A high-barrier medicinal packaging composite film and a preparation method thereof

Abstract

This invention discloses a high-barrier pharmaceutical packaging composite film and its preparation method. The composite film comprises a surface layer, a middle layer, and an inner layer arranged sequentially from the outside to the inside. The surface layer and the inner layer are polytetrafluoroethylene (PTFE) films, and the middle layer is obtained by plastic processing and molding of PET base resin doped with ascorbic acid tetraisopalmitate and nano-titanium dioxide. Compared with the prior art, the packaging composite film of this invention has excellent barrier properties against oxygen and moisture, high peel strength, and low cost, making it more suitable for user needs.

Description

Technical Field

[0001] This invention belongs to the technical field of pharmaceutical packaging materials, and relates to a high-barrier pharmaceutical packaging composite film and its preparation method. Background Technology

[0002] In pharmaceutical packaging, the barrier properties of packaging materials are crucial. Traditional pharmaceutical packaging materials, such as glass bottles and aluminum foil, while possessing certain barrier properties, have shortcomings in terms of lightweighting, flexibility, and processability. In recent years, with the development of composite film technology, pharmaceutical packaging composite films have gradually gained 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 this invention is to provide a high-barrier pharmaceutical packaging composite film and its preparation method, which can effectively balance mechanical processability and water and oxygen barrier properties.

[0005] The objective of this invention can be achieved through the following technical solutions:

[0006] A high-barrier pharmaceutical packaging composite film includes a surface layer, a middle layer, and an inner layer arranged sequentially 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 PET base resin doped with ascorbic acid tetraisopalmitate and nano titanium dioxide.

[0007] Here, the plastic processing and molding can be achieved by conventional PET film plastic molding.

[0008] In the above-mentioned high-barrier pharmaceutical packaging composite film, the outer polytetrafluoroethylene (PTFE) layer utilizes the inherent hydrophobic properties of PTFE to effectively block external moisture. Furthermore, as both the outer and inner layers, PTFE is non-stick, making it difficult for drug residues or contaminants to adhere, thus facilitating cleaning and maintenance. It also possesses high mechanical strength and good flexibility, making it resistant to breakage or tearing. Additionally, it exhibits excellent chemical stability, resisting the corrosive effects of most chemicals, including acids, alkalis, and salts.

[0009] Among ascorbic acid derivatives, ascorbic acid tetraisopalmitate (VC-IP) combines ascorbic acid with palmitic acid to form a lipophilic structure, which allows it to remain stable at high temperatures and resist oxidation and discoloration. Compared to water-soluble VC derivatives (such as sodium ascorbate phosphate (SAP) and ascorbate glucoside (AA2G), VC-IP has better lipophilicity, a more heat-resistant molecular structure, stronger permeability, and better stability.

[0010] The ascorbic acid tetraisopalmitate used in this application has reducing properties due to its ascorbic acid groups. It can effectively reduce the oxygen contained in the air that has penetrated into the outer polytetrafluoroethylene layer and extends to the middle layer, thereby consuming the oxygen in the air and ultimately achieving the oxygen barrier function. Nano-titanium dioxide compensates for the insufficient oxygen barrier properties of ascorbic acid tetraisopalmitate through the UV protection function of nanoparticles.

[0011] It is particularly noteworthy that, compared to ascorbic acid, the tetraisopalmitate of this application contains isopalmitate groups, which effectively improve the thermal stability of ascorbic acid. This ensures that the tetraisopalmitate can withstand the heating environment of plastic molding, preventing it from being damaged during the molding process and losing its oxygen barrier properties in the packaging composite film. Furthermore, the tetraisopalmitate contains ester groups, ensuring compatibility with the PET base resin and improving its dispersibility.

[0012] Preferably, the PET base resin is pre-dried to remove moisture; the ascorbic acid tetraisopalmitate and nano-titanium dioxide are mixed and dispersed with a dispersant to form a composite additive. Further, the drying temperature is ≤60℃.

[0013] Preferably, before infiltrating ascorbic acid tetraisopalmitate and nano-titanium dioxide into the PET base resin, the method further includes the following steps: mixing ascorbic acid tetraisopalmitate and nano-titanium dioxide, adding a dispersant, and then treating by 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 has undergone surface modification treatment beforehand. Specifically, the nano-titanium dioxide is modified using a silane coupling agent. As is well known to those skilled in the art, the conventional method of modification using silane coupling agents will not be elaborated here. The modification effect determined by the silane coupling agent modification process does not affect the oxygen barrier function of the intermediate layer in this application.

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

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

[0017] Furthermore, the PET base resin undergoes a pre-treatment surface activation process, which may include plasma treatment, corona treatment, or heat treatment, to further improve its performance and surface energy. Specifically, plasma treatment uses a power of 200-300W for 10-20 seconds; plasma treatment enhances surface wettability and improves the interlayer adhesion between the surface layer and the intermediate layer. Corona treatment uses a power of 30-50W for 10-20 seconds to improve surface adhesion.

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

[0019] Furthermore, 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 interlayer bonding and ensure the interlayer peel strength of the composite film. Preferably, the thickness of the adhesive layer is 2-10 μm.

[0020] Furthermore, the substrate of the adhesive layer is maleic anhydride-grafted polyethylene or modified polyurethane. The adhesive layer is cured by a thermosetting or UV curing process.

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

[0022] A. Add PET base resin containing ascorbic acid tetraisopalmitate and nano titanium dioxide to an extruder, and then melt-extrude, stretch or blow-mold it into a film to obtain the intermediate layer film.

[0023] B. Apply adhesive between the surface layer and the intermediate layer, and between the intermediate layer and the inner layer, and then perform hot pressing to obtain a composite film.

[0024] C. Place the composite membrane in an environment of 40-60℃ for curing.

[0025] Furthermore, to achieve better results, the outer polytetrafluoroethylene (PTFE) film also includes an anti-blocking agent and / or an antistatic agent, wherein the anti-blocking agent includes silica or talc; and the antistatic agent is glyceryl monostearate. The inner PTFE film also includes an opening agent and / or a plasticizer, wherein the opening agent is erucamide, and the plasticizer is a citrate ester, such as acetylthiol tributyl citrate (ATBC), which can improve interfacial compatibility.

[0026] Furthermore, the adhesive layer is applied between the surface layer and the intermediate layer / intermediate layer and the inner layer by gravure printing or solution coating.

[0027] Furthermore, the surface layer, intermediate layer, and inner layer are laminated using a dry lamination process or a co-extrusion lamination process, and are formed into a complete composite film by lamination using a multilayer laminator. Specifically, the lamination temperature is 50-80℃, preferably 50-60℃, and the pressure is 0.4-1.5MPa, preferably 0.4-0.6MPa.

[0028] Furthermore, the film-forming process in step A is a biaxial stretching process, including longitudinal stretching and transverse stretching. Specifically, the longitudinal stretching is performed at 115-125℃ with a stretching ratio of 3.5-5.0 to orient the molecular chains and reduce the surface energy. Specifically, the transverse stretching is performed at 60-70℃ with a stretching ratio of 3.0-4.0 to form a uniform network structure and enhance hydrophobicity.

[0029] Furthermore, the temperature conditions for the curing step are 40-60℃, preferably 40-50℃, and the time is 24-48 hours, in order to further improve the interlayer adhesion strength and stability.

[0030] The beneficial effects of this invention are:

[0031] Existing pharmaceutical packaging films typically address the barrier against oxygen and water vapor by incorporating aluminum foil. However, aluminum foil has poor mechanical properties, making it prone to defects such as pinholes, creases, and cracks. Over time, this allows oxygen and water vapor to penetrate, leading to drug degradation or spoilage. In this technical solution, ascorbic acid tetraisopalmitate (VC-IP) reduces oxygen that permeates the surface layer, preventing it from entering the inner layer. Furthermore, nano-titanium dioxide can photocatalytically decompose residual reactive oxygen species, further preventing oxygen from entering the inner layer while simultaneously improving the system's stability. Detailed Implementation

[0032] To further illustrate the technical means and effects of the present invention in achieving its intended purpose, the following detailed description of the specific implementation methods, structures, features, and effects of the present invention, in conjunction with embodiments, is provided below.

[0033] Example 1

[0034] A high-barrier pharmaceutical packaging composite film includes a surface layer, a middle layer, and an inner layer arranged sequentially from the outside to the inside, wherein the pharmaceutical packaging composite film is prepared by the following process:

[0035] A1. Mix 90 parts of dried polytetrafluoroethylene (PTFE) and 1 part of nano-silica, then add the mixture to the main feed inlet of a twin-screw extruder. Next, mix 95 parts of dried PTFE and 0.5 parts of erucamide, then add the mixture to the side feed inlet of the twin-screw extruder. Melt extrusion and blow molding are performed to form a film, which is then cooled and set. The drying temperature is 50℃, and the moisture content after drying should be less than 0.005%. The blow molding temperature is 160℃, and the traction speed is 8 m / min. The surface film thickness is approximately 20 μm, and the inner film thickness is approximately 25 μm.

[0036] A2. Mix 10 parts of ascorbic acid tetraisopalmitate and 5 parts of nano-titanium dioxide (particle size ≤50nm) evenly in a high-speed mixer, then add polyethylene glycol dispersant. After ultrasonic treatment for 30 minutes, mix with 90 parts of dried polyethylene terephthalate and add to a twin-screw extruder for melt extrusion, biaxial stretching to form a film, and then cooling and setting. The drying temperature is 50℃, and the moisture content after drying should be less than 0.005%. The specific steps for biaxial stretching to form the film are: first, longitudinal stretching at 120℃ with a stretch ratio of 4, and then transverse stretching at 65℃ with a stretch ratio of 3.5. The thickness of the intermediate layer is 15μm.

[0037] B. Maleic anhydride-grafted polyethylene adhesive is applied between the surface layer and the intermediate layer, and between the intermediate layer and the inner layer, with a coating amount of 3 g / m². 2 The activation temperature is 55℃, and the coating thickness is about 5μm; then hot-press lamination is performed at a lamination temperature of 55℃, a pressure of 0.5MPa, and a linear speed of 15m / min to obtain a composite film.

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

[0039] Example 2

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

[0041] Example 3

[0042] The difference between this embodiment and Embodiment 1 is that, in step B, a water-based polyurethane adhesive (40-50% solid content) is used for coating between the surface layer and the intermediate layer, and between the intermediate layer and the inner layer.

[0043] Example 4

[0044] The difference between this embodiment and Embodiment 1 is that the mass fraction of ascorbate tetraisopalmitate is 5 parts.

[0045] Example 5

[0046] The difference between this embodiment and Embodiment 1 is that the mass fraction of ascorbate tetraisopalmitate is 15 parts.

[0047] Example 6

[0048] The difference between this embodiment and Embodiment 1 is that the outer and inner layers of this embodiment are commercially available conventional polytetrafluoroethylene (PTFE) films manufactured by Wuxi Xiangjian PTFE Products Co., Ltd.

[0049] Example 7

[0050] The difference between this embodiment and Embodiment 1 is that the polyethylene terephthalate is pretreated with low-temperature plasma in this embodiment.

[0051] Example 8

[0052] The difference between this embodiment and embodiment 1 is that in step A2 of this embodiment, after the substrate of the intermediate layer is melt-extruded, it is blow-molded into a film using a blow molding machine. The blow molding temperature is 160°C and the traction speed is 8m / min.

[0053] Comparative Example 1

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

[0055] Comparative Example 2

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

[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, ascorbate tetraisopalmitate, nano titanium dioxide and polyethylene terephthalate are directly added to a twin-screw extruder, mixed and then 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 membranes measured in the above embodiments and comparative examples are numbered, with the composite membranes of Examples 1-8 being numbered 1-8 and the composite membranes of Comparative Examples 1-4 being 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 membrane was tested using a WTR-G3 tester. The test temperature was 38±0.5℃, and the relative humidity was 90%±2%.

[0065] (2) Oxygen permeability test

[0066] Referring to standard YBB00082003-2015, the oxygen permeation of the composite membrane was tested using a differential pressure gas permeameter. The test temperature was 23±2℃, the humidity was 50%RH, and the test pressure was atmospheric pressure (1atm).

[0067] Mechanical performance testing

[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 and placed in an environment of 23℃ ± 2℃ and 50% ± 5% humidity for 24 hours to eliminate the influence of temperature and humidity. A 50 mm pre-peel was made from one end of the composite film, and the peeled and unpeeled layers were clamped in the upper and lower fixtures of an electronic tensile testing machine, ensuring a peel angle of 180°. The peeling speed was set to 300 mm / min ± 30 mm / min, the test was started, and the force curve during the peeling process was recorded. After discarding the initial peak value, the average value of the stable segment was taken as the result. This 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] The results above show that the pharmaceutical packaging composite film of this application has excellent barrier properties against oxygen and water vapor, with an oxygen permeability of <0.9 cm⁻¹. 3 / (m 2 •day·atm), water vapor transmission rate <1.0g / (m 2The composite film (·day) effectively prevents drug oxidation and moisture absorption, ensuring drug stability. The composite films in Comparative Examples 1-3 (Nos. 9-11) have poor barrier properties against oxygen and water vapor. While the aluminum foil composite film in Comparative Example 4 (No. 12) has good barrier properties against oxygen and water vapor, aluminum foil is expensive and has poor mechanical properties. However, the pharmaceutical packaging composite film of this application, without using aluminum foil, has oxygen and water vapor permeability that are essentially comparable to those of the aluminum foil composite film, while its peel strength is better. Therefore, the pharmaceutical composite packaging film of this application has a higher cost-performance ratio and better meets user needs.

[0074] In summary, a comparison of items 1-8 with items 9-11 clearly shows that the high-barrier pharmaceutical packaging composite film of the present invention has a significant improvement in barrier performance.

[0075] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Although the present invention has been disclosed above with reference to preferred embodiments, it is not intended to limit the present invention. Any person skilled in the art can make some modifications or alterations to the above-disclosed technical content to create equivalent embodiments without departing from the scope of the present invention. Any simple modifications, equivalent changes and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. A high-barrier pharmaceutical packaging composite film, characterized in that, It includes a surface layer, a middle layer and an inner layer arranged sequentially 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 PET base resin doped with ascorbic acid tetraisopalmitate and nano titanium dioxide. Before incorporating ascorbic acid tetraisopalmitate and nano titanium dioxide into the PET base resin, the following steps are also included: mixing ascorbic acid tetraisopalmitate and nano titanium dioxide, then adding a dispersant, and treating by ball milling or ultrasonic treatment for 30-60 minutes to obtain a composite additive, wherein the dispersant is polyethylene glycol; The nano-titanium dioxide is silane coupling agent modified nano-titanium dioxide, and the particle size of the nano-titanium dioxide is ≤50nm. The mass ratio of ascorbic acid tetraisopalmitate to nano titanium dioxide is 1-3:1; the total amount of ascorbic acid tetraisopalmitate and nano titanium dioxide added is in a mass ratio of 1:4-19 to PET base resin. The PET base resin is pre-treated with surface activation, which may be plasma treatment, corona treatment, or heat treatment. The method for preparing the pharmaceutical packaging composite film includes the following steps: A. Add PET base resin containing ascorbic acid tetraisopalmitate and nano titanium dioxide to an extruder, and then melt-extrude, stretch or blow-mold it into a film to obtain the intermediate layer film. B. Apply adhesive between the surface layer and the intermediate layer, and between the intermediate layer and the inner layer, and then perform hot pressing to obtain a composite film. C. Place the composite membrane in an environment of 40-60℃ for curing.

2. 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 intermediate layer is 5-30 μm; and the thickness of the inner layer is 20-50 μm.

3. The pharmaceutical packaging composite film according to claim 1, characterized in that, The film stretching process in step A is a biaxial stretching process, which includes longitudinal stretching and transverse stretching. Specifically, the longitudinal stretching is performed at 115-125℃ with a stretching ratio of 3.5-5.0; the transverse stretching is performed at 60-70℃ with a stretching ratio of 3.0-4.0.

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