Improvements relating to filling and plugging of containers

Abstract

A method of filling and plugging a container body (10), comprising the steps of: a) providing a container body (10) open at a first end (11); b) filling the container body (10) with a fluid (23) through the first end (11); and c) inserting the stopper (20) into the container body (10) through the first end (11); wherein step c) comprises the following steps: i) inserting a stop (20) into the upper end (43) of the elongate loading member (40), during insertion, the outer dimension of the stop (20) being reduced by compression of the stop (20); ii) forcing a stop (20) along the elongate loading member (40) towards a lower end (42) of the elongate loading member (40) using a plunger (50) inserted into the upper end (43) of the elongate loading member (40); iii) inserting the elongate loading member (40), the plunger (50) and the stop (20) through the first end (11) into the container body (10); iv) withdrawing the elongated loading member (40) from the container body (10) while retaining the plunger (50) and the stopper (20) within the container body (10) such that the stopper (20) moves out of the lower end (42) of the elongated loading member (40) and decompresses to form a seal with the inner surface of the container body (10), and v) withdrawing the plunger (50) from the container body (10).

Description

[0001] This disclosure relates to methods of filling and plugging a container body, containers for fluids, and the use of such containers in dispensing devices. The container can be used, for example, in a nasal dispensing device. Background Technology

[0002] It is known to provide a metered dose of medicine in a sealed container, such as a vial, for dispensing from a dispensing device. An example is described in EP 0827 782 A2, in which a piercing element is disposed on a piston that pierces a sealing member in the vial. The sealing member is then displaced into the vial, forcing the medicine out of the vial through a piercing opening in the sealing member. The medicine then exits through a channel formed in the piston and from the dispenser. Another example is described in EP 3 820 625 A2, in which, according to its abstract, an apparatus for dispensing a fluid product comprises: a body; a reservoir containing one or two doses of the fluid product, the reservoir including a stopper that seals the reservoir in a sealing manner prior to actuation; a dispensing head provided with a dispensing orifice; and a dispensing device for dispensing at least some of the fluid product through the dispensing orifice during actuation, the device including a needle, the tip of the needle being adapted to pierce the stopper during actuation, the reservoir being filled with the fluid product and plugged with the stopper under vacuum such that the volume of residual air present in the reservoir between the fluid product and the stopper is substantially zero.

[0003] While sealed containers for fluids such as pharmaceuticals are available, there is still a need to provide improved or at least commercially acceptable alternative containers and methods for filling and sealing them. Summary of the Invention

[0004] A first aspect of this disclosure provides a method for filling and plugging a container body, the method comprising the following steps:

[0005] a) Provide a container body that is open at the first end;

[0006] b) Filling the container body with fluid through the first end; and

[0007] c) Insert the stop into the container body through the first end;

[0008] Step c) includes the following steps:

[0009] i) The stop is inserted into the upper end of the elongated loading member, and during the insertion, the external dimensions of the stop are reduced by compression of the stop;

[0010] ii) Use a plunger inserted into the upper end of the elongated loading member to force the stop along the elongated loading member toward the lower end of the elongated loading member;

[0011] iii) Insert the elongated loading member, the plunger, and the stop into the container body through the first end;

[0012] iv) Extract the elongated loading member from the container body while retaining the plunger and the stop within the container body, such that the stop is removed from the lower end of the elongated loading member and decompressed to form a seal with the inner surface of the container body; and

[0013] v) Pull the plunger out of the container body.

[0014] Advantageously, this method does not require vacuum equipment or a seal on or around the container body. Therefore, it avoids the need to balance the pressure between the container and the vacuum pump, and avoids any risk of positive pressure being generated in any headspace that could drive fluid diffusion / permeation from the container. Furthermore, compared to filling methods under vacuum, this method potentially allows for a smaller headspace volume. Additionally, this method avoids the risk of stop movement that can occur when filling under vacuum with high differential pressure.

[0015] In one embodiment, step iii) includes inserting the elongated loading member, plunger, and stop as a unit into the container body through the first end.

[0016] In one implementation, during step iv), the plunger and stop are held in a fixed position relative to the container body during the removal of the elongated loading member.

[0017] In one embodiment, in step iii), the elongated loading member, plunger, and stop are inserted into the container body at a speed of less than 10-50 mm / s for a length of less than 1.47 mm. 2 The venting area and / or radial clearance of less than 0.1 mm. While a larger venting area / radial clearance can achieve a faster plugging time, this would mean applying greater compression to the stop, which could damage the stop, for example, potentially abrading any silicone treatment on the stop. Using a specified insertion speed with the stop can beneficially limit fluid flow within the container body and / or any pressure buildup in the headspace by allowing sufficient time for gas to escape from the headspace.

[0018] In one embodiment, in step iii), a gap is maintained between the outer surface of the elongated loading member and the inner surface of the container body. For example, the gap may include a radial clearance greater than 0.1 mm. Advantageously, the gap may provide means for venting the top space during step iii).

[0019] In one embodiment, in step ii), the plunger forces the stop along the elongated loading member to a position where the lower surface of the stop is within 0.2 mm of the lower end of the elongated loading member; alternatively, the lower surface of the stop is flush with the lower end of the elongated loading member.

[0020] Advantageously, positioning the lower surface at or near the lower end of the elongated loading member allows the lower surface of the stop to be very close to the fluid, while the elongated loading member does not contact the fluid itself. Furthermore, such a position allows the lower sealing rib of the stop to pop out from the elongated loading member and engage with the container body as soon as the elongated loading member begins to be removed, thereby helping to secure the stop's position relative to the container body.

[0021] In step iii), the elongated loading member, plunger, and stop can be inserted into the container body such that the stop is positioned in the desired final position, and remains in the desired final position during step iv). Advantageously, this allows for more controlled and precise positioning of the end container's stop, particularly relative to the fluid surface.

[0022] In step iii), the elongated loading member, plunger, and stop can be inserted into the container body such that the stop is located at a distance of up to 1.5 mm from the upper surface of the fluid. Optionally, the top space volume is minimized.

[0023] The upper end of the elongated loading member may include an inwardly tapering portion for compressing the stop member during step i) when the stop member is forced through the inwardly tapering portion. In one embodiment, reducing the external dimensions of the stop member in step i) includes reducing the outer diameter of the stop member.

[0024] The container body can be closed at a second end opposite to the first end. Typically, the container body will be a vial or other tubular component that opens only at one end, with the other end closed as part of the integral forming of the container body. However, the method of this disclosure can also be used with a container body that is initially open at both ends and provided with means for closing the second end, such as a second stop.

[0025] In some implementations, the container body and the fluid are subjected to a vacuum or partial vacuum before and / or during step iii).

[0026] In some other implementations, steps i) through v) are performed at atmospheric pressure.

[0027] Optionally, steps i) and / or ii) can be performed before or after step b). Therefore, inserting the stop into the elongated loading member and / or positioning the stop toward the lower end of the elongated loading member can be performed at any time before step iii). For example, pre-prepared sub-units of the elongated loading member and the stop can be formed before the container body is filled with fluid.

[0028] Steps a) through c) and steps i) through v) can be performed in one or more locations. All steps can be performed on a single machine with one or more stations. Alternatively, multiple machines can be used to perform these steps. For example, steps a) and b) can be performed using a filling machine, and one or more of steps i) through iv) of step c) can be performed using a stopper machine. Steps i) and ii) can be performed in the same location as steps iii) through v) or in different locations. For example, one machine can be used to preload the stop into the elongated loading member, and different machines can be used to perform steps iii) through v). However, in one embodiment, all steps i) through v) are performed in a single location using a single machine.

[0029] A second aspect of this disclosure provides a container for fluids that is filled and plugged using the method described in the first aspect above.

[0030] The third aspect of this disclosure provides the use of the container of the second aspect in a dispensing device.

[0031] In one embodiment, during actuation of the dispensing device, a stop is pierced by a hollow needle to provide an outlet for the fluid, and the stop further moves toward a second end of the container body to pressurize and dispense the fluid.

[0032] A fourth aspect of this disclosure provides a dispensing device comprising a container according to the second aspect. The dispensing device may be a nasal dispensing device arranged to dispense a pharmaceutical preparation into a nasal cavity.

[0033] In some examples, the dispensing device may be a nasal dispensing device. In some examples, the fluid within the container may consist of a single dose of nasal medication.

[0034] The container body described above can be formed from any suitable material, such as glass or plastic polymers. Examples of suitable glass include Type I borosilicate glass 'Fiolax Clear' and Type II. Examples of suitable polymers include polypropylene, polyethylene, polystyrene, and cyclic olefin copolymers (examples include those manufactured by TOPAS Advanced Polymers GmbH, Frankfurt-Hirsch, Germany). COC) and liquid crystal polymers (examples are manufactured by DuPont Wilmington, USA). LCP).

[0035] The container body may be composed of an elongated tube. In one embodiment, the elongated tube is closed at one opening and open at the other. The elongated tube may be cylindrical. The container body may include an outwardly rotating flange at its open end. Alternatively, the edge at the open end may simply be formed by the end face of a tubular element without an outwardly rotating flange.

[0036] The aforementioned stop components can be formed from elastomer or thermoelastic materials, such as EPDM, polychloroprene, hydrogenated nitrile, butyl, halo-butyl, and dynamically vulcanized EPDM / PP (e.g., Styrenic block copolymers or blends thereof. Other suitable materials include high-density polyethylene and low-density polyethylene.

[0037] The outer surface of the stop may be provided with one or more sealing features (such as ribs, rings, etc.) to enhance the sealing function of the stop.

[0038] In some examples, the stop may have an H-shaped configuration, suitable for piercing the membrane. The H-shape allows pressure inside the container to be applied outward to the stop seal, thereby increasing contact pressure and reducing the likelihood of dynamic leakage.

[0039] In some examples, one or more sealing ribs may be provided to provide a seal against the container body while maintaining appropriate low friction between the stop and the container body.

[0040] In some examples, the stop may be coated with a friction-reducing coating, such as a silicone coating, which may be applied to the stop, for example, by spraying or baking. Fluorocarbon film coatings may also be used.

[0041] The fluid contained within the container described above may consist of a single-dose fluid or may include multiple-dose fluids. The fluid may contain a pharmaceutical preparation. As used herein, the term pharmaceutical preparation is intended to cover any pharmaceutical preparation, compound, composition, medicine, agent, or product that can be delivered or administered to a human or animal, such as pharmaceutical preparations, medicines, biological products, and pharmaceutical products. Examples include antihistamines, analgesics, bronchodilators, antihistamines, therapeutic proteins and peptides, antitussives, angina treatments, antibiotics, anti-inflammatory drugs, hormones or sulfonamides such as vasoconstrictiveamines, enzymes, alkaloids, or steroids, including combinations of two or more of these. In particular, examples include isoproterenol [alpha-(isopropylaminomethyl)protocatechuyl] [alcohol]), phenylephrine, phenylpropanolamine, glucagon, adrenochrome, trypsin, adrenaline, noscapine, codeine, atropine, heparin, dihydromorphone, ergotamine, scopolamine, metapyrilene, cyanocobalamin, terbutaline, limectin, salbutamol, ipratropium bromide, and salbutamol. Alcoholic compound preparations, flunisolide, colchicine, pibuterol, beclomethasone, orciprenaline, fentanyl, as well as streptomycin, penicillin, procaine penicillin, tetracycline, chlorotetracycline and hydroxytetracycline, adrenocorticotropic hormone and adrenocorticotropic hormone (e.g., cortisone, hydrocortisone, hydrocortisone acetate and prednisolone), insulin, sodium cromoglycate and mometasone, including combinations of two or more of these.The pharmaceutical formulation may be in the form of a free base or one or more salt forms conventional in the art, such as acetate, benzenesulfonate, benzoate, bicarbonate, tartrate, bromide, calcium edetate, camphor sulfonate, carbonate, chloride, citrate, dihydrochloride, edetate, edisylate, estolate, esylate, fumarate, peroctanoate, gluconate, glutamate, glycolyllarsanilate, hexylresorcinate, hydrobromide, hydrochloride, hydroxynaphthalate, iodine. Compounds, hydroxyethyl sulfonates, lactates, lacturonates, malates, maleates, mandelates, methanesulfonates, methyl bromides, methyl nitrates, methyl sulfates, mucates, napsylates, nitrates, pamoates, embonates, pantothenates, phosphates, diphosphates, polygalacturonates, salicylates, stearates, subacetates, succinates, sulfates, tannates, tartrates, and triethyl iodide, including combinations of two or more of these. Cationic salts, such as alkali metals (e.g., sodium and potassium salts), and ammonium and amine salts known in the art to be pharmaceutically acceptable, such as glycine salts, ethylenediamine salts, choline salts, diethanolamine salts, triethanolamine salts, octadecylamine salts, diethylamine salts, triethylamine salts, 1-amino-2-propanol-amino-2-(hydroxymethyl)propane-1,3-diol salts, and 1-(3,4-dihydroxyphenyl)-2-isopropylaminoethanol salts, may also be used. The pharmaceutical formulation is generally intended for nasal inhalation and can be prepared in any suitable fluid form, such as a solution or powder suspension dissolved or suspended in a solvent or carrier liquid such as ethanol or isopropanol. Alternatively, the pharmaceutical formulation may be suitable for sublingual or ophthalmic delivery. For example, the pharmaceutical formulation may be suitable for treating asthma.Examples include salbutamol, beclomethasone, salmeterol, fluticasone, formoterol, terbutaline, sodium cromoglycate, budesonide, and flunisolone, as well as their physiologically acceptable salts (e.g., salbutamol sulfate, salmeterol xinafoate, fluticasone propionate, beclomethasone dipropionate, and terbutaline sulfate), solvates, and esters, including combinations of two or more of them. A single isomer, such as R-salbutamol, may also be used. The pharmaceutical formulations may also be suitable for treating migraines. An example is sumatriptan. It should be understood that the pharmaceutical formulations may contain one or more active ingredients, such as flutiform. If desired, one or more surfactants may be included. Attached Figure Description

[0042] One or more embodiments of this disclosure will now be described by way of example only with reference to the accompanying drawings, in which:

[0043] Figures 1 to 6 The steps are shown: filling the container body with fluid and plugging the container body with a stop to form a container. Detailed Implementation

[0044] Unless otherwise defined, all technical and scientific terms used in this specification have the same meaning as commonly understood by one of ordinary skill in the art to which the claimed subject matter pertains. It should be understood that the foregoing overview and the following examples of this disclosure are merely exemplary and illustrative and do not limit any of the claimed subject matter.

[0045] The following description describes embodiments of this disclosure. This description of embodiments does not imply inclusion of all possible embodiments of this disclosure claimed in the appended claims. Many modifications, alterations, and equivalents not expressly described 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 explicitly requires otherwise.

[0046] Figures 1 to 6The steps of filling the container body 10 with fluid 23 and plugging the container body 10 with stop 20 to form container 1 are shown. In the following embodiments, the method will be described as being performed at atmospheric pressure and without applying any vacuum steps. However, it should be understood that one or more steps of the method may be performed under vacuum or partial vacuum if desired.

[0047] Figure 1 A container body 10 containing fluid 23 is shown. The container body 10 is open at a first end 11 and closed at a second end 12. The container body 10 may be cylindrical with a circular cross-section. Fluid 23 may be filled into the container body 10 by any suitable means. In one 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 will be at a known height within the container body 10. The gas-containing headspace 30 within the container body 10 may be defined as the volume above the upper surface 24 of the fluid 23.

[0048] Once the container body 10 is sealed using the stop 20, it forms container 1, such as Figure 6 As shown. In one embodiment, the container 1 consists of only two parts: the container body 10 and the stop member 20.

[0049] Figure 2 The container body 10 and fluid 23 are shown, along with an elongated loading member 40 and a stop 20 prepared for loading into the elongated loading member 40.

[0050] The elongated loading member 40 includes a hollow tubular body 41 extending from a lower end 42 toward an upper end 43. An enlarged head 44 is disposed at the upper end 43. In one embodiment, the aperture 41a of the tubular body 41 is constant, but the aperture 44a of the enlarged head 44 is opened by providing an inwardly tapered portion 45. The inwardly tapered portion 45 may, for example, have a tapered surface.

[0051] like Figure 2 The stop 20 shown can be configured as a slidable stop that can move along the length of the container body 10 during use. The stop 20 may include a plug-like form. The stop 20 may include, for example, a tubular portion 26 and a transverse portion 27 partially arranged along the tubular portion 26. One or more ribs 22 may be provided on the outer surface of the tubular portion 26 of the stop 20. Three ribs 22 may be provided. The ribs 22 may be annular. The ribs 22 may be used to enhance the sealing function of the stop 20 and / or enable the stop 20 to function as a sliding seal.

[0052] The external dimension of the stop 20 (in its uncompressed, stationary state) is larger than the inner diameter of the hole 41a in the tubular body 41. The external dimension can be considered, for example, the outer diameter of the stop 22. When the stop 20 is provided with rib 22 or other equivalent features, the outer diameter can be considered as the maximum outer diameter of the rib 22.

[0053] Figure 3 A stop 20 is shown, which is inserted via the upper end 43 of the elongated loading member 40 and forced along the elongated loading member 40 toward the lower end 42. In the example shown, the lower surface of the stop 20 is positioned flush with the lower end 42 of the elongated loading member 40.

[0054] The plunger 50 is used to insert the stop 20 into and along the elongated loading member 40. The plunger 50 includes a cylindrical portion 51 and an enlarged head 52 disposed 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 body 41, allowing the cylindrical portion 51 to move freely about the tubular portion 41.

[0055] The end face 53 of the cylindrical portion 51 is designed to contact the upper surface of the stop 20 and apply force to the upper surface of the stop 20.

[0056] As the plunger 50 forces the stop 20 through the inwardly tapered portion 45, the initial stage of insertion compresses the stop 20. Specifically, this compression reduces the external dimensions (e.g., outer diameter) of the stop 20, allowing it to fit within the tubular portion 41. Subsequently, the plunger 50 forces the now-compressed stop 20 along the tubular portion 41 until the lower surface of the stop 20 is positioned flush with the lower end 42 of the elongated loading member 40, as... Figure 3 As shown. Tolerances are allowed; the lower surface can be positioned, for example, within 0.20 mm of the lower end 42.

[0057] Next, as Figure 4 As shown, the elongated loading member 40, plunger 50, and stop 20 are inserted into the container body 10 through their first ends 11, forming a unit in one embodiment. The elongated loading member 40, plunger 50, and stop 20 can be inserted into the container body 10 at a speed of less than 50 mm / sec, optionally at a speed of 10-50 mm / sec, to help gas escape from the top space 30 through the gap provided between the outer surface of the elongated loading member 40 and the inner surface of the container body 10.

[0058] The elongated loading member 40, plunger 50, and stop 20 can be inserted into the container body 10 such that the stop 20 is positioned at its desired final location. For example, this can cause the lower surface of the stop 20 to be located at a distance of up to 1.5 mm from the upper surface 24 of the fluid 23.

[0059] Next, as Figure 5 As shown, the elongated loading member 40 is withdrawn from the container body 10 while the plunger 50 and the stop 20 are held within the container body 10, such that the stop 20 moves out of the lower end 42 of the elongated loading member 40 and decompresses (e.g., expands) to form a seal with the inner surface of the container body 10. In one embodiment, the plunger 50 remains stationary during this step, and thus the stop 20 is held in the desired final position due to the engagement of the end face 53 of the plunger 50 with the stop 20.

[0060] Finally, as Figure 6 As shown, the plunger 50 is completely withdrawn from the container body 10, and the plugging of the container 1 is completed.

[0061] It should be understood that at least some of the figures and descriptions in this disclosure have been simplified to focus on elements relevant to a clear understanding of this disclosure, while other elements that would be understood by those skilled in the art have been omitted for clarity. Because these elements are well-known to those skilled in the art, and because they do not necessarily contribute to a better understanding of this disclosure, descriptions of these elements are not provided herein.

Claims

1. A method for filling and plugging a container body, the method comprising the following steps: a) Provide a container body that is open at the first end; b) Filling the container body with fluid through the first end; as well as c) Insert the stop into the container body through the first end; Step c) includes the following steps: i) The stop is inserted into the upper end of the elongated loading member, and during the insertion, the external dimensions of the stop are reduced by compression of the stop; ii) Use a plunger inserted into the upper end of the elongated loading member to force the stop along the elongated loading member toward the lower end of the elongated loading member; iii) Insert the elongated loading member, the plunger, and the stop into the container body through the first end; iv) Extract the elongated loading member from the container body while retaining the plunger and the stop within the container body, such that the stop is removed from the lower end of the elongated loading member and decompressed to form a seal with the inner surface of the container body; and v) Pull the plunger out of the container body.

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

3. The method according to claim 1 or 2, wherein, In step iv), during the withdrawal of the elongated loading member, the plunger and the stop remain in a fixed position relative to the container body.

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

5. The method according to any of the preceding claims, wherein, In step iii), a gap 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 gap includes a radial gap greater than 0.1 mm.

7. The method according to any of the preceding claims, wherein, In step ii), the plunger forces the stop along the elongated loading member to a position where the lower surface of the stop is within 0.2 mm of the lower end of the elongated loading member; optionally, the lower surface of the stop is flush with the lower end of the elongated loading member.

8. The method according to any of the preceding claims, wherein, In step iii), the elongated loading member, the plunger, and the stop are inserted into the container body such that the stop is located at the desired final position, and during step iv), the stop is held in the desired final position.

9. The method according to any of the preceding claims, wherein, In step iii), the elongated loading member, the plunger, and the stop are inserted into the container body such that the stop is located at a distance of up to 1.5 mm from the upper surface of the fluid.

10. The method according to any of the preceding claims, wherein, The upper end of the elongated loading member includes an inwardly tapered portion for compressing the stop during step i) when the stop is forced through the inwardly tapered portion.

11. The method according to any of the preceding claims, wherein, In step i), reducing the external dimension of the stop includes reducing the outer diameter of the stop.

12. The method according to any of the preceding claims, wherein, The container body closes at a second end opposite to the first end.

13. The method according to any of the preceding claims, wherein, The container body and 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) through v) are performed at atmospheric pressure.

15. The method according to any of the preceding claims, wherein, Steps i) and / or ii) are performed before or after step b).

16. A nasal dispensing device comprising a container body filled and plugged by the method of any one of claims 1 to 15.

Images