JP5525678B2 - Oral administration - Google Patents

Description

  The present invention relates to an oral administration agent.

  Orally administered drugs have lower medication compliance due to various causes such as discomfort due to drug bitterness and astringency, nausea and vomiting due to medication, and medication rejection. For example, in the case of solid preparations (for example, tablets, capsules, etc.), which are common dosage forms for oral administration, it is difficult to swallow them as they are, so usually they must be taken with a large amount of water, resulting in reduced compliance. To do. Particularly in elderly people and infants, solid preparations cannot be swallowed, and medication compliance is often reduced. In the case of a solid preparation, there is a risk of accidentally clogging the trachea and a risk of sticking to the esophagus to form an esophageal tumor.

Therefore, an oral administration agent having a drug-containing layer and a water-swellable gel-forming layer, wherein the water-swellable gel-forming layer is provided in the outermost layer of the oral administration agent has been developed (patent) Reference 1). The water-swellable gel-forming layer provided in the outermost layer of the oral administration agent swells and gels with moisture such as saliva in the patient's mouth, and the oral administration agent is easy to swallow in size, shape, elasticity, viscosity To a dosage form having Therefore, the patient can easily take the oral administration agent. In addition, since the risk of the oral administration agent becoming clogged in the trachea of the patient during taking is reduced, it can be safely taken even if the patient is an elderly person or an infant. Furthermore, the water-swellable gel-forming layer provided in the outermost layer of the oral administration agent swells and gels with moisture such as saliva in the patient's mouth, and the taste of the drug contained in the drug-containing layer (for example, bitterness) , Astringency), odor, etc. can be masked.
International Publication WO02 / 087622

  In Patent Document 1, in order to impart sufficient gelation ability to the water-swellable gel-forming layer, the thickness of the water-swellable gel-forming layer needs to be 10 μm or more. However, increasing the thickness of the water-swellable gel-forming layer increases the amount of water and time required for the water-swellable gel-forming layer to gel, which may lead to a decrease in medication compliance.

  On the other hand, the reduction in the thickness of the water-swellable gel-forming layer can reduce the amount of water and time required for the water-swellable gel-forming layer to gel, but the gelation ability of the water-swellable gel-forming layer. Therefore, a gel with sufficient strength is not formed, and there is a risk of lowering compliance.

  Therefore, an object of the present invention is to provide an oral administration agent having a gel-forming laminate unit that can rapidly gel with a small amount of water and can form a gel with sufficient strength.

  In order to solve the above-mentioned problems, the present invention provides an oral administration agent having a drug-containing layer and a gel-forming laminated unit, wherein the gel-forming laminated unit is a first water-swellable gel having a thickness of less than 10 μm. Provided is an oral dosage form comprising: a forming layer; and a second water-swellable gel-forming layer having a thickness of less than 10 μm laminated on the first water-swellable gel-forming layer via an intermediate layer containing polyvinylpyrrolidone To do.

  Since the thickness of the first and second water-swellable gel-forming layers is less than 10 μm, the amount of water and time required for the first and second water-swellable gel-forming layers to gel are small. Therefore, the first and second water-swellable gel forming layers can be rapidly gelled with a small amount of water. On the other hand, the gelation ability of the first and second water-swellable gel-forming layers is also small, and each of them cannot form a gel with sufficient strength. However, due to the interaction between the polyvinylpyrrolidone contained in the intermediate layer and the water-swellable gel-forming agent contained in the first and second water-swellable gel-forming layers, the gel-forming laminated unit has sufficient strength as a whole. The gel can be formed.

  The lower limit of the thickness of the first and second water-swellable gel forming layers is not particularly limited, but is preferably 1 μm. The lower limit of the thickness of the intermediate layer containing polyvinyl pyrrolidone is not particularly limited, but is preferably 1 μm. The gel-forming laminate unit may be composed of a first water-swellable gel-forming layer, an intermediate layer, and a second water-swellable gel-forming layer, or may have other functional layers. . The total thickness of the gel-forming laminated unit may be less than 10 μm, or 10 μm or more.

  The oral administration agent of the present invention has one or more gel-forming laminated units on one side of the drug-containing layer, and one or more gel-forming laminated units on the other side of the drug-containing layer. It is preferable. The oral administration agent of the present invention has gel-forming units on both sides of the drug-containing layer, thereby improving the ease of swallowing, ease and safety when taking the oral administration agent of the present invention. The masking effect such as the taste and smell of the drug in the contained layer is improved.

  In the oral administration agent of the present invention, the water-swellable gel-forming agent contained in the first and second water-swellable gel-forming layers is preferably polyacrylic acid. When the water-swellable gel-forming agent contained in the first and second water-swellable gel-forming layers is polyacrylic acid, the interaction with the polyvinyl pyrrolidone contained in the intermediate layer increases, and the gel-forming laminate The unit as a whole can form a gel with sufficient strength.

In the oral administration agent of the present invention, it is preferable that a water-swellable gel-forming layer is provided on the outermost layer of the oral administration agent.
The water-swellable gel-forming layer provided in the outermost layer of the orally-administered agent may be a water-swellable gel-forming layer contained in the gel-forming laminate unit, or other water-swellable gel-forming layers. Good.

  In the present invention, the “outermost layer” means a layer constituting the outer surface of the oral administration agent when the oral administration agent is in the oral cavity of a patient or the like. Therefore, the “outermost layer” includes not only the layer constituting the outer surface of the orally-administered agent before administration but also the outer surface of the orally-administered agent before administration, but the oral-administered agent when in the oral cavity of the patient. A layer constituting the outer surface is also included. For example, even when another layer is provided as an outer layer of the water-swellable gel-forming layer, if this outer layer is decomposed or dissolved by moisture such as saliva in the patient's mouth, In the oral cavity, the water-swellable gel-forming layer constitutes the outer surface of the orally-administered agent, so that the water-swellable gel-forming layer is provided in the outermost layer of the orally-administered agent.

The water-swellable gel-forming layer provided on the outermost layer of the orally administered agent swells and gels with moisture such as saliva in the patient's mouth, and the orally administered agent has a size, shape, elasticity, viscosity, etc. that are easy to swallow. The dosage form changes. Accordingly, the patient can easily take the oral preparation. In addition, since the risk of the oral administration agent becoming clogged in the trachea of the patient during taking is reduced, it can be safely taken even if the patient is an elderly person or an infant. In the case of a patient who has little saliva and the water-swellable gel-forming layer does not sufficiently gel, the same effect can be exhibited by taking it together with a small amount of water or pre-dipping in water before administration. The amount of water required at this time is very small compared to the amount of water required when taking solid preparations such as tablets and capsules.
In addition, the water-swellable gel-forming layer provided in the outermost layer of the orally-administered agent swells and gels with moisture such as saliva in the oral cavity of the patient, and the taste of the drug contained in the drug-containing layer (for example, bitterness, Astringency), odor, etc. can be masked.

The oral administration agent of the present invention is preferably a film-form preparation.
When the oral administration agent of the present invention is a film-form preparation, the water content in the preparation can be kept low, so that the drug contained in the drug-containing layer (especially compared to the jelly-form preparation containing a large amount of water) The stability of drugs that are easily hydrolyzed can be improved. Furthermore, handling of the preparation becomes easy and the packaging cost of the preparation can be reduced. Further, when the orally administered agent is a film-form preparation, even if the drug amount of the drug-containing layer increases and the film strength of the drug-containing layer decreases, the film-forming property in the water-swellable gel-forming layer and / or intermediate layer The strength of the film-form preparation as a whole can be maintained. Therefore, the drug-containing layer can contain a wide variety of drugs ranging from a very small amount of drug to a large amount of drug.

  ADVANTAGE OF THE INVENTION According to this invention, the oral administration agent which has a gel formation lamination | stacking unit which can be rapidly gelatinized with a small water content and can form a gel of sufficient intensity | strength is provided.

Hereinafter, embodiments of the present invention will be described with reference to the drawings.
As shown in FIG. 1, an oral administration agent 1a according to an embodiment of the oral administration agent of the present invention includes a drug-containing layer 11a and a gel-forming laminated unit U1 provided on one side of the drug-containing layer 11a. And a gel-forming laminate unit U2 provided on the other side of the drug-containing layer 11a.

  The orally administered agent 1a is preferably a film-form preparation (sheet-form preparation). When the orally-administered agent 1a is a film-form preparation, the water content in the preparation can be kept low. Therefore, compared to a jelly-form preparation containing a large amount of water, the drug contained in the drug-containing layer 11a (especially water) It is possible to improve the stability of drugs that are easily decomposed. In addition, the preparation can be handled easily and the packaging cost of the preparation can be reduced.

  The thickness of the orally administered agent 1a can be appropriately adjusted within a range that can be administered orally. When the orally-administered agent 1a is a film-form preparation, the thickness of the orally-administered agent 1a is usually 10 to 1000 μm, preferably 30 to 800 μm, and more preferably 50 to 500 μm. When the thickness of the orally-administered agent 1a is less than 10 μm, the film may become brittle, while when the thickness of the orally-administered agent 1a exceeds 1000 μm, the film becomes stiff and difficult to take.

The drug-containing layer 11a is a layer containing a drug to be administered.
The thickness of the drug-containing layer 11a can be appropriately adjusted within a range that can be administered orally. When the orally administered agent 1a is a film-form preparation, the thickness of the drug-containing layer 11a is preferably 0.1 to 1000 μm, and more preferably 10 to 200 μm. If the thickness of the drug-containing layer 11a is less than 0.1 μm, it becomes difficult to form a film with high precision (that is, the drug content of the drug-containing layer 11a varies), while the thickness of the drug-containing layer 11a is 1000 μm. Exceeding this makes the film stiff and difficult to take.

  The drug-containing layer 11a may consist of only the drug to be administered, but is usually a pharmaceutically acceptable shaping as a base for holding the drug to be administered in a desired state in the drug-containing layer. An agent, a binder, a disintegrant, a masking agent, a colorant, a plasticizer, and the like may be included. Examples of the base include cellulose such as crystalline cellulose, carboxymethyl cellulose, hydroxypropyl cellulose, hydroxypropyl methyl cellulose, methyl cellulose, ethyl cellulose, cellulose acetate, cellulose acetate phthalate, hydroxypropyl methyl cellulose phthalate, hydroxypropyl methyl cellulose acetate succinate, carboxymethyl ethyl cellulose, and the like. And derivatives thereof or pharmaceutically acceptable salts thereof (for example, sodium salts); starch and derivatives thereof such as α-starch, oxidized starch, sodium carboxymethyl starch, hydroxypropyl starch, dextrin, dextran; pullulan, xanthan gum, Sugars such as cyclodextrin; xylitol, mannitol Sugar alcohols such as sorbitol; dimethylaminoethyl methacrylate / methacrylic acid copolymer, methacrylic acid / ethyl acrylate copolymer, methacrylic acid / methyl methacrylate copolymer, ethyl methacrylate / methacrylic acid trimethylammonium copolymer , Acrylic acid derivatives such as dimethylaminoethyl methacrylate / methacrylic acid methyl copolymer, methacrylic acid / ethyl acrylate copolymer; shellac; polyvinyl acetal diethylaminoacetate; polyvinyl acetate; polyvinyl alcohol; polyvinyl pyrrolidone; Vinylpyrrolidone copolymers; natural rubbers such as gum arabic and tragacanth; polyglucosamines such as chitin and chitosan; gelatin, casein, dye Proteins such as protein and the like can be mentioned, and one or more of them can be selected and used according to the purpose of addition. In addition, the drug-containing layer 11a has titanium oxide, calcium monohydrogen phosphate, calcium carbonate, talc, stearate, magnesium aluminate metasilicate, magnesium silicate, anhydrous silica for the purpose of coloring and improving shape retention. One or more kinds of inorganic fillers such as acids can be selected and added. Further, the drug-containing layer 11a is provided with propylene glycol, polyethylene glycol, glycerin, sorbitol, glycerin triacetate, diethyl phthalate, triethyl citrate, lauric acid, sucrose in order to impart appropriate flexibility to the drug-containing layer 11a. One or two of plasticizers such as these can be selected and added.

  The total amount of the base contained in the drug-containing layer 11a is an amount capable of forming the drug-containing layer 11a, and the amount can be appropriately adjusted according to the type of the base. It is usually 20% by mass or more, preferably 60% by mass or more, and more preferably 70% by mass or more of the containing layer 11a. When the total content of the base is less than 20% by mass, the drug-containing layer 11a is not sufficiently formed. In addition, the upper limit of the total content of the base can be appropriately set according to the content of the drug.

  The drug contained in the drug-containing layer 11a is a drug to be administered to a patient or the like, and is not particularly limited as long as it can be administered orally. As drugs that can be administered orally, for example, drugs acting on the central nervous system include hypnotics such as sodium pentobarbital; psychotropic drugs such as amitriptine hydrochloride, imipramine hydrochloride, chlorpromazine, levomepromazine; pronase, dipotassium glycyrrhizinate, loxoprofen sodium, etc. Analgesics and anti-inflammatory drugs; central nervous system metabolism stimulators such as disodium adenosine triphosphate; migraine treatments such as dimethothiazine mesylate; expectorants such as ethylcysteine hydrochloride; Anti-asthmatic drugs such as theophylline, terbutaline sulfate, tranilast, and procaterol hydrochloride; as drugs acting on the circulatory system, cardiotonic drugs such as aminophylline; antiarrhythmic drugs such as procainamide hydrochloride and mexiletine hydrochloride; alprenolol hydrochloride, dillar hydrochloride Antianginal drugs such as dihydrothiazem hydrochloride and trimetazidine hydrochloride; peripheral vasodilators such as kallidinogenase; antihypertensive drugs such as captopril, clonidine hydrochloride, metoprolol tartrate, hydralazine hydrochloride, propranolol hydrochloride; dextran sodium sulfate sodium, pravastatin sodium, etc. Anti-arteriosclerotic drugs; hemostatic agents such as tranexamic acid as blood and hematopoietic agents; antithrombotic agents such as ticlopidine hydrochloride and warfarin potassium; anti-anemic agents such as iron sulfate; famotidine as a drug acting on the digestive system , Cimetidine, ranitidine hydrochloride, rabeprazole sodium, etc .; antiemetics such as metoclopramide; digestive enzyme preparations; liver extract hydrolysates, glucuronolactone, diisopropylamine dichloroacetate, etc .; Laxatives; anti-diabetic drugs such as acarbose and voglibose as drugs acting on metabolic diseases; anti-vertigo drugs such as betahistine mesylate and isosorbide as drugs in otolaryngology; isoniazid and hydrochloric acid as chemotherapeutic drugs and antibiotics Ethambutol, erythromycin lactopionate, sodium fosfomycin, etc .; as antineoplastic agent, cyclophosphamide, etc .; as hormones and endocrine therapeutic agents, thiamazole, sodium prednisolone phosphate, sodium betamethasone phosphate, etc .; bioactive substance (autocoid) Antihistamines such as diphenhydramine hydrochloride, cetirizine hydrochloride, chlorpheniramine D- maleate; cetotiamine hydrochloride, thiamine hydrochloride, cobamide, pyridoxine hydrochloride, hydrosocobalamin acetate, nicotinic acid Examples include vitamins such as amide, panthenol, calcium pantothenate, riboflavin sodium phosphate, ascorbic acid and their derivatives, and one or more of these selected for use depending on the purpose of treatment or prevention can do.

  The amount of the drug contained in the drug-containing layer 11a is not particularly limited, but is usually 80% by mass or less, preferably 40% by mass or less, more preferably 30% by mass or less of the drug-containing layer 11a. When the drug content exceeds 80% by mass, the film strength decreases when the orally administered preparation 1a is a film-form preparation. The lower limit of the drug content is appropriately set according to the type of drug to be contained in the drug-containing layer 11a, and is usually about 0.01% by mass.

  The drug-containing layer 11a can contain a wide variety of drugs ranging from a very small amount of drug to a large amount of drug. Here, a small dose means that a single dose is 1 mg or less, and a large dose means that a single dose is 300 mg or more.

  Even when the orally-administered agent 1a is a film-form preparation, the drug-containing layer 11a can contain a wide variety of drugs ranging from a very small dose to a large amount of drug. This is because the drug-containing layer, the water-swellable gel-forming layer and the intermediate layer are formed as separate layers, so even if the drug content of the drug-containing layer increases and the film strength of the drug-containing layer decreases, This is because the strength of the film-form preparation as a whole can be maintained by imparting film-forming properties to the water-swellable gel-forming layer and / or the intermediate layer.

  As shown in FIG. 1, the gel-forming laminate unit U1 includes a water-swellable gel-forming layer 12a and a water-swellable gel-forming layer 12a ′ laminated on the water-swellable gel-forming layer 12a via an intermediate layer 13a. And is directly laminated on one side of the drug-containing layer 11a. Further, as shown in FIG. 1, the gel-forming laminate unit U2 includes a water-swellable gel-forming layer 12b and a water-swellable gel-forming layer 12b that is laminated on the water-swellable gel-forming layer 12b via an intermediate layer 13b. And is directly laminated on the other side of the drug-containing layer 11a.

  The thicknesses of the gel-forming laminate units U1 and U2 can be appropriately adjusted within a range that can be administered orally. When the orally administered agent 1a is a film-form preparation, the thickness of each of the gel-forming laminated units U1 and U2 is usually 3 μm or more and less than 50 μm, preferably 5 μm or more and less than 40 μm. When the thickness of the gel-forming laminate units U1 and U2 is less than 3 μm, gel formation is insufficient, while when the thickness of the gel-forming laminate units U1 and U2 is 50 μm or more, it is administered into the oral cavity of a patient or the like. When this is done, a sufficient gel cannot be formed quickly, making it difficult to take.

  The water-swellable gel-forming layers 12a, 12a ', 12b and 12b' contain a water-swellable gel-forming agent and can swell with water to form a gel.

  The water-swellable gel-forming layers 12a, 12a ', 12b and 12b' all have a thickness of less than 10 μm. By setting the thickness of each water-swellable gel-forming layer to less than 10 μm, it is possible to reduce the time and water content required for each water-swellable gel-forming layer to gel. That is, each water-swellable gel forming layer can be rapidly gelled with a small amount of water. On the other hand, by setting the thickness of each water-swellable gel-forming layer to less than 10 μm, the gelation ability of each water-swellable gel-forming layer is also reduced, and a gel with sufficient strength cannot be formed alone. However, due to the interaction between the polyvinylpyrrolidone contained in the intermediate layer 13a and the water-swellable gel-forming agents contained in the water-swellable gel-forming layers 12a and 12a ′, the gel-forming laminate unit U1 has sufficient strength as a whole. The gel can be formed. Similarly, the gel-forming laminated unit U2 can form a gel having sufficient strength as a whole.

  The lower limit of the thickness of the water-swellable gel-forming layers 12a, 12a ', 12b and 12b' is not particularly limited as long as the layers can be formed and gelled, but is preferably 1 µm. When the thickness of each water-swellable gel-forming layer is less than 1 μm, layer formation becomes difficult and gelation becomes insufficient.

  The water-swellable gel-forming agent contained in the water-swellable gel-forming layers 12a, 12a ′, 12b and 12b ′ is not particularly limited as long as it can swell with water to form a gel, It may be cross-linked or not cross-linked.

  Examples of the water-swellable gel-forming agent include carboxyvinyl polymer, starch and derivatives thereof, agar, alginic acid, arabinogalactan, galactomannan, cellulose and derivatives thereof, carrageen, dextran, tragacanth, gelatin, pectin, hyaluronic acid, gellan gum , Collagen, casein, xanthan gum, etc., and one or more of these can be selected and used.

  The water-swellable gel-forming agent contained in the water-swellable gel-forming layers 12a, 12a ′, 12b and 12b ′ is preferably a carboxyvinyl polymer, particularly polyacrylic acid, and a cross-linked carboxyvinyl polymer, particularly cross-linked. More preferably, it is polyacrylic acid. Polyacrylic acid does not adversely affect the film-forming ability of the film-forming agent, and can exhibit a moderate gel strength during swelling. Moreover, polyacrylic acid can interact with polyvinylpyrrolidone contained in the intermediate layers 13a and 13b at the time of gel formation, and can form a gel with high gel strength.

  Crosslinking can be performed with a crosslinking agent depending on the type of molecule to be crosslinked. As a polyacrylic acid crosslinking agent, for example, a polyvalent metal compound can be used. Specific examples of the polyvalent metal compound include calcium chloride, magnesium chloride, aluminum chloride, aluminum sulfate, potassium alum, iron chloride alum, ammonium alum, ferric sulfate, aluminum hydroxide, aluminum silicate, aluminum phosphate, citric acid. Examples thereof include iron oxide, magnesium oxide, calcium oxide, zinc oxide, and zinc sulfate. Among these, when a trivalent metal compound is used, the degree of cross-linking of polyacrylic acid increases, and when an interaction between cross-linked polyacrylic acid and polyvinyl pyrrolidone occurs, a gel with high gel strength is formed. Can do.

  The amount of the water-swellable gel-forming agent contained in the water-swellable gel-forming layers 12a, 12a ′, 12b and 12b ′ is not particularly limited and is appropriately adjusted according to the type of the water-swellable gel-forming agent. However, it is usually 10% by mass or more, preferably 20% by mass or more, more preferably 40% by mass or more of each water-swellable gel-forming layer. The upper limit of the amount of the water-swellable gel forming agent is 100% by mass.

  When the orally administered agent 1a is a film-form preparation, each water-swellable gel-forming layer contains a film-forming agent in order to improve the film-forming property of the water-swellable gel-forming layers 12a, 12a ′, 12b and 12b ′ It is preferable to make it.

  The type of the film forming agent is not particularly limited as long as it has film forming ability. Specific examples of the film forming agent include polyvinyl alcohol, polyvinyl pyrrolidone, polyvinyl acetate, polyvinyl acetate phthalate, hydroxyalkyl cellulose (for example, hydroxypropylcellulose, hydroxypropylmethylcellulose, hydroxymethylcellulose, hydroxyethylcellulose), alkylcellulose (for example, Methyl cellulose, ethyl cellulose), carboxyalkyl cellulose (for example, carboxymethyl cellulose), (meth) acrylic acid and esters thereof, xanthan gum, carrageenan, alginic acid, etc., and one or more of these should be selected and used Can do.

  The amount of the film-forming agent contained in the water-swellable gel-forming layers 12a, 12a ′, 12b and 12b ′ can be appropriately adjusted according to the type of the film-forming agent, but preferably each water-swellable gel It is 30-85 mass% of a formation layer.

  The film forming agent contained in the water-swellable gel-forming layers 12a, 12a ', 12b and 12b' is preferably water-soluble. When the film-forming agent is water-soluble, moisture easily enters each water-swellable gel-forming layer, and swelling and gel formation of each water-swellable gel-forming layer can be rapidly caused in the oral cavity.

  Examples of the water-soluble film forming agent include polyvinyl alcohol; hydroxyalkyl cellulose such as hydroxypropylcellulose, hydroxypropylmethylcellulose, and methylcellulose; xanthan gum; carrageenan; alginic acid and the like.

  The water-swellable gel-forming layers 12a, 12a ', 12b and 12b' may contain a plasticizer in order to impart appropriate flexibility to the water-swellable gel-forming layers. Examples of the plasticizer include propylene glycol, polyethylene glycol, glycerin, sorbitol, glycerin triacetate, diethyl phthalate, triethyl citrate, lauric acid, sucrose, and the like. Can be used.

  The water-swellable gel-forming layers 12a, 12a ', 12b, and 12b' may contain a masking agent that can mask the taste, smell, and the like of the drug contained in the drug-containing layer 11a. When the water-swellable gel-forming layer contains a masking agent, the masking effect such as the taste and smell of the drug by the water-swellable gel-forming layer can be improved. Masking agents include, for example, those that give sour taste such as citric acid, tartaric acid, fumaric acid, sweeteners such as saccharin, glycyrrhizic acid, sucrose, fructose, mannitol, acesulfame potassium, menthol, mint oil, peppermint, spearmint, etc. Examples thereof include naturalizing agents, natural or synthetic fragrances, and one or two of these can be selected and used.

  When the water-swellable gel-forming layers 12a, 12a ', 12b and 12b' contain polyvinyl alcohol or the like as a film forming agent, these film forming agents can also serve as a masking agent. Thus, it is preferable to use a film forming agent having a masking effect, and it is also preferable to use a water-swellable gel forming agent having a masking effect.

  The water-swellable gel-forming layers 12a, 12a ', 12b and 12b' may contain preservatives such as methyl hydroxybenzoate and propyl hydroxybenzoate; colorants such as edible lake colorants.

  Mixing of additives into the water-swellable gel-forming layers 12a, 12a ′, 12b and 12b ′ generally reduces the strength of the water-swellable gel-forming layer, so that water enters the water-swellable gel-forming layer. The water-swellable gel-forming agent is likely to swell and form gel due to the water that has entered the water-swellable gel-forming layer.

The intermediate layers 13a and 13b are layers containing polyvinyl pyrrolidone (hereinafter sometimes referred to as a polyvinyl pyrrolidone-containing intermediate layer).
The intermediate layers 13a and 13b may contain only polyvinyl pyrrolidone, or may contain a base for holding the polyvinyl pyrrolidone in the intermediate layers 13a and 13b in a desired state. The amount of polyvinylpyrrolidone contained in each intermediate layer is usually 10% by mass or more, preferably 20% by mass or more, and more preferably 40% by mass or more of each intermediate layer. When the amount of polyvinylpyrrolidone contained in each intermediate layer is less than 10% by mass of each intermediate layer, the water-swellable gel-forming agent contained in the water-swellable gel-forming layer and the polyvinylpyrrolidone contained in each intermediate layer And the interaction will be insufficient.

  The thicknesses of the intermediate layers 13a and 13b can be appropriately adjusted within a range that can be administered orally. When the orally administered agent 1a is a film preparation, the thickness of each intermediate layer is preferably 1 μm or more and less than 30 μm, and more preferably 2 μm or more and less than 20 μm. When the thickness of each intermediate layer is less than 1 μm, it becomes difficult to form a film with high precision (that is, the polyvinyl pyrrolidone content of each intermediate layer varies), and the interaction with the water-swellable gel-forming layer is On the other hand, if the thickness of each intermediate layer is 30 μm or more, the ratio of the thickness of the intermediate layer to the thickness of the water-swellable gel-forming layer increases, and sufficient gel strength cannot be obtained (that is, water The surplus components in the intermediate layers 13a and 13b that cause interaction with the swellable gel-forming layers 12a and 12b are dissolved, and no gel is formed as a whole unit, which makes it difficult to take.

  Examples of the base contained in the intermediate layers 13a and 13b include the same bases as the drug-containing layer 11a, and one or more of these can be selected and used.

  The K value of polyvinylpyrrolidone contained in the intermediate layers 13a and 13b is not particularly limited, but is preferably 30 or more, more preferably 60 or more, and most preferably 90 or more. Interaction between the water-swellable gel-forming agent contained in the water-swellable gel-forming layers 12a and 12a ′ and the polyvinyl pyrrolidone contained in the intermediate layer 13a, and the water-swellable gel-forming layers 12b and 12b ′ The interaction between the water-swellable gel-forming agent and the polyvinylpyrrolidone contained in the intermediate layer 13b increases as the K value of the polyvinylpyrrolidone contained in the intermediate layers 13a and 13b increases, and the strength of the formed gel increases. Become. When the K value of polyvinylpyrrolidone contained in the intermediate layers 13a and 13b is 30 or more, a gel having a sufficiently high gel strength can be formed. This improves the ease of swallowing, ease and safety when taking the oral administration agent 1a, and improves the masking effect such as the taste and smell of the drug in the drug-containing layer 11a.

The K value is the intrinsic viscosity of the polymer solution, and is also called the K value of Fikencher.
The K value can be obtained as a value of K that satisfies the following expression.
lnη _r = {75K ² /(1+1.5KC)+K}×C
[Wherein η _r represents relative viscosity, and C represents solute concentration (% (w / v)). ]

  As shown in FIG. 1, in the orally administered agent 1a, the water-swellable gel-forming layers 12a 'and 12b' are provided in the outermost layer of the orally administered agent 1a. When the water-swellable gel-forming layer 12a ′ provided in the outermost layer of the orally-administered agent 1a swells and gels with moisture such as saliva in the patient's oral cavity, polyvinylpyrrolidone and water contained in the intermediate layer 13a Due to the interaction with the water-swellable gel-forming agent contained in the swellable gel-forming layers 12a and 12a ′, the gel-forming laminate unit U1 can form a gel with sufficient strength as a whole. Further, when the water-swellable gel-forming layer 12b ′ provided in the outermost layer of the orally administered agent 1a swells and gels with water such as saliva in the patient's oral cavity, the polyvinylpyrrolidone contained in the intermediate layer 13b And the water-swellable gel-forming agent contained in the water-swellable gel-forming layers 12b and 12b ′, the gel-forming laminate unit U2 can also form a gel with sufficient strength as a whole. Thereby, the orally-administered drug 1a changes to a dosage form having a size, shape, elasticity, viscosity and the like that are easy to swallow. Therefore, the patient can easily take the orally administered agent 1a. In addition, since the risk of the oral administration agent becoming clogged in the trachea of the patient during taking is reduced, it can be safely taken even if the patient is an elderly person or an infant. Furthermore, the gelled water-swellable gel-forming layers 12a, 12a ', 12b, and 12b' can mask the taste (for example, bitterness, astringency) and smell of the drug contained in the drug-containing layer 11a. In addition, in the case of patients whose saliva is low and the water-swellable gel-forming layers 12a, 12a ′, 12b and 12b ′ are not sufficiently gelled, they should be taken together with a small amount of water or previously soaked in water before administration. The same effect can be exhibited. The amount of water required at this time is very small compared to the amount of water required when taking solid preparations such as tablets and capsules.

The orally administered agent 1a can be produced, for example, according to the following production method.
[First production method]
A coating liquid for forming a water-swellable gel-forming layer, an intermediate layer or a drug-containing layer is applied to a holding substrate (for example, a plastic film, a mount) or a predetermined layer, sprayed, and then dried. A water-swellable gel-forming layer, an intermediate layer, and a drug-containing layer are laminated in a predetermined order. At this time, as a coating liquid for forming a water-swellable gel-forming layer, a solution (a solvent is, for example, purified water, ethanol, etc.) to which a water-swellable gel-forming agent, a film-forming agent or the like is added, As a coating liquid for forming a drug-containing layer, a solution containing polyvinyl pyrrolidone, a base or the like (solvent is purified water, ethanol, etc.) is used as a coating liquid for forming a drug, A solution to which a base or the like is added (a solvent is, for example, purified water or ethanol) can be used.

[Second production method]
A coating liquid for forming the first water-swellable gel-forming layer is applied on the upper side of the holding substrate, sprayed, etc., and dried to form the first water-swellable gel-forming layer. The intermediate layer is formed by applying, spraying, and the like a coating liquid for forming the intermediate layer on the upper side of the water-swellable gel-forming layer. Next, a coating liquid for forming the second water-swellable gel-forming layer is applied on the upper side of the intermediate layer, sprayed, and dried to form the second water-swellable gel-forming layer, and then the second water-swellable gel-forming layer is formed. A coating liquid for forming a drug-containing layer is applied, sprayed, and dried on the upper side of the water-swellable gel-forming layer to form a drug-containing layer. In this way, an intermediate in which the first water-swellable gel-forming layer, the intermediate layer, the second water-swellable gel-forming layer, and the drug-containing layer are sequentially laminated on the holding substrate is manufactured, and the intermediate drug-containing layer Heat-seal together. Thermal fusion can be performed, for example, under conditions of 60 to 120 ° C., 1 to 5 kgf / cm ² , and 0.1 to 10 seconds.

  In the first production method and the second production method, the laminate in which the water-swellable gel-forming layer, the intermediate layer, and the drug-containing layer are laminated in a predetermined order is punched into an arbitrary shape such as a circle, an ellipse, or a polygon. May be.

  In the orally administered agent 1a, the gel-forming laminated unit U1 or U2 may be laminated on the drug-containing layer 11a via an intermediate layer. For example, as shown in FIG. 2, an oral administration agent 1b according to an embodiment of the oral administration agent of the present invention is provided via a drug-containing layer 11a and an intermediate layer 14a on one side of the drug-containing layer 11a. The gel-forming laminate unit U1 and the gel-forming laminate unit U2 provided on the other side of the drug-containing layer 11a via the intermediate layer 14b.

  Various functions, for example, a function as an adhesive layer, a function as a layer for adjusting the film thickness, and the like can be imparted to the intermediate layers 14a and 14b. When the functions as an adhesive layer are imparted to the intermediate layers 14a and 14b, the adhesive contained in the intermediate layers 14a and 14b is not particularly limited as long as it is a pharmaceutically acceptable adhesive, and a solvent is used. Examples of adhesives that exhibit adhesiveness when used in the state include carboxyvinyl polymer, polyacrylic acid such as sodium polyacrylate, or a pharmaceutically acceptable non-toxic salt thereof, an acrylic acid copolymer, or a pharmaceutical thereof Pharmaceutically acceptable salts, hydrophilic cellulose derivatives such as carboxymethylcellulose and sodium salt, pullulan, povidone, karaya gum, pectin, xanthan gum, tragacanth, alginic acid, gum arabic, acidic polysaccharides or derivatives thereof or pharmaceutically acceptable salts thereof Salt, etc. can be used, and the adhesiveness is exhibited by heating. The Chi heat-sealable) adhesives, for example, can be used vinyl acetate, homopolymers such as polyvinylpyrrolidone, copolymers such as of vinyl acetate and vinylpyrrolidone.

  In the orally administered agent 1a, the number of gel-forming laminated units provided on one or the other side of the drug-containing layer 11a is not particularly limited, and may be two or more. When a plurality of gel-forming laminated units are provided on one or the other side of the drug-containing layer 11a, the gel-forming laminated units may be directly laminated to each other, but are laminated via a polyvinylpyrrolidone-containing intermediate layer. It is preferable.

  For example, as shown in FIG. 3, an oral administration agent 1c according to an embodiment of the oral administration agent of the present invention includes a drug-containing layer 11a and a gel-forming laminated unit provided on one side of the drug-containing layer 11a. U1 and U1 ′, a polyvinylpyrrolidone-containing intermediate layer 15a provided between the gel-forming laminate units U1 and U1 ′, and gel-forming laminate units U2 and U2 ′ provided on the other side of the drug-containing layer 11a And a polyvinylpyrrolidone-containing intermediate layer 15b provided between the gel-forming laminate units U2 and U2 ′. The gel-forming lamination units U1 'and U2' can be configured in the same manner as the gel-forming lamination units U1 and U2. The polyvinylpyrrolidone-containing intermediate layers 15a and 15b can be configured in the same manner as the intermediate layers 13a and 13b.

In the orally administered agent 1a, the drug-containing layer 11a may be formed of a plurality of drug-containing layers.
For example, as shown in FIG. 4, an oral administration agent 1d according to an embodiment of the oral administration agent of the present invention includes a drug-containing layer 11a formed from drug-containing layers 11a ′ and 11a ″ provided sideways. The gel-forming laminate unit U1 provided on one side of the drug-containing layer 11a and the gel-forming laminate unit U2 provided on the other side of the drug-containing layer 11a.

When the drug-containing layer 11a is formed from a plurality of drug-containing layers, the drug-containing layers may be directly stacked on each other or may be stacked via an intermediate layer.
For example, as shown in FIG. 5, an oral administration agent 1e according to one embodiment of the oral administration agent of the present invention is a drug formed from drug-containing layers 11a ′ and 11a ″ laminated via an intermediate layer 16a. It includes a containing layer 11a, a gel-forming laminated unit U1 provided on one side of the drug-containing layer 11a, and a gel-forming laminated unit U2 provided on the other side of the drug-containing layer 11a. The intermediate layer 16a can be configured similarly to the intermediate layers 14a and 14b.

  The oral administration agents 1a to 1e are layered drugs in which a plurality of layers are laminated in a flat shape, but may be in any shape as long as they are layered. Orally administered agents 1a to 1e may be held on a holding substrate or may be peeled off from the holding substrate.

EXAMPLES Hereinafter, although an Example and a comparative example demonstrate this invention further in detail, this invention is not limited to an Example.
[Example 1 and Comparative Example 1]
(1) Preparation of water-swellable gel-forming layer forming liquid (coating liquid A) Coating liquid A was prepared in order to form a water-swellable gel-forming layer. 360 g of purified water was taken, 0.3 g of calcium chloride (calcium chloride H (Tonda Pharmaceutical)) was added therein, and the mixture was stirred and completely dissolved. Next, 11.3 g of polyacrylic acid (Carbopol 974P (Noveon)) was slowly added with stirring and stirred for about 1 hour to completely dissolve. Subsequently, 33.8 g of polyvinyl alcohol (Gosenol EG-05T (Nippon Synthetic Chemical)) was slowly added with stirring, and the mixture was stirred for about 1 hour while being heated to 70 ° C., and completely dissolved. 4.0 g of concentrated glycerin (Japanese Pharmacopoeia concentrated glycerin (Asahi Denka Kogyo)) was added to the solution returned to room temperature and stirred for about 5 minutes.

  Polyacrylic acid is cross-linked by calcium ions generated by the ionization of calcium chloride, and the cross-linked polyacrylic acid serves as a water-swellable gel-forming agent, and polyvinyl alcohol serves as a film-forming agent.

(2) Preparation of intermediate layer forming liquid (coating liquid B) A coating liquid B was prepared in order to form an intermediate layer containing polyvinylpyrrolidone. 62.7 g of purified water is taken, 0.6 g of titanium oxide (Typaque CR-50 (Ishihara Sangyo)) is added thereto, and after sufficiently dispersed using a homogenizer, polyvinylpyrrolidone (Prasudone K-90) is added therein. (ISP Japan), K value 90) 16.3 g was slowly added with stirring, and stirred for about 30 minutes to completely dissolve. Next, 4.0 g of concentrated glycerin (Japanese Pharmacopoeia Concentrated Glycerin (Asahi Denka Kogyo)) was added and stirred for about 5 minutes.

(3) Preparation of intermediate layer forming liquid (coating liquid C) Coating liquid C was prepared in order to form an intermediate layer containing polyvinyl alcohol instead of polyvinylpyrrolidone. 62.7 g of purified water is taken, 0.6 g of titanium oxide (Typaque CR-50 (Ishihara Sangyo)) is added therein, and after being sufficiently dispersed using a homogenizer, polyvinyl alcohol (Gosenol EG-05T) is added therein. (Nippon Synthetic Chemical Co., Ltd.) 16.3 g was slowly added with stirring, and the mixture was stirred for about 1 hour while being heated with warm water at 70 ° C. to be completely dissolved. After returning the solution to room temperature, 4.0 g of concentrated glycerin (Japanese Pharmacopoeia concentrated glycerin (Asahi Denka Kogyo)) was added and stirred for about 5 minutes.

(4) Preparation of drug-containing layer forming liquid (coating liquid D) Coating liquid D was prepared in order to form a drug-containing layer containing polyvinylpyrrolidone. Take 62.7 g of purified water, add 2.5 g of famotidine which is a gastric ulcer drug and 0.6 g of titanium oxide (Typaque CR-50 (Ishihara Sangyo)), and disperse it thoroughly using a homogenizer. 13.8 g of polyvinylpyrrolidone (Prasudone K-90 (ISP Japan), K value 90) was slowly added to the solution while stirring, and stirred for about 30 minutes to completely dissolve it. Next, 4.0 g of concentrated glycerin (Japanese Pharmacopoeia Concentrated Glycerin (Asahi Denka Kogyo)) was added and stirred for about 5 minutes.

(5) Preparation of drug-containing layer forming liquid (coating liquid E) Coating liquid E was prepared in order to form a drug-containing layer containing polyvinyl alcohol instead of polyvinylpyrrolidone. Take 62.7 g of purified water, add 2.5 g of famotidine which is a gastric ulcer drug and 0.6 g of titanium oxide (Typaque CR-50 (Ishihara Sangyo)), and disperse it thoroughly using a homogenizer. 13.8 g of polyvinyl alcohol (Gosenol EG-05T (Nippon Synthetic Chemical)) was slowly added with stirring, and the mixture was completely dissolved by stirring for about 1 hour while heating with warm water at 70 ° C. After returning the solution to room temperature, 4.0 g of concentrated glycerin (Japanese Pharmacopoeia concentrated glycerin (Asahi Denka Kogyo)) was added and stirred for about 5 minutes.

(6) Production of Laminate A1 (Example Product) After sufficiently defoaming the coating liquid A, a polyethylene terephthalate film (Lintec Co., Ltd.) was used using an applicator whose gap was adjusted so that the thickness after drying was 3 μm. The product was spread-coated on the surface opposite to the silicone resin release surface of the product made by the company, product name: SP-PET3811), and dried at 80 ° C. for 5 minutes to form a water-swellable gel-forming layer. Next, after sufficiently defoaming the coating liquid B, it was spread and applied on the water-swellable gel-forming layer using an applicator with a gap adjusted so that the thickness after drying was 3 μm. A polyvinylpyrrolidone-containing layer was formed by drying for minutes. Next, after sufficiently defoaming the coating liquid A, using an applicator in which the gap was adjusted so that the thickness after drying was 3 μm, it was spread applied on the polyvinylpyrrolidone-containing layer and dried at 80 ° C. for 5 minutes. Thus, a water-swellable gel forming layer was formed. Next, after sufficiently defoaming the coating liquid D, the coating liquid D was spread and applied on the water-swellable gel-forming layer using an applicator whose gap was adjusted so that the thickness after drying was 25 μm. Dried for minutes to form a drug-containing layer. Thus, an intermediate A1 ′ in which the water-swellable gel-forming layer (thickness 3 μm), the polyvinylpyrrolidone-containing intermediate layer (thickness 3 μm), the water-swellable gel-forming layer (thickness 3 μm) and the drug-containing layer (thickness 25 μm) are sequentially laminated. 2 sheets were manufactured, and the drug-containing layers of the intermediate A1 ′ were heat-sealed at 100 ° C., 1 kgf / cm ² , for 1 second, a water-swellable gel-forming layer (thickness 3 μm), and a polyvinylpyrrolidone-containing intermediate Layer (thickness 3 μm), water-swellable gel-forming layer (thickness 3 μm), drug-containing layer (thickness 25 μm + 25 μm), water-swellable gel-forming layer (thickness 3 μm), polyvinylpyrrolidone-containing intermediate layer (thickness 3 μm) and water-swellable gel A laminate A1 (total layer thickness 68 μm) in which the formation layers (thickness 3 μm) were sequentially laminated was manufactured.

(7) Production of Laminate B1 (Comparative Example Product) A water-swellable gel-forming layer (thickness: 3 μm) is obtained in the same manner as the laminate A1, except that the coating liquid C is used instead of the coating liquid B. Polyvinyl alcohol-containing intermediate layer (thickness 3 μm), water-swellable gel-forming layer (thickness 3 μm), drug-containing layer (thickness 25 μm + 25 μm), water-swellable gel-forming layer (thickness 3 μm), polyvinyl alcohol-containing intermediate layer (thickness 3 μm) and A laminate B1 (total layer thickness 68 μm) in which water-swellable gel-forming layers (thickness 3 μm) were sequentially laminated was produced.

(8) Production of Laminate C1 (Comparative Example Product) After sufficiently defoaming the coating liquid A, a polyethylene terephthalate film (Lintec Corporation) was prepared using an applicator whose gap was adjusted so that the thickness after drying was 9 μm. A product made by the company, product name: SP-PET3811) is spread-coated on the opposite surface of the silicone resin release treatment surface, dried at 80 ° C. for 5 minutes to form a water-swellable gel-forming layer, and then coating solution D After sufficiently defoaming, using an applicator with the gap adjusted so that the thickness after drying is 25 μm, it is spread-coated on the water-swellable gel-forming layer and dried at 80 ° C. for 5 minutes to contain the drug A layer was formed. In this way, two sheets of intermediate C1 ′ in which a water-swellable gel-forming layer (thickness 9 μm) and a drug-containing layer (thickness 25 μm) were sequentially laminated were produced, and the drug-containing layers of intermediate C1 ′ were combined at 100 ° C., 1 kgf / A laminate in which a water-swellable gel-forming layer (thickness: 9 μm), a drug-containing layer (thickness: 25 μm + 25 μm), and a water-swellable gel-forming layer (thickness: 9 μm) are sequentially laminated by heat sealing under conditions of cm ² for 1 second. A body C1 (total layer thickness 68 μm) was produced.

(9) Evaluation of gelation ability After punching the laminates A1, B1 and C1 into a circular shape with a diameter of 15 mm, the polyethylene terephthalate film was removed, and the subjects were randomly extracted and taken without water. The gelation ability was evaluated according to the following five evaluation criteria.

[Evaluation criteria for gelation ability]
5 ... Swells quickly and gels, gives a sufficient gel feeling and can be taken without water.
4 Slowly swells and gels and gives a sufficient gel feeling, but I want to take it with water if possible.
3 ... Swells and gels but dissolves with time, so if possible, take it with water.
2 Slightly swells and gels but dissolves in a short time, so it cannot be taken without water.
1 ... Since it dissolves without swelling or gelling, it cannot be taken without water.

[Example 2 and Comparative Example 2]
(1) Production of laminate A2 (Example product) In the same manner as laminate A1, a water-swellable gel-forming layer (thickness 8 μm), a polyvinylpyrrolidone-containing intermediate layer (thickness 9 μm), a water-swellable gel-forming layer (thickness) 8 μm), drug-containing layer (thickness 25 μm + 25 μm), water-swellable gel-forming layer (thickness 8 μm), polyvinylpyrrolidone-containing intermediate layer (thickness 9 μm), and water-swellable gel-forming layer (thickness 8 μm) (Total layer thickness 100 μm) was manufactured.

(2) Production of Laminate B2 (Comparative Example Product) Similarly to the laminate B1, a water-swellable gel-forming layer (thickness 8 μm), a polyvinyl alcohol-containing intermediate layer (thickness 9 μm), a water-swellable gel-forming layer (thickness) 8 μm), drug-containing layer (thickness 25 μm + 25 μm), water-swellable gel-forming layer (thickness 8 μm), polyvinyl alcohol-containing intermediate layer (thickness 9 μm), and water-swellable gel-forming layer (thickness 8 μm) (Total layer thickness 100 μm) was manufactured.

(3) Manufacture of Laminate C2 (Comparative Product) In the same manner as the laminate C1, a water-swellable gel-forming layer (thickness 25 μm), a drug-containing layer (thickness 25 μm + 25 μm), and a water-swellable gel-forming layer (thickness 25 μm) ) Were sequentially laminated to produce a laminate C2 (total layer thickness 100 μm).

(3) Production of Laminate D (Comparative Example Product) After sufficiently defoaming the coating liquid A, a polyethylene terephthalate film (Lintec Corporation) was used using an applicator whose gap was adjusted so that the thickness after drying was 25 μm. A product made by the company, product name: SP-PET3811) is spread-coated on the opposite surface of the silicone resin release-treated surface and dried at 80 ° C. for 5 minutes to form a water-swellable gel-forming layer. After sufficiently defoaming, using an applicator with a gap adjusted so that the thickness after drying is 50 μm, it is spread and applied on the water-swellable gel-forming layer and dried at 80 ° C. for 5 minutes to contain the drug A layer was formed. Next, after sufficiently defoaming the coating liquid A, using an applicator in which the gap was adjusted so that the thickness after drying was 25 μm, it was spread applied on the drug-containing layer and dried at 80 ° C. for 5 minutes. Thus, a drug-containing layer was formed. Thus, a laminate D (total layer thickness 100 μm) in which a water-swellable gel-forming layer (thickness 25 μm), a drug-containing layer (thickness 50 μm), and a water-swellable gel-forming layer (thickness 25 μm) were sequentially laminated was produced.

(4) Evaluation of gelation ability After punching out the laminates A2, B2, C2 and D into a circular shape with a diameter of 15 mm, the polyethylene terephthalate film was removed, and the subjects were randomly extracted and taken without water. The gelation ability was evaluated according to the following five-stage evaluation criteria.
[Evaluation criteria for gelation ability]
5 ... Swells quickly and gels, gives a sufficient gel feeling and can be taken without water.
4 Slowly swells and gels and gives a sufficient gel feeling, but I want to take it with water if possible.
3 ... Swells and gels but dissolves with time, so if possible, take it with water.
2 Slightly swells and gels but dissolves in a short time, so it cannot be taken without water.
1 ... Since it dissolves without swelling or gelling, it cannot be taken without water.

It is sectional drawing which shows one Embodiment of the oral administration agent of this invention. It is sectional drawing which shows one Embodiment of the oral administration agent of this invention. It is sectional drawing which shows one Embodiment of the oral administration agent of this invention. It is sectional drawing which shows one Embodiment of the oral administration agent of this invention. It is sectional drawing which shows one Embodiment of the oral administration agent of this invention.

Explanation of symbols

1a, 1b, 1c, 1d, 1e ... Orally administered U1, U2 ... Gel-forming laminate unit 11a ... Drug-containing layers 12a, 12a ', 12b, 12b' ... Water-swellable gel formation Layers 13a, 13b ... Polyvinylpyrrolidone-containing intermediate layer

Claims (3)

An orally administered agent that is a film-form preparation having a drug-containing layer and a gel-forming laminated unit,
The oral administration agent has one gel-forming laminated unit on one side of the drug-containing layer, and one gel-forming laminated unit on the other side of the drug-containing layer,
Thickness 3 in which the gel-forming laminate unit is laminated on the first water-swellable gel-forming layer via a first water-swellable gel-forming layer having a thickness of 3 to 8 μm and an intermediate layer containing polyvinylpyrrolidone. Having a second water-swellable gel-forming layer of ˜8 μm,
The oral administration agent wherein the water-swellable gel-forming agent contained in the first and second water-swellable gel-forming layers is polyacrylic acid. Oral administration agent according to claim 1, wherein K value is 30 or more of the polyvinylpyrrolidone. The oral administration agent according to claim 1 or 2 , wherein a water-swellable gel-forming layer is provided in the outermost layer of the oral administration agent.

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