Receptacle for pharmaceutical packaging with thickness profile for lubricant layer

Abstract

To provide a receptacle for pharmaceutical packaging characterized by a thickness profile for a lubricant layer.SOLUTION: A receptacle 100 is provided with a first opening 102 and a flange 105 projecting outward at a first end portion 119, and a second opening 103 and mounting means 104 at a second end portion 120. The receptacle has an elongate barrel section 501 extending from an axial position PA to an axial position PB, and the elongate barrel section has a hollow truncated cone with a diameter at the PA larger than a diameter at the PB. The elongate barrel section 501 has a length of LB, and an axis 101 oriented in a direction of an elongate extending portion of the receptacle 100 is a rotation axis of the elongate barrel section 501. A side wall 107 has an inner surface 118, with a lubricant layer 106 provided on the inner surface. The layer 106 extends over a part of, not all of, the side wall 107 and does not reach the end portions PA and PB. A portion X of the elongate barrel section 501 extends between axial positions P1 and P2.SELECTED DRAWING: Figure 1

Description

[Technical field]

[0001] The present invention generally relates to a container for pharmaceutical packaging characterized by a thickness profile of a lubricant layer. In particular, the present invention relates to a container, a kit including the container and a charge, an assembly including the container, a charge and a liquid pharmaceutical composition, a process for preparing the container and a use of the lubricant layer characterized by a thickness profile. [Background technology]

[0002] Medication can be provided in many forms and can be placed in a variety of different containers. For liquid medication, some common examples are ampoules, vials, cartridges and syringes. One widely used form uses a sliding plunger in the container to deliver the liquid from an opening. One approach is to provide a lubricating layer on the inside of the container to facilitate the sliding of the plunger.

[0003] US Pat. No. 4,767,414 describes plasma activation of the inner surface prior to deposition of the silicone lubricant layer.

[0004] EP 0 920 879 describes a formulation for a silicone-based mixture that contains reactive and non-reactive components.

[0005] There remains a need for improved approaches to lubrication of drug containers, particularly for single dose delivery. Summary of the Invention [Problem to be solved by the invention]

[0006] SUMMARY OF THE PRESENT EMBODIMENT It is an object of the present invention to at least partially overcome one or more of the above mentioned problems.

[0007] It is an object of the present invention to provide an improved pharmaceutical packaging container, particularly for single-dose delivery.

[0008] It is an object of the present invention to provide a kit, including a container and charge, that is particularly adapted for single dose delivery.

[0009] It is an object of the present invention to provide an improved process for preparing pharmaceutical packaging containers, particularly for single-dose delivery.

[0010] It is an object of the present invention to provide an assembly including a container, a charge and a liquid pharmaceutical composition, which is particularly improved for single dose delivery.

[0011] It is an object of the present invention to provide a pharmaceutical packaging container having improved dynamic friction characteristics, particularly for single dose delivery.

[0012] It is an object of the present invention to provide a kit having improved dynamic friction characteristics, particularly for single dose delivery.

[0013] It is an object of the present invention to provide a process for preparing a pharmaceutical packaging container that provides improved dynamic friction characteristics, particularly for single-dose delivery.

[0014] It is an object of the present invention to provide an assembly having improved dynamic friction characteristics, particularly for single dose delivery. [Means for solving the problem]

[0015] Each of the following embodiments, where the xth embodiment is referred to as |x|, represents a preferred apparatus for achieving the objectives of the present invention.

[0016] |1| A container for drug packaging, the container having an elongated cylindrical section, a. the elongated tubular section has an elongated extension direction and an axis in the elongated extension direction; b. an axial position p is defined along the axis; c. The elongated cylindrical section is at an axial position p AFrom axial position p B It extends to d. The length L of the elongated cylindrical section B p A andp B is the interval between e. the container has a sidewall extending across the elongated tubular section, the sidewall having an interior surface defining an interior, the interior having a predetermined diameter; f. a lubricant layer is disposed on at least a portion of the interior surface; gp A andp B At a given axial position p on the axis between i. the thickness of the side wall; ii. the thickness of said layer, and iii. said internal diameter are defined as the average of angles in a transverse plane perpendicular to the axis at the axial position p, h. The axis segment X is determined based on the following criteria: ip 1 and p 2 Both are p A andp B It is located between ii. Partial length L X p 1 andp 2 is the interval between iii.L X L B At least 1 / 4 of L B At least half of L B At least 80% of, most preferably L B At least 90% of the iv. the layer extends throughout portion X; iT mean is the average thickness of the layer defined in section X, j.Position p m p 1 andp 2 It is the midpoint between kT A p1 ~p m is the average thickness of the layer in the section lT B p m ~p 2 is the average thickness of the layer in the section mT A :T B is in the range of 5:1 to 1:5, preferably in the range of 3:1 to 1:3, more preferably in the range of 2:1 to 1:2, and most preferably in the range of 4:3 to 3:4; n. One or more container criteria are met, the container criteria being: i. The length L B is in the range of 3 to 20 cm, preferably in the range of 4 to 15 cm, more preferably in the range of 5 to 12 cm, and most preferably in the range of 6 to 8 cm; ii.p A ~p B the average value of the inner diameter defined over the range is in the range of 0.4 to 4 cm, preferably in the range of 0.6 to 3 cm, more preferably in the range of 0.8 to 2.5 cm, and most preferably in the range of 1 to 2 cm; iii.p A ~p B The average thickness of the side wall, as defined above, is in the range of 0.3 to 4 mm, preferably in the range of 0.7 to 3 mm, more preferably in the range of 1.1 to 2 mm, and most preferably in the range of 1.4 to 1.8 mm; and iv. The internal volume is in the range of 0.1 to 150 ml, preferably in the range of 0.5 to 50 ml, more preferably in the range of 1 to 25 ml, most preferably in the range of 2 to 10 ml, and most preferably in the range of 3 to 5 ml; is selected from the group consisting of:

[0017] In one aspect of this embodiment, T mean is in the range of 50 nm to 4100 nm.

[0018] In various aspects of this embodiment, the following combinations of container criteria i.-iv. are realized: i., ii., iii., iv., i.+ii., i.+iii., i.+iv., ii.+iii., ii.+iv., iii.+iv., i.+ii.+iii., i.+ii.+iv., i.+iii.+iv. and i.+ii.+iii.+iv.

[0019] |2| In the container according to embodiment |1|, the average thickness T mean is in the range of 100 nm to 3000 nm, preferably in the range of 300 to 2000 nm, more preferably in the range of 500 to 1500 nm, and most preferably in the range of 700 to 1200 nm.

[0020] |3| In the container according to embodiment |1| or |2|, a. The inner surface of the side wall has a roughness of r rms and br rms :T mean The ratio is within the range of 1:2 to 1:20, preferably within the range of 1:3 to 1:15, and more preferably within the range of 1:4 to 1:10.

[0021] |4| In a container according to any one of the preceding claims, the layer comprises p 1 andp 2 The maximum layer thickness T is specified between max , p 1 andp 2 The minimum layer thickness T is specified between min It has T min / T max The value of is at least 0.7, preferably at least 0.75, more preferably 0.8, most preferably 0.9, and most preferably 0.95.

[0022] |5| In a container according to any one of the preceding claims, the side wall comprises plastic or glass or both.

[0023] |6| In the container according to any one of the embodiments |1| to |5|, the lubricant comprises one or more silicone oils. Preferably, the lubricant comprises a total of at least 5 wt. %, more preferably at least 15 wt. %, and most preferably at least 25 wt. % of one or more silicone oils, based on the total weight of the lubricant in the layer.

[0024] |7| In the container according to embodiment |6|, one or more silicone oils are at least partially contained within a matrix, the matrix being bonded to the inner surface.

[0025] |8| In the container according to embodiment |7|, the matrix is ​​a polymer, preferably a cross-linked polymer.

[0026] In the container according to embodiment |8|, the polymer comprises a repeating unit comprising SiO. A preferred polymer is a polysiloxane, more preferably a crosslinked polysiloxane.

[0027] |10| The container according to any one of embodiments |1| to |9|, wherein the interior is cylindrical or frusto-conical across the elongated tube section. A preferred frusto-conical shape has a conical opening in the range of 0.04° to 0.4°, preferably in the range of 0.08° to 0.25°, more preferably in the range of 0.1° to 0.2°.

[0028] |11| A container according to any one of embodiments |1| to |10|, having a first opening at a first end and a second opening at a second end. In one aspect of this embodiment, the first opening has a larger area than the second opening, preferably at least 50% larger, more preferably at least 100% larger, and most preferably at least 200% larger based on the surface area of ​​the second opening. In one alternative embodiment, the container has the first opening at the first end and a dead end at the second end.

[0029] |12| In the container according to any one of the embodiments |1| to |11|, p 1 The inner diameter at is d 1 And p 2 The inner diameter at is d 2 and d 1 d 2 It is larger than d 1 is the diameter d 2 Based on this, preferably d 2 is at least 0.05%, more preferably at least 0.1%, and most preferably at least 0.2% greater than d. 1 is the diameter d 2 Based on this, preferably d 2 Preferably, the thickness of the first electrode is at most 5% greater, more preferably at most 4% greater, and more preferably at most 3% greater.

[0030] |13| The container according to any one of the embodiments |1| to |12|, having an attachment means provided at the opening. Preferably, the attachment means is provided at one end, more preferably at the second end. Preferred attachment means are adapted and arranged to attach one or both selected from the group consisting of a needle and a tube. Some preferred attachment means are a thread, a latch, a luer fitting and a bayonet fitting.

[0031] |14| In the container according to any one of the embodiments |1| to |13|, the layer has a minimum thickness t defined at the position X of at least 60 nm, preferably at least 90 nm, more preferably at least 100 nm, most preferably at least 110 nm. min It has.

[0032] |15| As a kit part a. A container according to any one of embodiments |1| to |14|, and b. Loading material wherein the charge is adapted and arranged to be positioned within the interior, thereby i. the charge seals the interior cross section between the inner surfaces of the side walls; ii. The charge is p B a forward end axially adjacent said layer or said inner surface at said forward end, iii. The charge is p A a rear end axially adjacent said layer or said inner surface at said rear end, iv. The length L of the charge C is the spacing between the front and rear ends, v. the charge has a charge axial position that is an axial position of the front end; The charge is movable in a direction parallel to the axis with kinetic friction g that is a function of the charge axial position.

[0033] In the kit according to embodiment |15|, the axial position of each charge is p 1 +L C ~p 2 The dynamic friction g is within the range of g max , minimum value g min and the average value g mean and g min / g max The value of is at least 0.7, preferably at least 0.8, more preferably at least 0.90, more preferably at least 0.94, and most preferably at least 0.98.

[0034] In the kit according to embodiment |15| or |16|, the axial position of each charge is p 1 +L C ~p 2 and the dynamic friction g has a standard deviation g of less than 2 N, preferably less than 1 N, more preferably less than 0.5 N, and most preferably less than 0.2 N. SD It has.

[0035] |18| An assembly comprising a container and a charge according to any one of embodiments |1| to |14|, a. the container has an opening; b. the charge is positioned within the interior and seals a cross section of the interior; c. the interior contains a liquid pharmaceutical composition located between the sealed cross section and the opening; and d. the assembly is adapted and arranged such that movement of said charge in a direction parallel to said axis causes said liquid pharmaceutical composition to be delivered through said opening.

[0036] |19| A process for preparing a container according to any one of embodiments |1| to |14|, a kit according to embodiment |15| or |16|, or an assembly according to embodiment |17|, comprising a process step of depositing a lubricant layer by application using an application tool.

[0037] |20| A lubricant layer is provided, and the ratio of the average thickness of the layer over the first half to the average thickness of the layer over the second half T A :T B The use of a lubricant layer to improve the uniformity of dynamic friction in a pharmaceutical container is in the range of 1:5 to 5:1, preferably in the range of 3:1 to 1:3, more preferably in the range of 2:1 to 1:2, and most preferably in the range of 4:3 to 3:4.

[0038] Diameter, layer thickness and roughness The axis of the container is used to define the axial position. At a given axial position, the sidewall, like the lubricant layer, is a circumference having a thickness lying in a cross-section perpendicular to the axis. The inner diameter, the thickness of the lubricant layer, the thickness of the sidewall and the surface roughness at a given point along the axis are preferably average values ​​defined over the entire circumference of the interface. One average over the entire circumference is an angular average. The angular average is preferably defined by measuring eight points separated by equal angles over the entire circumference.

[0039] container Suitable containers are adapted and arranged to contain a medical fluid. Some suitable containers are syringes, barrels, cartridges, dead-end containers and vials.

[0040] A preferred container has one or more openings. One opening is preferably located at one end of the container. In one embodiment, the container has one opening. In another embodiment, the container has two openings.

[0041] The container preferably has two ends: a first end and a second end.

[0042] A preferred container has a first opening at a first end. One type of preferred container has a second opening at a second end. Another type of preferred container has a dead end at the second end.

[0043] Long and thin tube section The container has an elongated cylindrical section. The elongated cylindrical section represents a portion of the container. The container may have other sections outside the elongated cylindrical section. Another name for the elongated cylindrical section is a tube section. One preferred elongated cylindrical section is tubular.

[0044] Possible embodiments of the elongated cylinder sections and axes are described herein in mathematical terms, such as axes of symmetry, axes of rotation or pivoting, planes and bodies of revolution, and shapes such as cylinders and truncated cones. It is understood that these embodiments allow for several variations from these exact mathematical concepts. Suitable variations based on mathematical concepts do not prevent the container from functioning as a plunger system cooperating with the load.

[0045] The elongated tube section has an axis. The axis may be a rotation axis of the elongated tube section. The axis may be a pivot axis of the elongated tube section. The side wall may be a body that pivots about the axis. The inner surface may be a surface that pivots about the axis. The layer may be a body that pivots about the axis.

[0046] The axis defines an axial position p, which is the axial location along the axis. In this specification, the symbol p represents the axial location in ordinary terms, and a specific axial location is represented by the letter p with a subscript.

[0047] The axial position p along the axis is used as a parameter that describes the position of a point or cross-section along the elongated cylindrical section, for example in a side wall. The axial position of a point that is not on the axis is found by projecting the point onto the axis with a displacement vector perpendicular to the axis. A cross-section is a plane perpendicular to the axis. The axial position of a cross-section is found at the point where the cross-section intersects the axis.

[0048] The elongated cylindrical section is at the axial position p A From axial position p B The long and narrow cylindrical section extends to p A and the cross section at p B The cross section at and is sandwiched between.

[0049] The container has a sidewall extending over an elongated cylindrical section. The sidewall has an inner surface. The inner surface defines an interior. Preferred shapes for the sidewall are a hollow cylinder, a hollow prism, and a hollow frustum. A preferred hollow frustum is a p A From p B The preferred internal shapes are cylinders, prisms and truncated cones. The preferred truncated cones are p A From p B The diameter of the slit is reduced to

[0050] The inner surface is preferably smooth, but may have some roughness.

[0051] The thickness of the sidewall is preferably measured as the difference in radial distance from the axis between the inner and outer surfaces of the sidewall.

[0052] The thickness of the sidewall is preferably measured as the difference in radial distance from the axis between the inner surface of the layer and the inner surface of the sidewall.

[0053] Preferred materials for the sidewalls are polymers and glasses.

[0054] In one embodiment, the sidewall comprises, and preferably consists of, a polymer, preferably one or both selected from the group consisting of one or more cyclic olefin copolymers and one or more cyclic olefin polymers. In one aspect of this embodiment, the polymer is preferably at least 30% by weight, more preferably at least 50% by weight, more preferably at least 80% by weight, and most preferably approximately 100% by weight of the sidewall.

[0055] In one embodiment, the sidewall comprises glass, and preferably consists of glass. Preferred glasses in this context include one or more selected from the group consisting of silicon, boron and aluminum. One preferred glass includes boron and silicon. One preferred glass includes aluminum and silicon. One preferred glass is an aluminosilicate glass. In one aspect of this embodiment, the glass is preferably at least 30% by weight, more preferably at least 50% by weight, more preferably at least 80% by weight, and most preferably approximately 100% by weight of the sidewall.

[0056] Lubricant Layer The lubricant layer is disposed on the inner surface of the side wall. The lubricant layer may extend over the entire elongated cylindrical section or only a portion of it. The lubricant layer extends over the entire portion X.

[0057] The preferred lubricants are silicone-based lubricants.

[0058] Suitable lubricants include one or more polysiloxanes.

[0059] A preferred lubricant comprises one or more silicone oils, the total content of the silicone oils being preferably in the range of 10-50 wt%, more preferably in the range of 20-40 wt%, most preferably in the range of 25-35 wt%, based on the total weight of the lubricant. A preferred silicone oil is polydimethyl silicone.

[0060] One preferred lubricant comprises a crosslinked polysiloxane matrix, the total content of which is preferably in the range of 50 to 90% by weight, more preferably in the range of 60 to 80% by weight, and most preferably in the range of 65 to 75% by weight, based on the total weight of the lubricant.

[0061] One suitable lubricant is -Reactive polysiloxane -Non-reactive polysiloxane -catalyst -Diluent The composition may be prepared from a mixture comprising one or more, preferably all, of:

[0062] One suitable reactive polysiloxane is adapted and arranged to undergo a crosslinking reaction to form a crosslinked network. The crosslinking may be catalyzed by a catalyst.

[0063] A preferred non-reactive polysiloxane does not crosslink. A preferred non-reactive polysiloxane contains one or more alkyl groups. A preferred non-reactive polysiloxane is fully substituted with alkyl groups.

[0064] One suitable catalyst catalyzes the crosslinking reaction of polysiloxanes.

[0065] A suitable diluent dissolves one or more other components of the mixture. A suitable diluent is silicon-based. A suitable diluent is a short-chain polysiloxane, preferably having 6 or less repeat units. A suitable diluent is hexamethyldisiloxane.

[0066] One preferred lubricant contains not more than 10% by weight water, preferably not more than 5% by weight, more preferably not more than 1% by weight water, based on the total weight of the lubricant.

[0067] The lubricant layer is p 1 ~p 2 The thickness profile is up to

[0068] p 2 Layer thickness at t 2 is preferably p 1 At thickness t 1 Preferably, t 2 :t 1 The ratio is in the range of 5:1 to 1:5, preferably in the range of 3:1 to 1:3, more preferably in the range of 2:1 to 1:2, and most preferably in the range of 4:3 to 3:4.

[0069] The thickness preferably has a decreasing gradient. In one embodiment, the layer is 1 andp 2 The maximum layer thickness T is specified between max and p 1 andp 2 The minimum layer thickness T is specified between min It has T min / T max is at least 0.7, preferably at least 0.8, more preferably at least 0.9, most preferably at least 0.95, and most preferably at least 0.98.

[0070] In one embodiment, the layer is formed over a length L of the elongated cylindrical section. B In another embodiment, the lubricant extends over at least 70%, more preferably at least 80%, more preferably at least 90%, and most preferably approximately 100% of the length L of the elongated cylindrical section. B It extends over 20-60% of the

[0071] In one embodiment, the lubricant layer comprises p 1 andp 2and a minimum thickness t min It has.

[0072] In one embodiment, the layer is 1 andp 2 The minimum thickness t specified between min and has a minimum thickness t min p 1 andp 2 and preferably at least 20 nm, more preferably at least 40 nm, and more preferably at least 60 nm, greater than the average roughness of the inner surface of the sidewall between the

[0073] The lubricant layer may be cured after deposition. Suitable curing may be effected by heat or radiation or a combination of both. Some suitable curing means are the application of ultraviolet light and the application of infrared light.

[0074] Liquid pharmaceutical composition The container is for pharmaceutical packaging. A suitable container is adapted and arranged to contain a liquid.

[0075] The liquid pharmaceutical composition preferably comprises an active compound.

[0076] A liquid pharmaceutical composition is fluid.

[0077] The preferred amount of the liquid pharmaceutical composition is in the range of 0.1 to 100 ml, preferably in the range of 0.5 to 70 ml, more preferably in the range of 0.8 to 40 ml, most preferably in the range of 1 to 10 ml, and most preferably in the range of 2 to 5 ml.

[0078] charge The container is adapted and arranged to house the charge. One preferred charge is adapted and arranged to be housed within the container. The containers are preferably complementary such that the charge can be introduced into the interior of the container and such that the charge is movable therein in a direction parallel to the axis.

[0079] One preferred charge comprises or includes a portion comprised of an elastic material. The charge is preferably adapted and arranged to seal the interior cross section. The charge is preferably adapted and arranged to move inside the container, preferably along an axis defined by the elongate extension of the container. When inside the container, movement of the charge is preferably prevented by frictional forces between the charge and the interior surface of the container.

[0080] The load may be attached to an elongated rod adapted and arranged to push or pull the load in a direction parallel to the axis.

[0081] One suitable charge is a plunger.

[0082] Load axial position When positioned within the vessel, the charge contacts the layer or the interior surface or both. The front end of the charge is A From p B The forward-most point of contact of the charge with the layer or inner surface in the direction of the p A From p B The charge axial position is the axial position of the front end.

[0083] The distance between the front and rear ends of the charge is the charge length L C It is.

[0084] kit A container according to the present disclosure and a kit including a charge according to the present disclosure contribute to at least partially achieving one or more of the above-mentioned objectives.

[0085] The charge and the container are preferably complementary such that the charge can be contained within the container and is movable therein in a direction parallel to the axis.

[0086] friction force Movement of a load within a container is accompanied by frictional forces between the load and the inner surface and / or layer of the sidewall, including both static friction, which resists relative movement of the load with respect to the container, and kinetic friction, which acts during load movement.

[0087] The kinetic friction depends on the load axial position. The kinetic friction at a given load axial position p is preferably 1 +L C The charge starts at p 1 +L C From p 2 The value of kinetic friction at a load axial position p is the force required to keep the load speed at 100 mm / min when the load is at load axial position p. The method of determining kinetic friction is shown in the drawings.

[0088] assembly An assembly including a container, a charge and a liquid pharmaceutical composition contributes to at least partially achieving one of the above-mentioned objectives. The charge is positioned within the container to seal a cross-section of the interior. The liquid pharmaceutical composition is between the sealed cross-section and an opening within the container.

[0089] In one embodiment, the liquid pharmaceutical composition fills at least 50% by volume of the interior, preferably at least 70% by volume, more preferably at least 80% by volume.

[0090] In one embodiment, the liquid pharmaceutical composition fills less than 50%, less than 30%, or less than 20% by volume of the interior.

[0091] The assembly is suitably adapted and arranged so that movement of the charge towards the second end in a direction parallel to the axis allows the liquid pharmaceutical composition to be delivered from within.

[0092] One suitable assembly functions as a plunger system whereby movement of the charge can expel the liquid pharmaceutical composition from the container.

[0093] A suitable container preferably has an attachment means at one end. A suitable attachment means is adapted and arranged for attachment of a needle or tube. The needle or tube may be attached to the container of the assembly.

[0094] Lure Fitting A suitable container, whether the container itself or as part of a kit or assembly, has a luer fitting. One suitable luer fitting conforms to ISO 80369. Suitable luer fittings are luer lock fittings and slip tip fittings, preferably luer lock fittings. In one embodiment, the container has a luer lock fitting. In another embodiment, the container has a slip tip fitting. One suitable luer fitting is a male luer fitting. Suitable luer lock fittings are one-piece luer lock fittings and two-piece luer lock fittings. In one embodiment, the container has a one-piece luer lock fitting. In another embodiment, the container has a two-piece luer lock fitting.

[0095] Preparation Process A container according to the present disclosure may be prepared by providing a container without a lubricant layer and applying a lubricant layer to the inner surface of the sidewall of the container. A preferred method of applying the layer is by painting and wiping, preferably with a suitable tool.

[0096] The assembly involves the following steps, namely: - providing a container according to the present disclosure, - introducing a charge into the container, preferably through the first end, preferably through the first opening; - introducing the liquid pharmaceutical composition into the interior of the container, preferably through the second end, preferably through the second opening. It can be prepared by:

[0097] The invention will now be further explained with reference to the drawings, which are exemplary and do not limit the scope of the invention, and in which some features are illustrated. [Brief description of the drawings]

[0098] [Figure 1] FIG. 2 is a cross-sectional view showing a container having a lubricant layer on the inner surface of the side wall. [Diagram 2] 2a to 2g are diagrams showing the movement of a load within a container with a single press. [Diagram 3] FIG. [Figure 4] 4a-4e show a process for preparing the assembly and delivering the pharmaceutical agent. [Diagram 5] FIG. 2 shows the thickness profile of a lubricant layer. [Figure 6] FIG. 1 shows the sliding force profile for the kit of Example 1. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0099] 1 shows a cross-sectional view of a container 100 with a lubricant layer 106 on the inner surface 118 of a side wall 107. The container 100 has a first end 119 and a second end 120. The first end 119 is provided with a first opening 102 and an outwardly extending flange 105. The second end 120 is provided with a second opening 103 and attachment means 104 for attaching a needle mounting member, in this case a screw thread. The container 100 is disposed at an axial position p A From axial position p BIn this case, the elongated cylindrical section 501 extends from p A The diameter at p B The length of the elongated cylindrical section 501 is L B The axis 101 is oriented in the direction of the elongated extension of the container 100 and is the axis of rotation of the elongated cylindrical section 501. The side wall 107 has an inner surface 118 on which a lubricant layer 106 is provided. The layer 106 extends over part, but not all, of the side wall 107 and is spaced apart from the end p A and p B The portion X of the elongated cylindrical section 501 does not reach the axial position p 1 ~p 2 The portion X is an extract portion selected according to the features set forth in each embodiment and claim. 1 and p 2 are both located within the layer 106. The purpose of selecting the extracted portion X of the elongated cylindrical section 501 is to ensure that the layer 106 is not limited to the end p A and p B The purpose of this is to ensure that irregularities at both ends of the elongated cylindrical section 501 are avoided since the elongated cylindrical section 501 may not extend entirely to the end of the elongated cylindrical section 501. Each axial position along the container 100 is measured along the axis 101. The axial positions are measured using p as a reference zero point. 1 A universal axial position p and the inner diameter 113 between the inner surfaces 118 of the side walls 107 at this axial position are shown. 1 At thickness t 1 and axial position p 2 At thickness t 2 is shown.

[0100] In Figures 2a-g the movement of a charge 203 in a container 100 in one push is shown. The series of figures shows how the charge 203 can be pushed along the axis 101 of the container 100 in one push at a constant speed of 100 mm / min. The illustrated process can be used to construct the profile of the dynamic friction between the charge 203 and the side wall 107 / lubricant layer 106 as a function of the axial position along the axis 101. Because the movement is done in one push, the static friction forces are only important for the starting point. The process is performed using a commercially available device TesT 106.2 kN from TesT GmbH, Germany.

[0101] In figure 2a the container 100 is shown ready for the single push transfer of the load 203. The apparatus is the same as that shown in figure 1.

[0102] In Fig. 2b, the container 100 shown in Fig. 2a is shown, where a pushing force 207 is applied to the elongated rod 202 in a direction along the axis 101. The force 207 is transferred to the charge 203. In this figure, the force 207 is dominated by the static friction force at the initial axial position 201, where the charge 203 is stationary, and the pushing force 207 is counterbalanced by the static friction force between the charge 203 and the sidewall 107 / lubricant layer 106. The static friction force at the axial position 201 is defined as the force 207 at which the charge 203 starts to move along the axis 101.

[0103] Figure 2c shows the container 100 just after the pushing force 207 shown in Figure 2b has exceeded the static friction force at axial position 201 pushing and moving the load 203. The load 203 is shown at axial position 201 but moving 208 along axis 101. The pushing force 207 is equal to the kinetic friction at axial position 201 and the load 203 is at a constant velocity along axis 101.

[0104] In Figure 2d, a vessel 100 is shown after the vessel 100 shown in Figure 2c, where the charge 203 has moved along the axis 101 a distance from axial position 201 to 204. The charge 203 is still moving at a constant speed 208 with a pushing force 207 equal to the kinetic friction at axial position 204. Thus, the pushing force is a measure of the kinetic friction at axial position 204.

[0105] In Figure 2e, the container 100 is shown after the situation in Figure 2d. The charge 203 has moved further along the axis 101 a distance from axial position 204 to 205. The charge 203 is still moving at a constant speed with the pushing force 207 being equal to the kinetic friction. Thus, the pushing force 207 is a measure of the kinetic friction at the axial position 205.

[0106] Figure 2f shows the container 100 after the situation of figure 2e. The charge 203 has moved further along the axis 101 a distance from axial position 205 to 206. The charge is still moving at a constant speed with the pushing force 207 equal to the kinetic friction. Thus, the pushing force 207 is a measure of the kinetic friction at the axial position 206.

[0107] In the container shown in FIG. 2g, the pressing force is relieved at axial position 206. Axial position 206 is the position where the front end of the charge is at p 2 and its final axial rest position.

[0108] The kinetic friction at any point along the axis 101 is directly translated into the pushing force 207 required at said point to keep a constant speed (100 mm / min) of the load 203 along the axis 101. The kinetic friction at points 201, 204, 205 and 206 is measured at each step in Figures 2c, 2d, 2e and 2f.

[0109] 3 shows a cross-sectional view of the container 100 at an axial location p along the axis 101. The sidewall 107 and the lubricant layer 106 are shown as concentric circular bands. The thickness 301 of the sidewall 107 and the thickness 302 of the lubricant layer 106 are shown at eight equidistant points around the circle, respectively. The thickness of the sidewall 107 or the lubricant layer 106 at the axial location p is the average of the thicknesses around the circle. It is measured as the average of multiple sample points, in this case eight, equally spaced around the circle.

[0110] 4a-4e show a process for preparing the assembly and delivering the pharmaceutical agent 401. FIG.

[0111] In Fig. 4a, a container 100 is shown prepared for forming an assembly. The container 100 has a rotation axis 101, a side wall 107 and an interior 121. The inside of the container 100 is provided with a lubricant layer 106. The lubricant layer 106 has been cured by heating at 175°C for 20 seconds. The container 100 has a first opening 102 and a second opening 103.

[0112] In Figure 4b, the container 100 shown in Figure 4a is shown with a charge 203 disposed in the interior 121. The front end of the charge 203 is located at an axial location 201 along the axis near the first opening 102. The rear end of the charge 203 is located at p1 near the beginning of the lubricant layer 106.

[0113] Figure 4c shows the container 100 shown in Figure 4b after it has been filled with a liquid pharmaceutical composition 401. The liquid pharmaceutical composition 401 is located in the interior 121 between the front end 201 of the load and the second opening 103. In this configuration, the container 100, the load 203 and the liquid pharmaceutical composition 401 are components and an assembly.

[0114] Figure 4d shows the assembly shown in Figure 4c with a pushing force 207 being applied, urging the charge 203 along the axis 101 in a direction from the first opening 102 towards the second opening 103. The movement 208 of the charge 203 forces 402 the liquid pharmaceutical composition 401 out of the container 100.

[0115] FIG. 4e shows that the charge 203 moves once along the axis 101 in a direction from the first opening 102 towards the second opening 103 to an axial position p 2 4d after reaching the second opening 103. The liquid pharmaceutical composition 401 has been dispensed through the second opening 103, with only a small amount remaining at the tip of the container at the second opening 103.

[0116] 5 shows the thickness profile of the lubricant layer 106 divided along the axial position. The thickness of the layer 106 decreases abruptly at the end point. Thus, p 1 ~p 2 The portion X of the layer (106) is slightly offset from the end of the layer (106) to avoid end effects. The thickness works well over the portion X. A p 1 ~midpoint p m is the average thickness of the section extending B p m ~p 2 Even if the thickness profile shows local variations over a short range, the slope of the distribution over a long range is the mean value T A and T B As is evident from the above, a relatively flat thickness profile is preferred in the present invention, as expressed by the related features of the claims and embodiments. In this case, the thickness profile is p 1 From p 2 It can be seen that the thickness profile decreases slightly towards p. Possible options are a flat thickness profile without a gradient or 1 From p 2 In the present invention, the thickness profile increases slightly toward p 1 From p2 A thickness profile having a large gradient increasing or decreasing from is undesirable.

[0117] The dynamic friction profile for the kit of Example 1 is shown in Figure 6. The dynamic friction profile is defined using the procedure as shown in Figures 2a-2g. Tests were performed multiple times with new kits (all lines are shown). A smooth dynamic friction profile level was observed for each stroke, with values ​​in the range of about 3-4 N, varying slightly between individual strokes. The smooth dynamic friction profile level is well suited for use in single dose syringes, particularly for use in automated delivery systems.

[0118] Test Method Layer Thickness The layer thickness is determined by optical interferometry using a RapID Explorer available from rap.ID Particle Systems GmbH. The measurement is performed from the outside of the container through the side wall. The instrument is operated using proprietary software and according to the proprietary instruction manual of 2014.

[0119] Surface roughness The surface roughness of the inner surface of the sidewall is measured using a white light interference microscope. A sample area of ​​2 μm × 2 μm is scanned in a tapping fashion, scanning this area with 256 lines per image and 256 dots per line. The scan rate is 0.7 Hz. The cantilever has a tip with a tip radius of 10 nm or less. The topography of the sample is measured by evaluating the change in the amplitude of the oscillating cantilever as it scans the surface. The raw data is averaged by a linear fit with a third order polynomial fit. The root mean square roughness R rms teeth,

number

[0120] resistance The resistance force is measured using a commercially available device TesT 106.2 kN from TesT GmbH, Germany. The load is moved at a speed of 100 mm / min.

[0121] example The following examples are intended to further illustrate the invention and are not intended to limit the scope of the invention as claimed.

[0122] The lubricant was prepared as follows: 10 g of vinyl-functionalized polydimethylsiloxane was first charged into a reaction vessel and mixed with 65 g of decamethylcyclopentasiloxane. Under constant stirring at 800 rpm, 0.5 g of methylhydrosiloxane / dimethylsiloxane copolymer, 6.25 g of liquid polydimethylsiloxane, 0.01 g of 10% hexachloroplatinic acid in isopropanol as catalyst and 0.05 g of 2,4,7,9-tetramethyl-5-decyne-4,7-diol as inhibitor were added to the reaction mixture. After a stirring time of 60 seconds, the reaction solution was used. Based on FIG. 1, a container was provided. The container was a 1 ml 1 g TopPac available from Schott AG, Germany. The inner surface of the sidewall of the cylindrical section was coated with a lubricant layer extending 1 mm from each of the two ends of the cylindrical section. The thickness profile of the deposited layer is given in Table 1. The lubricant layer was cured by heating at 175° C. for 20 seconds. The container was tested by inserting an elastomeric charge fitted with an elongated rod according to FIG. 2, namely charge FM257 / 2 available from Dedecke GmbH, Germany. A process similar to that shown in FIG. 2a-g, with measurements at 5 mm, 15 mm, 30 mm and 45 mm along the tube, was carried out to define the kinetic friction along the tube. The constant speed of the charge during the measurement movement was 100 mm / min. This process is carried out using a commercially available TesT 106.2 kN device from TesT GmbH, Germany.

[0123] p 1 From p 2 The root mean square roughness of the inner surface of the sidewall over the interval was determined to be 62 nm.

[0124] [Table 1]

[0125] [Table 2] [Explanation of symbols]

[0126] 100 containers 101 axis 102 First opening 103 Second Opening 104 Attachment means at the front end of the container 105 Flanges extending outside the container 106 Lubricant layer 107 Container Side Wall 118 Inner surface of side wall 119 First end of container 120 Second end of container 121 Inside the container 201 Initial axial position of the load 202 Long, thin rod for pressing the load 203 Charges 204 First axial intermediate position of the load 205 Second axial intermediate position of the load 206 Final axial position of the load 207 Pressing force 208 Load movement along an axis 210 Layer thickness at universal axial position 301 Sidewall Thickness 302 Layer Thickness 401 Liquid pharmaceutical composition 402 Delivery of Liquid Pharmaceutical Compositions 501 Long and thin tube section

Claims

1. A pharmaceutical packaging container (100), the container (100) having an elongated cylindrical section (501), a. the elongated tubular section (501) has an elongated extension direction and an axis (101) in the elongated extension direction; b. An axial position p is defined along said axis (101); c. The elongated cylindrical section (501) is Ａ From the axial position p Ｂ It extends to d. The length L of the elongated cylindrical section Ｂ , p Ａ and Ｂ is the interval between e. the container (100) has a sidewall (107) extending across the elongated cylindrical section (501), the sidewall (107) having an inner surface (118) defining an interior (121), the interior (121) having a predetermined diameter (113); f. a lubricant layer (106) disposed on at least a portion of said inner surface (118); g.p Ａ and Ｂ At a given axial position p on the axis (101) between i. the thickness of said sidewall (107); ii. the thickness of said layer (106), and iii. The inner diameter (113) are defined as the average of angles in a transverse plane perpendicular to the axis (101) at the axial position p, respectively; h. The portion X of said axis (101) is determined based on the following criteria: i.p. １ and p ２ Both are p Ａ and Ｂ It is located between ii. Partial length L Ｘ , p １ and ２ is the interval between iii. L Ｘ L Ｂ is at least one-quarter of iv. the layer (106) extends across the entire portion X; The axial position p is set so that the following criteria is satisfied: １ From the axial position p ２ It extends to i.T ｍｅａｎ is the average thickness of the layer (106) defined in the portion X; j. position p ｍ , p １ and ２ It is the midpoint between K.T. Ａ , p １ ~p ｍ is the average thickness of the layer (106) in the section l.T Ｂ , p ｍ ~p ２ is the average thickness of the layer (106) in the section m.T Ａ : T Ｂ is in the range of 5:1 to 1:5; n. one or more criteria are met, said criteria being: i. The length L Ｂ is in the range of 3 to 20 cm, ii.p Ａ ~p Ｂ the average value of the diameter (113) of the interior (121) defined over a range of 0.4 to 4 cm; iii.p Ａ ~p Ｂ the average thickness of the side wall (107) defined over the range is in the range of 0.3 to 4 mm; iv. The volume of the interior (121) is in the range of 0.1 to 150 ml; is selected from the group consisting of: Container (100).

2. The average thickness T of the layer (106) ｍｅａｎ is in the range of 100 nm to 3000 nm; The container (100) of claim 1.

3. a. The inner surface of the sidewall has a root mean square surface roughness r ｒｍｓ It has b.r ｒｍｓ :T ｍｅａｎ is in the range of 1:2 to 1:20; 3. The container according to claim 1 or 2.

4. The layer is p １ and ２ The maximum layer thickness T is defined between ｍａｘ and p １ and ２ The minimum layer thickness T is defined between ｍｉｎ and T ｍｉｎ / T ｍａｘ is at least 0.7; Container according to any one of claims 1 to 3.

5. The sidewall (107) comprises plastic or glass or both. The container (100) of any one of claims 1 to 4.

6. The lubricant comprises one or more silicone oils. The container (100) of any one of claims 1 to 5.

7. The one or more silicone oils are at least partially contained within a matrix. The container (100) of claim 6.

8. the interior (121) is cylindrical or frustoconical over the elongated tubular section (501); The container (100) according to any one of claims 1 to 7.

9. The container (100) has a first opening (102) at a first end (119) and a second opening (103) at a second end (120). The container (100) of any one of claims 1 to 8.

10. The container (100) has an attachment means (104) at the opening. The container (100) according to any one of claims 1 to 9.

11. As a kit part c. A container (100) according to any one of claims 1 to 10; d. a charge (203); 1. A kit comprising: The charge (203) is adapted and arranged to be positioned within the interior (121), such that: i. the charge seals a cross section of the interior (121) between the inner surfaces (118) of the side walls (107); ii. The charge (203) is Ｂ a forward end at an axial position closest to said bed (106) or said inner surface (118), at said forward end said charge contacting said bed (106) or said inner surface (118); iii. The charge (203) is Ａ and having an aft end at an axial position closest to said aft end, said charge (203) contacting said layer (106) or said inner surface (118); iv. The length L of the charge Ｃ is the spacing between the front and rear ends, v. the charge (203) has a charge axial position which is the axial position of the front end; the charge is movable in a direction parallel to the axis (101) with a kinetic friction g that is a function of the charge axial position; kit.

12. Each load axial position is p １ +L Ｃ ~p ２ and the dynamic friction g has a standard deviation g of less than 2 N. ＳＤ It has The kit of claim 11.

13. An assembly comprising a container (100) and a charge (203) according to any one of claims 1 to 10, e. the container (100) has an opening (103); f. said charge (203) is positioned in said interior (121) and seals a cross section of said interior (121); g. said interior (121) contains a liquid pharmaceutical composition located between said sealed cross section and said opening (103); h. the assembly is adapted and arranged such that movement of the charge (203) in a direction parallel to the axis (101) causes the liquid pharmaceutical composition to be delivered through the opening (103); assembly.

14. A process for preparing a container (100) according to any one of claims 1 to 10, a kit according to claims 11 or 12, or an assembly according to claim 13, comprising a process step of depositing the lubricant layer (106) by application with an application tool. process.

15. A lubricant layer (106) having a ratio T of an average thickness over a first half of the layer (106) to an average thickness over a second half of the layer (106). Ａ :T Ｂ A method for using a lubricant layer (106) to improve the uniformity of dynamic friction in a drug container (100) having a viscosity ratio (P / P) in the range of 1:5 to 5:1.

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