the first end. In some examples the fluid may be filled into the container body to a level that allows a first sealing rib of the second stopper to engage against the container body before the second stopper contacts the fluid.

A second aspect of the present disclosure provides a container for fluid comprising: a container body that is, before assembly, open at a first end and open at a second end; a first stopper located within the container body; and a second stopper located at the first end; the first stopper and the second stopper defining therebetween a chamber for retaining a fluid; wherein the second stopper comprises a flange portion that in use is engaged against at least a portion of a rim of the first end of the container body to prevent movement of the second stopper within the container body towards the second end of the container body.

The second stopper may comprise a plug portion that projects into the first end of the container body and a flange portion that extends over at least a portion of a rim of the first end of the container body. In use, the maximum radial extent of the flange portion is greater than the maximum radial extent of the plug portion.

In an embodiment the container body may be filled with a fluid and stoppered using the method of the first aspect as described above.

A third aspect of the present disclosure provides for use of the container of the second aspect in a dispensing apparatus, optionally a nasal spray apparatus.

In an embodiment during actuation of the dispensing apparatus, the first stopper is pierced by a hollow needle to provide an outlet for fluid, and the container body and second stopper are moved as a unit relative to the first stopper so as to pressurise and dispense the fluid.

For example, the second stopper is in an embodiment configured to remain axially stationary with respect to the container body during dispensation of the fluid from the container body.

A fourth aspect of the present disclosure provides a method of dispensing a fluid comprising the steps of: a) providing a container according to the second aspect; b) piercing the first stopper to provide an outlet for fluid; c) moving the container body and second stopper as a unit relative to the first stopper so as to pressurise the fluid within the container body and thereby dispense the fluid out of the outlet for fluid.

In an embodiment, the second stopper remains axially stationary with respect to the container body during dispensation of the fluid from the container body.

A fifth aspect of the present disclosure provides a dispensing apparatus comprising a container according to the second aspect.

In some examples the dispensing apparatus may be a nasal dispensing apparatus. In some examples, the fluid within the container of the dispensing apparatus may consist of a single dose of a nasal medicament.

The container body of the above aspects may be formed from a wide variety of suitable materials, as would be appreciated by a person skilled in the art, such as glass or a plastic polymer. Examples of suitable glass include Type 1 Borosilicate 'Fiolax Clear', & Type 2. Examples of suitable polymers include polypropylene, polyethylene, polystyrene, cyclic olefin copolymer -an example being Topas® COC available from TOPAS Advanced Polymers GmbH, Frankfurt-HOchst, Germany, and liquid crystal polymer -an example being Zenite® LCP available from DuPont, Wilmington, USA.

The container body may consist of an elongate tube, which may be cylindrical. The container body may comprise an outwardly-turned flange at either or both of its first end and second ends. Alternatively, either or both rims may simply consist of an end surface of a tubular element without an outwardly-turned flange.

The first stopper and/or the second stopper of the above aspects may be formed from a wide variety of suitable materials, as would be appreciated by a person skilled in the art, for example an elastomer or thermoelastomer material such as EPDM, polychloroprene, hydrogenated nitrile, butyl, halo-butyl, chlorobutyl, bromobutyl, dynamically cross-linked EPDM/PP (Santoprene®), Mediprene®, styrenic block copolymers or blends thereof. Other suitable materials include high-density polyethylene, low-density polyethylene and liquid silicone rubber (LSR).

An outer surface of either or both stoppers may be provided with one or more sealing features, for example, ribs, rings, etc. to enhance the sealing function of the stopper.

The first stopper may have an H-form configuration that directs fluid pressure to the radial seals, increasing contact pressure and reducing dynamic leakage.

The fluid contained within the container of the above aspects may consist of a single dose of fluid or may comprise multiple doses of fluid. The fluid may contain a pharmaceutical. The term pharmaceutical, as used herein, is intended to encompass any pharmaceutical, compound, composition, medicament, agent or product which can be delivered or administered to a human being or animal, for example pharmaceuticals, drugs, biological and medicinal products. Examples include antiallergics, analgesics, bronchodilators, antihistamines, therapeutic proteins and peptides, antitussives, anginal preparations, antibiotics, anti-inflammatory preparations, hormones, or sulfonamides, such as, for example, a vasoconstrictive amine, an enzyme, an alkaloid, or a steroid, including combinations of two or more thereof. In particular, examples include isoproterenol [alpha(isopropylaminomethyl) protocatechuyl alcohol], phenylephrine, phenylpropanolamine, glucagon, adrenochrome, trypsin, epinephrine, ephedrine, narcotine, codeine, atropine, heparin, morphine, dihydromorphinone, ergotamine, scopolamine, methapyrilene, cyanocobalamin, terbutaline, rimiterol, salbutamol, ipratropium bromide and salbutamol, flunisolide, colchicine, pirbuterol, beclomethasone, orciprenaline, fentanyl, and diamorphine, streptomycin, penicillin, procaine penicillin, tetracycline, chlorotetracycline and hydroxytetracycline, adrenocorticotropic hormone and adrenocortical hormones, such as cortisone, hydrocortisone, hydrocortisone acetate and prednisolone, insulin, cromolyn sodium, and mometasone, including combinations of two or more thereof. The pharmaceutical may be used as either the free base or as one or more salts conventional in the art, such as, for example, acetate, benzenesulphonate, benzoate, bicarbonate, bitartrate, bromide, calcium edetate, camsylate, carbonate, chloride, citrate, dihydrochloride, edetate, edisylate, estolate, esylate, fumarate, fluceptate, gluconate, glutamate, glycollylarsanilate, hexylresorcinate, hydrobromide, hydrochloride, hydroxynaphthoate, iodide, isethionate, lactate, lactobionate, malate, maleate, mandelate, mesylate, methylbromide, methylnitrate, methylsulphate, mucate, napsylate, nitrate, pamoate, (embonate), pantothenate, phosphate, diphosphate, polygalacturonate, salicylate, stearate, subacetate, succinate, sulphate, tannate, tartrate, and triethiodide, including combinations of two or more thereof. Cationic salts may also be used, for example the alkali metals, e.g. Na and K, and ammonium salts and salts of amines known in the art to be pharmaceutically acceptable, for example glycine, ethylene diamine, choline, diethanolamine, triethanolamine, octadecylamine, diethylamine, triethylamine, 1-amino-2-propanol-amino-2-(hydroxymethyl)propane-1,3-diol, and 1-(3,4-dihydroxyphenyl)-2 isopropylaminoethanol. The pharmaceutical will typically be one which is suitable for nasal inhalation and may be provided in any suitable fluid form for this purpose, for example as a solution or powder suspension in a solvent or carrier liquid, for example ethanol, or isopropyl alcohol. The pharmaceutical may alternatively be one suitable for sub-lingual or ophthalmic delivery. The pharmaceutical may, for example, be one which is suitable for the treatment of asthma. Examples include salbutamol, beclomethasone, salmeterol, fluticasone, formoterol, terbutaline, sodium chromoglycate, budesonide and flunisolide, and physiologically acceptable salts (for example salbutamol sulphate, salmeterol xinafoate, fluticasone propionate, beclomethasone dipropionate, and terbutaline sulphate), solvates and esters, including combinations of two or more thereof. Individual isomers such as, for example, R-salbutamol, may also be used. The pharmaceutical may, for example, be one which is suitable for the treatment of migraine. An example is sumatriptan. As will be appreciated, the pharmaceutical may comprise of one or more active ingredients, an example of which is flutiform. One or more surfactants may be included if desired.

Brief Description of the Drawings

One or more embodiments of the disclosure will now be described, by way of example only, with reference to the accompanying drawings in which: Figure 1 is a schematic illustration of a container containing a fluid; Figure 2 is a schematic illustrating the steps of a first method of filling and stoppering a container body; Figure 3 is a schematic illustrating the steps of a second method of filling and stoppering a container body; and Figure 4 is a cross-sectional view of a dispensing apparatus comprising a container filled using the method of Figure 2 or Figure 3.

Detailed Description

Unless defined otherwise, all technical and scientific terms used in this specification have the same meaning as is commonly understood by the reader skilled in the art to which the claimed subject matter belongs. It is to be understood that the foregoing summary of the disclosure and the following examples are exemplary and explanatory only and are not restrictive of any subject matter claimed.

The following description is directed to embodiments of the disclosure. The description of the embodiments is not meant to include all the possible embodiments of the disclosure that are claimed in the appended claims. Many modifications, improvements and equivalents which are not explicitly recited in the following embodiments may fall within the scope of the appended claims. Features described as part of one embodiment may be combined with features of one or more other embodiments unless the context clearly requires otherwise.

Figure 1 shows a container 1 containing a fluid 23. The container 1 comprises a container body 10 that is, before assembly, open at a first end 11 and open at a second end 12.

A first stopper 21 is located at or proximate the second end 12 of the container body 10. A second stopper 22 is located at the first end 11 of the container body 10. The first stopper 21 and the second stopper 22 define there between a chamber 24. The fluid 23 is retained in the chamber 24 between the first stopper 21 and the second stopper 22.

The container body 10 once sealed using the first stopper 21 and the second stopper 22 forms the container 1. In an embodiment the container 1 consists only of the three components of the container body 10, the first stopper 21 and the second stopper 22.

The second stopper 22 comprises a restraining element for engaging at least a portion of a rim 13 of the first end 11 of the container body 10 when the second stopper 22 is inserted into the first end 11 to prevent subsequent movement of the second stopper 22 axially within the container body 10 towards the second end 12 of the container body 10 when the fluid 23 is dispensed. As illustrated in the Figures, the restraining element comprises a flange portion 32 which can be engaged in use against at least a portion of the rim 13 of the first end 11 of the container body 10. In the illustrated example, the second stopper 22 comprises a plug portion 31 that projects axially into the first end 11 of the container body 10 and a flange portion 32 that extends from the plug portions 31 and radially over at least a portion of the rim 13 of the first end 11 of the container body 10. The flange portion 32 may be annular and configured to extend over an annular portion of the rim 13. The angular extent of the flange portion 32 may be continuous, such that in use substantially all of the angular extent of the rim 13 is covered. Alternatively, the angular extent of the flange portion 32 may be discontinuous. For example, the flange portion 32 may consist of one or more radial protrusions. Where the flange portion 32 comprises two or more radial protrusions, the angle between neighbouring radial protrusions may be the same. For example, where the flange portion 32 comprises three radial protrusions the angle between each neighbouring protrusion may be 120 degrees. One or more ribs 33 may be provided on the plug portion 31. Two ribs 33 may be provided. The ribs 33 may be annular. The ribs 33 may function to enhance the sealing function of the second stopper 22.

The first stopper 21 may be configured as a slidable stopper that can move axially along a length of the container body 10. The first stopper 21 may comprise a plug form having no flange portion of the type provided on the second stopper 22. One or more ribs 34 may be provided on the first stopper 21. Three ribs 34 may be provided. The ribs 34 may be annular. The ribs 34 may function to enhance the sealing function of the first stopper 21 and or may enable the first stopper 21 to function as a sliding seal.

The container body 10 may in an embodiment be filled with the fluid 23 and stoppered with the first stopper 21 and the second stopper 22 using one of the following methods.

A first method of filling and stoppering the container body 10 is illustrated schematically in Figure 2. A second method of filling and stoppering the container body 10 is illustrated schematically in Figure 3. Both methods comprise in general the following steps: In step i) the container body 10 is provided such that it is open at its first end 11 and open at its second end 12.

In step ii) the first stopper 21 is inserted into the container body 10 through the first end 11.

In alternative embodiments, the first stopper 21 may be inserted into the container body 10 through the second end 12.

In step iii) the first stopper 21 is located within the container body 10, optionally towards the second end 12. In some embodiments, the first stopper 21 is located within the container body 10 by being displaced within the container body 10 towards the second end 12 after having been inserted through the first end 11. In some other embodiments the first stopper 21 is located within the container body 10 by being inserted through the second end 12, optionally with some subsequent axial displacement within the container body 10.

In step iv) the fluid 23 is filled into the container body 10 through the first end 11.

In step v) the first end 11 of the container body 10 is sealed with the second stopper 22 such that the fluid 23 is retained in the container body 10 between the first stopper 21 and the second stopper 22.

The second stopper 22 comprises the flange portion 32 that in use engages against at least a portion of the rim 13 of the first end 11 of the container body 10 during step v) to prevent subsequent movement of the second stopper 22 axially within the container body 10 towards the second end 12 of the container body 10. The flange portion 32 extends over at least a portion of the rim 13 when the second stopper 22 is in its sealed position as shown in Figure 2(v). The abutment of the flange portion 32 against the rim 13 ads as a stop to limit the degree to which the second stoper 22 can be inserted axially into the container body 10 and prevent subsequent axial movement of the second stopper 22 within the container body 10 towards the second end 12 of the container body 10 during dispensation of the fluid 23 from the container 1.

In an embodiment of the first method of Figure 2, in step iii) the first stopper 21 is displaced within the container body 12 to a point close to or at the second end 12 as shown in Figure 2(W). For example, the first stopper 21 may be positioned flush with the second end 12 or optionally within 2.0mm or 1.0mm or 0.5mm of the second end 12.

In an embodiment of the first method of Figure 2, in step iv) the volume of fluid 23 filled into the container body 10 is limited so that a headspace 35 is present above a free surface of the fluid 23 after fluid filling is finished as shown in Figure 2(iv). In some examples the fluid 23 may be filled into the container body 10 to a level that allows at least the first rib 33 of the second stopper 22 to engage against the container body 10 in step v) before the second stopper 22 contacts the fluid 23.

In the first method of Figure 2, prior to step v), the container body 10 and fluid 23 within the container body 10 are in an embodiment subjected to at least a partial vacuum to remove gas from the headspace 35 of the container body 10 situated between the free surface of the fluid 23 and the first end 11 of the container body 10 as shown in Figure 2(iv).

Further, in an embodiment step v) is carried out under at least the partial vacuum. In this way the sealed container 1 is achieved by inserting and sealing the second stopper 22 under at least a partial vacuum. The same vacuum or partial vacuum of step iv) may be maintained throughout step v), for example where the fluid filling step iv) and the stoppering step v) are performed at the same station or within a common vacuum housing.

Alternatively, the vacuum or partial vacuum of step iv) may be released inbetween steps iv) and v) and a new vacuum or partial vacuum drawn prior to step v), for example where the fluid-filled container body 10 is required to be moved from a fluid filling station to a stopper sealing station at a different location or within a different housing.

In an embodiment of the second method of Figure 3, the filling and stoppering is carried out at atmospheric pressure. In particular the requirement to draw a vacuum or partial vacuum can be entirely dispensed with. To this end, in an embodiment in step iii) the first stopper 21 is located within the container body 10 at an intermediate point of the container body 10 as shown in Figure 3(iii). The first stopper 21 may be located by being displaced from either the first end 11 or second end 12 dependent through which end the first stopper 21 was inserted into the container body 10.

Further, in an embodiment of the second method in step iv) the volume of fluid 23 filled into the container body 10 is sufficient so that no or a very limited headspace is present above a free surface of the fluid 23 after fluid filling is finished as shown in Figure 3(iv). For example, the fluid 23 may be filled to within 2.0mm or 1.0mm or 0.5mm of the first end 11 or to the brim of the first end 11.

In an embodiment in the second method in step v), sealing the first end 11 of the container body 10 with the second stopper 22 also acts to displace the fluid 23 and the first stopper 21 towards the second end 12.

The container 1 may be used in a variety of dispensing apparatus. For example, the container 1 may be used in a manually activated, single-use apparatus. Figure 4 shows one example of a dispensing apparatus 100 that may be used to dispense the fluid 23 from the container 1. The dispensing apparatus 100 is of a type more fully described in W02015/008048A1, the contents of which are hereby incorporated by reference in their entirety.

The dispensing apparatus 100 comprises a housing 101 formed from an upper housing and a lower housing that are joined together to hold the container 1 therebetween. A slidable button 102 is mounted within the lower housing that has a lower end that can be manually pushed using a finger or thumb. A slide 110 is engaged against the flange portion 32 of the second stopper 22. The slide 110 is biased upwardly by a spring 111 but is initially restrained by a triggering mechanism (as described in W02015/008048A1) which prevents upward movement of the slide 110 until the slidable button 102 is pushed inwards.

The upper housing defines a nozzle 103 which may, for example, be configured as a nasal piece. An outlet orifice 105 is provided in the nozzle 103 that is in fluid communication with a hollow needle 104 that extends inwardly within a fixed plunger 106 mounted within the upper housing. The hollow needle 104 projects out of a lower end of the fixed plunger 106.

The lower end of the fixed plunger 106 can engage against the first stopper 21. Initially a gap may be provided between the first stopper 21 and the fixed plunger 106 such that the first stopper 21 is not at this time pierced by the hollow needle 104. Additionally or alternatively, the shaping of the first stopper 21 and or the length of the hollow needle 104 may be configured so that the first stopper 21 is not pierced when the first stopper 21 is initially engaged against the fixed plunger 106. For example, as shown in Figure 4, the first stopper 21 may have an H-form configuration and the end of the hollow needle 106 may initially be accommodated within an upper void of the first stopper 21 without piercing the cross-piece of the first stopper 21.

Thus, the container 1 is located at rest inbetween the fixed plunger 106 and the slide 110.

When the slidable button 102 is activated by being pushed inwards the restraint on the slide 110 is removed and the slide 110 moves upwards forcing the second stopper 22, the fluid 23, the first stopper 21 and the container body 10 of the container 1 upwards towards nozzle 103. This upward movement initially causes any initial gap between the first stopper 21 and the fixed plunger 106 to be closed and then the first stopper 21 to be pierced by the hollow needle 104. Continued upward movement of the second stopper 22, container body 10 and fluid 23 pressurises the fluid 23 since the first stopper 21 is restrained from further upward movement by contact with the fixed plunger 106. Consequently, the now pressurised fluid 23 is discharged along the hollow needle 104 and out of the outlet orifice 105. During dispensation, the container body 10 and the second stopper 22 move as a unit relative to the first stopper 21. For example, the second stopper 22 remains axially stationary with respect to the container body 10 during dispensation of the fluid 23 and does not itself slide within the container body 10.

The dispensing apparatus 100 is provided merely as an example and it will be understood that the container 1 may be used with other apparatus configured to dispense the fluid 23.

It is to be understood that at least some of the figures and descriptions of the disclosure have been simplified to focus on elements that are relevant for a clear understanding of the disclosure, while eliminating, for purposes of clarity, other elements that the reader skilled in the art will appreciate may also be required. Because such elements are well known to the reader skilled in the art, and because they do not necessarily facilitate a better understanding of the disclosure, a description of such elements is not provided herein.

Claims

Claims: 1. A method of filling and stoppering a container body, comprising the steps of: i) providing a container body that is open at a first end and open at a second end; ii) inserting a first stopper into the container body, optionally through the first end; iii) locating the first stopper within the container body, optionally by displacing the first stopper towards the second end; iv) filling a fluid into the container body through the first end; and v) sealing the first end of the container body with a second stopper such that the fluid is retained in the container body between the first stopper and the second stopper; wherein the second stopper comprises a flange portion that in use is engaged against at least a portion of a rim of the first end of the container body on sealing of the first end of the container body to prevent subsequent movement of the second stopper within the container body towards the second end of the container body.
2. The method of claim 1, wherein the first stopper is configured to be pierced during subsequent dispensation of the fluid from the container body and/or the second stopper is configured to remain axially stationary with respect to the container body during subsequent dispensation of the fluid from the container body.
3. The method of claim 1 or claim 2, wherein the second stopper comprises a plug portion that projects into the first end of the container body and a flange portion that extends over at least a portion of a rim of the first end of the container body when the second stopper is in its sealed position.
4. The method of any preceding claim, wherein the first stopper is configured as a slidable stopper that can move axially along a length of the container body.
5. The method of any preceding claim, wherein, prior to step v), the container body and fluid within the container body are subjected to at least a partial vacuum to remove gas from a headspace of the container body situated between a free surface of the fluid and the first end of the container body.
6. The method of claim 5, wherein step v) is carried out under at least the partial vacuum.
7. The method of any one of claims 1 to 4, wherein the filling and stoppering is carried out at atmospheric pressure.
8. The method of claim 7, wherein in step v), sealing the first end of the container body with the second stopper also acts to displace the fluid and the first stopper towards the second end.
9. The method of claim 7 to claim 8, wherein in step iv) the fluid is filled into the container body until the fluid fills, or substantially fills, the container body up to the level of the first end.
10. A container for fluid comprising: a container body that is, before assembly, open at a first end and open at a second end; a first stopper located within the container body; and a second stopper located at the first end; the first stopper and the second stopper defining therebetween a chamber for retaining a fluid; wherein the second stopper comprises a flange portion that in use is engaged against at least a portion of a rim of the first end of the container body to prevent movement of the second stopper within the container body towards the second end of the container body.
11. The container of claim 10, wherein the second stopper comprises a plug portion that projects into the first end of the container body and a flange portion that extends over at least a portion of a rim of the first end of the container body.
12. The container of claim 10 or claim 11, wherein the first stopper is configured as a slidable stopper that can move axially along a length of the container body.
13. The container of any one of claims 10 to 12, which is filled with a fluid and stoppered using the method of any one of claims 1 to 9.
14. Use of the container of any one of claims 10 to 13 in a dispensing apparatus, optionally a nasal spray apparatus.
15. The use of claim 14, wherein during actuation of the dispensing apparatus, the first stopper is pierced by a hollow needle to provide an outlet for fluid, and the container body and second stopper are moved as a unit relative to the first stopper so as to pressurise and dispense the fluid.
16. A method of dispensing a fluid comprising the steps of: a) providing a container as claimed in any of claims 10 to 13; b) piercing the first stopper to provide an outlet for fluid; c) moving the container body and second stopper as a unit relative to the first stopper so as to pressurise the fluid within the container body and thereby dispense the fluid out of the outlet for fluid.
17. The method of claim 16, wherein the second stopper remains axially stationary with respect to the container body during dispensation of the fluid from the container body.
18. A dispensing apparatus comprising a container according to any one of claims 10 to 13.
19. The dispensing apparatus of claim 18, wherein the dispensing apparatus is a nasal dispensing apparatus; optionally wherein the fluid consists of a single dose of a nasal medicament.