WO2012085619A1

WO2012085619A1 - Tool for forming medical glass containers free of contamination by a foreign element

Info

Publication number: WO2012085619A1
Application number: PCT/IB2010/003531
Authority: WO
Inventors: Céline DORGANS; Paolo Mangiagalli
Original assignee: Becton Dickinson France
Priority date: 2010-12-20
Filing date: 2010-12-20
Publication date: 2012-06-28

Abstract

The present invention relates to a tool (1 ) for forming an opening of a glass container, characterized in that at least an external surface of the tool (1 ) is made of a material comprising only chemical elements of at least one of class I borosilicate glass and/or carbon and/or nitrogen. In further aspects, a process for making a glass container free of contamination by chemical elements foreign to said container, and a syringe made with said process are also disclosed.

Description

TOOL FOR FORMING MEDICAL GLASS CONTAINERS FREE OF CONTAMINATION BY A FOREIGN ELEMENT

FIELD OF THE INVENTION

The field of the present invention is medical glass industry.

More precisely, the invention relates to a tool for manufacturing borosilicate glass containers free of any contaminants provided by elements which are in contact with the glass during the forming process.

BACKGROUND OF THE INVENTION Glass medical containers, and more specially glass syringes are shaped by heating and forming the ends of a borosilicate glass tube. This process is made up of two parts: the tip syringe forming and the flange forming.

The tip syringe forming follows different steps, represented by Figure 1 . Initially, the glass tube is heated to preshape the tip with carbon tool and/or steel tungsten carbide tools and/or tungsten tools (a). Then, the corresponding rough syringe is heated with flames in order to increase the viscosity of the glass and then its workability (b). Finally, a tool which is also called a pin is introduced inside the rough syringe at high temperature and tools are laterally pressing it in order to form the molten glass and give the final shape of the tip external shape and channel, as represented by the arrows (c). The pin is then withdrawn (d).

The tip forming step should be considered as critical because this is the step where the contact between the pin and the glass is the most important and as a consequence that pin-glass interactions are the most significant.

Usually, the tools introduced inside the rough syringe are made of tungsten. The nature of these tools is very important because they have to resist to high temperatures but also to dissipate the heat from the molten glass. Generally, the molten glass temperature is between 700 °C and 1000°C. The Tungsten (W) is preferably used because of its high melting temperature which is around 3422 °C. Furthermore, the tungsten is preferred because its thermal expansion coefficient is closed to the one of borosilicate, and especially because it has good mechanical properties such as resistance to fatigue, or non-toxicity. Indeed, during the syringe tip forming, tungsten-glass contact lasts less than two seconds for each cycle but the pin is used more than one thousand cycles.

Under these drastic conditions of manufacturing, the integrity of the pins can be affected and be detrimental to the quality of the final glass container. Indeed, because of the high temperature and/or the presence of the different elements in the closed environment of the forming step, the tungsten pins can interact and be transformed. For example, oxidation and wear could cause formation of tungsten by-products on the surface of the pins that can be can be released and can contaminate the glass containers.

Such contamination of the containers is a real problem, in particular because most of tungsten compounds (tungsten oxides, tungstates, bronzes, etc.) are chemically neutral but can interact with liquids or solids present inside the glass containers. For example, drugs or solutions containing proteins that are filled in a glass container, could be sensitive to the presence of tungsten derivatives present on the surface of the pin and that remains on the glass surface after the forming step.

Methods have been proposed to avoid such contamination by using tungsten and/or tungsten derivatives during the forming step. Most of these methods propose to replace the material of the pin itself from tungsten to another material that does not provide any tungsten containing residues or would not interact with drugs stored or contained in the glass containers.

As an example, in the document US2008/0103438, the pins are not in tungsten but are in a material like metals or alloys containing platinum or platinum group metal, metals or alloys containing nickel, ceramics, silicides and combinations thereof, preferably platinum/rhodium alloy. Although such pins reduce or eliminate the tungsten or derivatives thereof in the glass containers, these materials are sensitive to the drastic conditions of manufacturing and the surface of the pins made with such materials could be damaged very quickly during the process leading to a regular change of the pins to ensure the good quality of the glass containers.

The present invention provides a further improvement in which medical glass containers are produced free of any metallic contamination, using tools less expensive than the standard ones and that have a longer life cycle.

SUMMARY OF THE INVENTION

The present invention proposes in a first aspect a tool for forming an opening of a glass container, characterized in that at least an external surface of the tool is made of a material comprising only chemical elements of at least one of class I borosilicate glass and/or carbon and/or nitrogen.

Preferred but non limiting features of the present invention are as follow:

• said material has a melting point above 1000°C;

· said material has a wear resistance when in contact with molten glass at a temperature between 600 °C and 1000°C;

• said material is non-oxidizing when in contact with molten glass at a temperature between 600 °C and 1000°C;

• said material forms a self-limiting oxide passivation layer;

· said self-limiting oxide passivation layer acts as a thermal and oxygen barrier;

• said material is silicon carbide;

• said material is boron nitride;

• said tool has a first diameter, and wherein a distal part of said tool has a diameter that is smaller than said first diameter;

• the entire surface of said distal part is made of said material; • said tool comprises a core and wherein said external surface comprises a coating over said core;

• said core is made of a material different from that of said coating;

• the core is made of tungsten;

· the thickness of said coating is between 3 and 75 μιτι;

• the thickness of said coating is between 10 and 50 μιτι;

• said coating is deposited by High Thermal Chemical Vapor Deposition;

• said tool is entirely made of said material comprising only chemical elements of at least one of class I borosilicate glass and/or carbon and/or nitrogen.

In a further aspect the present invention provides a process for manufacturing a glass container free of contamination by chemical elements foreign to said container, wherein an opening of the glass container is formed by a tool according to the first aspect of the invention.

The present invention also provides a syringe made with a process according to the second aspect of the invention, said syringe being potentially free of chemical elements other than of at least one of class I borosilicate glass and/or carbon and/or nitrogen.

BRIEF DESCRIPTION OF THE DRAWINGS

The above, and other objects, features and advantages of this invention, will be apparent in the following detailed description of which is to be read in connection with the accompanying drawings wherein:

- Figure 1 , previously described, represents successive steps of a tip syringe forming process with a pin;

- Figure 2 is a schematic view of a transversal section of an example of a tool in accordance with the present invention;

- Figure 3 is a SEM picture of the evolution of a known tungsten pin over time, after being used; - Figure 4 is a SEM picture of a similar evolution of a pin according to the invention;

- Figure 5a-b are two graphs comparing the amount of soluble tungsten inside water filled syringes as a function of syringe tip formation duration according to process using a known pin, and according to process using an embodiment of the invention.

DETAILED DESCRIPTION OF THE INVENTION

The importance of temperature and mechanical loadings on the chemical and physical properties of tungsten-glass interactions are involved in the syringe tip forming process.

From a chemical standpoint, tungsten is expected to oxidize with a rate of oxidation that widely increases at temperatures higher than 800 °C because it is in contact with air at high temperature. While the glass temperature or the contact between glass and the tungsten pin is increased, the tungsten is at higher temperature and is expected to have a higher oxidization rate. The contact with glass damages the tungsten tool and this wear is temperature dependant due to the diffusivity (and solubility) of the oxygen and the tungsten in the glass which is increased at high temperatures. It is also time dependant: the more the metal remains in glass, the more it is damaged. Initial stresses applied on the glass containers also influence the chemical interaction because they give rise to a more or less tiny contact.

From a mechanical standpoint, the stresses applied on the surface of the tool would be dependant on initial stresses applied, on temperature and time. Initial stresses are given by the mechanical elements that press the glass and by the velocity of the relative motion between the tool and the borosilicate glass. When the tool stands inside the rough syringe at high temperature, shear stresses depend on the forces applied by the mechanical elements and on the relative motion of the rough syringe and the tungsten tool. When the tool is withdrawn from the just formed tip, the shear stresses are mainly dependant on the initial stress applied by the mechanical elements. Temperature can influence the stresses insofar that it influences the glass viscosity. The glass viscosity would be important because it would influence the wear mechanisms. Time where glass is in contact with tungsten has a direct effect on the wear of the materials in contact and probably on the local temperature that can be increased by wear.

Therefore in order to improve the quality of the forming process, but also to increase the life cycle of the tools used for forming the opening of medical containers, at least an external surface of the tool 1 according to the invention is made of a material comprising only chemical elements of at least one of class I borosilicate glass and/or carbon and/or nitrogen, and in particular this material does not comprise tungsten.

Figure 2 shows a schematic view of a transversal section of an embodiment of the tool 1 according to the invention. This tool is a pin comprising a core 3 covered with a coating 2. The core 3 is preferably made of tungsten, whose properties are known to be appropriate for shaping molten glass. Here, the tool 1 has a specific shape comprising parts 4, 5 and 6 in order to be used for forming syringe tips. However, this invention can also be applied to any tools for forming medical glass containers like vials, test tubes, bottles, flasks, pipes...

In Figure 2, the proximal part 6 is of the tool 1 is the main part of the pin intended to be maintained by a holder present in the equipment, while the distal part 4 is intended to be used for the formation of the channel of the syringe tip that will receive or not a needle. Part 5 is generally conical and bound the two parts 4 and 6 which have generally cylindrical shape but different diameters (the diameter of distal part 4 is advantageously smaller than the diameter of proximal part 6).

The coating 2 covers the core 3 and comprises only chemical elements of at least one of the class I borosilicate and/or carbon and/or nitrogen. The chemical elements included in different amounts in the coating 2 are in particular Boron, Carbon, Nitrogen, Oxygen, Sodium, Silicon, Aluminium, Potassium, Calcium. As these chemical elements are already present in the glass, the glass containers will not be contaminated by foreign chemical elements during their contact with the tool 1 during the formation of the syringe tip.

The nature and the thickness of the coating 2 of the tool 1 are chosen in order to have mechanical and physical properties compatible with its use during the manufacturing process where the working temperature is between 600 °C to 1000°C, and in particular, this coating 2 needs to have:

- a melting point above the molten glass maximum temperature, i.e. 1000°C,

- an oxidation resistance when it is in contact with molten glass at working temperature,

- a wear resistance (i.e. no abnormal erosion of material from the solid surface of the tool) when it is in contact with molten glass at working temperature,

- a good adhesion to the material of the core 3 (which is preferably tungsten).

The coating 2 protects the core 3 at the working temperature, and is advantageously chosen in such a way that a self-limiting oxide passivation layer is formed to act as a thermal and oxygen barrier. This layer avoids further oxidation and increase the protective effect of the coating 2.

Thus, in a preferred embodiment, the coating 2 is made of Silicon Carbide SiC, or of Boron Nitride BN. For example, when SiC is exposed to molten glass, a passivation layer made of silicon dioxide is formed. This layer is a hard non-reactive surface film that avoids further corrosion.

Moreover, the thickness of the coating 2 is selected in order to have a larger number of manufacturing cycles in comparison to a standard pin without any coating. In this way, the thickness of the coating is around 3 to 75 μιτι, in particular from 10 to μιτι, and in particular about 35 μιτι. Provided that the wear of the coating 2 is lower than its thickness, the core 3 remains protected.

As the distal part 4 of the core is the principal part used in the forming process, the coating is advantageously present on at least the whole surface of the distal part 4. In an embodiment, the coating is just present on parts 4 and 5. Alternatively, the coating may cover the global surface of the pin (parts 3, 4 and 5).

In another embodiment, the whole tool 1 is made of chemical elements of class I borosilicate glass and/or carbon. In this embodiment, the tool 1 does not contain any tungsten as it is a monobloc of SiC. Hence, with this kind of tool, the risk of a metallic contamination is discarded even if the physical wear is superior to 75 μιτι.

When industrially used for manufacturing syringes, the reduction in diameter of the distal part 4 of a conventional tungsten pin can reach more than 80 μιτι after 45 minutes of use. The evolution of the wear can be observed in Figure 2.

- New Pin a);

- Pin b) after 10 minutes of use;

- Pin c) after 20 minutes of use;

- Pin d) after 30 minutes of use;

- Pin e) after 45 minutes of use;

- Pin f) after 60 minutes of use.

After 45 minutes of process, the wear of the pin is clearly visible, and a significant amount of tungsten oxides have been released. Moreover, a pin after 60 minutes needs to be changed in order to guaranty that the tips would have the correct final shape.

Similar tests have been performed with a pin according to the present invention. In this case, the core of the pin is in Tungsten and it is covered with 25 μιτι of a SiC coating. Said thin layer of SiC is deposited by High Temperature Chemical Vapor Deposition (HTCVD), but any other methods known by a man skilled in high performance ceramics can be applied.

The coating pin is submitted to the same industrial process than the one disclosed previously, but in this case no significant reduction in diameter is noticed as it is shown on Figure 3.

- New Pin a');

- Pin b') after 10 minutes of use;

- Pin c') after 30 minutes of use; - Pin cT) after 60 minutes of use;

- Pin e') after 75 minutes of use;

- Pin f) after 6 hours of use.

Even after six hours, the coating is still present on the tungsten pin and fully covering, preventing the core of the pin to be exposed.

The effectiveness of the SiC coating for preventing the contamination has been demonstrated with ICP-MS (Inductively Coupled Plasma Mass Spectrometry) tests by analyzing the amount of tungsten released in liquid solutions stored in syringes formed with conventional tungsten pins, or formed with SiC coated pins (Figure 5a-b).

To this end, syringes have been regularly collected on the industrial manufacturing lines (every minute for manufacturing line using traditional tungsten pins, and every ten minutes for manufacturing line using SiC coated pins, both lines undergoing the same industrial production rate). Then, these syringes have been filled with water, and the amount of soluble tungsten per syringe (in ng) has been measured.

Figure 5a-b shows the results of these experiments. It can be observed that when using conventional tungsten pins, the average amount of soluble tungsten remains above 800 ng per syringe after 6 min of use. After 60 min of use, the pin has to be replaced. To the contrary, for syringes formed with SiC coated pins, the released tungsten amounts are below the limit of detection, even after 6 hours of use: these syringes are free of any tungsten contamination. According to a third aspect of the invention, a process for manufacturing syringes, and especially for tip forming, using previously described tools instead of conventional tungsten pins is provided. This process not only produces syringes free of contamination, but also reduces the time spent for the maintenance in the production lines: as shown in the experiments, tools according to the invention need to be replaced six times less often than previous art tungsten tools.

In such process a pin having a coating (and possibly being made) of chemical elements of class I borosilicate glass and/or carbon is used for forming the inner shape of the tip of a glass syringe made of borosilicate glass. In this way, the syringes formed with this pin are totally free of tungsten or tungsten derivatives. Finally, according to a last aspect of the invention, a syringe made with a process according to the third aspect of the invention is provided. Said syringe does not contain any foreign elements other than elements constituting the glass, and thus can be filled with all kinds a lot of drugs. For example, they can contain or store therapeutic proteins longer than a conventional syringe which would possibly contain foreign elements such as tungsten derivatives that should interact with the drug or degrade it.

Claims

1. Tool (1 ) for forming an opening of a glass container, characterized in that at least an external surface of the tool (1 ) is made of a material comprising only chemical elements of at least one of class I borosilicate glass and/or carbon and/or nitrogen.

2. Tool according to claim 1 , wherein said material has a melting point above 1000 °C.

3. Tool according to any one of previous claims, wherein said material has a wear resistance when in contact with molten glass at a temperature between 600 °C and 1000°C.

4. Tool according to any one of previous claims, wherein said material is non-oxidizing when in contact with molten glass at a temperature between 600 °C and 1000°C.

5. Tool according to any one of previous claims, wherein said material forms a self-limiting oxide passivation layer.

6. Tool according to claim 5 wherein said self-limiting oxide passivation layer acts as a thermal and oxygen barrier.

7. Tool according to any one of previous claims, wherein said material is silicon carbide.

8. Tool according to any one of claims 1 to 6, wherein said material is boron nitride.

9. Tool according to any one of previous claims, wherein said tool (1 ) has a first diameter, and wherein a distal part (4) of said tool (1 ) has a diameter that is smaller than said first diameter.

10. Tool according to claim 9 wherein the entire surface of said distal part (4) is made of said material.

11. Tool according to any one of previous claims, wherein said tool (1 ) comprises a core (3) and wherein said external surface comprises a coating (2) over said core (3).

12. Tool according to claim 1 1 , wherein said core (3) is made of a material different from that of said coating (2).

13. Tool according to claim 12, wherein the core (3) is made of tungsten.

14. Tool according to any one of claims 1 1 to 13, wherein the thickness of said coating (2) is between 3 and 75 μιτι.

15. Tool according to claim 14, wherein the thickness of said coating (2) is between 10 and 50 μιτι.

16. Tool according to any one of claims 1 1 to 15, wherein said coating (2) is deposited by High Thermal Chemical Vapor Deposition.

17. Tool according to any one of claims 1 to 10, wherein said tool (1 ) is entirely made of said material comprising only chemical elements of at least one of class I borosilicate glass and/or carbon and/or nitrogen.

18. Process for manufacturing a glass container free of contamination by chemical elements foreign to said container, wherein an opening of the glass container is formed by a tool (1 ) according to one of previous claims.

19. Syringe made with a process according to claim 18.

20. Syringe according to claim 19, wherein said syringe is free of chemical elements other than of at least one of class I borosilicate glass and/or carbon and/or nitrogen.