IE80463B1 - Flexible medical solution pouches - Google Patents

Description

UNDER THE LAWS OF THE STATE OF CONNECTICUT, UNITED STATES OF AMERICA, OF 1114 AVENUE OF THE AMERICAS, NEW YORK, NEW YORK 10036, UNITED STATES OF AMERICA.

(C) Copyright 1998, Government of Ireland. -2This invention relates to autoclavable flexible films suitable for the packaging of medical solutions.

Currently, it is common medical practice to supply liquids such as medical solutions for parenteral administration in the form of disposable, flexible pouches. These pouches should be characterized by collapsibi1ity, transparency, and adequate mechanical strength. They must also be able to resist the relatively high temperatures required for heat sterilization of their contents, for example in an autoclave. Typically, medical solutions are autoclaved at 123°C (253°F) for periods of 15 to 30 minutes .

Presently, such flexible pouches are typically made from a highly plasticized polyvinyl chloride. While meeting the requirements mentioned above, polyvinyl chloride may have some undesirable properties for use as a medical solution pouch because of the possibility of migration of plasticizer from the polyvinyl chloride into the medical solution or the other contents of the pouch so that the solution may become contaminated by potentially toxic material. A question has also arisen concerning whether PVC is adequately chemically neutral to medical solutions. It has also been found that polyvinyl chloride becomes brittle at relatively low temperatures. -3Embrittlement and stress-cracking, particularly of the outer surface of medical pouches, has been found to occur in other non-PVC pouches. It is desirable to provide a pouch for the packaging of medical solutions which substantially reduces or eliminates stress-cracking and embrittlement of the pouch material.

Of interest is U.S. Patent 4,401,536 issued to Lundell et al which discloses the use of a blend of medical grade radiation-stabilised polypropylene and a copolymer of ethylene and a comonomer selected from the group consisting of vinyl esters of saturated carboxylic acids and alkyl esters of alpha, beta ethylenically unsaturated carboxylic acids, the blend being irradiated.

EP-A-0 142 315, published after the priority date of the present application discloses, inter alia, films comprising an ethylene vinyl acetate copolymer layer and, on each side thereof, an ethylene propylene copolymer layer. The possibility of cross-linking at 10-60, preferably about 20 kGy (1-6, preferably about 2, MR) is mentioned. The Applicants have now discovered that certain specific films within the general scope of EP-A-0 142 315 possess advantageous properties.

The present invention provides a film suitable for the packaging of medical solutions. The film has good flexibility, good optical properties, a low degree of haze after autoclaving of the package, and high mechanical strength. In addition the film has sufficient barrier properties to eliminate or reduce the need for separate overwrap material to insure that the concentration of the medical solution in the pouch is not adversely affected.

DEFINITIONS The terms flexible and elastomeric are used herein to define specific polymeric materials as well as -4characteristics of a resulting pouch or bag whereby improved flexibility and/or collapsibility of the pouch or bag is obtained by the use of these specific polymeric materials. Flexible materials characterized by a modulus of .

PSI'; 3.515 x 106 g/cm2) (ASTM D-882-81) less than (40,000 PSI 2.812 x 106 g/cm2) may be less than (50,000 and more preferably (ASTM D-882-81).

The term film’ refers to a thermoplastic material suitable for packaging and having one or more layers of polymeric materials which may be bonded by any suitable means well known in the art.

The term polymer, polymeric unless specifically defined or otherwise limited, generally includes homopolymers, copolymers and terpolymers and blends and modifications thereof.

The term interior is used herein to refer to a layer of a multilayer film which is not a skin or surface layer, or sealant layer, of the film.

The term melt flow and melt flow index is used herein as the amount, in grams, of a thermoplastic resin which can be forced through a given orifice under a specified pressure and temperature within 10 minutes. The value should be determined in accordance with ASTM D 1238-79 . vinyl acetate copolymer (EVA) a copolymer formed from ethylene wherein the ethylene derived present in major amounts and the in the copolymer are present in The term ethylene is used herein to refer to and vinyl acetate monomers units in the copolymer are vinyl acetate derived units minor amounts. -5The term ethylene propylene copolymer (EPC) is used herein to refer to a copolymer formed from polypropylene monomer and minor amounts, usually less than 6%, of ethylene.

The invention provides a flexible film comprising a layer of an ethylene vinyl acetate copolymer, and on each side of the said layer, a layer of an ethylene propylene copolymer, said film being cross-linked, the film having a modulus of less than 50,000 PSI and being obtainable by cast coextrusion.

A flexible film in accordance with the invention comprises a sealant layer comprising ethylene propylene copolymer; an interior layer comprising an ethylene vinyl acetate copolymer which imparts flexibility to the film; and an outer layer comprising ethylene propylene copolymer, the said film being cross-linked.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a schematic cross-section of a three layer film made in accordance with the invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Figure 1 shows a three layer film in accordance with the invention. Sealing layer 10 is an ethylene propylene copolymer (EPC). A suitable EPC is Eltex KS (Trademark) 409X6206 available from Solvay. This copolymer has an ethylene content of about 3.8%. The sealing layer will be in contact with the medical solution or other material to be contained within flexible bags made from the flexible films of the present invention.

Interior layer 12 is an ethylene vinyl acetate copolymer (EVA).

Outside layer 14 of the three layer embodiment of -6the present invention is ethylene propylene copolymer.

The three-layer film of the invention is typically characterized by a second or interior layer which is considerably thicker than the remaining layers.

The films as described are preferably manufactured by a cast coextrusion process.

EXAMPLES Exemplary multi-layer structures were cast coextruded and irradiated. These structures are viewed as potential replacements for polyvinyl chloride bags.

Critical parameters which were measured include moisture barrier properties, tensile strength and elongation at break, and modulus of elasticity. Also important for medical solution applications are the optical properties such as haze, total transmission, and gloss. Examples 1 and 2, in part reflected in the detailed description of the preferred embodiments hereinbefore described, are listed below with their respective formulations, beginning with the outside layer and ending with the inside or sealant layer. Unless otherwise denoted, Examples 1-2 included the following materials: EPC: Eltex KS409x6206 EVA: ELVAX 3175 Example 1 is a control bag material comprising polyvinyl chloride. -ΊExample 2 includes a core layer of EVA sandwiched between outer layers of EPC.

Tables 1 and 2 demonstrate the results of physical testing of Examples 1 and 2 for selected physical properties . -8TABLE I Example 1 Tensile at Break and 23°C (73°F) g/cm2 x 100 < (PSI1 (x 100)) Av .2 Long 2700 (38.4) Std. Dev. 95% C.L.3 154 (2.2) 246 (3.5) Av. Trans. 2570 (36.5) Std. Dev. 168 (2.4) 95% C.L. 267 (3.8) Gauge Long.4 pm (mils) 344 (13.53) Std. Dev. 19.1 (0.75) 95% C.L. 30.2 (1.19) Gauge Trans. μτη (mils) 372 (14.63) Std. Dev. 5.59 (0.22) 95% C.L. 8.89 (0.35) Elongation at Break and 23°C (73°F) g/cm4 (PSI5) Av. Long 39400 (560) Std. Dev. 1410 (20) 95% C.L. 2250 (32) Av. Trans. 39500 (562) Std. Dev. 2950 (42) 95% C.L. 4640 (66) Modulus at 23°C (73°F) g/cm2 x 1000 (PSIf x (1000 Av. Long 344 (4.9) Std. Dev. 14 (0.2) 95% C.L. 21 (0.3) Av. Trans. 379 (5.4) Std. Dev. 21 (0.3) 95% C.L. 28 (0.4) Gauge Long. pm (mils) 361 (14.22) Std. Dev. 11.4 (0.45) 95% C.L. 18.0 (0.71) Gauge Trans. pm (mils) 340 (13.39) Std. Dev. 1.78 (0.07) 95% C.L. 2.79 (0.11) -9Example 1 Optical Properties 23°C P3CF7 Haze (¾)7 Avg.

St.cS. Dev. 95¾ C.L Gauge μιη (mils) Std. Dev. 95¾ C.L. 2.6 0.2 0.3 331 (13.03 ) 1.27 ( 0.05 ) 2.03 ( 0.06 ) Total Transmission (¾)8 Avg. 89.9 Std. Dev. 0.2 95¾ C.L. 0.4 Gloss (45°)9 Avg. 73.

Std. Dev. 1· 95¾ C.L. IVater Vapqtr Transmi ss i on at 38°C (ίΟΟΎ30) Sample 1 0.58 Sample 2 0.56 Sample 3 0.51 Gauge pmOrils? Sample 1 344 (13.54) Sample 2 369 (14.51 ) Sample 3 371 (14.59) -10EXAMPLE 2 TABLE 2 Tensile at Break and 23°C (73°F) g/cm2 x 100 (PSI1 (x 100 Av.2 Long 1410 (20.0) Std. Dev. 95% C.L.3 91 (1.3) 141 (2.0) Av. Trans. 3450 (49.0) Std. Dev. 400 (5.7) 95% C.L. 639 (9.1) Gauge Long, pm (mils) 217 (8.54) Std. Dev. 9.65 (0.38) 95% C.L. 15.5 (0.61) Gauge Trans, pm (mils) 211 (8.32) Std. Dev. 3.30 (0.13) 95% C.L. 5.08 (0.20) Elongation at 5 Break and 23°C (73°F) g/cm (PSI5) Av. Long 37300 (531) Std. Dev. 2500 (36) 95% C.L. 4010 (57) Av. Trans. 74800 (1064) Std. Dev. 2880 (41) 95% C.L. 4570 (65) Modulus at 23°C (73°F) g/cm2 x 1000 (PSI6 x : (1000)) Av. Long 1210 (17.2) Std. Dev. 35 (0.5) 95% C.L. 56 (0.8) Av. Trans. 1060 (15.1) Std. Dev, 77 (1.1) 95% C.L. 120 (1.7) Gauge Long. pm (mils) 220 (8.65) Std. Dev 10.7 (0.42) 95% C.L. 17.0 (0.67) Gauge Trans . pm (mils) 227 (8.94) Std. Dev 6.10 (0.24) 95% C.L. 9.65 (0.38) -11EXAMPLE 2 Optical Properties at 23 C (73°F) Haze (¾)7 Avg. 10.1 Std. Dev. 0.9 95¾ C.L. 1.4 Gauge pm (mils) 209 (8.23) Std. Dev. 6.35 (0.25) 95¾ C.L. 10.2 (0.40) Total Transmission (¾)8 Avg. 90.6 Std. Dev. 0.2 95¾ C.L. 0.3 Gloss (45°)s Avg. 51.

Std. Dev. 1. 95¾ C.L. 2.

Water Vapor Transmission at 38°C (100°F10) Sample 1 1.06 Sample 2 0.92 Sample 3 0.84 Gauge pm (mils) Sample 1 219 (8.64 · Sample 2 226 (8.89) Sample 3 225 ίβ.86) -12The following footnotes apply to Tables 1 and 2 . 1 ASTM D882-81. 2 All average values in Tables 1 and 2 are averages obtained from four (4) replicate measurements. 3C.L is Confidence Limit - for example, in a reported average value of 10 with a 95% C.L. of 2, in 100 replicate readings, 95 would have a value between 8 and 12 inclusive .

«Gauge measured in pm (mils). Values listed are for corresponding examples. Gauge values for tensile at break apply for elongation at break as well. Gauge values for haze apply for other optical properties as well.

ASTM D882-81.

ASTM D882-81.

ASTM D1003-61 {reapproved 1977).

ASTM D1003 Method A.

ASTM D2457-70 (reapproved 1977).

ASTM F372. β 0 Films in accordance with the present invention are cross-linked. This is preferably done by irradiation, i.e. bombarding the film with particulate and non-particulate radiations such as high energy electrons from an accelerator or cobalt-60 gamma rays, to cross-link the materials of the film. Cross-linking increases the structural strength of film and/or the force at which the material can be stretched before tearing apart, and may also improve the optical properties of the film and change the high temperature -13properties of the film. A preferred irradiation dosage level is in the range of from 20 to 50 kGy (2 Megarads (M.R.) to 5 M.R.). In the case of films having a copolyester, lower dosages of irradiation may be required to keep extractables at a tolerable level.

Cross-linking may also be accomplished chemically by the use of peroxides.

Pouches made in accordance with the present invention may be heat sealed by various means well known in the art. Impulse and hot bar sealing are preferred means. Some structures having a relatively thick layer of EVA may be sealed by radio-frequency sealing.

The films according to the present invention are .obtainable by cast coextrusion. A hot blown process 15 would provide a pouch having optical properties inferior to those from a cast coextrusion process.

An important property of a flexible medical solution bag is the moisture vapor transmission rate.

Typically, the concentrations of the medical solutions inside the pouch must be carefully maintained. Pouches or bags currently made from PVC require moisture barrier materials in an overwrap arrangement i.e. a separate overwrap material, to insure that the concentration of solutions obtained in the pouch is not affected.

Another key feature of the present invention, and of importance in medical solution packaging is the -14flexibility and collapsibility of the laminate material. Flexibility aids in the drainage of a medical solution from the bag or pouch.

The structure of Example 3 is listed below, beginning with the outside layer and ending with the inside or sealant layer. Example 3 includes commercial materials as in Example 2, except that the EPC for Example 3 was M7853-368A; a polyalloraer EPC block copolymer, melt flow index of about 12, from Eastman; and the EVA of example 3 was Exxon XQ92.36, 28% vinyl acetate, melt flow index of about 2.0.

Example 3: EPC/EVA/EPC.

The above Example was irradiated with 3 MR i rradiation .

The film was about 229 pm (9 mil) thickness Table 3 appearing below shows the results of physical testing of example 3 for selected physical properties. The footnote numbers appearing in Table 3 correspond to those for Tables 1-2, and designate ASTM test methodology. -15TABLE 3 EXAMPLE 3 Tensile at Break and 23°C (73°F), g/cm' x 100 (PSI1 (x 100)) Av.2 Long 3490 (49.7) Std. Dev. 752 (10.7) 95% C.L? 1200 (17.0) Av. Trans. 2390 (34.0) Std. Dev. 211 (3.0) 95% C.L. 337 (4.8) Gauge Long.4 urn (mils) 264 (10.38) Std. Dev. 18.0 (0.71) 95% C.L. 29.0 (1.14) Gauge Trans. μη\ (mils) 258 (10.15) Std. Dev. 4.32 (0.17) 95% C.L. 7.11 (0.28) Elongation at Break and 23°C (73°F) g/cm2 (PSI5) Av. Long 69000 (982) Std. Dev. 4570 (65) 95% C.L. 7310 (104) Av. Trans. 64800 (921) Std. Dev. 2600 (37) 95% C.L. 4220 (60) Modulus at 23°C (73°F) g/cm2 x 1000 (PSI6 x (1000)) Av. Long 1110 (15.8) Std. Dev. 253 (3.6) 95% C.L. 401 (5.7) Av. Trans. 1010 (14.3) Std. Dev, 204 (2.9) 95% C.L. 323 (4.6) Gauge Long. μτη (mils) 244 (9.62) Std. Dev 6.35 (0.25) 95% C.L. 10.2 (0.40) Gauge Trans . (SiTt (mils) 272 (10.70) Std. Dev 7.37 (0.29) 95% C.L. 11.7 (0.46) -16EXAMPLE 3 Optical Properties at 23°C (73°F) Hare (¾)7 Avg. 2.2 Std. Dev. 0.1 95¾ C.L. 0.2 Gauge pm (mils) 272 (10.70) Std. Dev. 12.4 (0.49) 95¾ C.L. 19.8 (0.78) Total Transmission (¾)8 Avg. 92.7 Std. Dev. 0.1 95¾ C.L. 0.1 Water Vapor T ransmi s s i on at 38°C (100°F10) Sample 1 0.7f> Sample 2 0.60 Sample 3 0.70 Gauge pm (mils) Sample 1 270 (10.62) Sample 2 250 (9.83) Sample 3 266 (10.48) -1ΊThe laminated films of the present invention also exhibit good seal strength, and abuse resistance, and do not substantially distort during autoclaving.

It should be noted that the detailed description 5 and specific examples which indicate the presently preferred embodiments of the invention are given by way of illustration only.

Claims (10)

1. A flexible film comprising a layer of an ethylene vinyl acetate copolymer, and on each side of the said layer, and attached directly thereto, a layer of an ethylene propylene copolymer, said film being cross-linked, the film having a modulus of less than 344.7 MPa (50,000 PSI) and being obtainable by cast coextrusion.
2. 2. A flexible film according to claim 1 having a modulus of less than 275.8 MPA (40,000 PSI).
3. 3. A flexible film according to claim 1 wherein the film is cross-linked by irradiation.
4. 4. A flexible film according to claim 3 wherein the film is cross-linked by irradiation at a dosage level between 2 MR and 5 MR (20 and 50 KGy).
5. 5. A flexible film according to claim 1 wherein the film is cross-linked by chemical cross-linking agents.
6. 6. A flexible film according to claim 1 wherein the ethylene propylene copolymer comprises less than 6% of ethylene.
7. 7. A flexible film according to claim 1 wherein the layer of ethylene vinyl acetate copolymer is thicker than either of the other layers.
8. 8. A flexible film according to claim 1 which is substantially as hereinbefore described with reference to any one of Examples 1 to 3.
9. 9. A flexible pouch made from a film of any of claims 1 to 7.
10. 10. A flexible pouch made from a film which is substantially as hereinbefore described with reference to any one of Examples 1 to 3.