Oral film and preparation method therefor

Abstract

Disclosed are an oral film and a preparation method therefor. The oral film comprises: an adhesive layer, a sustained-release layer, and a waterproof layer, wherein the adhesive layer comprises 0 wt% to 10 wt% of an antibacterial agent, 50 wt% to 80 wt% of an adhesive material, and 10 wt% to 30 wt% of a sustained-release material; and the sustained-release layer comprises 65 wt% to 85 wt% of an antibacterial agent, 0 wt% to 10 wt% of an adhesive material, and 10 wt% to 25 wt% of a sustained-release material.

Description

Oral film and preparation method thereof

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to Chinese patent application No. 2023114316583 filed in China on October 31, 2023, the entire contents of which are incorporated herein by reference. Technical Field

[0003] The present disclosure relates to the technical field of pharmaceutical preparations, and in particular to an oral film and a preparation method thereof. Background Art

[0004] Oral infections can lead to a series of acute and chronic diseases with high incidence, such as bad breath, swollen and painful gums, abscesses, gingivitis, periodontal disease and dental tartar. Compared with systemic medication, local medication is more suitable for the treatment of oral infections. It can not only increase the local drug concentration and reduce the dosage, but also avoid the various adverse reactions that may be caused by systemic medication, such as liver and kidney damage, allergic reactions, and dysbacteriosis. However, due to the special environment of the oral cavity, factors such as the movement of the lips, cheeks and tongue and saliva secretion, local medication in the oral cavity has the disadvantages of short residence time, rapid loss and difficulty in maintaining effective therapeutic concentrations in the affected area for a long time. The preparations used for local oral administration in the prior art are limited by the special environment in the oral cavity, making it difficult to achieve long-term and effective administration in a fixed position in the oral cavity, and the therapeutic effect is unsatisfactory.

[0005] Therefore, there is an urgent need to develop a patch for oral topical administration that takes into account both comfort and stable long-lasting sustained-release effects.

[0006] Summary of the Invention

[0007] The present disclosure solves at least one of the problems of the related art from the following aspects.

[0008] To this end, a first aspect of the present disclosure provides an oral film, comprising: an adhesive layer, a sustained-release layer, and a waterproof layer, wherein the adhesive layer comprises 0 wt % to 10 wt % of an antibacterial agent, 50 wt % to 80 wt % of an adhesive material, and 10 wt % to 30 wt % of a sustained-release material; and the sustained-release layer comprises 65 wt % to 85 wt % of an antibacterial agent, 0 wt % to 10 wt % of an adhesive material, and 10 wt % to 25 wt % of a sustained-release material.

[0009] In some embodiments, the waterproof layer comprises a waterproof material.

[0010] In some embodiments, the waterproof layer further comprises a plasticizer.

[0011] In some embodiments, the waterproof layer comprises 75 wt % to 95 wt % of waterproof material and 5 wt % to 25 wt % of plasticizer.

[0012] In some embodiments, the adhesive layer further comprises 5 to 25 wt % of a plasticizer.

[0013] In some embodiments, the adhesive layer further comprises 0 to 5 wt % flavoring agent.

[0014] In some embodiments, the sustained-release layer further comprises 0 to 10 wt % of a plasticizer.

[0015] In some embodiments, the sustained-release layer further comprises 0 to 3 wt % of a flavoring agent.

[0016] In some embodiments, in the oral film, the weight percentage of the adhesive layer is 25 wt % to 50 wt %, the weight percentage of the sustained-release layer is 35 wt % to 65 wt %, and the weight percentage of the waterproof layer is 5 wt % to 20 wt %.

[0017] In some embodiments, it is characterized in that the weight ratio of the antibacterial agent in the adhesive layer and the sustained-release layer is 1:(20 to 30).

[0018] In some embodiments, in the adhesive layer, the adhesive material is carbomer and hypromellose, and the weight ratio of the hypromellose to the carbomer is (0.5 to 2):1.

[0019] In some embodiments, in the adhesive layer, the weight ratio of the antibacterial agent to the sustained-release material is 1:(2.5 to 5).

[0020] In some embodiments, in the sustained-release layer, the weight ratio of the antibacterial agent to the sustained-release material is (3 to 6):1.

[0021] In some embodiments, the weight ratio of the antibacterial agent in the adhesive layer to the sustained-release layer is 1:24.

[0022] In some embodiments, in the adhesive layer, the adhesive material is carbomer and hypromellose, and the weight ratio of the hypromellose to the carbomer is 1:1.

[0023] In some embodiments, in the adhesive layer, the weight ratio of the antibacterial agent to the sustained-release material is 1:3.8.

[0024] In some embodiments, in the sustained-release layer, the weight ratio of the antibacterial agent to the sustained-release material is (4 to 5):1.

[0025] In some embodiments, in the sustained-release layer, the weight ratio of the antibacterial agent to the sustained-release material is 4.44:1.

[0026] In some embodiments, the antibacterial agent is ornidazole.

[0027] In some embodiments, the binding material is selected from one or more of carbomer, hydroxypropyl methylcellulose, polycarbophil, hydroxypropyl cellulose, xanthan gum, and polyvinyl pyrrolidone.

[0028] In some embodiments, the sustained-release material is selected from ethyl cellulose and / or acrylic resin.

[0029] In some embodiments, the waterproof material is selected from one or more of ethyl cellulose, polyacrylic acid resin, and ethyl acrylate-methyl methacrylate copolymer aqueous dispersion.

[0030] In some embodiments, the plasticizer is selected from one or more of polyethylene glycol, glycerol, propylene glycol, dibutyl phthalate, dioctyl phthalate, tricresyl phosphate, triethyl citrate, triphenyl phosphate, and dioctyl sebacate.

[0031] In some embodiments, the flavoring agent is selected from one or more of aspartame, food flavoring, vanillin, menthol, steviol glycosides, acesulfame potassium, saccharin sodium and sucralose.

[0032] The second embodiment of the present disclosure provides a method for preparing the oral film according to any embodiment of the first aspect, comprising the following steps S1 to S4:

[0033] S1: mixing the adhesive material and the sustained-release material for preparing the adhesive layer, adding ethanol to soak, then adding the antibacterial agent and plasticizer for preparing the adhesive layer, and degassing to obtain solution 1;

[0034] S2: mixing the adhesive material and the sustained-release material for preparing the sustained-release layer, adding ethanol to soak, then adding the antibacterial agent and plasticizer for preparing the sustained-release layer, and degassing to obtain solution 2;

[0035] S3: mixing the sustained-release material and the plasticizer for preparing the sustained-release layer of the waterproof layer, adding ethanol for soaking, and degassing to obtain solution 3; and

[0036] S4: using the solution 1, solution 2 and solution 3 to apply a film in sequence to prepare an oral film comprising the adhesive layer, the sustained-release layer and the waterproof layer.

[0037] In some embodiments, in step S1 and / or step S2, the flavoring agent is added at the same time as the antimicrobial agent and the plasticizer.

[0038] In some embodiments, the concentration of ethanol is 70 wt % to 100 wt %.

[0039] In some embodiments, the soaking time is 8 to 24 hours.

[0040] The embodiments of the present disclosure achieve the following beneficial effects:

[0041] The oral film proposed in the disclosed embodiments, through its unique three-layer structure and the specific composition ratios of the ingredients in each layer, ensures rapid onset of action and stable, long-lasting sustained-release effects upon administration. It also offers advantages such as close adherence to the affected area, long-lasting adhesion, and excellent mechanical properties. The preparation method proposed in the disclosed embodiments utilizes a layer-by-layer coating process, combined with specific process parameters, to produce an oral film with an appropriate thickness and a pleasant taste. DETAILED DESCRIPTION

[0042] The present disclosure is further described in detail below in conjunction with specific embodiments. The examples provided are only for the purpose of illustrating the present disclosure and are not intended to limit the scope of the present disclosure. The examples provided below can serve as a guide for further improvements by those of ordinary skill in the art and do not in any way limit the present disclosure.

[0043] The present disclosure is made based on the following knowledge of the inventors:

[0044] Due to the special environment of the oral cavity, there are factors such as lip, cheek and tongue movement and saliva secretion, and local medication in the oral cavity has the disadvantages of short residence time, fast loss and difficulty in maintaining effective therapeutic concentration in the affected area for a long time. The preparations used for oral topical administration in the prior art are limited by the special environment in the oral cavity, making it difficult to achieve long-term and effective administration in a fixed position in the oral cavity, and the therapeutic effect is not ideal. Traditional oral administration dosage forms (such as solutions and chewable tablets) and non-adhesive oral administration dosage forms (such as orally disintegrating tablets and buccal tablets) disappear rapidly in the oral cavity with the swallowing action and saliva secretion, and the residence time is too short, resulting in most drugs not playing a role in the oral cavity. Adhesive oral dosage forms, such as oral patches, use hypromellose as the main excipient, are water-soluble, easily dissolved by saliva, and can only adhere to the oral cavity for a short time; and oral patches, although they can firmly adhere to the affected area of ​​oral ulcers, have defects such as poor mechanical properties, obvious foreign body sensation after water absorption and swelling, and bidirectional adhesion.

[0045] After extensive research, the inventors designed a three-layer composite structure and component ratio for an oral film, achieving rapid and long-lasting therapeutic effects after oral administration. The oral film proposed in the disclosed embodiments offers advantages such as close contact with the affected area, long-lasting adhesion, and excellent mechanical properties.

[0046] An embodiment of the first aspect of the present disclosure provides an oral film, comprising an adhesive layer, a sustained-release layer, and a waterproof layer, wherein the adhesive layer comprises 0 wt% to 10 wt% (e.g., 1 wt%, 2 wt%, 3 wt%, 4 wt%, 5 wt%, 6 wt%, 7 wt%, 8 wt%, 9 wt%) of an antibacterial agent, 50 wt% to 80 wt% (e.g., 55 wt%, 60 wt%, 65 wt%, 70 wt%, 75 wt%) of an adhesive material, and 10 wt% to 30 wt% (e.g., 15 wt%, 20 wt%) of a water-repellent agent. the sustained-release layer comprises 65 wt % to 85 wt % (e.g., 70 wt %, 75 wt %, 80 wt %) of an antibacterial agent, 0 wt % to 10 wt % (e.g., 1 wt %, 2 wt %, 3 wt %, 4 wt %, 5 wt %, 6 wt %, 7 wt %, 8 wt %, 9 wt %) of a bonding material and 10 wt % to 25 wt % (e.g., 12.5 wt %, 15 wt %, 17.5 wt %, 20 wt %, 22.5 wt %) of a sustained-release material.

[0047] The oral film provided by the embodiments of the present disclosure can adhere to the oral cavity, including but not limited to the palate, cheeks, and gums, and remain adhered for more than 6 hours (e.g., 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours), unaffected by factors such as lip, cheek, and tongue movement and saliva secretion. The total content of the antibacterial agent in the oral film is 5 to 20 mg / tablet (e.g., 7.5 mg / tablet, 10 mg / tablet, 12.5 mg / tablet, 15 mg / tablet, 17.5 mg / tablet).

[0048] The oral film provided in the disclosed embodiments has an antimicrobial agent content of up to 65% to 85% by weight of the sustained-release layer, enabling the film to effectively and long-term release of the antimicrobial agent to the affected area. By employing a dual-layer drug-loading structure and composition of an adhesive layer and a sustained-release layer, the disclosed embodiments achieve both immediate and long-term sustained release of the antimicrobial agent within the oral cavity.

[0049] In some embodiments, the waterproof layer comprises a waterproof material.

[0050] In some embodiments, the waterproof layer further comprises a plasticizer.

[0051] In some embodiments, the waterproof layer includes 75wt% to 95wt% (e.g., 80wt%, 85wt%, 90wt%) of waterproof material and 5wt% to 25wt% (e.g., 10wt%, 15wt%, 20wt%) of plasticizer.

[0052] In some embodiments, the adhesive layer further comprises 5 to 25 wt % (eg, 10 wt %, 15 wt %, 20 wt %) of a plasticizer.

[0053] In some embodiments, the adhesive layer further comprises 0 to 5 wt % (eg, 1 wt %, 2 wt %, 3 wt %, 4 wt %) of a flavoring agent.

[0054] In some embodiments, the sustained-release layer further comprises 0 to 10 wt% (e.g., 1 wt%, 2 wt%, 3 wt%, 4 wt%, 5 wt%, 6 wt%, 7 wt%, 8 wt%, 9 wt%) of a plasticizer.

[0055] In some embodiments, the sustained-release layer further comprises 0 to 3 wt% (eg, 0.5 wt%, 1 wt%, 1.5 wt%, 2 wt%, 2.5 wt%) of a flavoring agent.

[0056] In some embodiments, in the oral film, the weight percentage of the adhesive layer is 25 wt % to 50 wt % (e.g., 30 wt %, 35 wt %, 40 wt %, 45 wt %), the weight percentage of the sustained-release layer is 35 wt % to 65 wt % (e.g., 40 wt %, 45 wt %, 50 wt %, 55 wt %, 60 wt %), and the weight percentage of the waterproof layer is 5 wt % to 20 wt % (e.g., 7.5 wt %, 10 wt %, 12.5 wt %, 15 wt %, 17.5 wt %).

[0057] In some embodiments, the weight ratio of the antimicrobial agent in the adhesive layer to the sustained-release layer is 1:(20 to 30) (e.g., 1:21, 1:22, 1:23, 1:24, 1:25, 1:26, 1:27, 1:28, 1:29).

[0058] In some embodiments, the weight ratio of the antimicrobial agent in the adhesive layer to the sustained-release layer is 1:24.

[0059] In some embodiments, in the adhesive layer, the adhesive material is carbomer and hypromellose, and the weight ratio of hypromellose to carbomer is (0.5 to 2):1 (e.g., 0.75:1, 1:1, 1.25:1, 1.5:1, 1.75:1).

[0060] In some embodiments, in the adhesive layer, the adhesive material is carbomer and hypromellose, and the weight ratio of hypromellose to carbomer is 1:1.

[0061] In some embodiments, in the adhesive layer, the weight ratio of the antimicrobial agent to the sustained-release material is 1:(2.5 to 5) (eg, 1:3, 1:3.5, 1:4, 1:4.5).

[0062] In some embodiments, the weight ratio of the antimicrobial agent to the sustained-release material in the adhesive layer is 1:3.8.

[0063] In some embodiments, in the sustained-release layer, the weight ratio of the antibacterial agent to the sustained-release material is (3 to 6):1 (eg, 3.5:1, 4:1, 4.5:1, 5:1, 5.5:1).

[0064] In some embodiments, in the sustained-release layer, the weight ratio of the antibacterial agent to the sustained-release material is (4 to 5):1 (e.g., 4.1:1, 4.2:1, 4.3:1, 4.4:1, 4.5:1, 4.6:1, 4.7:1, 4.8:1, 4.9:1).

[0065] In some embodiments, in the sustained-release layer, the weight ratio of the antibacterial agent to the sustained-release material is 4.44:1.

[0066] In some embodiments, the antibacterial agent is ornidazole.

[0067] In some embodiments, the binding material is selected from one or more of carbomer, hypromellose, polycarbophil, hydroxypropyl cellulose, xanthan gum, and polyvinyl pyrrolidone.

[0068] In some embodiments, the sustained-release material is selected from ethylcellulose and / or acrylic resin.

[0069] In some embodiments, the waterproof material is selected from one or more of ethyl cellulose, polyacrylic acid resin, and ethyl acrylate-methyl methacrylate copolymer aqueous dispersion.

[0070] In some embodiments, the plasticizer is selected from one or more of polyethylene glycol, glycerol, propylene glycol, dibutyl phthalate, dioctyl phthalate, tricresyl phosphate, triethyl citrate, triphenyl phosphate, and dioctyl sebacate.

[0071] In some embodiments, the flavoring agent is selected from one or more of aspartame, food flavoring, vanillin, menthol, steviol glycosides, acesulfame potassium, saccharin sodium and sucralose.

[0072] The second aspect of the present disclosure provides a method for preparing the oral film according to any one of the first aspects, comprising the following steps S1 to S4:

[0073] S1: mixing an adhesive material and a sustained-release material for preparing an adhesive layer, adding ethanol to soak, then adding an antibacterial agent and a plasticizer for preparing an adhesive layer, and degassing to obtain a solution 1;

[0074] S2: mixing the adhesive material and the sustained-release material for preparing the sustained-release layer, adding ethanol to soak, then adding the antibacterial agent and plasticizer for preparing the sustained-release layer, and degassing to obtain solution 2;

[0075] S3: mixing the sustained-release material and the plasticizer for preparing the sustained-release layer of the waterproof layer, adding ethanol for soaking, and degassing to obtain solution 3; and

[0076] S4: using solution 1, solution 2 and solution 3 to apply a film in sequence to prepare an oral film comprising an adhesive layer, a sustained-release layer and a waterproof layer.

[0077] In some embodiments, in step S1 and / or step S2, a flavoring agent is added at the same time as the antimicrobial agent and the plasticizer.

[0078] In some embodiments, the concentration of ethanol is 70 wt% to 100 wt% (eg, 75 wt%, 80 wt%, 85 wt%, 90 wt%, 95 wt%).

[0079] In some embodiments, the soaking time is 8 to 24 hours (eg, 10 hours, 14 hours, 18 hours, 22 hours).

[0080] In some embodiments, the soaking time is 10 to 14 hours (eg, 11 hours, 12 hours, 13 hours).

[0081] Unless otherwise defined, all technical and scientific terms used in this disclosure have the same meaning as understood by any person skilled in the art to which this disclosure belongs. The terms used to describe the present disclosure are intended only to describe specific implementations and are not intended to limit the scope of the teachings. Unless otherwise stated, all numbers expressing quantities, percentages and parts by weight, as well as other numerical values ​​used in the specification and claims, are to be understood as being modified by the term "about" in all cases. Therefore, unless otherwise stated, the numerical parameters shown in the specification and claims are approximate and may vary depending on the properties to be obtained.

[0082] The technical terms appearing in this disclosure are used according to their common sense or meaning to those skilled in the art. If specific meanings are expressed for certain terms, the definitions of the terms will be given below in the context of using these terms.

[0083] The following examples are used to further illustrate the advantages and characteristics of the present method, but are not intended to limit the present disclosure. The experimental methods in the following examples, unless otherwise specified, are conventional methods and are performed according to the techniques or conditions described in the literature in the field or according to the product instructions.

[0084] Unless otherwise specified, the materials and reagents used in the following examples can be obtained from commercial sources. Unless otherwise specified, the quantitative analysis experiments in the following examples were performed in triplicate and the results were averaged.

[0085] Example 1

[0086] Ornidazole oral films (625 tablets) were prepared according to the ratios in Table 1 below. The size was 1 cm×1 cm. The content of ornidazole in the oral films was 10 mg / tablet.

[0087] Table 1

[0088] In Table 1 above, the adhesive layer, the sustained-release layer and the waterproof layer account for 35.75 wt%, 50.05 wt% and 14.2 wt% of the total weight of the oral film, respectively.

[0089] The preparation step includes the following steps S1 to S4.

[0090] S1: The adhesive material and the sustained-release material for preparing the adhesive layer are mixed, and 90 wt % ethanol is added to soak for 12 h. Then, the antibacterial agent, plasticizer and flavoring agent for preparing the adhesive layer are added, and the solution 1 is prepared by degassing.

[0091] S2: The adhesive material and the sustained-release material for preparing the sustained-release layer were mixed, and 90 wt % ethanol was added to soak for 12 h. Then, the antibacterial agent, plasticizer and flavoring agent for preparing the sustained-release layer were added, and the solution 2 was prepared by degassing.

[0092] S3: The sustained-release material and plasticizer for preparing the sustained-release layer of the waterproof layer were mixed, added with 90 wt % ethanol, and immersed for 12 h, and degassed to obtain Solution 3.

[0093] S4: Apply solution 1, solution 2 and solution 3 in sequence to prepare an oral film 1.

[0094] Example 2

[0095] Ornidazole oral films (625 tablets) were prepared according to the ratios in Table 2 below. The size was 1 cm×1 cm. The content of ornidazole in the oral film was 6.4 mg / tablet.

[0096] Table 2

[0097] In Table 2 above, the adhesive layer, sustained-release layer and waterproof layer account for 36.3 wt%, 44.7 wt% and 19 wt% of the total weight of the oral film, respectively.

[0098] The preparation step includes the following steps S1 to S4.

[0099] S1: The adhesive material and the sustained-release material for preparing the adhesive layer are mixed, and 90 wt % ethanol is added to soak for 12 h. Then, the antibacterial agent, plasticizer and flavoring agent for preparing the adhesive layer are added, and the solution 1 is prepared by degassing.

[0100] S2: The adhesive material and the sustained-release material for preparing the sustained-release layer were mixed, and 90 wt % ethanol was added to soak for 12 h. Then, the antibacterial agent, plasticizer and flavoring agent for preparing the sustained-release layer were added, and the solution 2 was prepared by degassing.

[0101] S3: The sustained-release material and plasticizer for preparing the sustained-release layer of the waterproof layer were mixed, added with 90 wt % ethanol, and immersed for 12 h, and degassed to obtain Solution 3.

[0102] S4: using solution 1, solution 2 and solution 3 to apply a film in sequence to prepare an oral film 2.

[0103] Example 3

[0104] Ornidazole oral films (625 tablets) were prepared according to the ratios in Table 3 below. The size was 1 cm×1 cm. The content of ornidazole in the oral films was 16 mg / tablet.

[0105] Table 3

[0106] In Table 3 above, the adhesive layer, sustained-release layer and waterproof layer account for 33.33 wt%, 50 wt% and 16.67 wt% of the total weight of the oral film, respectively.

[0107] The preparation step includes the following steps S1 to S4.

[0108] S1: The adhesive material and the sustained-release material for preparing the adhesive layer are mixed, and 90 wt % ethanol is added to soak for 12 h. Then, the antibacterial agent, plasticizer and flavoring agent for preparing the adhesive layer are added, and the solution 1 is prepared by degassing.

[0109] S2: The adhesive material and the sustained-release material for preparing the sustained-release layer were mixed, and 90 wt % ethanol was added to soak for 12 h. Then, the antibacterial agent, plasticizer and flavoring agent for preparing the sustained-release layer were added, and the solution 2 was prepared by degassing.

[0110] S3: The sustained-release material and plasticizer for preparing the sustained-release layer of the waterproof layer were mixed, added with 90 wt % ethanol, and immersed for 12 h, and degassed to obtain Solution 3.

[0111] S4: using solution 1, solution 2 and solution 3 to apply a film in sequence to prepare an oral film 3.

[0112] Example 4

[0113] Ornidazole oral films (625 tablets) were prepared according to the ratios in Table 4 below. The size was 1 cm×1 cm. The content of ornidazole in the oral films was 14.784 mg / tablet.

[0114] Table 4

[0115] In Table 4 above, the adhesive layer, the sustained-release layer and the waterproof layer account for 25 wt%, 65 wt% and 10 wt% of the total weight of the oral film, respectively.

[0116] The preparation step includes the following steps S1 to S4.

[0117] S1: The adhesive material and the sustained-release material for preparing the adhesive layer are mixed, and 90 wt % ethanol is added to soak for 12 h. Then, the antibacterial agent, plasticizer and flavoring agent for preparing the adhesive layer are added, and the solution 1 is prepared by degassing.

[0118] S2: The adhesive material and the sustained-release material for preparing the sustained-release layer were mixed, and 90 wt % ethanol was added to soak for 12 h. Then, the antibacterial agent, plasticizer and flavoring agent for preparing the sustained-release layer were added, and the solution 2 was prepared by degassing.

[0119] S3: The sustained-release material and plasticizer for preparing the sustained-release layer of the waterproof layer were mixed, added with 90 wt % ethanol, and immersed for 12 h, and degassed to obtain Solution 3.

[0120] S4: using solution 1, solution 2 and solution 3 to apply a film in sequence to prepare an oral film 4.

[0121] Example 5

[0122] Ornidazole oral films (625 tablets) were prepared according to the ratios in Table 5 below. The size was 1 cm×1 cm. The content of ornidazole in the oral film was 6.84 mg / tablet.

[0123] Table 5

[0124] In Table 5 above, the adhesive layer, sustained-release layer and waterproof layer account for 50 wt%, 35 wt% and 15 wt% of the total weight of the oral film, respectively.

[0125] The preparation step includes the following steps S1 to S4.

[0126] S1: The adhesive material and the sustained-release material for preparing the adhesive layer are mixed, and 90 wt % ethanol is added to soak for 12 h. Then, the antibacterial agent, plasticizer and flavoring agent for preparing the adhesive layer are added, and the solution 1 is prepared by degassing.

[0127] S2: The adhesive material and the sustained-release material for preparing the sustained-release layer were mixed, and 90 wt % ethanol was added to soak for 12 h. Then, the antibacterial agent, plasticizer and flavoring agent for preparing the sustained-release layer were added, and the solution 2 was prepared by degassing.

[0128] S3: The sustained-release material and plasticizer for preparing the sustained-release layer of the waterproof layer were mixed, added with 90 wt % ethanol, and immersed for 12 h, and degassed to obtain Solution 3.

[0129] S4: Apply solution 1, solution 2 and solution 3 in sequence to prepare oral film 5.

[0130] Example 6

[0131] The method is basically the same as Example 1, except that the content of ornidazole in the adhesive layer is 0 wt % and the content of ethyl cellulose is 21.66 wt %. The specific amounts are shown in Table 6 below.

[0132] An oral film 6 was prepared, in which the content of ornidazole was 9.6 mg / tablet.

[0133] Table 6

[0134] Example 7

[0135] The method is basically the same as Example 1, except that the amount of hydroxypropyl methylcellulose in the adhesive layer is 68.6 wt %, and the amount of carbomer is 0 wt %, wherein the specific amounts are shown in Table 7 below.

[0136] An oral film 7 was prepared, in which the content of ornidazole in the oral film was 6.84 mg / tablet.

[0137] Table 7

[0138] Example 8

[0139] Ornidazole oral films (625 tablets) were prepared according to the ratios in Table 8 below. The size was 1 cm×1 cm. The content of ornidazole in the oral films was 14.784 mg / tablet.

[0140] Table 8

[0141] In Table 8 above, the adhesive layer, the sustained-release layer and the waterproof layer account for 25 wt%, 65 wt% and 10 wt% of the total weight of the oral film, respectively.

[0142] The preparation step includes the following steps S1 to S4.

[0143] S1: The adhesive material and the sustained-release material for preparing the adhesive layer are mixed, and 90 wt % ethanol is added to soak for 12 h. Then, the antibacterial agent, plasticizer and flavoring agent for preparing the adhesive layer are added, and the solution 1 is prepared by degassing.

[0144] S2: The adhesive material and the sustained-release material for preparing the sustained-release layer were mixed, and 90 wt % ethanol was added to soak for 12 h. Then, the antibacterial agent, plasticizer and flavoring agent for preparing the sustained-release layer were added, and the solution 2 was prepared by degassing.

[0145] S3: The sustained-release material and plasticizer for preparing the sustained-release layer of the waterproof layer were mixed, added with 90 wt % ethanol, and immersed for 12 h, and degassed to obtain Solution 3.

[0146] S4: Apply solution 1, solution 2 and solution 3 in sequence to prepare an oral film 8.

[0147] Example 9

[0148] The method is basically the same as Example 1, except that the carbomer in the adhesive layer is replaced with hydroxypropyl cellulose, and the specific amount is shown in Table 9 below.

[0149] An oral film 9 was prepared, in which the content of ornidazole was 10 mg / tablet.

[0150] Table 9

[0151] Comparative Example 1

[0152] Ornidazole oral films (625 tablets) were prepared according to the ratios in Table 10 below, with a size of 1 cm×1 cm. The content of ornidazole in the comparative oral film 1 was 15.504 mg / tablet.

[0153] Table 10

[0154] In Table 10 above, the adhesive layer, sustained-release layer and waterproof layer account for 20 wt%, 65 wt% and 15 wt% of the total weight of the oral film, respectively.

[0155] The preparation step includes the following steps S1 to S4.

[0156] S1: The adhesive material and the sustained-release material for preparing the adhesive layer are mixed, and 90 wt % ethanol is added to soak for 12 h. Then, the antibacterial agent, plasticizer and flavoring agent for preparing the adhesive layer are added, and the solution 1 is prepared by degassing.

[0157] S2: The adhesive material and the sustained-release material for preparing the sustained-release layer were mixed, and 90 wt % ethanol was added to soak for 12 h. Then, the antibacterial agent, plasticizer and flavoring agent for preparing the sustained-release layer were added, and the solution 2 was prepared by degassing.

[0158] S3: The sustained-release material and plasticizer for preparing the sustained-release layer of the waterproof layer were mixed, added with 90 wt % ethanol, and immersed for 12 h, and degassed to obtain Solution 3.

[0159] S4: Solution 1, solution 2 and solution 3 were used to apply films in sequence to prepare a comparative oral film 1.

[0160] The types and proportions of the components in the adhesive layer, sustained-release layer, and waterproof layer of the comparative oral film 1 prepared in this comparative example are substantially the same as those of the oral film 4 prepared in Example 4. The main difference between the two is that in Example 4, the adhesive layer, sustained-release layer, and waterproof layer account for 25 wt%, 65 wt%, and 10 wt% of the total weight of the oral film 4, respectively, while in this comparative example, the adhesive layer, sustained-release layer, and waterproof layer account for 20 wt%, 65 wt%, and 15 wt% of the total weight of the comparative oral film 1, respectively.

[0161] As shown in Table 14 of Test Example 1 below, since the adhesive layer accounts for only 20 wt %, the mechanical and adhesive properties of the comparative oral film 1 prepared in this comparative example are significantly reduced compared to those in Example 4. In addition, in the in vitro release experiment, the oral film exhibited an overall faster release rate than that in Example 1, and the sustained-release effect was reduced.

[0162] Comparative Example 2

[0163] A comparative oral film 2 having only a two-layer structure of a sustained-release layer and a waterproof layer was prepared using the same raw materials as those in Example 6. The specific dosages are shown in Table 11 below. The content of ornidazole in the comparative oral film 2 was 9.6 mg / tablet.

[0164] Table 11

[0165] The comparative oral film 2 prepared in this comparative example does not include an adhesive layer, and the formulations of the sustained-release layer and the waterproof layer are the same as those in Example 6.

[0166] Table 14 in Test Example 1 below shows that due to the lack of an adhesive layer, the mechanical properties and adhesion of the comparative oral film 2 prepared in this comparative example were significantly lower than those of Example 6. Furthermore, in an in vitro sustained-release experiment, the cumulative release rate increased sharply from 24% to 52% between 60 and 120 minutes, indicating that the concentrated release of the active ingredient during the early release phase prevented long-term sustained release in the oral cavity. In comparison, the cumulative release rate of the oral film prepared in Example 6 was 18% over 120 minutes, indicating a steady and increasing trend in overall sustained-release performance.

[0167] Comparative Example 3

[0168] It is basically the same as Example 1, except that the amount of ethyl cellulose in the adhesive layer is 9 wt % and the amount of triethyl citrate is 17.17 wt %. The specific amounts are shown in Table 12 below.

[0169] A comparative oral film 3 was prepared, in which the content of ornidazole in the oral film was 10 mg / tablet.

[0170] Table 12

[0171] In this comparative example, compared with Example 1, only the amounts of ethyl cellulose and triethyl citrate in the adhesive layer were changed.

[0172] As shown in Table 14 of Test Example 1 below, the comparative oral film 3 prepared in this comparative example had significantly decreased folding resistance and adhesion time compared to Example 1. Furthermore, the in vitro release rate was unstable, with the cumulative release rate increasing sharply from 14% to 32% within 30 to 60 minutes. This showed rapid release in the early stages of release and weak release in the later stages, failing to achieve a long-term, stable sustained-release effect.

[0173] Test Example 1

[0174] According to the method in Table 13 below, the mechanical properties, adhesion, in vitro release and water resistance of the oral films 1 to 9 and comparative examples 1 to 3 prepared in Examples 1 to 9 and Comparative Examples 1 to 3 were tested. The test results are shown in Table 14 below.

[0175] Table 13

[0176] Table 14

[0177] According to the in vitro release test results in Table 14 above, it can be seen that the oral films prepared in Examples 1 to 6 have the best sustained-release stability, especially showing a stable sustained-release effect within the range of 60 to 360 minutes. Specifically, at 120 minutes, the cumulative release of the oral films prepared in Examples 1 to 6 was stable at 15% to 20%, and at 240 minutes, it was stable at 36% to 43%, and further stable at 73% to 79% at 360 minutes, achieving a long-term and stable sustained-release effect of the oral films.

[0178] The in vitro release test results of the oral films prepared in Examples 7 to 9 showed that the release rates within the range of 60 to 360 minutes were higher than those of the oral films prepared in Examples 1 to 6, but overall showed a release trend similar to that of the oral films prepared in Examples 1 to 6.

[0179] In vitro release test results for the oral films prepared in Comparative Examples 1 to 3 showed not only a significantly higher overall release rate than that of the oral films prepared in Examples 1 to 9, but also significant variations in release rates at different time stages, resulting in not only a faster overall release rate but also an unstable trend. For example, the cumulative release of Comparative Example 2 increased sharply from 24% to 52% between 60 and 120 minutes. This suggests that the oral films prepared in Comparative Examples 1 to 3 were unable to achieve a long-term sustained release in the oral cavity due to the concentrated release of the active ingredients during the early release phase. In particular, the cumulative release rates of Comparative Examples 2 and 3 at 120 minutes were 52% and 41%, respectively, while the oral films of Examples 1 to 6 of the present disclosure all maintained a stable cumulative release rate of 15% to 20% at 120 minutes.

[0180] In the description of this specification, the description with reference to the terms "one embodiment", "some embodiments", "example", "specific example", or "some examples" means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present disclosure. In this specification, the schematic representations of the above terms do not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described may be combined in any one or more embodiments or examples in a suitable manner. In addition, those skilled in the art may combine and combine different embodiments or examples described in this specification and features of different embodiments or examples, unless they are mutually inconsistent.

[0181] Although the embodiments of the present disclosure have been shown and described above, it is understood that the above embodiments are illustrative and are not to be construed as limitations on the present disclosure. A person skilled in the art may change, modify, replace and vary the above embodiments within the scope of the present disclosure.

Claims

1. An oral film, comprising: an adhesive layer, a sustained-release layer and a waterproof layer, wherein the adhesive layer comprises 0wt% to 10wt% of an antibacterial agent, 50wt% to 80wt% of an adhesive material and 10wt% to 30wt% of a sustained-release material; and the sustained-release layer comprises 65wt% to 85wt% of an antibacterial agent, 0wt% to 10wt% of an adhesive material and 10wt% to 25wt% of a sustained-release material.

2. The oral film of claim 1, wherein the waterproof layer comprises a waterproof material.

3. The oral film of claim 2, wherein the waterproof layer further comprises a plasticizer. 4 . The oral film according to claim 3 , wherein the waterproof layer comprises 75 wt % to 95 wt % of a waterproof material and 5 wt % to 25 wt % of a plasticizer.

5. The oral film of any one of claims 1 to 4, wherein the adhesive layer further comprises 5 to 25 wt% of a plasticizer; Optionally, the adhesive layer further comprises 0 to 5 wt % of a flavoring agent; Optionally, the sustained-release layer further comprises 0 to 10 wt % of a plasticizer; Optionally, the sustained-release layer further comprises 0 to 3 wt % of a flavoring agent.

6. The oral film according to any one of claims 1 to 5, wherein in the oral film, the weight percentage of the adhesive layer is 25wt% to 50wt%, the weight percentage of the sustained-release layer is 35wt% to 65wt%, and the weight percentage of the waterproof layer is 5wt% to 20wt%.

7. The oral film according to any one of claims 1 to 6, wherein the weight ratio of the antibacterial agent in the adhesive layer and the sustained-release layer is 1:(20 to 30); Optionally, in the adhesive layer, the adhesive material is carbomer and hypromellose, and the weight ratio of the hypromellose to the carbomer is (0.5 to 2):1; Optionally, in the adhesive layer, the weight ratio of the antimicrobial agent to the sustained-release material is 1:(2.5 to 5); Optionally, in the sustained-release layer, the weight ratio of the antibacterial agent to the sustained-release material is (3 to 6):

1.

8. The oral film according to any one of claims 1 to 7, wherein the weight ratio of the antibacterial agent in the adhesive layer and the sustained-release layer is 1:24; Optionally, in the adhesive layer, the adhesive material is carbomer and hypromellose, and the weight ratio of the hypromellose to the carbomer is 1:1; Optionally, in the adhesive layer, the weight ratio of the antibacterial agent to the sustained-release material is 1:3.8; Optionally, in the sustained-release layer, the weight ratio of the antibacterial agent to the sustained-release material is (4 to 5):

1.

9. The oral film according to any one of claims 1 to 8, wherein In the sustained-release layer, the weight ratio of the antibacterial agent to the sustained-release material is 4.44:

1.

10. The oral film according to any one of claims 1 to 9, wherein the antibacterial agent is ornidazole; Optionally, the adhesive material is selected from one or more of carbomer, hydroxypropyl methylcellulose, polycarbophil, hydroxypropyl cellulose, xanthan gum, and polyvinyl pyrrolidone; Optionally, the sustained-release material is selected from ethyl cellulose and / or acrylic resin; Optionally, the waterproof material is selected from one or more of ethyl cellulose, polyacrylic acid resin and ethyl acrylate-methyl methacrylate copolymer aqueous dispersion; Optionally, the plasticizer is selected from one or more of polyethylene glycol, glycerol, propylene glycol, dibutyl phthalate, dioctyl phthalate, tricresyl phosphate, triethyl citrate, triphenyl phosphate and dioctyl sebacate; Optionally, the flavoring agent is selected from one or more of aspartame, edible flavors, vanillin, menthol, stevioside, acesulfame potassium, saccharin sodium and sucralose.

11. The method for preparing the oral film according to any one of claims 5 to 10, comprising the following steps S1 to S4, S1: mixing the adhesive material and the sustained-release material for preparing the adhesive layer, adding ethanol to soak, then adding the antibacterial agent and the plasticizer for preparing the adhesive layer, and degassing to obtain solution 1; S2: mixing the adhesive material and the sustained-release material for preparing the sustained-release layer, adding ethanol to soak, then adding the antibacterial agent and the plasticizer for preparing the sustained-release layer, and degassing to obtain solution 2; S3: mixing the sustained-release material and the plasticizer for preparing the sustained-release layer of the waterproof layer, adding ethanol for soaking, and degassing to obtain solution 3; and S4: using the solution 1, solution 2 and solution 3 to sequentially apply a film to prepare an oral film comprising the adhesive layer, the sustained-release layer and the waterproof layer.

12. The preparation method according to claim 11, wherein In the step S1 and / or step S2, the flavoring agent is added at the same time as the antibacterial agent and the plasticizer; Optionally, the concentration of ethanol is 70wt% to 100wt%; Optionally, the soaking time is 8 to 24 hours.

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