High-barrier-property medicinal packaging composite film and preparation method thereof

Abstract

The invention discloses a high-barrier-property medicinal packaging composite film and a preparation method thereof.The composite film comprises a surface layer, a middle layer and an inner layer which are sequentially arranged from outside to inside, and the surface layer and the inner layer are polytetrafluoroethylene films; and the middle layer is prepared from PET base resin doped with ascorbyl tetraisopalmitate and nano titanium dioxide through plastic processing and molding. Compared with the prior art, the packaging composite film disclosed by the invention has the advantages of excellent barrier property to oxygen and water vapor, high peel strength, low cost and high cost performance, and better meets the requirements of users.

Description

Technical Field

[0001] The present invention belongs to the technical field of pharmaceutical packaging materials, and relates to a high-barrier pharmaceutical packaging composite film and a preparation method thereof. Background Art

[0002] In pharmaceutical packaging, the barrier performance of packaging materials is crucial. Traditional pharmaceutical packaging materials such as glass bottles and aluminum foils have certain barrier properties, but they have deficiencies in terms of lightweight, flexibility, and processing performance. In recent years, with the development of composite film technology, pharmaceutical packaging composite films have gradually attracted attention.

[0003] However, existing pharmaceutical packaging films are difficult to effectively balance mechanical processability and water and oxygen barrier properties. Summary of the Invention

[0004] The purpose of the present invention is to provide a high-barrier pharmaceutical packaging composite film and a preparation method thereof, and this packaging film can effectively balance mechanical processability and water and oxygen barrier properties.

[0005] The purpose of the present invention can be achieved by the following technical solutions:

[0006] A high-barrier pharmaceutical packaging composite film includes a surface layer, an intermediate layer, and an inner layer arranged in sequence from outside to inside. The surface layer and the inner layer are polytetrafluoroethylene films, and the intermediate layer is obtained by plastic processing and forming of a PET base resin incorporated with ascorbyl tetraisopalmitate and nano-titanium dioxide.

[0007] Herein, the plastic processing and forming can be obtained by the plastic forming of a conventional PET film.

[0008] In the above high-barrier pharmaceutical packaging composite film, the polytetrafluoroethylene layer located on the outer layer has good hydrophobicity due to the inherent properties of the polytetrafluoroethylene material, achieving the barrier effect on external water vapor. In addition, polytetrafluoroethylene as the surface layer and the inner layer has non-stickiness, is not easily attached by drug residues or contaminants, and is convenient for cleaning and maintenance; it has high mechanical strength and good flexibility, and is not easily damaged or torn; it has excellent chemical stability and can resist the erosion of most chemical substances, including acids, alkalis, salts, etc.

[0009] Among ascorbic acid derivatives, ascorbyl tetraisopalmitate (VC-IP) forms a lipophilic structure by combining ascorbic acid with palmitic acid, so that it can still remain stable at high temperatures and is not easily oxidized and discolored. Compared with water-soluble VC derivatives (such as sodium ascorbyl phosphate SAP, ascorbyl glucoside AA2G, etc.), VC-IP has better lipophilicity, molecular structure that is more heat-resistant, stronger permeability, and better stability.

[0010] The ascorbyl tetraisopalmitate used in this application has reducibility due to the presence of ascorbic acid groups. It can be better reduced by the oxygen contained in a part of the air that penetrates the outer polytetrafluoroethylene layer and reaches the middle layer, so as to consume the oxygen contained in the air and finally achieve the oxygen barrier function. Nano-titanium dioxide makes up for the deficiency of the oxygen barrier property of ascorbyl tetraisopalmitate through the anti-ultraviolet function of nanoparticles.

[0011] It should be noted that, compared with ascorbic acid, the isopalmitate groups contained in the ascorbyl tetraisopalmitate of this application can effectively improve the thermal stability of ascorbic acid, so as to ensure that ascorbyl tetraisopalmitate can withstand the heating environment of plastic molding and avoid being damaged during the plastic molding process and losing its oxygen barrier performance in the packaging composite film. Moreover, the ascorbyl tetraisopalmitate contains an ester group, which ensures compatibility with the PET base resin and improves its dispersibility.

[0012] Preferably, the PET base resin is pre-dried to remove moisture; the ascorbyl tetraisopalmitate and nano-titanium dioxide are mixed and then added with a dispersant and dispersed to form a composite additive. Further, the temperature condition of the drying treatment is ≤60°C.

[0013] Preferably, before infiltrating ascorbyl tetraisopalmitate and nano-titanium dioxide into the PET base resin, the following steps are also included: mixing ascorbyl tetraisopalmitate and nano-titanium dioxide, adding a dispersant, and performing ball milling or ultrasonic treatment for 30 - 60 minutes to obtain a composite additive. Preferably, the dispersant is polyethylene glycol (PEG).

[0014] Preferably, the nano-titanium dioxide is pre-treated by surface modification. Specifically, the nano-titanium dioxide is modified by a silane coupling agent. Since those skilled in the art are familiar with the conventional methods of surface modification with silane coupling agents, it will not be elaborated here. The modification effect determined by the silane coupling agent modification process does not affect the oxygen barrier function that can be exerted by the middle layer of this application.

[0015] Further, the thickness of the surface layer is 10 - 30 μm, preferably 15 - 25 μm; the thickness of the middle layer is 5 - 30 μm, preferably 10 - 20 μm; the thickness of the inner layer is 20 - 50 μm, preferably 20 - 30 μm.

[0016] Preferably, the mass ratio of ascorbyl tetraisopalmitate to nano-titanium dioxide is 1 - 3:1. The total addition amount of ascorbyl tetraisopalmitate and nano-titanium dioxide and the mass ratio of the PET base resin is 1:4 - 19; preferably 1:5 - 10.

[0017] Further, the PET base resin is pre-treated by surface activation, and the surface activation treatment is plasma treatment, corona treatment or heat treatment to further improve its performance and surface energy. Among them, the power of plasma treatment is 200 - 300 W, and the time is 10 - 20 seconds; plasma treatment is beneficial to enhancing surface wettability and improving the interfacial bonding strength between the surface layer and the intermediate layer. The treatment power of corona treatment is 30 - 50 W, and the treatment time is 10 - 20 seconds to improve its surface adhesion.

[0018] Further, the PET base resin is polyethylene terephthalate, polybutylene terephthalate or polyarylate.

[0019] Further, an adhesive layer is provided between the surface layer and the intermediate layer, and / or between the intermediate layer and the inner layer to enhance the interfacial bonding strength and ensure the interlayer peel strength of the composite film. Preferably, the thickness of the adhesive layer is 2 - 10 μm.

[0020] Further, the base material of the adhesive layer is maleic anhydride grafted polyethylene or modified polyurethane. The adhesive layer is cured by a thermal curing or ultraviolet curing process.

[0021] A method for preparing a pharmaceutical packaging composite film as described above includes the following steps:

[0022] A. Add the PET base resin incorporated with tetraisopalmitate ascorbate and nano-titanium dioxide into an extruder, melt and extrude, and stretch or blow it into a film to obtain the film of the intermediate layer;

[0023] B. Coat an adhesive between the film surfaces of the surface layer and the intermediate layer, and between the film surfaces of the intermediate layer and the inner layer, and then perform hot pressing and compounding to obtain a composite film;

[0024] C. Cure the composite film in an environment of 40 - 60 °C.

[0025] Further, for better effects, the polytetrafluoroethylene film of the surface layer further includes an anti-blocking agent and / or an antistatic agent. The anti-blocking agent includes silica or talcum powder; the antistatic agent is glycerol monostearate. The polytetrafluoroethylene film of the inner layer further includes an antiblocking agent and / or a plasticizer. The antiblocking agent is erucamide, and the plasticizer is a citrate ester such as tributyl acetyl citrate (ATBC), which can improve the interfacial compatibility.

[0026] Further, the adhesive layer is coated between the film surfaces of the surface layer and the intermediate layer / intermediate layer and the inner layer by gravure printing or by solution coating.

[0027] Further, the films of the surface layer, the intermediate layer and the inner layer are made by dry lamination process or co-extrusion lamination process, and are laminated through a multi-layer laminator to form a complete composite film. Specifically, the temperature for lamination is 50 - 80°C, preferably 50 - 60°C, and the pressure is 0.4 - 1.5 MPa, preferably 0.4 - 0.6 MPa.

[0028] Further, the film stretching process in step A is a biaxial stretching process, including longitudinal stretching and transverse stretching. The longitudinal stretching is specifically carried out at 115 - 125°C with a stretching ratio of 3.5 - 5.0 times to align the molecular chains and reduce the surface energy; the transverse stretching is specifically carried out at 60 - 70°C with a stretching ratio of 3.0 - 4.0 times to form a uniform network structure and enhance the hydrophobicity.

[0029] Further, the temperature condition for the curing step is 40 - 60°C, preferably 40 - 50°C, and the time is 24 - 48 hours; to further improve the interlayer adhesion strength and stability.

[0030] Advantages of the present invention:

[0031] In the prior art, the medicinal packaging film generally solves the problems of oxygen, water vapor, etc. in drug packaging by adding aluminum foil. However, the mechanical properties of aluminum foil are poor, and defects such as pinholes, creases, cracks, etc. are likely to occur, which easily leads to the infiltration of oxygen, water vapor, etc. over a long time, resulting in the degradation or deterioration of drug efficacy. In this technical solution, ascorbyl tetraisopalmitate (VC-IP) can reduce the oxygen permeating through the surface layer to prevent oxygen from entering the inner layer. And nano-titanium dioxide can further prevent oxygen from entering the inner layer and improve the stability of the system by photocatalytically assisting in the decomposition of residual reactive oxygen. Specific embodiments

[0032] To further illustrate the technical means and effects adopted by the present invention to achieve the predetermined invention purpose, the following examples are used to detail the specific embodiments, structures, features and their effects according to the present invention.

[0033] Example 1

[0034] A high-barrier medicinal packaging composite film includes a surface layer, an intermediate layer and an inner layer arranged in sequence from outside to inside. Among them, this medicinal packaging composite film is prepared by the following process:

[0035] A1. Mix 90 parts of dried polytetrafluoroethylene and 1 part of nano-silica, and add them to the main feeding port of a twin-screw extruder; then mix 95 parts of dried polytetrafluoroethylene and 0.5 part of erucamide, and add them to the side feeding port of the twin-screw extruder, melt and extrude, blow into a film, and cool and shape. Among them, the drying temperature is 50°C, and the water content after drying is preferably less than 0.005%. The temperature for blowing into a film is 160°C, and the traction speed is 8 m / min. The thickness of the surface layer film is about 20 μm, and the thickness of the inner layer film is about 25 μm.

[0036] A2. Mix 10 parts of ascorbyl tetraisopalmitate and 5 parts of nano-titanium dioxide (particle size ≤ 50 nm) evenly in a high-speed mixer, then add polyethylene glycol dispersant, and after ultrasonic treatment for 30 minutes, mix with 90 parts of dried polyethylene terephthalate and add them to a twin-screw extruder, melt and extrude, biaxially stretch into a film, and then cool and shape. Among them, the drying temperature is 50°C, and the water content after drying is preferably less than 0.005%. The specific steps for biaxially stretching into a film are: first longitudinally stretch at 120°C with a 4-fold stretch ratio, and then horizontally stretch at 65°C with a 3.5-fold stretch ratio. The thickness of the middle layer film is 15 μm.

[0037] B. Coat between the surface layer and the middle layer, and between the middle layer and the inner layer with maleic anhydride grafted polyethylene adhesive, the coating amount is 3 g / m 2 , the activation temperature is 55°C, and the coating thickness is about 5 μm; then hot press and laminate, the lamination temperature is 55°C, the pressure is 0.5 MPa, and the linear speed is 15 m / min to obtain a composite film;

[0038] C. Place the composite film in a curing chamber at 40 - 60°C for 48 hours to promote the cross-linking of the adhesive.

[0039] Example 2

[0040] The difference between this example and Example 1 is that in step S2, nano-titanium dioxide is pre-treated with a silane coupling agent, where the treatment temperature is 70°C and the time is 40 minutes.

[0041] Example 3

[0042] The difference between this example and Example 1 is that in step B, between the surface layer and the middle layer, and between the middle layer and the inner layer, a waterborne polyurethane adhesive (solid content 40 - 50%) is used for coating.

[0043] Example 4

[0044] The difference between this example and Example 1 is that the mass part of ascorbyl tetraisopalmitate is 5 parts.

[0045] Example 5

[0046] The difference between this example and Example 1 is that the mass fraction of ascorbyl tetraisopalmitate is 15 parts.

[0047] Example 6

[0048] The difference between this example and Example 1 is that the surface layer and the inner layer of this example are commercially available conventional polytetrafluoroethylene membranes, and the manufacturer is Wuxi Xiangjian Teflon Products Co., Ltd.

[0049] Example 7

[0050] The difference between this example and Example 1 is that this example pre-treats polyethylene terephthalate by low-temperature plasma.

[0051] Example 8

[0052] The difference between this example and Example 1 is that in step A2 of this example, after the base material of the intermediate layer is melt-extruded, it is blown into a film by a blow molding machine. The temperature of blow molding into a film is 160 °C, and the drawing speed is 8 m / min.

[0053] Comparative Example 1

[0054] The difference between this comparative example and Example 1 is that this comparative example replaces ascorbyl tetraisopalmitate with ascorbic acid.

[0055] Comparative Example 2

[0056] The difference between this comparative example and Example 1 is that this comparative example replaces nano-titanium dioxide with nano-aluminum oxide.

[0057] Comparative Example 3

[0058] The difference between this comparative example and Example 1 is that in steps A1 and A2 of this comparative example, polytetrafluoroethylene, ascorbyl tetraisopalmitate, nano-titanium dioxide and polyethylene terephthalate are directly added to a twin-screw extruder, and after mixing, they are melt-extruded.

[0059] Comparative Example 4

[0060] The difference between this comparative example and Example 1 is that the intermediate layer of this comparative example is aluminum foil, which is directly coated between the surface layer and the inner layer.

[0061] The composite films measured for the above examples and comparative examples are numbered. Among them, the composite films of Examples 1-8 are numbered 1-8, and the composite films of Comparative Examples 1-4 are numbered 9-12.

[0062] Barrier performance test

[0063] (1) Water vapor transmission rate test

[0064] Referring to Standard YBB00092003-2015, the water vapor transmission rate of the composite film was tested using a WTR-G3 tester. Among them, the test temperature was 38 ± 0.5 °C, and the relative humidity was 90% ± 2%.

[0065] (2) Oxygen transmission rate test

[0066] Referring to Standard YBB00082003-2015, the oxygen transmission rate of the composite film was tested using a differential pressure gas permeation instrument. Among them, the test temperature was 23 ± 2 °C, the humidity was 50% RH, and the test pressure was normal pressure (1 atm).

[0067] Mechanical property test

[0068] (1) Peel strength test

[0069] Referring to Standard YBB00132002-2015, a composite film with a width of 15.0 mm ± 0.1 mm and a length of 200 mm was cut. It was left standing in an environment of 23 °C ± 2 °C and a humidity of 50% ± 5% for 24 hours to eliminate the influence of temperature and humidity. 50 mm was pre-peeled at one end of the composite film, and the peeling layer and the non-peeling layer were respectively clamped by the upper and lower fixtures of an electronic tensile testing machine to ensure that the peeling angle was 180°. The peeling speed was set at 300 mm / min ± 30 mm / min, the test was started, the force value curve during peeling was recorded, and the average value of the stable section was taken as the result after excluding the initial peak. It was repeated 5 times, and the average peel strength was calculated.

[0070] The results of the above tests are shown in Table 1.

[0071] Table 1

[0072]

[0073] From the above results, it can be seen that the pharmaceutical packaging composite film of this application has excellent barrier properties to oxygen and water vapor, and its oxygen transmission rate < 0.9 cm 3 / (m 2 ·day·atm), and the water vapor transmission rate < 1.0 g / (m 2· day), it can effectively prevent the oxidation and moisture absorption deterioration of drugs and ensure the stability of drugs. The composite films of Comparative Examples 1-3 (Nos. 9-11) have poor barrier properties to oxygen and water vapor. In Comparative Example 4 (No. 12), although the aluminum foil composite film has good barrier properties to oxygen and water vapor, the cost of aluminum foil is high and its mechanical properties are poor. Without using aluminum foil, the oxygen transmission rate and water vapor transmission rate of the pharmaceutical packaging composite film of the present application are basically the same as those of the aluminum foil composite film, and the peel strength is better than that of the aluminum foil composite film. Therefore, the pharmaceutical composite packaging film of the present application has a higher cost performance and better meets the needs of users.

[0074] In summary, through the comparison between Nos. 1-8 and Nos. 9-11, it can be clearly seen that the high-barrier pharmaceutical packaging composite film of the present invention has a significant improvement in barrier properties.

[0075] The above are only the preferred embodiments of the present invention, and do not impose any form of limitation on the present invention. Although the present invention has been disclosed above with the preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some changes or modifications to the above-disclosed technical content to form equivalent embodiments with equivalent changes, but as long as they do not depart from the technical content of the present invention, any simple modifications, equivalent changes and modifications made to the above embodiments based on the technical essence of the present invention still fall within the scope of the technical solution of the present invention.

Claims

1. A high barrier composite film for pharmaceutical packaging, characterized in that: It comprises a surface layer, a middle layer and an inner layer which are arranged in sequence from the outside to the inside. The surface layer and the inner layer are polytetrafluoroethylene films, and the middle layer is obtained by plastic processing and molding of a PET base resin mixed with ascorbic acid tetraisopalmitate and nano titanium dioxide.

2. The pharmaceutical packaging composite film according to claim 1, characterized in that: The nano titanium dioxide is nano titanium dioxide modified by a silane coupling agent.

3. The pharmaceutical packaging composite film according to claim 1, characterized in that: The thickness of the surface layer is 10-30 μm; the thickness of the middle layer is 5-30 μm; and the thickness of the inner layer is 20-50 μm.

4. The pharmaceutical packaging composite film according to claim 1, characterized in that: The mass ratio of ascorbyl tetraisopalmitate and nano-titanium dioxide is 1-3:1; the mass ratio of the total addition amount of ascorbyl tetraisopalmitate and nano-titanium dioxide to the PET base resin is 1:4-19.

5. The pharmaceutical packaging composite film according to claim 1, characterized in that: The PET base resin is preliminarily subjected to a surface activation treatment, wherein the surface activation treatment is a plasma treatment, a corona treatment or a heat treatment.

6. The pharmaceutical packaging composite film according to claim 1, characterized in that: The PET base resin is polyethylene terephthalate, polybutylene terephthalate or polyarylate.

7. The pharmaceutical packaging composite film according to claim 1, characterized in that: An adhesive layer is provided between the surface layer and the middle layer, and / or between the middle layer and the inner layer.

8. The pharmaceutical packaging composite film according to claim 1, characterized in that: The thickness of the adhesive layer is 2-10 μm.

9. A method for preparing a composite film for pharmaceutical packaging as claimed in any one of claims 1 to 8, characterized in that: The preparation method comprises the following steps: A. Adding PET base resin mixed with ascorbic acid tetraisopalmitate and nano titanium dioxide into an extruder, and then melt-extruding, stretching or blowing into a film to obtain a film of the middle layer; B. Applying adhesive between the film surfaces of the surface layer and the middle layer, and between the film surfaces of the middle layer and the inner layer, and then performing hot pressing and laminating to obtain a composite film; C. Place the composite film in a 40-60℃ environment for maturation.

10. The preparation method according to claim 9, characterized in that: The stretching process for film formation in step A is a biaxial stretching process, including longitudinal stretching and transverse stretching. The longitudinal stretching is specifically performed at 115-125°C with a stretching ratio of 3.5-5.0 times; the transverse stretching is specifically performed at 60-70°C with a stretching ratio of 3.0-4.0 times.

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