Method Of Reducing Friction Between Syringe Components

Abstract

A method of making a syringe assembly includes providing a first syringe component defining a first sliding surface that is substantially free of lubricant. The first sliding surface is contacted with water. The first sliding surface and the water in contact with the first sliding surface are heated at a temperature of at least 121 C. The first sliding surface is dried.

Claims

1. A method of treating a syringe assembly comprising: providing a glass barrel having a glass sliding surface for sliding engagement with a complementary component of a syringe assembly; applying saturated steam to heat the glass sliding surface; maintaining the saturated steam at a temperature at or above 120 C. for at least 60 minutes; and drying the glass sliding surface, wherein a friction force of the glass sliding surface is reduced.

2. The method of claim 1, wherein the glass sliding surface is an interior surface of the glass barrel.

3. The method of claim 2, wherein the glass sliding surface is substantially free of silicone oil.

4. The method of claim 1, wherein the method is achieved within a sterilization cycle.

5. The method of claim 1, wherein the glass sliding surface is dried at about 90 C. or greater.

6. The method of claim 1, comprising rinsing the glass sliding surface with an organic solvent.

7. The method of claim 1, wherein the complementary component is a syringe stopper or a syringe tip cap.

8. The method of claim 1, wherein the glass barrel contains therein water for injection.

9. The method of claim 7, comprising removing the water for injection prior to the drying.

10. The method of claim 1, comprising placing the barrel into an autoclave prior to the application of saturated steam.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

[0011] FIG. 1 is a schematic view of a syringe assembly prepared according to some embodiments.

[0012] FIG. 2 provides flow charts illustrating the methods of Examples 2 to 5.

[0013] FIG. 3 is a chart reflecting functional forces of Comparative Example 1 and Example 2.

[0014] While the invention is amenable to various modifications and alternative forms, specific embodiments have been shown by way of example in the drawings and are described in detail below. The intention, however, is not to limit the invention to the particular embodiments described. On the contrary, the invention is intended to cover all modifications, equivalents, and alternatives falling within the scope of the invention as defined by the appended claims.

DETAILED DESCRIPTION

[0015] Various embodiments described herein address reducing sliding friction between complementary sliding components in syringe assemblies, such as friction reduction between a first, softer component and a second, more rigid component of a syringe assembly. For example, some embodiments relate to reducing friction between a syringe stopper and a barrel, between a syringe tip cap and a barrel, or between a syringe valve body and valve plug, or other complementary syringe components. In some embodiments, the first component (e.g., a stopper) includes an elastomeric material, such as butyl rubber, and the second component (e.g., a syringe barrel) includes a ceramic material, such as borosilicate glass. While various embodiments are described in association with syringe assembly applications, a variety of applications where reduced friction is sought are contemplated.

[0016] FIG. 1 is a schematic view of a syringe assembly 10, according to some embodiments. As shown, the syringe assembly 10 includes a syringe barrel 12, a stopper 14 that forms a complementary fit with the syringe barrel 12, a plunger rod 16, a tip cap or needle shield 18, and, in the case of a pre-filled embodiment, a liquid 20, such as a medicament, for dispensing from the syringe assembly 10. As shown, the syringe barrel 12 and the stopper 14 are first and second complementary syringe components that are slidably engaged with one another, the stopper 14 forming a slidable seal within the syringe barrel 12. Although the syringe barrel 12 and the stopper 14 are slidably engaged in a linear relationship, it should be understood that other sliding relationships (e.g., rotational sliding between a valve body and a valve plug) are contemplated.

[0017] As shown, the syringe barrel 12 defines a bore or inner surface 30, also described as a sliding surface. The syringe barrel 12 is formed of a suitable material, such as suitable ceramic, polymeric, and metal materials. In some embodiments, the syringe barrel 12 includes a substantially rigid or hard material, such as a glass material. Although any of a variety of glass compositions are contemplated, according to the examples that follow borosilicate glass has been shown to be an effective material in association with friction-reduction methods according to some embodiments.

[0018] As indicated in FIG. 1, the stopper 14 defines an outer surface 32 for slidably engaging the inner surface 30 of the syringe barrel 12. In some embodiments, the stopper 14 includes a softer material than the syringe barrel 12. For example, the stopper 14 is optionally constructed with one or more barrier films applied to an elastomeric core, where the barrier film(s) define the outer surface 32 of the stopper 14. The elastomeric core can be formed of a variety of elastomeric materials, including: Butyl Rubber, Silicon, materials sold under the trade name VITON, and the like. The barrier film or films optionally include expanded fluoropolymer films and, such as expanded polytetrafluoroethylene films. Barrier films based on expanded PTFE help provide for thin and strong barrier layers to leachables and extractables. Some examples of suitable stopper designs utilizing expanded PTFE and elastomeric materials are described in U.S. application Ser. No. 12/915,850, SYRINGE STOPPER by Ashmead et al., filed Oct. 29, 2010, the entire contents of which are incorporated herein by reference for all purposes.

[0019] In some embodiment methods of reducing friction between the stopper 14 and the syringe barrel 12 of the syringe assembly 10, the syringe barrel 12 is filled with WFI water and sealed to prevent leakage. A cap, a second stopper, or other sealing member (not shown) different than the stopper 14 is optionally utilized to seal the WFI water within the syringe barrel 12. In other embodiments, the assembly 10, including the stopper 14 is filled with WFI water. The WFI water filled syringe barrel 12 is exposed to a source of heat, such as saturated steam. For example, the WFI water filled syringe barrel 12 may be placed in an autoclave with the temperature set at 121 C. or above. The saturated steam will heat the WFI water and the syringe barrel 12. The WFI water is removed and the syringe barrel 12 is dried. Following drying, the syringe barrel 12 is ready for use. Syringe assemblies with syringe barrels thus prepared display lower frictional forces between the syringe barrel 12 and the stopper 14.

[0020] In some embodiments, the syringe barrel 12 is rinsed with an organic solvent after the syringe barrel 12 and associated WFI water have been heated with steam. For example, a Hexane solvent may be used to rinse the syringe barrel 12. After the rinsing step, the syringe barrel 12 is dried. Drying may be conducted at room temperature (RT) or at elevated temperatures (e.g., at about 90 C. or greater, from about 70 C. to about 110 C., other at other temperature(s) as desired). The following examples are illustrative of methods of preparing a syringe assembly 10 with reduced friction according to some embodiments. While various methods of reducing friction between the syringe barrel 12 and the stopper 14 have been described, it should be understood that in other implementations similar methodology is applied to reduce friction between alternative or additional components of the syringe assembly 10, such as between the syringe barrel 12 and the tip cap 18, for example.

EXAMPLES

[0021] A syringe stopper was constructed in the following manner: A layer of FEP about 0.5 mils in thickness (FEP 100, DuPont) was laminated to a layer of densified expanded PTFE film [thickness: 1 mil; tensile strength: 13.85 ksi (longitudinal), 13.9 ksi (transverse); modulus: 19.8 ksi (longitudinal), 20.7 ksi (transverse); strain to break: 425% (longitudinal), 425% (transverse)]. The two layers were stacked on top of each other in a pin frame and heating to 380 C. in an oven for 15 minutes. A layer of porous expanded PTFE [thickness: 27.5 micrometers, matrix tensile strength: 66.8 MPa (longitudinal), 75.8 MPa (transverse), strain to break: 131% (longitudinal), 91% (transverse), bubble point: 22.6 psi] was placed on the densified ePTFE-FEP laminate such that the porous expanded PTFE layer faced the FEP layer in the laminate. These three layers were placed between two smooth metal plates, the plates were clamped to a clamping pressure of about 1 psi. The plates were then placed in an oven at 305 C. for 15 minutes. The resulting three layer composite material (densified ePTFEFEPporous ePTFE) was then cooled to about 40 C.

[0022] This composite material was then thermoformed using heat and vacuum to create a pre-form. The pre-form was constructed by heating the composite to a sufficiently high temperature and then drawing the composite over a male plug using differential pressure. The composite material was loaded into the thermoforming apparatus such that the densified ePTFE layer faced the plug. The composite was heated using a hot air gun (Steinel HG2310) with air exit temperature of 380 C. by placing the gun about 5 mm away from the surface of the composite. After 5 seconds, the film was subjected to a vacuum of 85 kPa. The composite was continued to be heated for another 15 seconds and cooled to about 40 C. under vacuum.

[0023] The resulting pre-form sample was then inverted and then placed into a rubber molding cavity charged with 3.5 grams of elastomer (50 Durometer halobutyl rubber), and the stopper was formed by compression molding. The mold was built to geometry specified for 1 mL long plunger per the ISO standard ISO11040-5:2001(E), with an additional 2% shrinkage factor incorporated.

[0024] The cavity was loaded in a press with both platens preheated to 120 C. The platens were closed to 55,500 lbs (about 8700 psi total internal pressure). The platens were then heated at 180 C. for 5 minutes and then cooled under pressure to 40 C. The pressure was released and the stopper was ejected. The resulting stopper was washed using a detergent and triple rinsed with de-ionized water. Stopper samples were then cut from the release sheet using a razor blade. They were subjected to two 30 minute cycles in an autoclave at 121 C.

[0025] As constructed, the stoppers were used as in the following examples, which reflect the improved sliding friction of the present invention when compared to that of the comparative example. A new stopper was used in each of the examples. FIG. 2 provides flow charts illustrating the methods of Examples 2 to 5.

Comparative Example 1

As delivered

[0026] A borosilicate glass syringe (1 mL Long Schott form a 3 s with a staked needle) was obtained. The syringe was obtained without silicone oil applied. A stopper constructed as described above was inserted into the barrel of the syringe and the Dynamic force was measured. Results are reported in Table 1.

Example 2

[0027] A syringe according to the inventive method was constructed in the following manner: A glass syringe free of silicone oil identical to that used in Example 1 was filled with WFI grade water and placed in an autoclave (121 C. for 1 hr), the glass syringe was then dried at 90 C. for 60 minutes and allowed to cool overnight. The stopper was then inserted into the syringe and the dynamic force was measured to be 4.7N. Results are reported in Table 1.

Example 3

[0028] A glass syringe free of silicone oil identical to that of Example 1 was filled with WFI grade water and placed in an autoclave (121 C. for 1 hr), the glass syringe was then removed from the autoclave, rinsed with hexane and dried at room temperature overnight in a laboratory hood. Another stopper was then inserted into this syringe and the dynamic force was measured to be 1.1N. Results are reported in Table 1.

Example 4

[0029] A glass syringe free of silicone oil identical to that of Comparative Example 1 was filled with WFI grade water and placed in an autoclave (121 C. for 1 hr), the glass syringe was then removed from the autoclave and dried at room temperature overnight in a laboratory hood. The stopper was then inserted into this syringe and the dynamic force was measured to be 5.9N. Results are reported in Table 1.

Example 5

[0030] A glass syringe free of silicone oil identical to that of Comparative Example 1 was filled with WFI grade water and placed in an autoclave (121 C. for 1 hr), the glass syringe was then removed from the autoclave and then dried at 90 C. for 60 minutes. The syringe was then rinsed with hexane and allowed to dry overnight in a laboratory hood. The stopper was then inserted into this syringe and the dynamic force was measured to be 4.4 N. Results are reported in Table 1.

Example 6

[0031] The syringe of Example 2 was tested per the dye ingress test in USP <381> to evaluate the seal between the inside of the syringe barrel and the stopper from Example 1. No significant dye ingress was observed.

TABLE-US-00001 TABLE 1 Static Dynamic Force (N) Force (N) Comparative 10.1 8.5 Example 1 Example 2 7.0 4.7 Example 3 7.3 1.1 Example 4 8.5 5.9 Example 5 6.4 4.4

[0032] As shown in Table 1, subjecting the glass syringe to the treatments described in Examples 2 through 5 lower the dynamic and static force of the stopper.

[0033] Test Methods:

[0034] Static and Dynamic Force Test

[0035] The test was performed as specified by I.S. EN ISO 7886-1:1998 Annex G, with the following exceptions: i) Syringe is mounted so that nozzle is pointing down, ii) No liquid was expelled; only air was expelled, and iii) Forces resulting from travel from the total graduated capacity position to 20 mm from that point were recorded. Static force is defined as the value at the first inflection point in the force versus displacement graph. Dynamic force is the value after the inflection point during travel.

[0036] Tensile, Modulus, Strain to Break

[0037] Materials were evaluated for tensile strength, modulus and strain to break according to ATM D882-10 using 0.25 inch by 3 inch samples and a cross head rate of 20 inches/min and one inch gauge length.

[0038] Various modifications and additions can be made to the exemplary embodiments discussed without departing from the scope of the present invention. For example, while the embodiments described above refer to particular features, the scope of this invention also includes embodiments having different combinations of features and embodiments that do not include all of the described features. Accordingly, the scope of the present invention is intended to embrace all such alternatives, modifications, and variations as fall within the scope of the claims, together with all equivalents thereof.