Improvements related to container filling and closure

Abstract

The present invention provides improved or at least commercially acceptable alternative containers and methods for filling and sealing them. [Solution] A method for filling and sealing a container body, comprising the steps of: c) inserting a stopper into the container body through a first end, i) inserting the stopper into the upper end of an elongated loading member, wherein the outer dimensions of the stopper are reduced by compression of the stopper during insertion; ii) using a plunger inserted into the upper end of the elongated loading member to push the stopper along the elongated loading member toward the lower end of the elongated loading member; iii) inserting the elongated loading member, plunger, and stopper into the container body through the first end; iv) withdrawing the elongated loading member from the container body, while simultaneously maintaining the plunger and stopper inside the container body so that the stopper is displaced from the lower end of the elongated loading member and depressurized, forming a seal with the inner surface of the container body; and v) withdrawing the plunger from the container body.

Description

Technical Field

[0001] The disclosure of the present invention relates to a method for filling and closing a container body, a container for a fluid, and the use of such a container in a dispensing device. The container may be intended for use, for example, in a nasal dispensing device.

Background Art

[0002] It is known to provide for a metered dose of a pharmaceutical product in a sealed container, such as a vial, to be dispensed from a dispensing device. One example is described in EP0827782A2, in which a piercing element is provided on a piston that pierces a sealing member within the vial. The sealing member is then displaced into the vial and the pharmaceutical product is pushed out of the vial through the pierced opening in the sealing member. The pharmaceutical product then passes through a channel formed within the piston and is discharged from the dispenser. Another example is described in EP3820625A2, which according to its abstract, a device for dispensing a fluid product comprises a body, a reservoir containing one or two doses of the fluid product, the reservoir including a plug for closing the reservoir in a sealed manner prior to operation, a dispensing head provided with a dispensing orifice, and dispensing means for dispensing at least a portion of the fluid product through the dispensing orifice during operation, the device includes a needle, the tip of which is adapted to pierce the plug during operation, the reservoir being filled with the fluid product and being crimped under vacuum by the plug such that the residual air volume present in the reservoir between the fluid product and the plug is substantially zero.

Prior Art Documents

Patent Documents

[0003]

Patent Document 1

Patent Document 2

Summary of the Invention

Problems to be Solved by the Invention

[0004] While sealed containers for fluids such as pharmaceuticals are available, there remains a need to provide improved or at least commercially acceptable alternative containers and methods for filling and sealing them. [Means for solving the problem]

[0005] A first aspect of the disclosure of the present invention is the following steps: a) A step of providing a container body that is open at the first end, b) The step of filling the container body with fluid through the first end, c) Inserting the stopper into the container body through the first end, Including stage c), the following stages: i) The step of inserting the stopper into the upper end of the elongated loading member, wherein the outer dimensions of the stopper are reduced by compression of the stopper during the insertion step, ii) The step of using a plunger inserted into the upper end of the elongated loading member to push the stopper along the elongated loading member toward the lower end of the elongated loading member, iii) The step of inserting the elongated loading member, plunger, and stopper into the container body through the first end, iv) The step of withdrawing the elongated loading member from the container body while simultaneously maintaining the plunger and stopper inside the container body such that the stopper is displaced from the lower end of the elongated loading member to reduce pressure and form a seal with the inner surface of the container body, and v) The step of withdrawing the plunger from the container body, The present invention provides a method for filling and sealing a container body, including the following:

[0006] Beneficially, this method does not require the provision of seals on or around the vacuum equipment and the container body. As a result, this method avoids the need to balance the pressure between the container and the vacuum pump, and avoids any risk of positive pressure in any headspace that could potentially drive fluid diffusion / infiltration from the container. In addition, this method potentially allows for the achievement of smaller headspace volumes compared to vacuum filling methods. Furthermore, this method can avoid the risk of plug displacement that may occur with vacuum filling when high differential pressures occur.

[0007] In the embodiment, step iii) includes inserting the elongated loading member, plunger, and stopper as a unit into the container body through the first end.

[0008] In this embodiment, during step iv), the plunger and stopper are maintained in a fixed position relative to the container body while the elongated loading member is being withdrawn.

[0009] In this embodiment, in step iii), the elongated loading member, plunger, and stopper are 1.47 mm 2 For a smaller permeability area and / or radial gap smaller than 0.1 mm, the plug is inserted into the vessel body at a speed of less than 10-50 mm / s. A faster plugging time may be achievable with a larger permeability area / radial gap, but this is thought to impose greater compression on the plug, which may damage the plug and potentially wear away any silicone coating from the plug. Using the specified insertion speed for the plug can beneficially limit fluid accumulation in the vessel body and / or any pressure buildup in the headspace by allowing sufficient time for the gas to permeate from the headspace.

[0010] In the embodiment, in step iii), a clearance is maintained between the outer surface of the elongated loading member and the inner surface of the container body. For example, the clearance includes a radial gap greater than 0.1 mm. Beneficially, the clearance can provide a means for ventilating the headspace during step iii).

[0011] In the embodiment, in step ii), the stopper is optionally pushed by the plunger along the elongated loading member until the lower surface of the stopper is flush with the lower end of the elongated loading member, to a point where the lower surface of the stopper is within 0.2 mm of the lower end of the elongated loading member.

[0012] Beneficial positioning the underside at or near the lower end of the elongated loading member allows the underside of the stopper to be brought very close to the fluid without the elongated loading member coming into contact with the fluid itself. In addition, such a location allows the lower sealing rib of the stopper to be released from the elongated loading member and engage with the container body as soon as possible when the elongated loading member begins to be removed, helping to fix the stopper's position relative to the container body.

[0013] In step iii), the elongated loading member, plunger, and stopper can be inserted into the container body so that the stopper is positioned in the desired final position, and during step iv), the stopper is maintained in the desired final position. Beneficially, this can allow for more controlled and precise positioning of the stopper of the end container, particularly relative to the fluid surface.

[0014] In step iii), the elongated loading member, plunger, and stopper can be inserted into the container body so that the stopper is positioned at a distance of 1.5 mm from the top surface of the fluid. Optionally, the headspace volume is minimized.

[0015] The upper end of the elongated loading member may include an inwardly tapered portion for compressing the plug during step i), which is pushed through this inwardly tapered portion. In the embodiment, reducing the outer dimensions of the plug in step i) includes reducing the outer diameter of the plug.

[0016] The container body can be closed at a second end opposite the first end. Typically, the container body will be a vial or other tubular member that is open at only one end, and the other end is closed as part of the formation of a single container body. However, the disclosed method of the present invention may also be used in conjunction with a container body that is initially open at both ends and provided with means for closing the second end, for example, a second stopper.

[0017] In some embodiments, the container body and the fluid are subjected to a vacuum or partial vacuum before and / or during step iii).

[0018] In some other embodiments, steps i) to v) are carried out at atmospheric pressure.

[0019] Optionally, steps i) and / or ii) may be performed before or after step b). That is, the step of inserting the stopper into the elongated loading member and / or the step of positioning the stopper towards the lower end of the elongated loading member can be carried out at any time before step iii). For example, a pre-prepared sub-unit of the elongated loading member and the stopper can be formed before the container body is filled with fluid.

[0020] Steps a) to c) and steps i) to v) can be carried out at one location or at multiple locations. All steps can be carried out on a single machine having one or more stations. Alternatively, the steps can be carried out using multiple machines. For example, steps a) and b) can be carried out using a filling machine, and one or more of steps i) to iv) of step c) can be carried out using a stopper machine. Steps i) and ii) can be carried out at the same location as or at a different location from steps iii) to v). For example, a stopper can be pre-loaded into the elongated loading member using one machine, and steps iii) to v) can be carried out using a different machine. However, in an embodiment, all of steps i) to v) are carried out at a single location and using a single machine.

[0021] A second aspect of the disclosure of the present invention provides a container for a fluid filled and stoppered using the method of the first aspect as described above.

[0022] A third aspect of the disclosure of the present invention provides for the use of a container of the second aspect in a dispensing device.

[0023] In an embodiment, during operation of the dispensing device, the stopper is pierced by a hollow needle to provide an outlet for the fluid, and the stopper is further moved towards the second end of the container body to pressurize and dispense the fluid.

[0024] A fourth aspect of the disclosure of the present invention provides a dispensing device including a container according to the second aspect. The dispensing device may be a nasal dispensing device arranged to dispense medicine into the nostril.

[0025] In some examples, the dispensing device may be a nasal dispensing device. In some examples, the fluid in the container may consist of a single dosage of a nasal medicine.

[0026] The container body of the above aspect can be formed from any suitable material such as glass or a plastic polymer. Examples of suitable glasses include type 1 borosilicate "Fiolax Clear" and type 2. Examples of suitable polymers include polypropylene, polyethylene, polystyrene, cyclic olefin copolymer, for example Topas® COC available from TOPAS Advanced Polymers GmbH, Frankfurt-Höchst, Germany, and liquid crystal polymer, for example Zenite® LCP available from DuPont, Wilmington, USA.

[0027] The container body can be made of an elongated tube. In this embodiment, the elongated tube has one end closed and the other end open. The elongated tube can be cylindrical. The container body may include an outwardly rotated flange at its open end. Alternatively, the rim at the open end can simply be made of the end face of a tubular element without an outwardly rotated flange.

[0028] The stoppers in the above embodiments may be formed from elastomer or thermoelastomer materials such as EPDM, polychloroprene, hydrogenated nitrile, butyl, halobutyl, dynamically crosslinked EPDM / PP (e.g., Santoprene®), styrene-based block copolymers, or formulations thereof. Other suitable materials include high-density polyethylene and low-density polyethylene.

[0029] The outer surface of the stopper may be provided with one or more sealing features, such as ribs or rings, to enhance the stopper's sealing function.

[0030] In some cases, the stopper may have an H-shaped configuration suitable for puncturing through a thin membrane. The H-shape allows the pressure inside the container to be applied outward over the stopper seal, increasing the contact pressure and reducing the possibility of dynamic leakage.

[0031] In some cases, one or more sealing ribs may be provided to provide a seal to the container body while maintaining a moderately low level of friction between the stopper and the container body.

[0032] In some cases, the stopper can be coated with a friction-reducing coating, such as a silicone coating, which can be sprayed or baked onto the stopper. Fluorocarbon film coatings may also be used.

[0033] The fluid confined within the container of the above embodiment may consist of a single-dose fluid or may contain multiple doses of fluid. The fluid may contain a pharmaceutical. The term pharmaceutical is intended to encompass any pharmaceutical, compound, composition, drug, agent, or product that can be delivered or administered to a human or animal when used herein, such as pharmaceuticals, drugs, biological products, and pharmaceutical products. Examples include antiallergic agents, analgesics, bronchodilators, antihistamines, therapeutic proteins and peptides, antitussives, angina preparations, antibiotics, anti-inflammatory agents, hormones, or sulfonamides, such as vasoconstrictive amines, enzymes, alkaloids, or steroids, or combinations of two or more thereof. In particular, examples include isoproterenol [α-(isopropylaminomethyl)protocatecuyl alcohol], phenylephrine, phenylpropanolamine, glucagon, adrenochrome, trypsin, epinephrine, ephedrine, narcotin, codeine, atropine, heparin, morphine, dihydromorphinone, ergotamine, scopolamine, metapyrylene, cyanocobalamin, terbutaline, limiterol, salbutamol, ipratropium bromide, and salbutamol, fluni Solid, colchicine, pirbuterol, beclomethasone, orciprenaline, fentanyl, diamorphine, streptomycin, penicillin, procaine penicillin, tetracycline, chlortetracycline, hydroxytetracycline, adrenocorticotropic hormone and adrenocortical hormones, such as cortisone, hydrocortisone, hydrocortisone acetate and prednisolone, insulin, cromolyn sodium and mometasone, and combinations of two or more of these.Pharmaceuticals may be used as free bases or as one or more salts conventional in the art, such as acetate, benzenesulfonate, benzoate, bicarbonate, tartrate, bromide, calcium edetate, camusylate, carbonate, chloride, citrate, dihydrochloride, edetate, edisylate, estrate, esylate, fumarate, fluoceptate, gluconate, glutamate, glycolyl sanilate, hexylresorcinate, hydrobromide, hydrochloride, hydroxy This includes naphthoates, iodides, isethionates, lactates, lactobionates, malates, maleates, mandelates, mesylates, methyl bromides, methylnitrates, methyl sulfates, mucinates, napsylates, nitrates, pamoates (embonates), pantothenates, phosphates, dicosphosphates, polygalacturonates, salicylates, stearates, acetates, succinates, sulfates, tannates, tartrates, triethiozides, and one or more combinations thereof. Cationic salts may also be used, such as glycine, ethylenediamine, choline, diethanolamine, triethanolamine, octadecylamine, diethylamine, triethylamine, 1-amino-2-propanol-amino-2-(hydroxymethyl)propane-1,3-diol, 1-(3,4-dihydroxyphenyl)-2-isopropylaminoethanol, etc. Pharmaceuticals are typically suitable for nasal inhalation and can be provided in any fluid form suitable for this purpose, such as a solution in a solvent or carrier liquid, such as ethanol or isopropyl alcohol, or as a powder suspension. Alternatively, pharmaceuticals may be suitable for sublingual or ophthalmic administration. Pharmaceuticals may, for example, be suitable for the treatment of asthma. Examples include salbutamol, beclomethasone, salmeterol, fluticasone, formoterol, terbutaline, sodium cromoglycate, budesonide, and flunisolide, and physiologically acceptable salts (e.g., salbutamol sulfate, salmeterol xinafoate, fluticasone propionate, beclomethasone dipropionate, and terbutaline sulfate), solvates, and esters, and combinations of two or more of these. Individual isomers, such as R-salbutamol, may also be used.The pharmaceutical product is suitable for the treatment of, for example, migraines. An example is sumatriptan. As is recognized, the pharmaceutical product may consist of one or more active ingredients, an example being flutiform. If desired, one or more surfactants may be included.

[0034] With reference to the attached drawings, one or more embodiments of the disclosure of the present invention will be described below simply as examples. [Brief explanation of the drawing]

[0035] [Figure 1] This diagram shows the steps of filling the container body with fluid and sealing the container body with a stopper to form the container. [Figure 2] This diagram shows the steps of filling the container body with fluid and sealing the container body with a stopper to form the container. [Figure 3] This diagram shows the steps of filling the container body with fluid and sealing the container body with a stopper to form the container. [Figure 4] This diagram shows the steps of filling the container body with fluid and sealing the container body with a stopper to form the container. [Figure 5] This diagram shows the steps of filling the container body with fluid and sealing the container body with a stopper to form the container. [Figure 6] This diagram shows the steps of filling the container body with fluid and sealing the container body with a stopper to form the container. [Modes for carrying out the invention]

[0036] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art in the field to which the claimed subject matter pertains. It should be understood that the above summary of the disclosure of the invention and the following examples are merely illustrative and descriptive and do not limit any of the claimed subject matter.

[0037] The following description relates to embodiments of the disclosure of the present invention. The description of embodiments does not mean that all possible embodiments of the disclosure of the present invention claimed in the appended claims are included. Many modifications, improvements, and equivalents not expressly listed in the following embodiments may fall under the appended claims. Features described as part of one embodiment can be combined with features of one or more other embodiments unless the other is clearly required in relation to the present.

[0038] Figures 1 to 6 show the steps of filling the container body 10 with fluid 23 and sealing the container body 10 with a stopper 20 to form the container 1. In the following examples, the method will be described assuming that it is carried out at atmospheric pressure and without any vacuum steps. However, it will be acknowledged that one or more steps of the method may be carried out under vacuum or partial vacuum if desired.

[0039] Figure 1 shows a container body 10 that confines the fluid 23. The container body 10 is open at a first end 11 and closed at a second end 12. The container body 10 can be cylindrical with a circular cross-section. The fluid 23 can be filled into the container body 10 by any suitable means. In the embodiment, a known and predetermined volume of fluid 23 is filled into the container body 10 such that the upper surface 24 of the fluid 23 is at a known height inside the container body 10. The headspace 30 that confines the gas inside the container body 10 can be defined as the volume above the upper surface 24 of the fluid 23.

[0040] The container body 10 is sealed using the stopper 20 to form the container 1 shown in Figure 6. In this embodiment, the container 1 consists of only two components: the container body 10 and the stopper 20.

[0041] Figure 2 shows the container body 10 and the fluid 23 together with the elongated loading member 40 and the stopper 20 waiting to be loaded into the elongated loading member 40.

[0042] The elongated loading member 40 includes a hollow tubular body 41 extending from a lower end 42 to an upper end 43. An enlarged head portion 44 is provided at the upper end 43. In this embodiment, the bore 41a of the tubular body 41 is constant, but the bore 44a of the enlarged head portion 44 is widened by the provision of an inwardly tapering portion 45. The inwardly tapering portion 45 may, for example, have a conical surface.

[0043] The stopper 20, as shown in Figure 2, can be configured as a sliding stopper that can move along the length of the container body 10 during use. The stopper 20 may include a plug form. The stopper 20 may include, for example, a tubular portion 26 and a transverse portion 27 positioned partway along the tubular portion 26. One or more ribs 22 may be provided on the outer surface of the tubular portion 26 of the stopper 20. Three ribs 22 may be provided. The ribs 22 may be annular. The ribs 22 may function to enhance the sealing function of the stopper 20, or to allow the stopper 20 to slide and function as a seal.

[0044] The outer dimensions of the plug 20 (uncompressed, in a static state) are greater than the inner diameter of the bore 41a of the tubular body 41. The outer dimensions can be considered, for example, as the outer diameter of the plug 22. If the plug 20 is provided with ribs 22 or other equivalent features, the outer diameter can be considered as the maximum outer diameter of the ribs 22.

[0045] Figure 3 shows the plug 20 inserted through the upper end 43 of the elongated loading member 40 and pushed along the elongated loading member 40 toward the lower end 42. In the illustrated example, the lower surface of the plug 20 is positioned flush with the lower end 42 of the elongated loading member 40.

[0046] The plunger 50 is used to insert the stopper 20 into and along the elongated loading member 40. The plunger 50 includes a cylindrical portion 51 and an expanding head 52 provided at the upper end of the cylindrical portion 51. The outer diameter of the cylindrical portion 51 is slightly smaller than the inner diameter of the tubular portion 41 so that the cylindrical portion 51 can move freely relative to the tubular portion 41.

[0047] The end face 53 of the cylindrical portion 51 is sized to contact the upper surface of the plug 20 and to allow force to be applied to it.

[0048] The initial stage of inserting the plug 20 compresses the plug 20 as it is pushed through the inwardly tapering portion 45 by the plunger 50. In particular, this compression reduces the external dimensions of the plug 20, for example, its outer diameter, so that it can fit within the tubular portion 41. The plunger 50 then acts to push the now compressed plug 20 along the tubular portion 41 until the lower surface of the plug 20 is positioned flush with the lower end 42 of the elongated loading member 40, as shown in Figure 3. Taking tolerances into consideration, the lower surface may be positioned within, for example, 0.20 mm of the lower end 42.

[0049] Next, as shown in Figure 4, the elongated loading member 40, plunger 50, and stopper 20 are inserted into the container body 10 as a unit through their first end 11 in the embodiment. The elongated loading member 40, plunger 50, and stopper 20 can be inserted into the container body 10 at a speed of less than 50 mm / sec, and optionally at a speed of 10 to 50 mm / sec, to assist in the ventilation of gas from the headspace 30 through the clearance provided between the outer surface of the elongated loading member 40 and the inner surface of the container body 10.

[0050] The elongated loading member 40, the plunger 50, and the stopper 20 can be inserted into the container body 10 so that the stopper 20 is positioned in the desired final position. For example, this may be such that the lower surface of the stopper 20 is positioned at a distance of 1.5 mm from the upper surface 24 of the fluid 23.

[0051] Next, as shown in Figure 5, the elongated loading member 40 is withdrawn from the container body 10, while simultaneously retaining the plunger 50 and stopper 20 inside the container body 10. To this end, the stopper 20 is displaced from the lower end 42 of the elongated loading member 40, reducing the pressure and, for example, expanding to form a seal with the inner surface of the container body 10. In this embodiment, the plunger 50 remains stationary during this stage, and as a result, the stopper 20 is maintained in the desired final position due to the engagement of the end face 53 of the plunger 50 with the stopper 20.

[0052] Finally, as shown in Figure 6, the plunger 50 is completely withdrawn from the container body 10, and the container 1 is sealed.

[0053] It should be understood that at least portions of the drawings and descriptions in the disclosure of the present invention have been simplified to focus on elements relevant to a clear understanding of the disclosure of the present invention, while other elements that may also be necessary but would be recognized by those skilled in the art have been omitted for clarity. Since such elements are well known to those skilled in the art and do not necessarily facilitate a better understanding of the disclosure of the present invention, no description of such elements is provided herein. [Explanation of Symbols]

[0054] 20 stoppers 23 Fluid 42 Lower end of the elongated loading member 43 Upper end of the elongated loading member 50 plungers

Claims

1. A method for filling a container and sealing it, a) A step of providing a container body that is open at the first end, b) The step of filling the container body with fluid through the first end, and c) Inserting the stopper into the container body through the first end, Includes, Stage c) is, i) The step of inserting the stopper into the upper end of the elongated loading member, wherein the outer dimensions of the stopper are reduced by compression of the stopper during insertion. ii) The step of using a plunger inserted into the upper end of the elongated loading member to push the stopper along the elongated loading member toward the lower end of the elongated loading member, iii) The step of inserting the elongated loading member, the plunger, and the stopper into the container body through the first end, iv) The step of withdrawing the elongated loading member from the container body, while simultaneously maintaining the plunger and the stopper inside the container body so that the stopper is displaced from the lower end of the elongated loading member, reducing the pressure and forming a seal with the inner surface of the container body, and v) Steps to withdraw the plunger from the container body, including, method.

2. The method according to claim 1, wherein step iii) includes inserting the elongated loading member, the plunger, and the stopper as a unit into the container body through the first end.

3. The method according to claim 1 or 2, wherein in step iv), the plunger and the stopper are maintained in a fixed position relative to the container body while the elongated loading member is being withdrawn.

4. The method according to any one of claims 1 to 3, wherein in step iii), the elongated loading member, the plunger, and the stopper are inserted into the container body at a speed of less than 50 mm / sec.

5. The method according to any one of claims 1 to 4, wherein in step iii), a clearance is maintained between the outer surface of the elongated loading member and the inner surface of the container body.

6. The method according to claim 5, wherein the clearance includes a radial gap greater than 0.1 mm.

7. The method according to any one of claims 1 to 6, wherein in step ii), the stopper is optionally pushed by the plunger along the elongated loading member until the lower surface of the stopper is flush with the lower end of the elongated loading member, to a point where the lower surface of the stopper is within 0.2 mm of the lower end of the elongated loading member.

8. The method according to any one of claims 1 to 7, wherein in step iii), the elongated loading member, the plunger, and the stopper are inserted into the container body such that the stopper is positioned in a desired final position, and in step iv), the stopper is maintained in the desired final position.

9. The method according to any one of claims 1 to 8, wherein in step iii), the elongated loading member, the plunger, and the stopper are inserted into the container body such that the stopper is positioned at a distance of 1.5 mm from the top surface of the fluid.

10. The method according to any one of claims 1 to 9, wherein the upper end of the elongated loading member includes an inwardly tapered portion for compressing the plug during step i) when the plug is pushed through the inwardly tapered portion.

11. The method according to any one of claims 1 to 10, wherein step i) reducing the outer dimensions of the stopper includes reducing the outer diameter of the stopper.

12. The method according to any one of claims 1 to 11, wherein the container body is closed at a second end opposite to the first end.

13. The method according to any one of claims 1 to 12, wherein the container body and the fluid are subjected to a vacuum or partial vacuum before and / or during step iii).

14. The method according to any one of claims 1 to 12, wherein steps i) to v) are carried out at atmospheric pressure.

15. The method according to any one of claims 1 to 14, wherein step i) and / or ii) is performed before or after step b).

16. A container body filled and sealed by the method described in any one of claims 1 to 15, A nasal dispensing device that includes a nasal dispensing device.

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