JP2024030812A - Oral film preparation - Google Patents

Abstract

[Problem] To provide an oral film preparation with excellent disintegration properties, mechanical properties, storage stability, and mucoadhesiveness. [Solution] An oral film preparation containing a cellulose derivative and an active ingredient. [Selection diagram] None

Description

The present invention relates to oral film preparations and the like.

Stomatitis is one of the most painful adverse events experienced by cancer patients during cancer chemotherapy and radiotherapy, and when it becomes severe, it becomes difficult to continue treatment. Furthermore, it has been reported that the incidence of stomatitis is higher in pediatric patients than in adult patients. On the other hand, no drug has been approved to be effective against stomatitis in Japan. Non-Patent Document 1 reports that suspension preparations and troches of Polaprezinc exhibit excellent stomatitis preventive effects against stomatitis caused by radiation therapy. However, it has been difficult to apply this formulation to pediatric patients due to problems with its taste and feel.

Funato, et al. Prophylactic Effect of Polaprezinc, a Zinc-L-carnosine, Against Chemotherapy-induced Oral Mucositis in Pediatric Patients Undergoing Autologous Stem Cell Transplantation. Anticancer Res. 2018;38(8):4691-4697. doi: 10.21873/ anticanres.12775.PMID: 30061237.

The present inventor focused on a film formulation that can be easily taken even by children. Since the film formulation can be applied to adults as well, it is considered to be particularly effective for elderly patients and other patients with decreased oral function who find it burdensome to take lozenges.

An object of the present invention is to provide an oral film preparation with excellent disintegrability, mechanical properties, storage stability, and mucoadhesiveness. An object of the present invention is to provide an oral film preparation that preferably has a high content of active ingredients (particularly Polaprezinc) and yet has excellent properties as described above.

As a result of extensive research in view of the above-mentioned problems, the present inventors have found that the above-mentioned problems can be solved by using an oral film preparation containing a cellulose derivative and an active ingredient. The present inventor conducted further research based on this knowledge and completed the present invention. That is, the present invention includes the following aspects.

Item 1. An oral film preparation containing a cellulose derivative and an active ingredient.

Item 2. Item 2. The oral film preparation according to item 1, wherein the cellulose derivative is hydroxypropyl cellulose.

Item 3. Item 3. The oral film preparation according to Item 2, wherein the content of the hydroxypropylcellulose is 90% or more based on 100% by mass of the polymer component.

Item 4. Item 3. The oral film preparation according to item 2, wherein the content of the hydroxypropylcellulose is 50 to 90% by mass based on 100% by mass of the solid content of the oral film preparation.

Item 5. Item 2. The oral film preparation according to item 1, wherein the active ingredient is a prophylactic or therapeutic agent for stomatitis.

Item 6. Item 2. The oral film preparation according to Item 1, wherein the active ingredient is Polaprezinc.

Section 7. Item 7. The oral film preparation according to item 6, wherein the content of the Poraprezinc is 10 to 30% by mass based on 100% by mass of the solid content of the oral film preparation.

Section 8. Item 2. The oral film preparation according to item 1, which contains a plasticizer.

Item 9. Item 9. The oral film preparation according to Item 8, wherein the plasticizer is glycerin.

Item 10. Item 9. The oral film preparation according to Item 8, wherein the content of the plasticizer is 1 to 25% by mass based on 100% by mass of the solid content of the oral film preparation.

Item 11. Item 11. The oral film preparation according to any one of Items 1 to 10, which is an orally disintegrating film.

Item 12. Item 11. The oral film preparation according to any one of Items 1 to 10, which is used by being attached to the oral mucosa.

Item 13. Item 11. The oral film preparation according to any one of Items 1 to 10, which is for preventing stomatitis.

According to the present invention, it is possible to provide an oral film preparation with excellent disintegrability, mechanical properties, storage stability, and mucoadhesiveness. In a preferred embodiment of the present invention, it is possible to provide an oral film preparation that has a high content of active ingredients (particularly Polaprezinc) and yet has the above-mentioned properties.

A photographic image showing the state of disintegration in the Petri dish method of Test Example 1-1 is shown. The upper left of the photo shows the elapsed time since the film was floated on the Petri dish. The measurement results of disintegration time and contact angle of Test Example 1-2 are shown. The horizontal axis shows the proportion of plasticizer added to the film. The measurement results of tensile strength in Test Example 1-3 are shown. The horizontal axis shows the proportion of plasticizer added to the film. The measurement results of the elastic modulus and fracture strain rate of Test Example 1-4 are shown. The horizontal axis shows the proportion of plasticizer added to the film. The outline of the mucoadhesive evaluation test of Test Example 4 is shown below. The measurement results of mucosal adhesion and contact angle in Test Example 4 are shown. Blank indicates that no film is used. HPC Film indicates the film of Example 1. The measurement results of the disintegration time, tensile strength, elastic modulus, and fracture strain rate of Test Example 5 are shown. On the horizontal axis, "without" indicates a film to which no sweetener was added, and "with" indicates a film to which a sweetener was added.

In this specification, the expressions "contain" and "including" include the concepts of "containing", "comprising", "consisting essentially" and "consisting only".

In one aspect, the present invention relates to an oral film preparation (herein sometimes referred to as "the film preparation of the present invention") containing a cellulose derivative and an active ingredient. This will be explained below.

The cellulose derivative is one in which a substituent is introduced into the hydroxyl group of cellulose, and is not particularly limited as far as this is concerned. Examples of cellulose derivatives include cellulose ether and cellulose ester, but cellulose ether is particularly preferred. Examples of the cellulose ether include hydroxypropylcellulose, hydroxyethylcellulose, hydroxypropylmethylcellulose, carboxymethylcellulose, carboxyethylcellulose, methylcellulose, and ethylcellulose. Among these, hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methyl cellulose, etc. Cellulose derivatives in which a substituent containing a hydroxy group is introduced into the hydroxy group of cellulose are preferred, and hydroxypropyl cellulose is particularly preferred. In the present invention, the above characteristics can be further enhanced by using hydroxypropyl cellulose. Note that hydroxypropyl cellulose includes both hydroxypropyl cellulose that does not have a low degree of substitution and hydroxypropyl cellulose that does not have a low degree of substitution, but from the viewpoint of the above-mentioned characteristics, hydroxypropyl cellulose that does not have a low degree of substitution is particularly preferable.

The weight average molecular weight of the cellulose derivative is not particularly limited as long as it can be used as a base for forming a film. The molecular weight is, for example, from 40,000 to 2,500,000, preferably from 40,000 to 1,000,000, from the viewpoint of disintegration, mechanical properties, storage stability, mucoadhesiveness, etc., and the above-mentioned properties at a high content of active ingredients (especially Pola Prezinc). Preferably 40,000 to 500,000, more preferably 60,000 to 200,000. The weight average molecular weight is a value measured by GPC method.

The cellulose derivatives can be used alone or in combination of two or more.

The film preparation of the present invention can contain polymer components other than cellulose derivatives as a polymer component serving as a film base, but from the viewpoint of disintegration, mechanical properties, storage stability, mucoadhesiveness, etc., the active ingredients ( In particular, from the viewpoint of the above-mentioned properties at a high content (particularly Pola Prezinc), it is preferable that the content of the polymer component is low.

Examples of polymer components other than cellulose derivatives include polyalkylene glycol, acrylic acid polymer, acrylic acid copolymer, methacrylic acid polymer, methacrylic acid copolymer, polyacrylamide, polyvinylpyrrolidone, polyvinyl alcohol, carboxymethylcellulose, starch, xanthan gum, karaya gum, and locust bean. Gum, tragacanth gum, guar gum, acacia gum, gum arabic, carrageenan, dextrin, dextran, amylose, alginic acid, alginate, carboxyvinyl polymer, pullulan, chitosan, sodium carboxymethyl starch, plantago seed coat, galactomannan, eudragit, casein, alkyl alginate Esters, gelatin, cyclodextrin, water-soluble pullulan ethers (pullulan methyl ether, pullulan ethyl ether, pullulan propyl ether, etc.), water-soluble pullulan esters (pullulan acetate, pullulan butyrate, etc.), agar, delacant, chitin, tara gum, tamarind gum etc.

The content of the cellulose derivative is preferably 80% by mass or more, more preferably 90% by mass or more, even more preferably 95% by mass or more, even more preferably 98% by mass or more, particularly preferably is 99% by weight or more, most preferably 100% by weight. The content of hydroxypropylcellulose is preferably 80% by mass or more, more preferably 90% by mass or more, even more preferably 95% by mass or more, even more preferably 98% by mass or more, especially Preferably it is 99% by mass or more, most preferably 100% by mass. By setting the content as above, the properties such as disintegration, mechanical properties, storage stability, mucoadhesiveness, etc. can be further improved when the content of the active ingredient (particularly Pola Prezinc) is high.

The content of the cellulose derivative is preferably 50 to 90% by mass, more preferably 55 to 80% by mass, still more preferably 60 to 75% by mass, and even more preferably Preferably it is 62 to 70% by weight, particularly preferably 66 to 70% by weight. The content of hydroxypropylcellulose is preferably 50 to 90% by mass, more preferably 55 to 80% by mass, even more preferably 60 to 75% by mass, based on 100% by mass of the solid content of the film preparation of the present invention. More preferably 62 to 70% by weight, particularly preferably 66 to 70% by weight. By setting the content as above, the properties such as disintegration, mechanical properties, storage stability, mucoadhesiveness, etc. can be further improved when the content of the active ingredient (particularly Pola Prezinc) is high. Note that in this specification, the solid content refers to components excluding the solvent (water, monohydric C1-4 alcohol).

The active ingredient is not particularly limited as long as it can exert its medicinal effect by contacting with the oral mucosa or by being dispersed in the oral cavity and contacted with or absorbed by the mucous membrane in the oral cavity or the gastrointestinal tract. The active ingredient can be, for example, a pharmaceutical ingredient, a food ingredient, a cosmetic ingredient, etc.

The pharmaceutical component may be either an orally administered drug or a parenterally administered drug, but since the film preparation of the present invention is preferably administered in the oral cavity, drugs such as orally administered drugs and transdermally absorbable drugs are particularly preferred.

Pharmaceutical ingredients include, for example, stomatitis preventive or therapeutic agents (e.g., polaprezinc, dexamethasone, triamcinolone acetonide, dipotassium glycyrrhizinate, sodium azulene sulfonate, hydrocortisone acetate, etc.);
Oral local anesthetics (e.g., lidocaine, ethyl para-aminobenzoate, oxyprocaine, tetracaine, procaine, para-butylaminobenzoic acid, diethylaminoethyl, etc.);
Examples include salivary secretion enhancers (eg, salivary gland muscarinic (M3) receptor agonist cevimeline (hydrochloride hydrate), pilocarpine hydrochloride, anethole trithione, etc.).

Food ingredients include (intraoral) antibacterial substances (e.g. lactoferrin, epigallocatechin gallate, propolis, etc.); (intraoral) deodorizing substances (e.g. catechin, parsley seed oil, rosemary extract, champignon extract, green tea extract) etc.), but are not limited to these.

Cosmetic ingredients include, but are not limited to, vitamins (eg, vitamin C, vitamin E, multivitamins, etc.), arbutin, ellagic acid, CoQ10, collagen, hyaluronic acid, and the like. Although these cosmetic ingredients are not orally administered drugs, they can be made into film cosmetics with excellent portability, which is very useful.

The active ingredients can be used alone or in combination of two or more.

The active ingredient is particularly preferably Polaprezinc. Polaprezinc has a chemical name of catena-Poly{zinc-μ-[β-alanyl-L-histidinato(2-)-N,NN,O:N τ]} and a molecular formula of (C ₉ H ₁₂ N ₄ O ₃ Zn) _n . Pola Prezinc is almost insoluble in water, methanol, and ethanol.

The film preparation of the present invention can have excellent disintegration properties, mechanical properties, storage stability, mucoadhesiveness, etc. even if it has a high content of active ingredients (particularly Polaprezinc). In particular, in order to create a film formulation that can be expected to have the same effect as conventional formulations (suspension formulations, troche formulations) to exhibit the stomatitis preventive effect, the content of Polaprezinc must be high. , suitable for incorporation into the film formulation of the present invention. In addition, the combination of cellulose derivatives and poraprezinc, especially hydroxypropylcellulose and poraprezinc, is important from the viewpoint of properties such as disintegration, mechanical properties, storage stability, and mucoadhesiveness (particularly these properties when the poraprezinc content is high). Particularly preferred.

The content of the active ingredient is preferably 5% by mass or more, more preferably 10% by mass or more, even more preferably 10 to 30% by mass, and even more preferably 15 to 25% by weight, particularly preferably 17 to 23% by weight. The content of Pola Prezinc is preferably 5% by mass or more, more preferably 10% by mass or more, even more preferably 10 to 30% by mass, even more preferably 15% by mass, based on 100% by mass of the solid content of the film formulation of the present invention. ~25% by weight, particularly preferably 17-23% by weight.

The film preparation of the present invention preferably contains a plasticizer from the viewpoints of disintegration, mechanical properties, storage stability, mucoadhesiveness, etc., and from the viewpoint of the above-mentioned properties at a high content of active ingredients (particularly Polaprezinc). The plasticizer can suppress a decrease in flexibility, warping of the film due to shrinkage during drying, appearance of hardness, etc. when containing an active ingredient (particularly Pola Prezinc).

Examples of the plasticizer include glycerin, ethylene glycol, propylene glycol, diethylene glycol, polyethylene glycol, dipropylene glycol, triethyl citrate, and triacetin. Among these, glycerin is particularly preferred from the viewpoints of disintegration, mechanical properties, storage stability, mucoadhesiveness, etc., and from the viewpoint of the above-mentioned properties at a high content of active ingredients (particularly Polaprezinc).

The plasticizer can be used alone or in combination of two or more.

The content of the plasticizer is determined from the viewpoints of disintegration, mechanical properties, storage stability, mucoadhesiveness, etc., and from the viewpoint of the above-mentioned properties at a high content of active ingredients (particularly Pola Prezinc), etc. It is preferably 1 to 25% by weight, more preferably 5 to 20% by weight, even more preferably 10 to 18% by weight, particularly preferably 10 to 14% by weight, based on 100% by weight. The content of glycerin is determined based on the solid content of the oral film preparation of the present invention, from the viewpoints of disintegration, mechanical properties, storage stability, mucoadhesiveness, etc., and the above-mentioned properties at a high content of active ingredients (especially Polaprezinc). Based on 100% by weight, it is preferably 1 to 25% by weight, more preferably 5 to 20% by weight, even more preferably 10 to 18% by weight, particularly preferably 10 to 14% by weight.

The film formulation of the present invention can contain other components than those mentioned above. Examples of other components include sugars, sweeteners, flavoring agents, coloring agents, pH adjusters, surfactants, stabilizers, and fragrances. Examples of sugars include maltose, reduced maltose starch syrup, maltitol, erythritol, xylitol, sucrose, sorbitol, mannitol, trehalose, and the like. Examples of sweeteners include sodium saccharin, aspartame, potassium acesmufame, sucralose, dipotassium glycyrrhizinate, and the like. Examples of flavoring agents include l-menthol and the like. Examples of the coloring agent include titanium oxide, iron sesquioxide, yellow iron sesquioxide, and food coloring. Other pH adjusters include sodium hydroxide, potassium hydroxide, calcium hydroxide, sodium dihydrogen phosphate, disodium hydrogen phosphate, and the like. Examples of the surfactant include polyoxyethylene sorbitan fatty acid ester, polyoxyethylene hydrogenated castor oil, glycerin fatty acid ester, polyoxyethylene alkyl ether, and the like. Examples of the stabilizer include calcium chloride.

The other components can be used alone or in combination of two or more.

The content of other components is not particularly limited as long as it does not significantly adversely affect properties such as disintegration, mechanical properties, storage stability, and mucoadhesiveness. The content of other components can be, for example, 10% by mass or less, 5% by mass or less, or 2% by mass or less, based on 100% by mass of the solid content of the oral film preparation of the present invention.

The thickness of the film preparation of the present invention is not particularly limited as long as it is suitable for use in the oral cavity. The thickness can be, for example, 10 μm to 3 mm. The lower limit of the thickness can be, for example, 20 μm, 50 μm, 80 μm, or 100 μm. The upper limit of the thickness can be, for example, 2 mm, 1 mm, 500 μm, 300 μm, 200 μm, or 150 μm.

The film formulation of the present invention may have a single layer or a multilayer. In the case of a multi-layer structure, it is preferable to consist of a layer containing the above-mentioned components (cellulose derivative and drug (preferably further a plasticizer, and optionally further components)) and another layer.

The film formulation of the present invention can be manufactured according to a known film formulation manufacturing method, for example, with reference to Example 1 described below. The film formulation of the present invention can be prepared by, for example, using a base solution (suspension solution if insoluble components are present) containing a cellulose derivative and a drug (preferably further a plasticizer and optionally further ingredients) as a base (e.g. It can be manufactured by coating it on a resin film and drying it.

The solvent for the base solution is not particularly limited, and water and monohydric alcohol (eg, ethanol) can be used. When adding an insoluble component during the preparation of the base solution, a uniform base solution can be prepared by stirring and ultrasonication as necessary.

The film preparation of the present invention can be used by being attached to the oral mucosa. This allows the active ingredient to come into contact with the mucous membrane. Furthermore, the film preparation of the present invention releases the active ingredient by disintegrating in the oral cavity (that is, by functioning as an orally disintegrating film), thereby bringing the active ingredient into contact with the mucous membrane of the oral cavity or the gastrointestinal tract. Alternatively, it can be absorbed through the mucous membrane. In this way, the film preparation of the present invention can exhibit various effects depending on the type of active ingredient.

The film preparation of the present invention (particularly when it contains Polaprezinc) is preferably used for the prevention of stomatitis. In this case, the target is not particularly limited as long as it is a target that is likely to cause or worsen stomatitis. Such a subject is preferably a subject who has undergone or is scheduled to undergo cancer chemotherapy and/or radiation therapy.

The amount of application (e.g., administration, ingestion) of the active ingredient using the film preparation of the present invention is not particularly limited as long as it is an effective amount that produces the effect of the active ingredient, and is usually expressed as the weight of the active ingredient, for example, per day. 0.001-1000 mg/kg body weight. The above application amount can be adjusted as appropriate depending on the type of active ingredient, age, purpose, pathological condition, symptoms, etc.

The present invention will be described in detail below based on Examples, but the present invention is not limited to these Examples.

Example 1. Oral film preparation <Materials used>
Film base: Hydroxypropyl cellulose (HPC-SL, weight average molecular weight (GPC method): 100,000, Nippon Soda Co., Ltd.)
Plasticizer: Glycerin (special grade glycerin, Kishida Chemical Co., Ltd.)
Drug: Polaprezinc (Yantai Valiant Pharmaceutical Co. Ltd) Japanese Pharmacopoeia Solvent for manufacturing: Distilled water, ethanol (special grade ethanol, Kishida Chemical Co., Ltd.).

<Equipment used>
・Baker applicator (registered trademark) (YBA-6 type, Yoshimitsu Seiki)
・Automatic coating machine (G-7 type, Orihara Seisakusho)
- Ventilation dryer (KCV-4D, ADVANTEC)
・Base film (Pyrene (registered trademark), polypropylene film, Toyobo Co., Ltd.)
・Desktop ultrasonic cleaning machine (BRANSON 2510)
・Sheet cut press (designed by Muto).

<Preparation of base solution>
Predetermined amounts of the film base, plasticizer, and sweetener were weighed out and dissolved in a water-ethanol mixed solvent (3:1) so as to have the composition shown in Table 1. Ultrasonic treatment was performed for 30 minutes using a tabletop ultrasonic cleaner (BRANSON 2510). Polaprezinc was added to this solution, stirred until the aggregates disappeared, and then ultrasonicated for 30 minutes again to disperse the drug in the HPC solution. Air bubbles contained in the solution were removed using a vacuum pump to prepare a base solution (a cloudy suspension).

<Film molding>
A base film (Pylene (registered trademark), polypropylene film, Toyobo Co., Ltd.) was fixed on a heat-resistant glass plate. Using a Baker applicator (registered trademark) (YBA-6 model, Yoshimitsu Seiki), the base solution prepared on the base film was spread using an automatic coating device (G-7 model, Orihara Seisakusho) (spreading speed: : 100 mm/sec). This was dried in a ventilation dryer (KCV-4D, ADVANTEC) at 40°C for 3 hours. After confirming that the film was dry, it was cut into 20 mm x 30 mm using a sheet cut press (designed by Muto) equipped with a Thomson blade. The thickness was approximately 130 μm. The cut film was placed in an aluminum pouch and aged for 24 hours at room temperature.

The film containing 0% plasticizer warped after drying, but the film containing plasticizer did not warp after drying.

Test example 1. Improvement of flexibility of Pora Prezinc-containing film by adding plasticizer <Test Example 1-1. Evaluation of disintegration characteristics (1) Petri dish method>
A petri dish with a diameter of 10 cm was filled with 50 mL of distilled water, a 12% plasticizer film (Example 1) was floated on the water surface, and the time required for the film to completely disintegrate was measured.

A photographic image showing the state of collapse is shown in Figure 1. After about 4 minutes, the film collapsed to such an extent that its shape could not be discerned.

<Test example 1-2. Disintegration characteristics evaluation (1) Tricorp tester method and wettability evaluation>
The film of Example 1 was set in a disintegration testing device for orally disintegrating tablets, Tricorp Tester (Okada Seiko), and the disintegration time was measured under the following conditions. Test solution: artificial saliva, dropping rate: 6 mL/min (128 drops/min, 46.9 μl/drop), dropping amount: amount until holes are formed in the film, cell size: 10 x 10 x 0.05 (mm).

Further, 2.4 μL of distilled water was dropped onto the surface of the film of Example 1 using a DropMaster (Kyowa Interface Science), and the angle formed by the droplet when the film and the droplet came into contact was measured.

The measurement results of disintegration time and contact angle are shown in FIG. 2. The addition of plasticizer improved the wettability of the film and reduced the disintegration time.

<Test example 1-3. Mechanical property evaluation>
A tensile test was conducted on the film of Example 1 using a creep meter (YAMADEN). The conditions are as follows. Distance between grips: 17 mm, tensile speed: 0.5 mm/sec, sample size: 5 mm x 30 mm. Based on the stress-strain curve, tensile strength (MPa) (= maximum load (N) / cross-sectional area (mm ² )), elastic modulus (MPa) (= Δ stress / Δ strain), strain rate at break (%) ( The rate at which the film was deformed (strain) before breaking was calculated.

The measurement results of tensile strength are shown in FIG. Although the tensile strength decreased due to the addition of plasticizer, the target value of 2 MPa was achieved at all concentrations.

The measurement results of elastic modulus and fracture strain rate are shown in FIG. 4.

Test example 2. Evaluation of content uniformity using the content uniformity test method Ten locations were randomly selected on the surface of the film containing 12% plasticizer (Example 1), samples were taken from each location, and the Pora Prezinc content in each sample was determined using high-performance liquid chromatography. It was measured using a graph. Judgment values were calculated based on the measurement results. The formula for calculating the judgment value is as follows. The 18th revision of the Japanese Pharmacopoeia states that a substance is compliant if the judgment value does not exceed 15%.

The results are shown in Table 2. The film of Example 1 was found to pass the content uniformity test.

Test example 3. Storage stability evaluation The film containing 12% plasticizer (Example 1) was sealed in an aluminum bag with a zipper immediately after production, and the inside of the bag was maintained at 25°C and humidity of 50 to 60%, and stored for 4 weeks. The disintegration time (tricop tester method), tensile strength, drug content, and moisture content in the film were measured before and after storage. The disintegration time (tricop tester method), tensile strength, and drug content were measured by the method described in the above test example. The moisture content was calculated by heating the film at 105° C. for 120 minutes in a micro vacuum dryer (SANSYO), measuring the amount of moisture in the film from the difference in mass before and after heating, and based on the obtained measurement value.

As a result, the disintegration time after storage, tensile strength after storage, and drug content after storage were 99.2%, 109.6%, and 102.9%, respectively, when the value before storage was 100%. Moreover, the moisture content was 7.8% before storage and 9.4% after storage. Thus, there were no significant changes in the physical properties of these films during the 4-week storage period.

Test example 4. Mucoadhesiveness evaluation Wet film of 12% plasticizer (Example 1), commercial product A (oral tablet: Oravi tablet for oral use 50 mg), commercial product B (oral patch: Aftouch oral patch 25 μg) It was subjected to sex evaluation and mucoadhesiveness evaluation test. Wettability was evaluated using the method described in the above test example. In the mucosal adhesion evaluation test, as shown in Figure 5, 100 μL of the test solution was dropped onto the pig buccal mucosa on the stage, a film was attached from above and the film was left in contact for a certain period of time, and then the stage was moved downward. This was done by measuring the elongation of the spring until the film and mucous membrane separated. The conditions are as follows. Equipment: Jolly spring balance (JS-70A Shimadzu Rika), test liquid: artificial saliva, weight: 5, 20 g (0.049 N, 0.196 N), liquid volume: 100 μL, contact time: 20 seconds.

The results are shown in FIG. The film of Example 1 exhibited mucoadhesiveness comparable to commercially available products. Moreover, it had excellent wettability compared to commercially available products.

Test example 5. Preparation and evaluation of sweetener-added films A film with 12% plasticizer (Example 1) and a film prepared in the same manner as the above film except that the film base was reduced by 1% and 1% sucralose was added as a sweetener instead. prepared. For these films, the disintegration time, tensile strength, elastic modulus, and strain at break were measured using the test examples and methods described above.

The results are shown in FIG. It was found that sweetener addition did not affect film properties.

Claims (13)

An oral film preparation containing a cellulose derivative and an active ingredient. The oral film preparation according to claim 1, wherein the cellulose derivative is hydroxypropylcellulose. The oral film preparation according to claim 2, wherein the content of the hydroxypropylcellulose is 90% or more based on 100% by mass of the polymer component. The oral film preparation according to claim 2, wherein the content of the hydroxypropylcellulose is 50 to 90% by mass based on 100% by mass of the solid content of the oral film preparation. The oral film preparation according to claim 1, wherein the active ingredient is a prophylactic or therapeutic agent for stomatitis. The oral film preparation according to claim 1, wherein the active ingredient is Polaprezinc. The oral film preparation according to claim 6, wherein the content of the Polaprezinc is 10 to 30% by mass based on 100% by mass of the solid content of the oral film preparation. The oral film preparation according to claim 1, containing a plasticizer. The oral film formulation according to claim 8, wherein the plasticizer is glycerin. The oral film preparation according to claim 8, wherein the content of the plasticizer is 1 to 25% by mass based on 100% by mass of solid content of the oral film preparation. The oral film preparation according to any one of claims 1 to 10, which is an orally disintegrating film. The oral film preparation according to any one of claims 1 to 10, which is used by adhering to the oral mucosa. The oral film preparation according to any one of claims 1 to 10, which is used for preventing stomatitis.

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