A multi-layer oral film and preparation method thereof

Abstract

The invention discloses a method for preparing a multilayer oral film, comprising the following steps: preparation of a basement membrane liquid; preparation of a sandwich membrane liquid; preparation of a covering membrane liquid; storing the prepared basement membrane liquid in a plastic box of a casting device, adjusting the wet film thickness by a thickness regulator on the plastic box, and combining the traction of a conveyor belt to make the film liquid in the plastic box uniformly cast, and obtaining a basement membrane after drying in a drying area; flowing the prepared sandwich membrane liquid into a sandwich plastic box after passing through a twin-screw extruder, and uniformly flowing to the top of the basement membrane after controlling the required thickness, and forming the sandwich membrane after drying in a drying area; using a spraying device to evenly spray the prepared covering membrane liquid on the top of the sandwich membrane, and obtaining a multilayer oral film with a three-layer structure after drying in a drying area; cutting the obtained three-layer film into a certain size, sealing and packaging, and irradiating and sterilizing to obtain a finished product. The multilayer oral film obtained by the invention has a large drug dosage, and the film quality is less affected by the ambient temperature and humidity.

Description

Technical Field

[0001] The present invention relates to the technical field of oral films, and in particular to a multi-layer oral film and a preparation method thereof. Background Art

[0002] Oral film is a new drug delivery system. It is made into a thin film sheet by loading a certain dose of chemical drugs or Chinese medicine extracts into the film material for oral or mucosal use. Its size, shape and thickness are similar to stamps. It is placed on the tongue and can dissolve in saliva and release drugs without drinking water. In recent years, oral films have been rapidly developed due to their beautiful appearance, small size, light weight, easy to carry, rapid dissolution in the mouth, and ability to effectively improve drug bioavailability.

[0003] The existing oral membranes are basically in the form of single layer or double layer, the drug loading capacity of the oral membrane is low and the quality of the membrane is greatly affected by the ambient temperature and humidity. Summary of the invention

[0004] In view of the deficiencies of the prior art, the present invention provides a multi-layer oral film and a preparation method thereof. The multi-layer oral film obtained by the preparation method has a large amount of medicine and the quality of the film is less affected by the environmental temperature and humidity.

[0005] The present invention is achieved through the following technical solutions:

[0006] A method for preparing a multilayer oral film comprises the following steps:

[0007] Preparation of basement membrane solution: dissolve the components in the formula amount in distilled water, stir evenly, and prepare a basement membrane solution with a concentration of 1% to 30%. After vacuum degassing, let it stand at a temperature of 0 to 35°C for 0 to 2 hours;

[0008] Preparation of sandwich film liquid: dissolve the formulated amount of gelling agent, acidity regulator and 1% to 20% of powdered sugar in distilled water, stir evenly, and prepare a gel solution with a concentration of 1% to 20%. After vacuum degassing, stand at a temperature of 0 to 35° C. for 0 to 2 hours, and pour the prepared gel solution and the remaining other components into a twin-screw extruder to prepare a sandwich film liquid;

[0009] Preparation of covering film liquid: dissolve the components in the formula amount in 85% ethanol solution, stir evenly, prepare a covering film liquid with a concentration of 1% to 20%, and let it stand at a temperature of 0 to 35°C for 0 to 2 hours;

[0010] The prepared base film liquid is stored in the glue box of the casting equipment, and the wet film thickness is adjusted by the thickness regulator on the glue box. Combined with the traction of the conveyor belt, the film liquid in the glue box is cast at a uniform speed. After drying at 30℃ to 90℃ in the first drying area, the base film is obtained, and the thickness of the base film is controlled at 50 to 150μm;

[0011] The prepared sandwich film liquid flows into the sandwich plastic box after passing through the twin-screw extruder, and flows uniformly to the top of the base film after controlling the required thickness. After drying in the second drying area at 30℃~100℃, the sandwich film is formed, and the thickness of the sandwich film is controlled at 0.2-2.5mm;

[0012] The prepared covering film liquid is sprayed evenly on the top of the sandwich film by using a spraying device, and after drying in the third drying area at 30°C to 80°C, a multilayer oral film with a three-layer structure is obtained, and the thickness of the covering film is controlled to be 60 to 100 μm;

[0013] The obtained three-layer film is cut into a certain size, sealed and packaged, and irradiated and sterilized to obtain a finished product.

[0014] Furthermore, the step of cutting the obtained three-layer film into a certain size, sealing and packaging, and irradiating and sterilizing to obtain a finished product specifically includes:

[0015] The obtained three-layer film is cut into a size of 20×(18-32) mm, sealed and packaged, and irradiated and sterilized to obtain a finished product.

[0016] Furthermore, based on 100 parts by weight, the basement membrane fluid includes the following components: 20 to 80 parts of hydrophilic film-forming materials, 10 to 30 parts of plasticizers, 0 to 10 parts of surfactants, 0 to 15 parts of active ingredients, 0 to 10 parts of flavoring agents, and 0 to 20 parts of other auxiliary materials.

[0017] Furthermore, based on 100 parts by weight, the sandwich membrane liquid includes the following components: 1-10 parts of gelling agent, 1-2 parts of acidity regulator, 10-60 parts of sugar solution, 10-60 parts of sugar powder, 0-20 parts of active ingredient, 0-10 parts of flavoring agent and 0-20 parts of other auxiliary materials.

[0018] Furthermore, based on 100 parts by weight, the covering film liquid includes the following components: 10 to 50 parts of hydrophobic film-forming material, 10 to 50 parts of thickener, 10 to 30 parts of plasticizer, 0 to 10 parts of flavoring agent and 0 to 20 parts of other auxiliary materials.

[0019] Furthermore, the hydrophilic film-forming material includes one or more of polyvinyl alcohol, gelatin, sodium alginate, carrageenan, agar, gum arabic, hydroxypropyl methylcellulose, starch, maltodextrin, pullulan, polyvinyl pyrrolidone, and sodium carboxymethyl cellulose.

[0020] Furthermore, the gelling agent includes one or more of pectin, gelatin, carrageenan, gellan gum, konjac flour, locust bean gum, and guar gum.

[0021] Furthermore, the hydrophobic film-forming material includes one or more of shellac, ethyl cellulose, carnauba wax, beeswax, hydroxyethyl methacrylate, polyacrylic acid resin, methyl methacrylate copolymer, and corn protein.

[0022] Furthermore, the thickener includes one or more of highly substituted hydroxypropyl cellulose, low substituted hydroxypropyl cellulose, and hydroxypropyl methyl cellulose.

[0023] Furthermore, the multilayer oral film prepared by the multilayer oral film preparation method comprises a base layer adhered to the oral cavity, a sandwich layer connected to the base layer, and a covering layer connected to the sandwich layer.

[0024] Compared with the prior art, the advantages of the present invention are:

[0025] 1. The multilayer oral film prepared by the present invention can control the drug loading by changing the thickness of the sandwich film. While the drug loading is significantly increased, the taste and mouthfeel can be adjusted by changing the component content in the sandwich film formula. The application scope of the multilayer oral film is expanded to the health care product industry, thereby improving the application breadth of the oral film.

[0026] 2. The preparation process of the multi-layer oral film can be efficiently and continuously prepared in one step without repeated operations.

[0027] 3. The multi-layer oral film of the present invention is covered with a hydrophobic cover film so that the multi-layer oral film is less affected by the environmental temperature and humidity during the production process to the finished product.

[0028] 4. The multilayer oral film prepared by the present invention has a good sustained release effect, and the sustained release time can reach 5-6 hours.

[0029] 5. The multi-layer oral film prepared by the present invention has strong adhesion, and its adhesion time can meet the high-efficiency adhesion of the entire sustained-release time in the oral cavity. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 A flowchart of a method for preparing a multi-layer oral film according to an embodiment of the present invention;

[0031] Figure 2 A schematic diagram of a working platform of a method for preparing a multi-layer oral film according to an embodiment of the present invention;

[0032] Figure 3 is a schematic diagram of the structure of the adhesion force measuring device;

[0033] Figure 4 Schematic diagram of the multi-layer oral membrane structure.

[0034] 1. Viscometer; 2. 10g weight; 3. Glass plate; 4. Multilayer oral film; 40. Cover layer; 41. Sandwich layer; 42. Base layer; 5. Glue box; 50. Thickness regulator; 51. First drying area; 6. Twin-screw extruder; 61. Second drying area; 7. Spraying equipment; 71. Third drying area. DETAILED DESCRIPTION

[0035] In order to make the purpose, technical scheme and advantages of the present invention clearer, the present invention is further described in detail below in conjunction with the embodiments, so that those skilled in the art can fully understand the technical content of the present invention. It should be understood that the following examples are used to further illustrate the present invention and cannot be interpreted as limiting the scope of protection of the present invention. Some non-essential improvements and adjustments made by those skilled in the art according to the above content of the present invention belong to the scope of protection of the present invention. The following examples of specific preparation method parameters are also only an example in a suitable range, that is, those skilled in the art can make a selection within a suitable range according to the description herein, and are not limited to the specific numerical values ​​​​exemplified below.

[0036] refer to Figure 4 A multilayer oral film according to an embodiment of the present invention includes a base layer 42 adhered to the oral cavity, a sandwich layer 41 connected to the base layer 42 , and a cover layer 40 connected to the sandwich layer 41 .

[0037] like Figure 1 and Figure 2 As shown, the multilayer oral film is prepared by the following method:

[0038] S1: Preparation of basement membrane solution: dissolve the components in the formula amount in distilled water, stir evenly, and prepare a basement membrane solution with a concentration of 1% to 30%. After vacuum degassing, let it stand at a temperature of 0 to 35°C for 0 to 2 hours.

[0039] Based on 100 parts by weight, the basement membrane liquid includes the following components: 20-80 parts of hydrophilic film-forming materials, 10-30 parts of plasticizers, 0-10 parts of surfactants, 0-15 parts of active ingredients, 0-10 parts of flavoring agents and 0-20 parts of other auxiliary materials.

[0040] The hydrophilic film-forming material is preferably 75 parts; the plasticizer is preferably 15 parts; and the surfactant is preferably 0.5 parts.

[0041] The hydrophilic film-forming material includes one or more of polyvinyl alcohol, gelatin, sodium alginate, carrageenan, agar, gum arabic, hydroxypropyl methylcellulose, starch, maltodextrin, pullulan, polyvinyl pyrrolidone, and sodium carboxymethyl cellulose; preferably pullulan.

[0042] The plasticizer includes one or more of glycerol, polyethylene glycol, propylene glycol, and sorbitol liquid; preferably propylene glycol.

[0043] The surfactant includes one or more of phospholipids, polysorbate 80, sorbitan fatty acid, medium chain triglycerides, and glyceryl monostearate; preferably, polysorbate 80.

[0044] The active ingredients can be conventional functional materials, drugs, probiotics, etc.

[0045] The flavoring agent is selected from sweeteners, sour agents and aromatics.

[0046] The sweetener includes one or more of mannitol, xylitol, aspartame, sucralose, steviol glycosides, and neotame; preferably sucralose.

[0047] The acidulant includes one or more of malic acid, citric acid, lactic acid and tartaric acid; preferably malic acid.

[0048] The fragrance includes one or more combinations of peppermint oil, sweet orange oil and characteristic essences.

[0049] Other excipients include colorants, fillers, antioxidants or preservatives.

[0050] S2: Preparation of sandwich membrane liquid: dissolve the formulated amount of gelling agent, acidity regulator and 1% to 20% of powdered sugar in distilled water, stir evenly, and prepare a gel solution with a concentration of 1% to 20%. After vacuum degassing, let it stand at a temperature of 0 to 35°C for 0-2h, and pour the prepared gel solution and the remaining other components into a twin-screw extruder to prepare a sandwich membrane liquid.

[0051] Based on 100 parts by weight, the sandwich film liquid includes the following components: 1-10 parts of gelling agent, 1-2 parts of acidity regulator, 10-60 parts of sugar solution, 10-60 parts of sugar powder, 0-20 parts of active ingredients, 0-10 parts of flavoring agent and 0-20 parts of other auxiliary materials.

[0052] The preferred amount of gelling agent is 5 parts; the preferred amount of acidity regulator is 1.3 parts; the preferred amount of sugar solution is 50 parts; and the preferred amount of sugar powder is 40 parts.

[0053] The gelling agent includes one or more of pectin, gelatin, carrageenan, gellan gum, konjac flour, locust bean gum, and guar gum; preferably pectin.

[0054] The acidity regulator includes one or more combinations of citric acid, malic acid, and tartaric acid; preferably citric acid.

[0055] The sugar solution includes one or more combinations of maltose syrup, glucose syrup, oligosaccharide syrup, and fructose syrup; preferably, it is glucose syrup.

[0056] The powdered sugar includes one or more combinations of white sugar, maltose, oligofructose and polydextrose; preferably white sugar.

[0057] The active ingredients can be conventional functional materials, drugs, probiotics, etc.

[0058] The flavoring agent is selected from sweeteners, sour agents and aromatics.

[0059] The sweetener includes one or more of mannitol, xylitol, aspartame, sucralose, steviol glycosides, and neotame; preferably sucralose.

[0060] The acidulant includes one or more of malic acid, citric acid, lactic acid and tartaric acid; preferably malic acid.

[0061] The fragrance includes one or more combinations of peppermint oil, sweet orange oil and characteristic essences.

[0062] Other excipients include colorants, fillers, antioxidants or preservatives.

[0063] S3: Preparation of covering film liquid: dissolve the components in the formula amount in 85% ethanol solution, stir evenly, prepare a covering film liquid with a concentration of 1% to 20%, and let it stand at a temperature of 0 to 35°C for 0-2h.

[0064] Based on 100 parts by weight, the covering film liquid includes the following components: 10 to 50 parts of hydrophobic film-forming material, 10 to 50 parts of thickener, 10 to 30 parts of plasticizer, 0 to 10 parts of flavoring agent and 0 to 20 parts of other auxiliary materials.

[0065] The hydrophobic film-forming material is pre-selected at 35 parts, the thickener is preferably 30 parts, and the plasticizer is preferably 15 parts.

[0066] The hydrophobic film-forming material includes one or more of shellac, ethyl cellulose, carnauba wax, beeswax, hydroxyethyl methacrylate, polyacrylic acid resin, methyl methacrylate copolymer, and corn protein; preferably ethyl cellulose.

[0067] The thickener includes one or more of high-substituted hydroxypropyl cellulose, low-substituted hydroxypropyl cellulose, and hydroxypropyl methyl cellulose.

[0068] The plasticizer is one or more of glycerol, polyethylene glycol, propylene glycol, and sorbitol liquid; preferably glycerol.

[0069] The flavoring agent is selected from sweeteners, sour agents and aromatics.

[0070] The sweetener is one or more of mannitol, xylitol, aspartame, sucralose, steviol glycosides, and neotame; preferably sucralose.

[0071] The acidulant is one or more of malic acid, citric acid, lactic acid and tartaric acid; preferably malic acid.

[0072] The aromatic agent includes one or more combinations of peppermint oil, sweet orange oil and characteristic essences.

[0073] Other excipients include colorants, fillers, antioxidants or preservatives.

[0074] S4: The prepared base film liquid is stored in the glue box of the casting equipment, and the wet film thickness is adjusted by the thickness regulator 50 on the glue box 5. Combined with the traction of the conveyor belt, the film liquid in the glue box is cast at a uniform speed. After passing through the first drying area 51, the base film is dried at 30°C to 90°C, and the thickness of the base film is controlled at 50 to 150 μm.

[0075] The casting equipment can use a film laying machine scraper.

[0076] S5: The prepared sandwich film liquid flows into the sandwich plastic box after passing through the twin-screw extruder 6, and flows uniformly to the top of the base film after controlling the required thickness. After passing through the second drying area 61, the sandwich film is dried at 30°C to 100°C to form a sandwich film, and the thickness of the sandwich film is controlled to be 0.2-2.5mm.

[0077] By arranging a thickness regulator 50 in the plastic box 5, the thickness of the sandwich membrane is changed by the thickness regulator 50 so as to control the drug loading amount thereof.

[0078] S6: The prepared covering film liquid is sprayed evenly on the top of the sandwich film using the spraying device 7, and after passing through the third drying area 71, it is dried at 30° C. to 80° C. to obtain a multilayer oral film with a three-layer structure, and the thickness of the covering film is controlled to be 60 to 100 μm.

[0079] The covering film can ensure that the quality of the three-layer oral film is less affected by the environmental temperature and humidity.

[0080] S7: Cut the obtained three-layer film into certain sizes, seal and package, and sterilize by irradiation to obtain a finished product.

[0081] Specifically, the obtained three-layer film is cut into a size of 20×(18-32) mm, sealed and packaged, and irradiated and sterilized to obtain a finished product.

[0082] The multilayer oral film prepared by the present invention can control the drug loading by changing the thickness of the sandwich film. While the drug loading is significantly improved, the taste and mouthfeel can be adjusted by changing the component content in the sandwich film formula. The application scope of the multilayer oral film is extended to the health care product industry, which improves the application breadth of the oral film. The preparation process of the multilayer oral film can be efficiently "one-step" continuously prepared without repeated operations. The multilayer oral film of the present invention is covered by a hydrophobic covering film, so that the multilayer oral film finished product is less affected by the environmental temperature and humidity. The multilayer oral film obtained by the preparation method has a large drug dosage, the film quality is less affected by the environmental temperature and humidity, and the packaging requirements are low.

[0083] The following is combined with specific embodiments to further illustrate and describe the concept of the present invention, but it does not mean that the present invention is limited to the specific scheme described below. In the embodiments, any specific numerical value within the scope of the present invention is applicable.

[0084] Embodiment 1:

[0085] A multi-layer oral film, wherein the base film liquid, the sandwich film liquid and the cover film liquid each comprise the following components based on 100 parts by weight:

[0086]

[0087] The multilayer oral film is prepared by the following method:

[0088] Step 1: Preparation of basement membrane solution: Dissolve the components in the formula amount in distilled water, stir evenly, and prepare a basement membrane solution with a concentration of 10%. After vacuum degassing, let it stand at 25°C for 2 hours;

[0089] Step 2: Preparation of sandwich film liquid: Dissolve the formulated amount of pectin, citric acid and 10% white sugar in distilled water, stir evenly to prepare a pectin solution with a concentration of 10%, vacuum degassing, and let stand at a temperature of 28°C for 1.5 hours, pour the prepared pectin solution and the remaining white sugar and glucose syrup into a twin-screw extruder to prepare a sandwich film liquid;

[0090] Step 3: Preparation of covering film solution: Dissolve the components in the formula amount in 85% ethanol solution, stir evenly, prepare a covering film solution with a concentration of 10%, and let it stand at a temperature of 25°C for 2 hours;

[0091] Step 4: The prepared base film liquid is stored in the plastic box of the film laying machine scraper equipment, and the thickness of the wet film is adjusted by the thickness regulator on the plastic box. Combined with the traction of the conveyor belt, the film liquid in the plastic box is uniformly cast, and the base film is obtained after drying at 70°C in the drying area. The thickness of the base film is controlled at 80-90μm;

[0092] Step 5: The prepared sandwich film liquid flows into the sandwich plastic box after passing through the twin-screw extruder, and flows uniformly to the top of the base film after controlling the required thickness. After drying at 90°C in the drying area, the sandwich film is formed, and the thickness of the sandwich film is controlled at 0.9-1mm;

[0093] Step 6: Use a spraying device to evenly spray the prepared covering film liquid on the top of the sandwich film, and after drying in a drying area at 50° C., a multilayer oral film with a three-layer structure is obtained, and the thickness of the covering film is controlled at 70 to 80 μm;

[0094] Step 7: Cut the obtained three-layer film into 20×28 mm size, seal and package, and sterilize by irradiation to obtain the finished product.

[0095] Embodiment 2:

[0096] A multi-layer oral film, wherein the base film liquid, the sandwich film liquid and the cover film liquid each comprise the following components based on 100 parts by weight:

[0097]

[0098] The multilayer oral film is prepared by the following method:

[0099] Step 1: Preparation of basement membrane solution: Dissolve the components in the formula amount in distilled water, stir evenly, and prepare a basement membrane solution with a concentration of 10%. After vacuum degassing, let it stand at 20°C for 1.5 hours;

[0100] Step 2: Preparation of sandwich film liquid: Dissolve the formulated amount of pectin, citric acid and 15% white sugar in distilled water, stir evenly, and prepare a pectin solution with a concentration of 12%. After vacuum degassing, let it stand at a temperature of 25°C for 2 hours, and pour the prepared pectin solution and the remaining white sugar and glucose syrup into a twin-screw extruder to prepare a sandwich film liquid;

[0101] Step 3: Preparation of covering film solution: Dissolve the components in the formula amount in 85% ethanol solution, stir evenly, prepare a covering film solution with a concentration of 10%, and let it stand at a temperature of 25°C for 2 hours;

[0102] Step 4: The prepared base film liquid is stored in the plastic box of the film laying machine scraper equipment, and the thickness of the wet film is adjusted by the thickness regulator on the plastic box. Combined with the traction of the conveyor belt, the film liquid in the plastic box is uniformly cast, and the base film is obtained after drying at 80°C in the drying area. The thickness of the base film is controlled at 80-90μm;

[0103] Step 5: The prepared sandwich film liquid flows into the sandwich plastic box after passing through the twin-screw extruder, and flows uniformly to the top of the base film after controlling the required thickness. After drying at 90°C in the drying area, the sandwich film is formed, and the thickness of the sandwich film is controlled at 0.9-1mm;

[0104] Step 6: Use a spraying device to evenly spray the prepared covering film liquid on the top of the sandwich film, and after drying in a drying area at 60° C., a multilayer oral film with a three-layer structure is obtained, and the thickness of the covering film is controlled at 70 to 80 μm;

[0105] Step 7: Cut the obtained three-layer film into 20×25 mm size, seal and package, and sterilize by irradiation to obtain the finished product.

[0106] Embodiment three:

[0107] A multi-layer oral film, wherein the base film liquid, the sandwich film liquid and the cover film liquid each comprise the following components based on 100 parts by weight:

[0108]

[0109] The multilayer oral film is prepared by the following method:

[0110] Step 1: Preparation of basement membrane solution: Dissolve the components in the formula amount in distilled water, stir evenly, and prepare a basement membrane solution with a concentration of 10%. After vacuum degassing, let it stand at 22°C for 1.5 hours;

[0111] Step 2: Preparation of sandwich film liquid: Dissolve the formulated amount of pectin, citric acid and 14% white sugar in distilled water, stir evenly, and prepare a pectin solution with a concentration of 4%. After vacuum degassing, let it stand at a temperature of 23°C for 2 hours, and pour the prepared pectin solution and the remaining white sugar and glucose syrup into a twin-screw extruder to prepare a sandwich film liquid;

[0112] Step 3: Preparation of covering film solution: Dissolve the components in the formula amount in 85% ethanol solution, stir evenly, prepare a covering film solution with a concentration of 10%, and let it stand at a temperature of 25°C for 1.5 hours;

[0113] Step 4: The prepared base film liquid is stored in the plastic box of the film laying machine scraper equipment, and the thickness of the wet film is adjusted by the thickness regulator on the plastic box. Combined with the traction of the conveyor belt, the film liquid in the plastic box is uniformly cast, and the base film is obtained after drying at 80°C in the drying area. The thickness of the base film is controlled at 80-90μm;

[0114] Step 5: The prepared sandwich film liquid flows into the sandwich plastic box after passing through the twin-screw extruder, and flows uniformly to the top of the base film after controlling the required thickness. After drying at 100°C in the drying area, the sandwich film is formed, and the thickness of the sandwich film is controlled at 0.9-1mm;

[0115] Step 6: Use a spraying device to evenly spray the prepared covering film liquid on the top of the sandwich film, and after drying in a drying area at 50° C., a multilayer oral film with a three-layer structure is obtained, and the thickness of the covering film is controlled at 70 to 80 μm;

[0116] Step 7: Cut the obtained three-layer film into 20×32 mm size, seal and package, and sterilize by irradiation to obtain the finished product.

[0117] Embodiment 4:

[0118] A multi-layer oral film, wherein the base film liquid, the sandwich film liquid and the cover film liquid comprise the following components based on 100 parts by weight:

[0119]

[0120] The multilayer oral film is prepared by the following method:

[0121] Step 1: Preparation of basement membrane solution: Dissolve the components in the formula amount in distilled water, stir evenly, and prepare a basement membrane solution with a concentration of 10%. After vacuum degassing, let it stand at 26°C for 2 hours;

[0122] Step 2: Preparation of sandwich film liquid: Dissolve the formulated amount of pectin, citric acid and 11% white sugar in distilled water, stir evenly, and prepare a pectin solution with a concentration of 10%. After vacuum degassing, let it stand at a temperature of 28°C for 1 hour, and pour the prepared pectin solution and the remaining white sugar and glucose syrup into a twin-screw extruder to prepare a sandwich film liquid;

[0123] Step 3: Preparation of covering film solution: Dissolve the components in the formula amount in 85% ethanol solution, stir evenly, prepare a covering film solution with a concentration of 10%, and let it stand at a temperature of 22°C for 1.5 hours;

[0124] Step 4: The prepared base film liquid is stored in the plastic box of the film laying machine scraper equipment, and the thickness of the wet film is adjusted by the thickness regulator on the plastic box. Combined with the traction of the conveyor belt, the film liquid in the plastic box is uniformly cast, and the base film is obtained after drying at 70°C in the drying area. The thickness of the base film is controlled at 80-90μm;

[0125] Step 5: The prepared sandwich film liquid flows into the sandwich plastic box after passing through the twin-screw extruder, and flows uniformly to the top of the base film after controlling the required thickness. After drying at 90°C in the drying area, the sandwich film is formed, and the thickness of the sandwich film is controlled at 0.9-1mm;

[0126] Step 6: Use a spraying device to evenly spray the prepared covering film liquid on the top of the sandwich film, and after drying in a drying area at 50° C., a multilayer oral film with a three-layer structure is obtained, and the thickness of the covering film is controlled at 70 to 80 μm;

[0127] Step 7: Cut the obtained three-layer film into a size of 20×18 mm, seal and package, and sterilize by irradiation to obtain the finished product.

[0128] The multilayer oral films of Examples 1-4 were subjected to performance testing tests respectively, including base layer adhesion testing, product disintegration time testing and product evaluation.

[0129] refer to Figure 3 and Figure 4 , the method for detecting the adhesion of the basal layer is as follows:

[0130] An adhesion measuring device was prepared using a viscometer 1, a 10 g weight 2 and a glass plate 3. The measurement process was as follows: the cover film 40 of the prepared multi-layer oral film 4 was completely adhered to the bottom of the circular surface of the 10 g weight 2 using double-sided tape, the side of the base layer 42 of the multi-layer oral film 4 facing the glass plate 3 was moistened with pure water, and after moistening for 5 seconds, this side was pressed onto the glass plate 3 for 6 seconds, and then the viscometer 1 was operated to move the 10 g weight 2 adhered to the glass plate 3 upwards to separate the base layer 42 from the glass plate 3. The maximum adhesion value generated during this period was the sum of the adhesion of the base film 3 and the weight of the weight. The test results are shown in Table 1 below.

[0131] Table 1 Base layer adhesion data of multi-layer oral film examples

[0132] Serial number <![CDATA[Basal layer adhesion force (g / cm 2 )]]> Example 1 92 Example 2 80 Example 3 68 Example 4 55

[0133] The multilayer oral film prepared by the present invention has strong adhesion, and its adhesion time can meet the high-efficiency adhesion of the entire sustained-release time in the oral cavity.

[0134] Disintegration time test: Use a fully automatic disintegrator and clamp the multi-layer oral membrane with a paper clip in 37°C pure water for sedimentation detection.

[0135] Product evaluation: The product is evaluated by a group of 5 people, and the product evaluation column is the average score of 1-5 points given by the 5 people after using the product.

[0136] Table 2 Disintegration time and product evaluation of multilayer oral film examples

[0137] Serial number Disintegration time (min) Product Reviews Example 1 92 4.2 Example 2 80 4.5 Example 3 68 4.8 Example 4 55 4.8

[0138] The multi-layer oral film of the present invention has good product evaluation of mouthfeel and taste, good sustained release effect, and the disintegration time can reach 5-7 hours.

[0139] It should be pointed out that the above preferred embodiments are only for illustrating the technical concept and features of the present invention, and their purpose is to enable people familiar with the technology to understand the content of the present invention and implement it accordingly, and they cannot be used to limit the protection scope of the present invention. Any equivalent changes or modifications made according to the spirit of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for preparing a multilayer oral film, characterized in that: The following steps are involved: Preparation of basement membrane solution: dissolve the components in the formula amount in distilled water, stir evenly, prepare a basement membrane solution with a concentration of 10%, and stand at a temperature of 20-26°C for 1.5-2h after vacuum degassing; the basement membrane solution includes the following components based on 100 parts by weight: 69.5-80 parts of hydrophilic film-forming material, 19.5-30 parts of plasticizer, 0.5 parts of surfactant, 0-15 parts of active ingredient, 0-10 parts of flavoring agent and 0-20 parts of other auxiliary materials; the hydrophilic film-forming material is one or more of maltodextrin, pullulan, and sodium carboxymethyl cellulose; the plasticizer is glycerol; the surfactant is polysorbate 80; Preparation of sandwich membrane liquid: dissolve the formulated amount of gelling agent, acidity regulator and 10% to 15% of powdered sugar in distilled water, stir evenly, prepare a gel solution with a concentration of 4% to 12%, and after vacuum degassing, stand at a temperature of 23 to 28°C for 1 to 2 hours, pour the prepared gel solution and the remaining other components into a twin-screw extruder to prepare a sandwich membrane liquid; based on 100 parts by weight, the sandwich membrane liquid includes the following components: 5 to 10 parts of gelling agent, 1 to 2 parts of acidity regulator, 28 to 54 parts of sugar solution, 40 to 60 parts of powdered sugar, 0 to 20 parts of active ingredients, 0 to 10 parts of flavoring agent and 0 to 20 parts of other auxiliary materials; the gelling agent is pectin; the acidity regulator is citric acid; the sugar solution is glucose syrup; the powdered sugar is white granulated sugar; Preparation of the covering film liquid: dissolve the components of the formula amount in 85% ethanol solution, stir evenly, prepare a covering film liquid with a concentration of 10%, and let it stand at a temperature of 22-25°C for 1.5-2h; based on 100 parts by weight, the covering film liquid includes the following components: 23.95-38.21 parts of hydrophobic film-forming material, 31.87-47.92 parts of thickener, 17.95-19.1 parts of plasticizer, 1.2-10 parts of flavoring agent and 0-20 parts of other auxiliary materials; the hydrophobic film-forming material is one or more of shellac, ethyl cellulose and corn protein; the thickener is one or more of high-substituted hydroxypropyl cellulose, low-substituted hydroxypropyl cellulose and hydroxypropyl methylcellulose; the plasticizer is glycerol; the flavoring agent is one or more of sweetener and acidulant; the sweetener is sucralose, and the acidulant is citric acid; The prepared base film liquid is stored in the glue box of the casting equipment, and the wet film thickness is adjusted by the thickness regulator on the glue box. Combined with the traction of the conveyor belt, the film liquid in the glue box is cast at a uniform speed. After drying at 70℃~80℃ in the first drying area, the base film is obtained, and the thickness of the base film is controlled at 80~90μm; The prepared sandwich film liquid flows into the sandwich plastic box after passing through the twin-screw extruder, and flows uniformly to the top of the base film after the required thickness is controlled. After drying at 90℃~100℃ in the second drying area, the sandwich film is formed, and the thickness of the sandwich film is controlled at 0.9-1mm; The prepared covering film liquid is sprayed evenly on the top of the sandwich film by using a spraying device, and after drying in the third drying area at 50°C to 60°C, a multilayer oral film with a three-layer structure is obtained, and the thickness of the covering film is controlled at 70 to 80 μm; The obtained three-layer film is cut into a certain size, sealed and packaged, and irradiated and sterilized to obtain a finished product.

2. The method for preparing a multilayer oral film according to claim 1, characterized in that: The step of cutting the obtained three-layer film into a certain size, sealing and packaging, and irradiating and sterilizing to obtain a finished product specifically includes: The obtained three-layer film is cut into a size of 20×(18-32) mm, sealed and packaged, and irradiated and sterilized to obtain a finished product.

3. The multilayer oral film prepared by the method for preparing a multilayer oral film according to any one of claims 1 to 2, characterized in that: It comprises a base layer (42) for oral adhesion, a sandwich layer (41) connected to the base layer (42), and a covering layer (40) connected to the sandwich layer (41).

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