Patent Application
20240042136
This application claims the benefit under 35 USC 119 of European Application 22186887.0 filed Jul. 26, 2022, the entire contents of which are incorporated by reference herein.
The present invention relates to a glass syringe barrel comprising with a top end through which a liquid can be ejected and a bottom end into which a plunger stopper can be pushed, the glass syringe barrel comprising in a direction from the top end to the bottom i) a cone region, ii) a shoulder region, iii) a body region and iv) a flange region, wherein the flange region is characterized by defined shape. The present invention also relates to a plurality of glass syringe barrels, to a process for the preparation of a glass syringe barrel, to a glass syringe barrel obtainable by such a process and to a syringe that comprises a glass syringe barrel.
In order to guarantee a reliable use of pharmaceutical products, pre-filled one-time-use syringes are available commercially. They permit a rapid injection of the product that they contain after a comparatively simple manipulation or handling. This sort of pre-filled syringe has a syringe barrel made from glass or polymer with a syringe head formed on it, in which either a syringe needle is integrated or which has a Luer connecting cone of a conical connection, if necessary, a lockable cone connection (Luer lock). On the side opposite the cone end (i. e., at the open end into which the plunger stopper can be introduced), the syringe body comprises a flange region. By allowing the operator's fingers to be positioned below the flange when the plunger is pushed in, the flange facilitates the injection of a drug located in the syringe when the plunger is pushed in, for example with the operator's thumb.
The aforementioned single-use syringe, also called a ready-made syringe, with a syringe barrel made of glass, is described in Norm DIN ISO 11040, in which, for example, the syringe barrel is described in part 4. The elastomeric standard piston stopper and standard piston rod made of polymer with a cruciform cross section are described in part 5.
A known step in the preparation of pre-filled syringes is the manufacture of a syringe barrel and then the loading of a plurality of those syringe barrels into a so-called nest box, for storage and transport purposes to a location where the syringe barrels will be charged with a medicament and fitted with a plunger or a plug. The nest box comprises a nest tray with a base plate having a plurality of apertures arranged in an array and appropriately sized so that one syringe barrel is closely received in each aperture, with the flange region resting on the upper surface of a base plate. The syringe barrel is loaded into the tray with the lower side of the flange resting on the upper surface of the base plate (as shown in
However, with syringe bodies known from the prior art it has often been observed that, if they are inserted into the above-described nest box, they often do not rest level but partially canted with the lower side of the flange region resting on the base plate. This “canting” can be countered by forming the lower side of the flange region with as little “indentation” as possible, i.e., with a lower side of the flange region having an outer contour as even as possible. However, such a design of the lower side of the flange region is disadvantageous as it may lead to a reduction of the breaking resistance in the transition area between the flange region and the body region of the syringe body. Such a reduced breaking resistance may result in a breakage of the syringe body in the flange region if the syringes, particularly when being handled in automated filling and sealing machines, hit each other in the flange area.
In general, it is an object of the present invention to at least partly overcome a disadvantage arising from the prior art. It is a further object of the present invention to provide a glass syringe barrel comprising a cone region, a shoulder region, a body region and a flange region, which, compared to similar glass syringe barrels known from the prior art, can be inserted into the apertures of a nest box as even as possible (i. e., without “canting”), but which still have a sufficiently high breaking resistance towards forces that are applied onto the flange region of the glass syringe barrel, making the syringe bodies particularly suitable to be handled in automated syringe fill-finish machines. It is a further object of the present invention to provide a glass syringe barrel comprising a cone region, a shoulder region, a body region and a flange region, wherein, compared to similar glass syringe barrels known from the prior art, less force is required to insert a plunger or stopper, also making the syringe barrels particularly suitable to be filled and sealed in automated syringe fill-finish machines. It is a further object of the present invention to provide a glass syringe barrel comprising a cone region, a shoulder region, a body region and a flange region, which, compared to similar glass syringe barrels known from the prior art, can more easily be washed by means of wash liquids that are introduced into the opening of a glass syringe body in an automatically operated cleaning station.
A contribution to at least partly solving at least one, preferably more than one, of the above objects is made by the independent claims. The dependent claims provide preferred embodiments which contribute to at least partly solving at least one of the objects.
A contribution to solving at least one of the objects according to the invention is made by a 1st embodiment of a glass syringe barrel 1 having a longitudinal axis Lbarrel, the glass syringe barrel comprising a bottom end through which a liquid can be ejected and a top end into which a plunger stopper can be pushed, the glass syringe barrel comprising in a direction from the bottom end to the top end: a cone region having a first end that corresponds to the bottom end of the glass syringe barrel and a second end; a shoulder region having a first end that is adjacent to the second end of the cone region and a second end; a body region with an outer diameter d1 having a first end that is adjacent to the second end of the shoulder region and a second end; a flange region having at least in parts of the flange region a circular shape, the flange region having a first end that is adjacent to the second end of the body region and a second end that corresponds to the top end of the glass syringe barrel, wherein the flange region has an outer diameter d2>d1 and wherein the flange region is characterized by an outer contour c1 at its first end and an outer contour c2 at its second end; wherein, for any cut surface of the glass syringe barrel that includes the longitudinal axis Lbarrel and that is obtainable by cutting the glass syringe barrel in a plane at which the shape of the flange region is circular, fo and f′o are straight lines that run vertically to longitudinal axis Lbarrel, wherein fo touches the outer contour c1 at its deepest point P1 and f′o touches the outer contour c2 at its highest point P2; f(x) defines the absolute value of the vertical distance between any point of the outer contour c1 and straight line fo at a position x (with f(x)=0 at point P1), wherein x is the horizontal distance between any given point on straight line fo and point P0 at which straight line fo crosses a line L1 that runs parallel to longitudinal axis Lbarrel and that touches the outer surface of the body region and wherein the maximum value for the term f(x) in the range from x=P0 to x=P1 is f(x)max determined at position xmax; wherein f′(x) defines the absolute value of the vertical distance between any point of the outer contour c2 and straight line f′o at a position x (with f(x)=0 at point P2); wherein the following condition is fulfilled: f′(xmax)/f(x)max>1; preferably f′(xmax)/f(x)max>1.2; more preferably f′(xmax)/f(x)max>1.3; even more preferably f′(xmax)/f(x)max>1.4; most preferably f′(xmax)/f(x)max>1.5; wherein it is also preferred that preferably f′(xmax)/f(x)max is less than 5, more preferably less than 3 and most preferably less than 2. Parameter f(x)max thus represents the deepest indentation on the lower side of the flange region and parameter f′(xmax) represents the indention on the upper side of the flange region determined at the same vertical position (i. e., at position x=xmax) as the deepest indentation on the lower side of the flange region.
In a preferred embodiment of the glass syringe barrel 1 according to the invention, f′(xmax) is in the range from 0.15 to 0.7 mm, preferably in the range from 0.15 to 0.5 mm, more preferably in the range from 0.2 to 0.45 mm and most preferably in the range from 0.2 to 0.4 mm. This preferred embodiment is a 2nd embodiment of glass syringe barrel 1 according to the invention that preferably depends on the 1st embodiment of the invention.
In a further preferred embodiment of the glass syringe barrel 1 according to the invention, f(xmax) is in the range from 0.01 to 0.65 mm, preferably in the range from 0.1 to 0.4 mm, more preferably in the range from 0.15 to 0.3 mm and most preferably in the range from 0.2 to 0.3 mm. This preferred embodiment is a 3rd embodiment of glass syringe barrel 1 according to the invention that preferably depends on the 1st or the 2nd embodiment of the invention.
In a further preferred embodiment of the glass syringe barrel 1 according to the invention, for any cut surface of the glass syringe barrel that includes the longitudinal axis Lbarrel and that is obtainable by cutting the glass syringe barrel in a plane at which the shape of the flange region is circular, D1 is the distance between point P1 on the outer contour c1 and a point P3 on outer contour c2, point P3 being located vertically above point P1(=thickness of the flange region at its deepest point with f(x)=0) and D2 is the distance between a point of the outer contour c1 and outer contour c2 at position xmax, wherein D1 and D2 are both determined in a direction that is parallel to longitudinal axis Lbarrel and wherein the following condition is fulfilled: D1/D2<1.6. preferably D1/D2<1.55; more preferably D1/D2<1.50; even more preferably D1/D2<1.47; most preferably D1/D2<1.45; wherein it is also preferred that preferably D1/D2 is at least 1.2, more preferably at least 1.3 and most preferably at least 1.4. This preferred embodiment is a 4th embodiment of glass syringe barrel 1 according to the invention that preferably depends on any of the 1st to the 3rd embodiment of the invention.
In a further preferred embodiment of the glass syringe barrel 1 according to the invention, for any cut surface of the glass syringe barrel that includes the longitudinal axis Lbarrel and that is obtainable by cutting the glass syringe barrel in a plane at which the shape of the flange region is circular, D1 is in the range from 1.85 to 2.5 mm, preferably in the range from 1.88 to 2.4 mm, more preferably in the range from 1.91 to 2.3 mm, even more preferably in the range from 1.94 to 2.2 mm and most preferably in the range from 1.97 to 2.1 mm. This preferred embodiment is a 5th embodiment of glass syringe barrel 1 according to the invention that preferably depends on the 4th embodiment of the invention.
In a further preferred embodiment of the glass syringe barrel 1 according to the invention, for any cut surface of the glass syringe barrel that includes the longitudinal axis Lbarrel and that is obtainable by cutting the glass syringe barrel in a plane at which the shape of the flange region is circular, D2 is in the range from 1.1 to 2.0 mm, preferably in the range from 1.25 to 1.8 mm, more preferably in the range from 1.30 to 1.6 mm, even more preferably in the range from 1.35 to 1.55 mm and most preferably in the range from 1.4 to 1.5 mm. This preferred embodiment is a 6th embodiment of glass syringe barrel 1 according to the invention that preferably depends on the 4th or the 5th embodiment of the invention.
In a further preferred embodiment of the glass syringe barrel 1 according to the invention, for any cut surface of the glass syringe barrel that includes the longitudinal axis Lbarrel and that is obtainable by cutting the glass syringe barrel in a plane at which the shape of the flange region is circular, d′ is the distance between point x′max on the left side of the flange region and point x″max on the right side of the flange region on straight line fo, x′max and x″max corresponding to the points at which function f(x) reaches its maximum value on the left side and the right side of the flange region, respectively, wherein d′ is in the range from 12.5 to 15 mm, preferably in the range from 12.5 to 14.5 mm, more preferably in the range from 12.75 to 14 mm and most preferably in the range from 13.0 to 13.5 mm. This preferred embodiment is a 7th embodiment of glass syringe barrel 1 according to the invention that preferably depends on any of the 1st to the 6th embodiment of the invention.
In a further preferred embodiment of the glass syringe barrel 1 according to the invention, for any cut surface of the glass syringe barrel that includes the longitudinal axis Lbarrel and that is obtainable by cutting the glass syringe barrel in a plane at which the shape of the flange region is circular, d″ is the distance between point P′1 on the left side of the flange region and point P″1 on the right side of the flange region on straight line fo, wherein d″/d2 is in the range from 0.8 to 0.95, preferably in the range from 0.82 to 0.9, more preferably in the range from 0.83 to 0.87 and most preferably in the range from 0.84 to 0.86. This preferred embodiment is an 8th embodiment of glass syringe barrel 1 according to the invention that preferably depends on any of the 1st to the 7th embodiment of the invention.
In a further preferred embodiment of the glass syringe barrel 1 according to the invention, d″ is in the range from 8 to 20 mm, preferably in the range from 9 to 19 mm, more preferably in the range from 10 to 18.5 mm and most preferably in the range from 11 to 18 mm and d2 is in the range from 12 to 22 mm, preferably in the range from 14 to 21 mm, more preferably in the range from 16 to 20 mm and most preferably in the range from 17 to 19 mm. This preferred embodiment is a 9th embodiment of glass syringe barrel 1 according to the invention that preferably depends on the 8th embodiment of the invention.
In a further preferred embodiment of the glass syringe barrel 1 according to the invention, for any cut surface of the glass syringe barrel that includes the longitudinal axis Lbarrel and that is obtainable by cutting the glass syringe barrel in a plane at which the shape of the flange region is circular, a tangent that touches outer contour c2 at position xmax includes an angle α with straight line f′o, wherein α is in the range from 10 to 28 degree, preferably in the range from 14 to 26 degree, more preferably in the range from 18 to 25 degree and most preferably in the range from 20 to 24 degree. This preferred embodiment is a 10 embodiment of glass syringe barrel 1 according to the invention that preferably depends on any of the 1st to the 9th embodiment of the invention.
In a further preferred embodiment of the glass syringe barrel 1 according to the invention, for any cut surface of the glass syringe barrel that includes the longitudinal axis Lbarrel and that is obtainable by cutting the glass syringe barrel in a plane at which the shape of the flange region is circular, L2 is a straight line at touches the deepest point P′1 of the outer contour c1 on the left side of the flange region and the deepest point P″1 of the outer contour c1 on the right side of the flange region; L3 is a straight line at touches the outer contour c1 on the left side of the flange region at a position x at which f(x) reaches the maximum value f(x)max and the deepest point P″1 of the outer contour c1 on the right side of the flange region; wherein straight lines L2 and L3 enclose an angle β of less than 3 degree, preferably less than 2.5 degree, more preferably less than 2 degree, more preferably less than 1.5 degree and most preferably less than 1 degree. This preferred embodiment is an 11th embodiment of glass syringe barrel 1 according to the invention that preferably depends on any of the 1st to the 10th embodiment of the invention.
In a further preferred embodiment of the glass syringe barrel 1 according to the invention, d1 is in the range from 6 to 20 mm, preferably in the range from 7.5 to 16 mm, more preferably in the range from 8 to 14 mm and most preferably in the range from 10 to 12 mm. This preferred embodiment is a 12th embodiment of glass syringe barrel 1 according to the invention that preferably depends on any of the 1st to the 11th embodiment of the invention.
In a further preferred embodiment of the glass syringe barrel 1 according to the invention, difference d2−d1 is in the range from 5 to 8 mm, preferably in the range from 6 to 7.7 mm, more preferably in the range from 6.5 to 7.5 mm and most preferably in the range from 6.7 to 7.2 mm. This preferred embodiment is a 13th embodiment of glass syringe barrel 1 according to the invention that preferably depends on any of the 1st to the 12th embodiment of the invention.
In a further preferred embodiment of the glass syringe barrel 1 according to the invention, the wall thickness h in the body region is in the range from 0.6 to 1.6 mm, preferably in the range from 0.7 to 1.5 mm, more preferably in the range from 0.8 to 1.4 mm, even more preferably in the range from 0.9 to 1.3 mm and most preferably in the range from 1 to 1.2 mm. This preferred embodiment is a 14th embodiment of glass syringe barrel 1 according to the invention, that preferably depends on any of the 1st to the 13th embodiment of the invention.
In a further preferred embodiment of the glass syringe barrel 1 according to the invention, the flange region, in a plane that is perpendicular to the longitudinal axis Lbarrel, has the shape of a circle or the shape of a circle where two opposite sections of the circle have been removed. This preferred embodiment is a 15th embodiment of glass syringe barrel 1 according to the invention, that preferably depends on any of the 1st to the 14th embodiment of the invention.
In a further preferred embodiment of the glass syringe barrel 1 according to the invention, the outer surface of glass syringe barrel in the cone region is roughened or is provided with a coating. This preferred embodiment is a 16th embodiment of glass syringe barrel 1 according to the invention, that preferably depends on any of the 1st to the 15th embodiment of the invention.
In a further preferred embodiment of the glass syringe barrel 1 according to the invention, l1 is the length of the body region and wherein l1 is in the range from 30 to 60 mm, preferably in the range from 35 to 55 mm, more preferably in the range from 38 to 50 mm, even more preferably in the range from 39.5 to 45 mm and most preferably in the range from 39.5 to 41 mm. This preferred embodiment is a 17th embodiment of glass syringe barrel 1 according to the invention, that preferably depends on any of the 1st to the 16th embodiment of the invention.
In a further preferred embodiment of the glass syringe barrel 1 according to the invention, the glass syringe barrel has a nominal volume V and wherein V is in a range from 0.5 to 11 ml, preferably from 0.5 to 9 ml, more preferably from 0.5 to 7 ml, even more preferably from 0.5 to 5 ml, most preferably from 0.5 to 3 ml. This preferred embodiment is an 18th embodiment of glass syringe barrel 1 according to the invention, that preferably depends on any of the 1st to the 17th embodiment of the invention.
In a further preferred embodiment of the glass syringe barrel 1 according to the invention, the glass syringe barrel is rotation-symmetric around the longitudinal axis Lbarrel that runs parallel to the body region and that preferably goes through the center of the top end and the bottom end. This preferred embodiment is a 19th embodiment of glass syringe barrel 1 according to the invention, that preferably depends on any of the 1st to the 18th embodiment of the invention.
In a further preferred embodiment of the glass syringe barrel 1 according to the invention, the glass syringe barrel is designed for a Luer-slip style connector and is sealed with a tip cap that is attached to the at least partially conically shaped upper portion. This preferred embodiment is a 20th embodiment of glass syringe barrel 1 according to the invention, that preferably depends on any of the 1st to the 19th embodiment of the invention.
In a further preferred embodiment of the glass syringe barrel 1 according to the invention, a needle is attached to the at least partially conically shaped upper portion via a Luer connector and wherein the needle is sealed with a needle cap. This preferred embodiment is a 21st embodiment of glass syringe barrel 1 according to the invention, that preferably depends on any of the 1st to the 20th embodiment of the invention.
In a further preferred embodiment of the glass syringe barrel 1 according to the invention, the glass is of a type selected from the group consisting of a borosilicate glass, an aluminosilicate glass, soda lime glass and fused silica. This preferred embodiment is a 22nd embodiment of glass syringe barrel 1 according to the invention, that preferably depends on any of the 1st to the 21st embodiment of the invention.
In a further preferred embodiment of the glass syringe barrel 1 according to the invention, the glass syringe barrel comprises a coating that at least partially superimposes the interior surface of the body region. This preferred embodiment is a 23rd embodiment of glass syringe barrel 1 according to the invention, that preferably depends on any of the 1st to the 22nd embodiment of the invention.
A contribution to solving at least one of the objects according to the invention is made by an embodiment 1 of a process for the production of a glass syringe barrel, more preferably a glass syringe barrel 1 according to the invention, comprising as process steps:
To form a flange region by pushing the glass mass out beyond the edge of the body region at the top end of the glass syringe barrel precursor in process step II), different approaches can be applied, which may also depend on the diameter and the thickness of the glass tube and thus also on the size of the glass syringe bodies to be prepared. According to one approach, the mass of molten glass can be pushed out beyond the edge of the body region at the top end of the glass syringe barrel precursor simply by means of the centrifugal force that is applied to the mass of molten glass while the glass syringe barrel precursor is rotating around its longitudinal axis Lbarrel. According to a further approach, an air stream can be directed onto the mass of molten glass from the top to somehow push the mass of molten glass to the side. In this context it is preferred that this air stream is applied in an angle in a range between 20 to 70 degrees, preferably in the range from 40 to 60 degrees, relative to longitudinal axis Lbarrel. Also, this air stream is preferably applied in an amount of 8 to 17 NL/min, more preferably in an amount of 10 to 14 NL/min.
In process step III) a moulding tool is moved directly to the bottom side of the flange region, preferably by means of a lifting cylinder. By means of this molding tool it is prevented that the flange region formed in process step II), which is still in a molten state, deforms downwards. The moulding tool thus stabilises the flange and ensures the flange height position. In this context it is preferred that the whole process of forming the final shape of the flange region does not require the use of any oil to actively lubricate the machine tools used to form the final shape of the flange region.
In a preferred embodiment of process 1 according to the invention in process step III) the flange region is brought into the desired flange shape by additionally directing an air stream to the top side of the flange region. The blown-on glass surface cools down faster and a sagging of the flange is thus prevented. In this context it is preferred that this air stream is applied in an angle in a range between 40 to 80 degrees, preferably in the range between 50 to 70 degrees, relative to longitudinal axis Lbarrel. Also, the air stream is preferably applied in an amount of 4 to 10 NL/min, more preferably in an amount of 6 to 8 NL/min. This preferred embodiment is a 2nd embodiment of process 1 according to the invention, that preferably depends on the 1st embodiment of the invention.
In a further preferred embodiment of process 1 according to the invention, the shaping tool used to shape the bottom side of the flange region is made of carbon, preferably graphite R7710. This preferred embodiment is a 3rd embodiment of process 1 according to the invention, that preferably depends on the 1st or the 2nd embodiment of the invention.
In a further preferred embodiment of process 1 according to the invention, in process steps II) and III) the glass syringe barrel precursor is rotating around its longitudinal axis Lbarrel with a rotating speed in the range from 700 to 900 rpm, preferably in the range from 740 to 790 rpm. This preferred embodiment is a 4th embodiment of process 1 according to the invention, that preferably depends on any of the 1st to the 3rd embodiment of the invention.
In a further preferred embodiment of process 1 according to the invention, shaping in process step III) is performed under such conditions that a flange region is obtained having at least in parts of the flange region a circular shape, the flange region having a first end that is adjacent to the second end of the body region and a second end that corresponds to the top end of the glass syringe barrel, wherein the flange region has an outer diameter d2>d1 and wherein the flange region is characterized by an outer contour c1 at its first end and an outer contour c2 at its second end. This preferred embodiment is a 5th embodiment of process 1 according to the invention, that preferably depends on any of the 1st to the 4th embodiment of the invention.
In a further preferred embodiment of process 1 according to the invention, shaping in process step III) is performed under such conditions that a flange region is obtained in which, for any cut surface of the glass syringe barrel that includes the longitudinal axis Lbarrel and that is obtainable by cutting the glass syringe barrel in a plane at which the shape of the flange region is circular, fo and f′o are straight lines that run vertically to longitudinal axis Lbarrel, wherein fo touches the outer contour c1 at its deepest point P1 and f′o touches the outer contour c2 at its highest point P2; f(x) defines the absolute value of the vertical distance between any point of the outer contour c1 and straight line fo at a position x (with f(x)=0 at point P1), wherein x is the horizontal distance between any given point on straight line fo and point P0 at which straight line fo crosses a line L1 that runs parallel to longitudinal axis Lbarrel and that touches the outer surface of the body region and wherein the maximum value for the term f(x) in the range from x=P0 to x=P1 is f(x)max determined at position xmax; wherein f′(x) defines the absolute value of the vertical distance between any point of the outer contour c2 and straight line f′o at a position x (with f(x)=0 at point P2); wherein the following condition is fulfilled: f′(xmax)/f(x)max>1; preferably f′(xmax)/f(x)max>1.2; more preferably f′(xmax)/f(x)max>1.3; even more preferably f′(xmax)/f(x)max>1.4; most preferably f′(xmax)/f(x)max>1.5; wherein it is also preferred that preferably f′(xmax)/f(x)max is less than 5, more preferably less than 3 and most preferably less than 2.
This preferred embodiment is a 6th embodiment of process 1 according to the invention, that preferably depends on any of the 1st to the 5th embodiment of the invention.
In a further preferred embodiment of process 1 according to the invention, shaping in process step III) is performed under such conditions that a flange region is obtained in which f′(xmax) is in the range from 0.15 to 0.7 mm, preferably in the range from 0.15 to 0.5 mm, more preferably in the range from 0.2 to 0.45 mm and most preferably in the range from 0.2 to 0.4 mm. This preferred embodiment is an 7th embodiment of process 1 according to the invention that preferably depends on the 6th embodiment of the invention.
In a further preferred embodiment of process 1 according to the invention, shaping in process step III) is performed under such conditions that a flange region is obtained in which f(xmax) is in the range from 0.01 to 0.65 mm, preferably in the range from 0.1 to 0.4 mm, more preferably in the range from 0.15 to 0.3 mm and most preferably in the range from 0.2 to 0.3 mm. This preferred embodiment is an 8th embodiment of process 1 according to the invention that preferably depends on the 6th or the 7th embodiment of the invention.
In a further preferred embodiment of process 1 according to the invention, shaping in process step III) is performed under such conditions that a flange region is obtained in which, for any cut surface of the glass syringe barrel that includes the longitudinal axis Lbarrel and that is obtainable by cutting the glass syringe barrel in a plane at which the shape of the flange region is circular, D1 is the distance between point P1 on the outer contour c1 and a point P3 on outer contour c2, point P3 being located vertically above point P1 (=thickness of the flange region at its deepest point) and D2 is the distance between a point of the outer contour c1 and outer contour c2 at position xmax, wherein D1 and D2 are both determined in a direction that is parallel to longitudinal axis Lbarrel and wherein the following condition is fulfilled: D1/D2<1.6. preferably D1/D2<1.55; more preferably D1/D2<1.50; even more preferably D1/D2<1.47; most preferably D1/D2<1.45; wherein it is also preferred that preferably D1/D2 is at least 1.2, more preferably at least 1.3 and most preferably at least 1.4. This preferred embodiment is a 9th embodiment of process 1 according to the invention that preferably depends on any of the 6th to the 8th embodiment of the invention.
In a further preferred embodiment of process 1 according to the invention, shaping in process step III) is performed under such conditions that D1 is in the range from 1.85 to 2.5 mm, preferably in the range from 1.88 to 2.4 mm, more preferably in the range from 1.91 to 2.3 mm, even more preferably in the range from 1.94 to 2.2 mm and most preferably in the range from 1.97 to 2.1 mm. This preferred embodiment is a 10th embodiment of process 1 according to the invention that preferably depends on the 9th embodiment of the invention.
In a further preferred embodiment of process 1 according to the invention, shaping in process step III) is performed under such conditions that D2 is in the range from 1.1 to 2.0 mm, preferably in the range from 1.25 to 1.8 mm, more preferably in the range from 1.30 to 1.6 mm, even more preferably in the range from 1.35 to 1.55 mm and most preferably in the range from 1.4 to 1.5 mm. This preferred embodiment is an 11th embodiment of process 1 according to the invention that preferably depends on the 9th or the 10th embodiment of the invention.
In a further preferred embodiment of process 1 according to the invention, shaping in process step III) is performed under such conditions that a flange region is obtained in which, for any cut surface of the glass syringe barrel that includes the longitudinal axis Lbarrel and that is obtainable by cutting the glass syringe barrel in a plane at which the shape of the flange region is circular, d′ is the distance between point x′max on the left side of the flange region and point x″max on the right side of the flange region on straight line fo, x′max and x″max corresponding to the points at which function f(x) reaches its maximum value on the left side and the right side of the flange region, respectively, wherein d′ is in the range from 12.5 to 15 mm, preferably in the range from 12.5 to 14.5 mm, more preferably in the range from 12.75 to 14 mm and most preferably in the range from 13.0 to 13.5 mm. This preferred embodiment is a 12th embodiment of process 1 according to the invention that preferably depends on any of the 6th to the 11th embodiment of the invention.
In a further preferred embodiment of process 1 according to the invention, shaping in process step III) is performed under such conditions that a flange region is obtained in which, for any cut surface of the glass syringe barrel that includes the longitudinal axis Lbarrel and that is obtainable by cutting the glass syringe barrel in a plane at which the shape of the flange region is circular, d″ is the distance between point P′1 on the left side of the flange region and point P″1 on the right side of the flange region on straight line fo, wherein d″/d2 is in the range from 0.8 to 0.95, preferably in the range from 0.82 to 0.9, more preferably in the range from 0.83 to 0.87 and most preferably in the range from 0.84 to 0.86. This preferred embodiment is a 13th embodiment of process 1 according to the invention that preferably depends on any of the 6th to the 12th embodiment of the invention.
In a further preferred embodiment of process 1 according to the invention, shaping in process step III) is performed under such conditions that a flange region is obtained in which d″ is in the range from 8 to 20 mm, preferably in the range from 9 to 19 mm, more preferably in the range from 10 to 18.5 mm and most preferably in the range from 11 to 18 mm and d2 is in the range from 12 to 22 mm, preferably in the range from 14 to 21 mm, more preferably in the range from 16 to 20 mm and most preferably in the range from 17 to 19 mm. This preferred embodiment is a 14th embodiment of process 1 according to the invention that preferably depends on the 13th embodiment of the invention.
In a further preferred embodiment of process 1 according to the invention, shaping in process step III) is performed under such conditions that a flange region is obtained in which, for any cut surface of the glass syringe barrel that includes the longitudinal axis Lbarrel and that is obtainable by cutting the glass syringe barrel in a plane at which the shape of the flange region is circular, a tangent that touches outer contour c2 at position xmax includes an angle α with straight line f′o, wherein α is in the range from 14 to 26 degree, more preferably in the range from 18 to 25 degree and most preferably in the range from 20 to 24 degree. This preferred embodiment is a 15th embodiment of process 1 according to the invention that preferably depends on any of the 6th to the 14th embodiment of the invention.
In a further preferred embodiment of process 1 according to the invention, shaping in process step III) is performed under such conditions that a flange region is obtained in which, for any cut surface of the glass syringe barrel that includes the longitudinal axis Lbarrel and that is obtainable by cutting the glass syringe barrel in a plane at which the shape of the flange region is circular, L2 is a straight line at touches the deepest point P′1 of the outer contour c1 on the left side of the flange region and the deepest point P″1 of the outer contour c1 on the right side of the flange region; L3 is a straight line at touches the outer contour c1 on the left side of the flange region at a position x at which f(x) reaches the maximum value f(x)max and the deepest point P″1 of the outer contour c1 on the right side of the flange region; wherein straight lines L2 and L3 enclose an angle β of less than 3 degree, preferably less than 2.5 degree, more preferably less than 2 degree, more preferably less than 1.5 degree and most preferably less than 1 degree. This preferred embodiment is a 16th embodiment of process 1 according to the invention that preferably depends on any of the 6th to the 15th embodiment of the invention.
In a further preferred embodiment of process 1 according to the invention, shaping in process step III) is performed under such conditions that a flange region with d1 is in the range from 6 to 20 mm, preferably in the range from 7.5 to 16 mm, more preferably in the range from 8 to 14 mm and most preferably in the range from 10 to 12 mm. This preferred embodiment is a 17th embodiment of process 1 according to the invention that preferably depends on any of the 6th to the 16th embodiment of the invention.
In a further preferred embodiment of process 1 according to the invention, shaping in process step III) is performed under such conditions that a flange region is obtained in which d2-d1 is in the range from 5 to 8 mm, preferably in the range from 6 to 7.7 mm, more preferably in the range from 6.5 to 7.5 mm and most preferably in the range from 6.7 to 7.2 mm. This preferred embodiment is an 18th embodiment of process 1 according to the invention that preferably depends on any of the 6th to the 17th embodiment of the invention.
In a further preferred embodiment of process 1 according to the invention, shaping in process step III) is performed by adjusting at least one of the following parameters:
Particularly preferred embodiments of process 1 according to the present invention are characterized in that the following parameters or combination of parameters are adjusted: a), b), c), d), a)b), a)c), a)d), b)c), b)d), c)d), a)b)c), a)b)d), b)c)d) and a)b)c)d), wherein the combination a)b)c)d) is most preferred. This preferred embodiment is a 19th embodiment of process 1 according to the invention, that preferably depends on any of the 1st to the 18th embodiment of the invention.
In a further preferred embodiment of process 1 according to the present invention, the thickness h of the glass in the body region of the glass syringe barrel precursor is in the range from 0.6 to 1.6 mm, preferably in the range from 0.7 to 1.5 mm, more preferably in the range from 0.8 to 1.4 mm, even more preferably in the range from 0.9 to 1.3 mm and most preferably in the range from 1 to 1.2 mm. This preferred embodiment is a 20th embodiment of process 1 according to the invention, that preferably depends on any of the 1st to the 19th embodiment of the invention.
In a further preferred embodiment of process 1 according to the present invention, the glass syringe barrel precursor provided in process step I) further comprises: a cone region having a first end that corresponds to the bottom end of the glass syringe barrel precursor and a second end; a shoulder region having a first end that is adjacent to the second end of the cone region and a second end that corresponds to the bottom end of the body region.
This preferred embodiment is a 21st embodiment of process 1 according to the invention, that preferably depends on any of the 1st to the 20th embodiment of the invention.
In a further preferred embodiment of process 1 according to the present invention, the process further comprises the step of: roughening the outer surface of glass syringe barrel in the cone region or applying coating onto the outer surface of glass syringe barrel in the cone region.
This preferred embodiment is a 22nd embodiment of process 1 according to the invention, that preferably depends on any of the 1st to the 21st embodiment of the invention.
In a further preferred embodiment of process 1 according to the present invention, the process further comprises the step of: cutting off two parts of the flange region that are located on opposing sides of the flange region, wherein cutting can be accomplished mechanically by means of a cutting device or can be accomplished thermally by means of a flame with which the glass is molten at the predetermined position and is then pulled apart.
This preferred embodiment is a 23rd embodiment of process 1 according to the invention, that preferably depends on any of the 1st to the 22nd embodiment of the invention.
In a further preferred embodiment of process 1 according to the present invention, the glass is of a type selected from the group consisting of a borosilicate glass, an aluminosilicate glass and fused silica. This preferred embodiment is a 24th embodiment of process 1 according to the invention, that preferably depends on any of the 1st to the 23rd embodiment of the invention.
In a further preferred embodiment of process 1 according to the present invention, the process further comprises the step of: superimposing at least a part of the interior surface of the body region with a coating.
This preferred embodiment is a 25th embodiment of process 1 according to the invention, that preferably depends on any of the 1st to the 24th embodiment of the invention.
A contribution to solving at least one of the objects according to the invention is made by an embodiment 1 of a glass syringe barrel 2 obtainable by the process of the invention according to the present invention, preferably by the process 1 according to any of its preferred embodiments. In a preferred embodiment of the glass syringe barrel 2, this glass syringe barrel 2 shows the technical features of the glass syringe barrel 1 of the invention.
A contribution to solving at least one of the objects according to the invention is made by a plurality of glass syringe barrels 1 or 2 according to the present invention, preferably a plurality of glass syringe barrels 1 according to any of its preferred embodiments, wherein at least one of the following conditions, preferably both of them, is/are fulfilled:
According to a preferred embodiment of the plurality of glass syringe barrels 1 or 2 according to the present invention, at least one of the following conditions, preferably both of them, is/are fulfilled:
The relative standard deviation of the of the maximum flange thickness D1 and of length l2 of the syringe in % is the standard deviation relative to the average value determined for these parameters in the plurality of syringe bodies.
“A plurality of glass syringes” in the sense of the present invention preferably comprises at least 10 glass syringes, preferably at least 25 glass syringes, more preferably at least 50 glass syringes, even more preferably at least 100 glass syringes even more preferably at least 200 glass syringes and most preferably at least 400 glass syringes. Furthermore, the plurality of glass syringes preferably has been collected arbitrarily and particularly has not been selected with regard to any property. For example, the plurality glass syringes may be the group of syringes which are packed together in a typical transport tray.
A contribution to solving at least one of the objects according to the invention is made by an embodiment 1 of a syringe comprising: a glass syringe barrel 1 according to the present invention, preferably according to any of its preferred embodiments, a plurality 1 of glass syringe barrels according to the present invention, preferably according to any of its preferred embodiments, or the glass syringe barrel 2; a plunger that has been pushed into the bottom end of the glass syringe barrel or into the bottom end of each of the glass syringe barrels contained in the plurality 1 of glass syringe barrels.
In a further preferred embodiment of the syringe according to the present invention, the syringe further comprises: a pharmaceutical composition that is filled into at least a part of the inner volume of the body region.
The glass syringe barrel according to the invention may have any size or shape which the skilled person deems appropriate in the context of the invention. The bottom end of the glass syringe barrel comprises an opening in the form of a channel located within the cone region through which a pharmaceutical composition that is contained in the glass syringe can be squeezed out of the glass syringe barrel and a top end with a flange region into which a plunger stopper can be pushed. Preferably, the glass syringe barrel is of a one-piece design that is prepared by providing a glass tube, preferably in form of a hollow cylinder, and forming the desired shape of the flange region. A preferred glass syringe barrel is a prefilled glass syringe barrel that is filled with a pharmaceutical preparation. Preferably, the glass syringe barrel is rotationally symmetrical around the longitudinal axis Lbarrel that preferably goes perpendicular through the centre of the body region.
The glass of the glass syringe barrel be any type of glass and may consist of any material or combination of materials which the skilled person deems suitable in the context of the invention. Preferably, the glass is suitable for pharmaceutical packaging. Particularly preferable, the glass is of type I, more preferably type I b, in accordance with the definitions of glass types in section 3.2.1 of the European Pharmacopoeia, 7th edition from 2011. Additionally, or alternatively preferable to the preceding, the glass is selected from the group consisting of a borosilicate glass, an aluminosilicate glass, soda lime glass and fused silica; or a combination of at least two thereof. For the use in this document, an aluminosilicate glass is a glass which has a content of Al2O3 of more than 8 wt.-%, preferably more than 9 wt.-%, particularly preferable in a range from 9 to 20 wt.-%, in each case based on the total weight of the glass. A preferred aluminosilicate glass has a content of B2O3 of less than 8 wt.-%, preferably at maximum 7 wt.-%, particularly preferably in a range from 0 to 7 wt.-%, in each case based on the total weight of the glass. For the use in this document, a borosilicate glass is a glass which has a content of B2O3 of at least 1 wt.-%, preferably at least 2 wt.-%, more preferably at least 3 wt.-%, more preferably at least 4 wt.-%, even more preferably at least 5 wt.-%, particularly preferable in a range from 5 to 15 wt.-%, in each case based on the total weight of the glass. A preferred borosilicate glass has a content of Al2O3 of less than 7.5 wt.-%, preferably less than 6.5 wt.-%, particularly preferably in a range from 0 to 5.5 wt.-%, in each case based on the total weight of the glass. In a further aspect, the borosilicate glass has a content of Al2O3 in a range from 3 to 7.5 wt.-%, preferably in a range from 4 to 6 wt.-%, in each case based on the total weight of the glass.
A glass which is further preferred according to the invention is essentially free from B. Therein, the wording “essentially free from B” refers to glasses which are free from B which has been added to the glass composition by purpose. This means that B may still be present as an impurity, but preferably at a proportion of not more than 0.1 wt.-%, more preferably not more than 0.05 wt.-%, in each case based on the weight of the glass.
An important element of the glass syringe barrel 1 according to the invention is the shape of the flange region that is formed in process step III) of the process 1 according to the present invention, particularly the outer contour c1 at the first end of the flange region and the outer contour c2 at the second end of the flange region. The outer contour c1 and the outer contour c2 are characterized in that ratio of the depth of indention on the second end to the depth of indention on the first end (f′(xmax)/f(x)max) as determined at a position at which the indention on the end first end riches its maximum value is >1. Surprisingly, it has been discovered that, if the outer contour c1 at the first end of the flange region and the outer contour c2 at the second end of the flange region are characterized by such a relative depth of indention, not only the positioning of the glass syringe barrels in the nest can be significantly improved by reducing the risk of the syringes “canting” and thus not coming to rest straight with the bottom side of the flange region on the base plate, the flange breaking resistance can also be significantly improved.
In the context of the invention, every liquid pharmaceutical composition which the skilled person deems suitable to be used in a syringe comes into consideration. A pharmaceutical composition is a composition comprising at least one active ingredient. A preferred active ingredient is a vaccine. A further preferred pharmaceutical composition is a parenterialium, i.e. a composition which is intended to be administered via the parenteral route, which may be any route which is not enteral. Parenteral administration can be performed by injection, e.g. using a needle (usually a hypodermic needle) and a syringe.
The following measurement methods are to be used in the context of the invention. Unless otherwise specified, the measurements have to be carried out at an ambient temperature of 23° C., an ambient air pressure of 100 kPa (0.986 atm) and a relative atmospheric humidity of 50%.
Determination of f(x) and f′(x)
The outer contour c1 and c2 of the glass syringe barrel in the flange region defined by the function f(x) and f′(x), respectively, can be determined in a non-destructive manner using a profile projector. This approach is particularly suitable for glass syringe barrels that have been chemically and/or thermally tempered and that therefore cannot be easily sliced in half without the glass cracking or bursting. For determining the values for f(x) and f′(x) in a non-destructive manner the outer contour c1 and c2 of the glass syringe barrel in the flange region is visualized using a Mitutoyo PJ-3000 profile projector. The profile projector has a 10× magnification and is operated with transmitted light illumination. The barrels are placed in Hallbrite® BHB (a butyloctyl salicylate obtainable from the Hallstar Company, Chicago, USA), which is filled into a glass bowl. Hallbrite® BHB is used to visualize the outer contour of the flange region. It is ensured that the cross-section of the glass syringe barrel that is inspected in the profile projector corresponds to the plane that is centrically located in the glass syringe barrel and that comprises the longitudinal axis Lbarrel of the glass syringe barrel, i. e. the axis that goes perpendicular through the barrel (see
To improve the measuring accuracy, the outer contour c1 and c2 of the glass syringe barrel in the flange region can also be determined from a physical cross-sectional cut parallel along to the longitudinal axis Lbarrel of the barrel (it is again ensured that the cross-section of the glass syringe barrel corresponds to the plane that is centrically located in the glass syringe barrel and that comprises the longitudinal axis of the glass syringe barrel as shown in
The relevant outer contour c1 and c2 of the glass syringe barrel in the flange region can be extracted and numerically approximated from the images obtained by means of the two approaches described above. For the extraction of the relevant contour, the images undergo the image processing steps implemented in Python [https://www.python.org/] based on the image processing library OpenCV [https://open-cv.org/].
First, the images are denoised using a median filter. The denoised images are then processed with an edge detection algorithm based on a Sobel filter, in which the contours are identified by thresholding the gradient image.
The flange thickness D1 is determined by means of a Round Flange Camera.
A glass tube (FIOLAX® clear, SCHOTT AG, Germany) having an outer diameter d1 of 10.85 mm and a wall thickness n of 1.1 mm made of borosilicate glass is loaded into the head of a rotary machine. While rotating around its longitudinal axis Ltube one end of the glass tube (i. e. at the end of which the Luer cone will be localized) is heated to its softening point with flames (see
In a further process step, the final shape of the flange region is obtained by means of the set up shown in
It has been observed that the glass syringe barrels according to the present invention do rest more level when being placed in a nest box as (i. e., they are less prone to “canting”), compared to the glass syringe barrels known from the prior art.
| Number | Date | Country | Kind |
|---|---|---|---|
| 22 186 887.0 | Jul 2022 | EP | regional |
