JPH05310561A - Base for intraoral cavily application and preparation for intraoral cavily application - Google Patents

Abstract

PURPOSE:To obtain a base or a preparation for intraoral cavity application having a double layer membrane structure of uniform thickness excellent in sustained release function of medicine by one casting and drying operation simply and at low cost. CONSTITUTION:A solution comprising 10-60wt.%, preferably 20-40wt.% total amount of a polyacrylate (preferably alkali metal salt) and a carboxy polymer in the blending ratio of 10:1 to 6:4, preferably 9:1 to 9:3 by weight and 4-90wt.% preferably 60-80wt.% polyvinyl alcohol having >=70mol% saponification degree is adjusted to pH>=8, preferably 8.5-11.0 to prepare a solution for forming a film. The solution is cast into a mold, dried, subjected to phase separation to give a double layer structure film of uniform thickness. The solution is added with one or more selected from a medicine, a salt, a plasticizer a dissolution controlling agent, a stabilizer, a colorant, a flavor and an extender to give a preparation for intraoral cavity application, having a double layer structure.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention is applied as an oral cavity protector, an agent for preventing and treating oral diseases, and an agent for preventing bad breath, and is composed of a simple and uniform two-layer structure film having an excellent drug sustained-release function. The present invention relates to a base for oral application and a preparation for oral application.

[0002]

2. Description of the Related Art Conventionally, an oral patch base adheres to the oral cavity for a long time, protects the affected area, and has a hydrophilic surface that directly adheres to the affected area for the purpose of sustained drug release.
A base having a two-layer structure film composed of a water-resistant surface that is not easily dissolved by saliva or the like has been proposed.

For example, in JP-A-63-160649 and JP-A-63-18923, in order to form a water-insoluble or sparingly-soluble support layer on one surface of a film material having an adhesive property, the first step As the adhesive layer component is dissolved in a solvent,
This is spread and dried to form an adhesive layer first, and as a second step, a two-stage manufacturing method is performed in which a support component dissolved in a solvent is spread and dried on the adhesive layer to form a support layer. Has been adopted.

In the preparation for intraperitoneal pocket administration, a two-layer or three-layer structure base has been proposed in Japanese Patent Application No. 2-301861 in order to improve the sustained release function of the drug. A two- or three-stage manufacturing method in which each layer is sequentially laminated is adopted.

[0005]

DISCLOSURE OF THE INVENTION The present invention provides a base for oral application and a preparation for oral application which has a two-layer structure film having a uniform thickness, which can be obtained more simply and at a lower cost than a conventional two-step manufacturing method. Is proposed.

[0006]

[Means for Solving the Problems] As a simple and low-cost manufacturing method, as a result of extensive studies on a method of preparing a two-layer structure film having a uniform thickness by one casting / drying operation, a blending weight ratio of 10 was obtained. : 1 to 6: 4 in a liquid containing a polyacrylic acid salt, a carboxyvinyl polymer, and polyvinyl alcohol in a liquid, if necessary, a drug, a salt, a plasticizer, a dissolution control agent, a stabilizer, a coloring agent, and a flavoring agent. When one or two or more agents, flavoring agents and extenders are added and a film-forming solution in which the pH of the solution is adjusted to 8 or more is cast, phase separation naturally occurs during the ordinary drying operation. The inventors have found that a two-layer structure film can be manufactured, and completed the present invention.

[0007]

BEST MODE FOR CARRYING OUT THE INVENTION The film forming solution in the present invention contains a formulation component such as a polyacrylic acid salt, a carboxyvinyl polymer and polyvinyl alcohol or a drug.

Here, (a) polyacrylate and (b)
The compounding weight ratio of the carboxyvinyl polymer is (a):
It is necessary that (b) = 10: 1 to 6: 4, and preferably 9: 1 to 9: 3. If this ratio exceeds 10: 1, a two-layer structure film having a uniform thickness cannot be manufactured. On the other hand, when it is less than 6: 4, sufficient phase separation does not occur in the drying process, and a two-layer structure film cannot be manufactured. Further, there are no restrictions on the type and degree of polymerization of the polyacrylic acid salt and carboxyvinyl polymer, and any linearly or branched type, low to high degree of polymerization, and any pharmaceutically acceptable one can be used. As the polyacrylic acid salt, those having an average degree of polymerization of 2,000 to 100,000 are generally suitable, and preferably 20,000 to 70,000. Further, as the carboxyvinyl polymer, B.I. F. Goodri
Carbopole 907,910,941,934,934P, 94 made by ch Chemical Company
0, Hibiswako 103, 10 manufactured by Wako Pure Chemical Industries, Ltd.
4,105,204,304 etc. can be used.

The polyacrylic acid salt is preferably an alkali metal salt of polyacrylic acid, and sodium salt and potassium salt can be preferably used. In addition, in the case where one surface of the two-layer structure film is made to be highly adhesive, it is preferable to increase the mixing ratio of the carboxyvinyl polymer, for example, the mixing weight ratio of the polyacrylic acid salt and the carboxyvinyl polymer is 10: 2 to 6:
The range is 4.

Further, when a drug is blended, the grade of polyacrylate or carboxyvinyl polymer that obtains the optimum sustained release effect of the drug is selected from the above range.

The total amount of polyacrylic acid salt and carboxyvinyl polymer compounded in the two-layer structure film composition is from 10 to 10.
It is preferably 60% by weight, more preferably 20 to 40% by weight. If it is less than 10% by weight, sufficient phase separation does not occur in the drying process, and it becomes difficult to produce a two-layer structure film. 60% by weight
If it exceeds, it becomes difficult to manufacture a two-layer structure film having a uniform thickness.

Polyvinyl alcohol has a saponification degree of 70.
Although those having a mol% or more can be suitably used, when one surface of the two-layer structure film is desired to have water resistance, the saponification degree is 95 mol%.
One or more of the above are selected. on the other hand,
When one surface of the two-layer structure film is not desired to have water resistance, one or two or more kinds having a saponification degree of 70 to 95 mol% are selected. Also, there is no restriction on the degree of polymerization of the polyvinyl alcohol used, but when a drug is compounded, a grade that gives an optimum sustained release effect of the drug is selected. The polymerization degree of polyvinyl alcohol is preferably 100 to 10,000, more preferably 200 to 5,000.

The polyvinyl alcohol is preferably contained in the two-layer structure film composition in an amount of 40 to 90% by weight, more preferably 60 to 80% by weight. The drug is
One or two or more of the following may be used, and the compounding amount thereof may be appropriately selected depending on the type as described below, but generally 0.001 to 20% by weight, particularly 0. It can be from 01 to 10% by weight.

(1) Antibiotics: (blending amount) 0.001
10% by weight tetracycline, tetracycline hydrochloride, benzylpenicillin, ampicillin, carpenicillin, acetylkitasamycin, amoxicillin, pacitracin, cephalothin sodium, cephaloridine, cephalexin, erythromycin, chloramphenicol, oxytetracycline hydrochloride, doxycycline hydrochloride, polymyxin sulfate B, fradiomycin sulfate, gentamicin sulfate,
Minocycline hydrochloride, clindamycin hydrochloride, etc.

(2) Drugs having plaque-dissolving action:
0.1 to 10% by weight Lysozyme chloride, amylase, dextranase, protease and the like.

(3) Sulfa drugs: 0.05 to 1% by weight Sulfamine, sulfathiazole, sulfadiazine, homosulfamine, sulfisoxazole, sulfisomidine, sulfamethizole, nitrofurazone and the like.

(4) Bactericidal disinfectant: 0.01 to 10% by weight of chlorhexidine or salts thereof, protein silver, thimerosal, chloramine, iodoglycerin, iodoform, boric acid, paraformaldehyde, phenol, hexylresorcin, benzalkonium chloride, Benzethonium chloride, phenododecium bromide, decalinium chloride, cetylpyridinium chloride, ofloxacin, popidone iodine, eugenol, etc.

(5) Vasoconstrictor: 0.01-1% by weight Naphazoline hydrochloride, Naphazoline nitrate, Tetrahydrozoline hydrochloride, Oxymetazoline hydrochloride, Phenylephrine hydrochloride, Tramazoline hydrochloride and the like.

(6) Hemostatic agents: 0.05 to 1% by weight noscanol, hesperidin, rutin, carbazochrome sodium sulfonate, carbazochrome, tranexamic acid, aminocaproic acid, protamine sulfate, thrombin, phytonadione and the like.

(7) Analgesic and anti-inflammatory agent: 0.1 to 5% by weight flufenamic acid, mefenamic acid, methyl salicylate, glycol salicylate, acetaminophen, aspirin, indomethacin, diclofenac, alclofenac, diclofenac sodium, ibuprofen, ketoprofen, Naproxen, pranoprofen, fenoprofen, salindac, fenglofen, clindac, flurbiprofen, fentiazac, bufexamac, benzadac, piroxicam, phenylbutazone, oxyphenbutazone, clofezone, bentazocine, mepyrizole , Tiaramid hydrochloride, etc.

(8) Steroid anti-inflammatory agent: 0.002
0.5 wt% hydrocortisone, prednisolone, dexamethasone, triamcinolone acetonide, fluonocinolone acetonide, hydrocortisone acetate, prednisolone acetate, methylprednisolone acetate, dexamethasone acetate, betamethasone, betamethasone valerate, flumethasone, beclomethasone propionate, etc. ..

(9) Antihistamine: 0.1 to 2% by weight diphenhydramine hydrochloride, diphenhydramine salicylate, diphenhydramine, chlorpheniramine hydrochloride, chlorpheniramine maleate, isothipendyl hydrochloride, triperenamine hydrochloride, promethazine hydrochloride, metzirazine hydrochloride and the like.

(10) Local anesthetic: 0.05-2% by weight dibucaine hydrochloride, dibucaine, lidocaine hydrochloride, lidocaine, benzocaine, thecaine, procaine hydrochloride, tetracaine hydrochloride, chloroprocaine hydrochloride, oxyprocaine hydrochloride, mepivacaine hydrochloride, cocaine hydrochloride , Piperocaine hydrochloride, etc.

As the salts, one or more of the following can be used, and the compounding amount is appropriately 0.1 to 5% by weight based on the whole base composition. Chlorides such as sodium chloride, potassium chloride, calcium chloride, magnesium chloride. Sulfates such as sodium sulfate, potassium sulfate, sodium hydrogen sulfate. Acetates such as sodium acetate and potassium acetate. Carbonates such as sodium carbonate and potassium carbonate. Phosphates such as sodium phosphate and sodium hydrogen phosphate. Organic acid salts such as gluconate, citrate and succinate.

As the plasticizer, one or more of the following may be used, and the compounding amount is suitably 0.1 to 25% by weight. Polyethylene glycol (200 to 6000), glycerin, propylene glycol, 1,3-butylene glycol, sorbit, ethylene oxide / propylene oxide copolymer, diethyl phthalate, dibutyl phthalate,
Butylphthalyl butyl glycolate, ethylene glycol, dipropylene glycol, triacetin, spun fatty acid lauric acid, etc.

As the dissolution control agent, one or more of the following may be used, and the compounding amount is suitably 0.1 to 10% by weight. Higher fatty acids such as shellac, stearic acid and palmitic acid, water-insoluble polymers such as ethyl cellulose, PH-sensitive polymers such as Eudragit E, L, S, higher alcohols such as cetanol, lipophilic surfactants of HLB 1-8, Inorganic powder such as titanium oxide.

As the stabilizer, one or more of the following can be used, and the compounding amount is suitably 0.1 to 3% by weight. Vitamin C, vitamin E, sodium sulfite, sodium bisulfite, sodium pyrosulfite, butylhydroxytoluene, propyl gallate, butylhydroxyanisole, etc.

As the colorant, one kind or two or more kinds such as a tar dye can be used, and the compounding amount is 0.001 to 0.1.
Weight percent is suitable. Flavoring agents include natural or synthetic flavors, saccharin, fumaric acid, menthol, peppermint oil,
One or more selected from tartaric acid, aspartame, etc. can be used, and the compounding amount is suitably 0.01 to 0.2% by weight.

As the bulking agent, one or two or more kinds used as excipients in the case of ordinary tablets such as Avicel, mannitol, lactose, sorbitol, dextrin, starch, anhydrous calcium phosphate and amylose can be used. Is suitably 0.1 to 5% by weight.

In the present invention, a film-forming solution is obtained by dissolving or dispersing the above-mentioned base material component or further formulation component in water and adjusting the pH. If necessary, the pH of the film-forming liquid is adjusted to 8 or higher, preferably 8.5 to 11.0 by using a suitable pH adjuster. When the pH is less than 8, layer separation does not occur during casting / drying, and a two-layer structure film cannot be obtained. In addition, the pH is 11.
When it exceeds 0, irritation to the mucous membrane occurs.

The pH adjusting agent is not particularly limited as long as it is a pharmaceutically acceptable acid or basic substance. For example, hydrochloric acid, citric acid, acetic acid, boric acid, sulfuric acid, carbonic acid, phosphoric acid, aqueous ammonia, One or more selected from sodium hydroxide, ethanolamine, diethanolamine, triethanolamine and the like can be used.

When the solution for film formation is cast on a mold and dried, phase separation naturally occurs, and a single-layer casting / drying operation gives a two-layer structured film having a uniform thickness. The drying method is not limited, and various drying methods can be adopted, and examples thereof include blast drying, natural drying, heat drying, low temperature drying, reduced pressure drying, reduced pressure heating drying, and reduced pressure low temperature drying.

In the present invention, the thickness of the two-layer structure film is not limited, but in the case of an intraoral patch base, it should not exceed 1 mm so as not to give a feeling of foreign matter when it is adhered and used. Good, and particularly preferably 30 to 300 μm. The shape can be appropriately set according to the position of the affected area and the like. The size of the base for administration in the periodontal pocket is also not particularly limited, but is usually 0.5 to 2.0 mm in width and 3 to in length.
It preferably has a thickness of 15 mm and a thickness of 0.02 to 1.2 mm.

[0034]

EFFECTS OF THE INVENTION According to the present invention, a base for oral application and a preparation for oral application having a two-layer structure film having a uniform thickness can be obtained easily and at low cost by one casting / drying operation. be able to.

The base for oral application and the preparation for oral application of the present invention easily adhere to the affected area of the oral cavity when applied in the oral cavity,
Its stickiness lasts for a long time. Therefore, it is excellent in protection of the affected area and causes less discomfort, and when a drug is mixed, the drug can be sustainedly released. Further, when a double-layered structure film cut into strips is administered into the periodontal pocket, the retention property in the pocket is good and the drug can be expected to be sustained.

[0036]

【Example】

Experimental Example 1 The components shown in Table 1 were added to 250 g of water, dissolved and defoamed to prepare a film-forming solution, which was cast in a fixed mold and forcedly dried at 30 ° C. And the film thickness is 150 μm
A base for oral application was obtained.

As a result of analyzing the structure of the dried film, Comparative Examples 1, 2 and 3 were single layer films, and only Example 1 was a double layer structure film. As shown in this example, the compounding weight ratio is 1
P of liquid containing 0: 1 to 6: 4 polyacrylate, carboxyvinyl polymer and polyvinyl alcohol
It was confirmed that a two-layer structure film can be produced by casting and drying the film-forming solution in which H is adjusted to 8 or more once.

[0038]

[Table 1] Ingredients Comparative Example 1 Comparative Example 2 Comparative Example 3 Example 1 PANa - 7.0 g 3.3 g 3.3 g CVP - 3.0 g 1.4 g 1.4 g PVA 10.0 g - 5.3 g 5.3 g pH adjusting agent suitable amount qs qs qs pH 9.2 7.2 7.4 9.1 Structure of dry film 1 layer 1 layer 1 layer 2 layers PANa: sodium polyacrylate, average degree of polymerization: about 50,000 CVP: carboxyvinyl polymer, B.I. F. Goo
Carbopole 94 made by drich Chemical Company
0 PVA: polyvinyl alcohol, average degree of polymerization: 1,0
00 or less, saponification degree: 98.5 mol% pH adjusting agent: sodium hydroxide or hydrochloric acid

Experimental Example 2 The components shown in Table 2 were added to 250 g of water, dissolved and defoamed to prepare a film-forming solution, which was cast in a fixed mold at 30 ° C. The film thickness is 150μm after forced drying.
To obtain an intraoral patch base. Only Example 2 had a two-layer structure film.

This patch was applied to the lower labial gingiva of a healthy adult male to evaluate the adhesiveness, and the results are shown in Table 2. In Example 2, the upper layer of the two-layer structure film obtained by casting and drying the film-forming solution in the mold was a layer mainly composed of PVA, and the lower layer was a layer mainly composed of PANa, CVP and PVA. It was Therefore, the lower layer, which is highly adhesive, was used as the adhesive surface to the gingiva.

[0041]

[Table 2] Ingredient Comparative Example 4 Comparative Example 5 Comparative Example 6 Example 2 PANa - 5.95 g 2.8 g 2.8 g CVP - 2.55 g 1.2 g 1.2 g PVA 8.5 g - 4.5 g 4.5 g Glycerin 1.5 g 1.5 g 1.5 g 1.5 g pH adjusting agent Appropriate amount Proper amount Proper amount Proper amount pH 9.2 7.2 7.4 9.1 Structure of dry film 1 layer 1 layer 1 layer 2 layers Adhesion evaluation × △ × to △ ○ PANa: sodium polyacrylate, average degree of polymerization: about 20,000 CVP: carboxyvinyl Polymers, B.I. F. Goo
Carbopole 94 made by drich Chemical Company
1 PVA: polyvinyl alcohol, average degree of polymerization: 1,0
00-1,500, Saponification degree: 98.5 mol% pH adjuster: Sodium hydroxide or hydrochloric acid Adhesiveness evaluation x: No adhesion Δ: Short adhesion time ○: Long adhesion time

Only Example 2 in which the pH was adjusted to 9 formed a two-layer structure film, was water resistant, and had a saponification degree of 98.5%.
The layer A did not dissolve even when contacted with saliva or the like, and adhered to the gingiva for a long time. The base of the present invention may be applied as an intraoral dressing to protect the affected area of the oral cavity and promote healing.

Experimental Example 3 In Example 2 of Experimental Example 2, 0.1% of chlorhexidine hydrochloride was added.
A formulation with a weight percentage blended was prepared and an in vitro release test was conducted. The experimental method was prepared with reference to the Japanese Bureau, general test method, dissolution test method, and basket method. Sample is 2x
Using a membrane cut into 2 cm, the amount of chlorhexidine hydrochloride released in the eluate of 500 ml of Ringer's solution was measured at regular intervals. The results are shown in Table 3.

[0044]

[Table 3] Table 3: Releasability of drugs from the formulation of the present invention 30 minutes 1 hour 2 hours 3 hours 4 hours Chlorhexidine hydrochloride 11.0 18.7 29.2 36.4 42.5 release rate (%) *

[0045]

[Equation 1]

From the results shown in Table 3, the sustained release of the drug from the preparation of the present invention was confirmed. Experimental Example 4 In the same manner as in Experimental Example 2, an oral patch base comprising the components shown in Table 4 was prepared.

[0047]

[Table 4] Ingredient Comparative Example 7 Comparative Example 8 Comparative Example 9 Comparative Example 10 Example 3 PANa - 2.8 g 2.0 g 4.0 g 2.8 g CVP - 1.2 g 2.0 g - 1.2 g CMCNa 4.0 g - - - - PVA400 4.5 g - 4.5 g 4.5 g 4.5 g HPC − 4.5 g − − − PEG 1.5 g 1.5 g 1.5 g 1.5 g 1.5 g pH adjuster Suitable amount Suitable amount Suitable amount Suitable amount PANa / CVP ratio − 7/3 5/5 10/0 7/3 pH 8.8 9.0 9.2 9.0 8.9 Structure of dry film 1 layer 1 layer 1 layer 2 layer 2 layers Thickness uniformity of dry film × △ ○ × ○ PANa: sodium polyacrylate, average degree of polymerization: about 20,000 CVP: carboxyvinyl polymer, Hibiswako 104 CMCNa: Carboxymethylcellulose PVA: Polyvinyl alcohol, average degree of polymerization: 1,0
00-1,500, Saponification degree: 99.0 mol% HPC: Hydroxypropylcellulose sodium PEG400: Polyethylene glycol 400 pH adjuster: Sodium hydroxide or hydrochloric acid Dry film thickness uniformity x: Thickness uniformity, poor Δ : Uniformity of thickness, slightly good ○: Uniformity of thickness, good

From the results of Comparative Examples 7 and 8 and Example 3,
It was observed that the dry film had a two-layer structure only when the pH of the solution containing polyacrylate, carboxyvinyl polymer, polyvinyl alcohol was adjusted to 8 or higher.

From the results of Comparative Examples 9 and 10, a dry film having a uniform two-layer structure film was formed only when the polyacrylic acid salt and the carboxyvinyl polymer having a compounding weight ratio of 10: 1 to 6: 4 were used. It has been found that can be prepared.

Experimental Example 5 To 250 g of water, the components shown in Table 5 were added, dissolved, defoamed, cast in a fixed mold, and dried under reduced pressure at 25 ° C. to give a periodontal thickness of 250 μm. An in-pocket formulation was obtained.

[0051]

[Table 5] Ingredient Comparative Example 11 Example 4 Example 5 PANa 1.6 g 1.6 g 3.2 g CVP 0.4 g 0.4 g 0.8 g PVA 6.3 g 6.3 g 4.3 g Propylene glycol 1.5 g 1.5 g 1.5 g clindamycin hydrochloride 0.2 g 0.2 g 0.2 g pH adjuster Proper amount Proper amount Proper amount PH 7.0 9.1 8.9 Structure of dry film 1 layer 2 layers 2 layers PANa: sodium polyacrylate, average degree of polymerization: about 50,000 CVP: carboxyvinyl polymer, Wako Pure Chemical Industries, Ltd. Hibis Wako 103 PVA: Polyvinyl alcohol, average degree of polymerization: 1,0
00 or less, saponification degree: 88.0 mol% pH adjusting agent: sodium hydroxide or hydrochloric acid

An in vitro release test similar to that of Experimental Example 3 was carried out for these agents in the periodontal pocket, and the results are shown in Table 6. However, as the sample, 40 strips cut into a width of 1 mm and a length of 10 mm were used.

[0053]

[Table 6] Table 6: Releasability of drugs from the preparation of the present invention Release rate of clindamycin hydrochloride (%) * Rag time 15 minutes 30 minutes 1 hour 2 hours 3 hours Comparative Example 11 3.3 16.7 50.6 74.3 94.0 About 10 minutes Example 4 12.4 23.1 35.0 53.8 66.1 None Example 5 10.1 19.9 27.8 38.0 46.2 None

[0054]

[Equation 2]

From the results shown in Table 6, Examples 4 and 5 have no initial drug release lag time and have sustained drug release properties over a long period of time. Therefore, the formulations of the present invention were administered into the periodontal pocket. When the drug is applied, the drug is immediately released, and the effect of the drug can be expected to continue for a long time.

The reason why such an effect can be expected is that the preparation of the present invention has the PVA layer and PANa / CVP /
The PVA layer is separated into two layers to provide a fast-dissolving PVA layer (PVA
Has a saponification degree of 88.0 mol% and uses a low polymerization degree grade), which first dissolves in the leachate and the like to give release of the drug without time lag, and then the PANa / CVP / PVA layer gradually dissolves, It is considered to release the drug over a long period of time.

As described above, the preparation of the present invention has a fast-acting and long-lasting drug delivery system.
It is considered to be useful as a dosage form based on.

Experimental Example 6 Using a film-forming solution (pH is shown in Table 8) in which 250 g of water was mixed with the base material components of Table 7 below and the formulation components such as the drug substances shown in Table 8 below, Each preparation for oral application having a thickness of 150 μm was produced according to Experimental Example 1. When a release test was conducted on these film-form preparations in accordance with Experimental Example 3, sustained release was confirmed in all cases.

[0059]

[Table 7] PANa: sodium polyacrylate, average degree of polymerization: about
20,000 CVP: carboxyvinyl polymer, B.I. F. Goo
Carbopole 93 made by drich Chemical Company
4 PVA: Polyvinyl alcohol, average degree of polymerization: 1,0
00 or less, saponification degree: 98.5 mol% pH adjusting agent: sodium hydroxide or hydrochloric acid

[0060]

[Table 8] Formulation components pH Membrane structure Thickness uniformity Lysozyme chloride 8.9 2 layers ○ Sulfamine 9.2 2 layers ○ Cetylpyridinium chloride 9.0 2 layers ○ Nafazoline hydrochloride 8.5 2 layers ○ Tranexamic acid 9.5 2 layers ○ Indomethacin 8.8 2 layers ○ Dibucaine hydrochloride 9.1 2 layers ○ Prednisolone acetate 8.9 2 layers ○ Thickness uniformity ×: Poor △: Slightly good ○: Good

Claims (2)

[Claims] 1. A film-forming solution in which the pH of a liquid containing a polyacrylic acid salt and a carboxyvinyl polymer in a proportion of 10: 1 to 6: 4 and polyvinyl alcohol in a blending weight ratio is adjusted to 8 or more is flowed. A base for oral application, which is obtained by spreading and drying to form a two-layer structure film. 2. A liquid containing a polyacrylic acid salt, a carboxyvinyl polymer, and polyvinyl alcohol in a compounding weight ratio of 10: 1 to 6: 4 is added to a drug, a salt, a plasticizer, a dissolution control agent, and a stabilizing agent. One or two or more selected from agents, colorants, corrigents, flavoring agents, and extenders are mixed, and a film-forming solution in which the pH of the solution is adjusted to 8 or more is cast and dried to form a two-layer structure film. The preparation for oral application characterized in that