Solid Formulations

Abstract

To provide a solid preparation having an outer layer part and an inner layer part which is improved in rapid disintegrating property of the inner layer part.SOLUTION: There is provided a solid preparation having at least one or more outer layer parts and an inner layer part composed of a foamable composition. Thereby, there can be provided a solid preparation which has an outer layer part and an inner layer part and is improved in rapid disintegrating property of the inner layer part.SELECTED DRAWING: None

Description

[Technical field]

[0001] The present invention relates to a solid preparation, more particularly to a solid preparation for use in the fields of medicines, health foods, and the like. [Background technology]

[0002] As a solid preparation, a conventional pulsed release preparation is known in which an inner layer containing an active ingredient is coated with a sustained-release outer layer, and the active ingredient is dissolved in a specific site in the body such as the intestine. For example, in an enteric pulsed release preparation, a coating that does not dissolve in the acidic environment of the stomach but dissolves in the intestine is provided as the outer layer, and an inner layer containing the active ingredient is provided inside the coating.

[0003] For example, Patent Document 1 discloses a pulsed release formulation in which a disintegrant is blended in the inner layer portion in order to more quickly release the active ingredient contained in the inner layer portion at a specific site in the body. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] International Publication No. 2007 / 037259 Summary of the Invention [Problem to be solved by the invention]

[0005] However, in conventional pulsed release formulations, although the active ingredient contained in the inner layer is released after the outer layer is dissolved, the release rate of the active ingredient at the time of release is not sufficient because the inner layer does not disintegrate rapidly enough.

[0006] An object of the present invention is to provide a solid preparation which comprises an outer layer and an inner layer, the inner layer having improved rapid disintegration properties. [Means for solving the problem]

[0007] Means for Solving the Problems The present inventors have conducted intensive research into the above-mentioned problems, and have come to the discovery that in a solid preparation comprising an outer layer and an inner layer, the rapid disintegration property of the inner layer can be improved by forming the inner layer from a foamable composition, thereby completing the present invention.

[0008] That is, the present invention provides the following [1] to [5]. [1] A solid preparation comprising at least one outer layer and an inner layer made of a foamable composition. This makes it possible to provide a solid preparation having an inner layer portion with improved rapid disintegration properties. [2] The solid formulation according to [1], characterized in that the inner layer portion contains an active ingredient, and when the solid formulation is immersed in purified water, the dissolution time until 20 mass% of the active ingredient is dissolved is 1 hour or more. This makes it possible to provide a solid preparation that can rapidly release the active ingredient after a predetermined period of time. [3] The solid formulation according to [1] or [2], characterized in that the difference between the dissolution time required for 20% by mass of the active ingredient to be dissolved and the dissolution time required for 80% by mass of the active ingredient to be dissolved is 3 hours or less. This makes it possible to provide a solid preparation capable of rapidly releasing the active ingredient in the inner layer portion. [4] The solid formulation according to any one of [1] to [3], wherein the foamable composition contains a foaming component and a foaming assistant. This can improve the foaming power and storage stability of the foamable composition. [5] The solid formulation according to any one of [1] to [4], wherein the outer layer portion contains one or more selected from dextrin, hydroxypropyl methylcellulose, crystalline cellulose, and fats and oils. This makes it possible to more accurately control the dissolution time of the components in the inner layer portion by controlling the dissolution time of the outer layer portion. [6] The solid formulation according to any one of [1] to [5], wherein the active ingredient is caffeine. This makes it possible to provide a solid preparation that rapidly releases caffeine from the inner layer after a predetermined time has elapsed. Effect of the Invention

[0009] According to the present invention, it is possible to provide a solid preparation which comprises an outer layer and an inner layer, and in which the rapid disintegration property of the inner layer is improved. [Brief description of the drawings]

[0010] [Figure 1] 1 is a graph showing the results of a dissolution test of a solid formulation according to the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0011] Hereinafter, embodiments of the solid preparation according to the present invention will be described in detail. The solid preparations described in the embodiments are merely exemplified to explain the present invention, and the present invention is not limited thereto.

[0012] The solid preparation of the present invention is characterized by having at least one outer layer and an inner layer made of a foamable composition, thereby making it possible to provide a solid preparation in which the rapid disintegration property of the inner layer is improved, and preferably the release rate of the active ingredient from the inner layer is improved.

[0013] In the solid preparation of the present invention, the outer layer portion inhibits the intrusion of moisture into the inner layer portion, thereby controlling the disintegration time. When moisture intrudes into the inner layer portion after a predetermined time has elapsed, gas is generated from the inner layer portion made of the foamable composition, causing the inner layer portion to rapidly disintegrate. By utilizing this characteristic, it is possible to provide a solid preparation that contains an active ingredient in the inner layer portion and releases the active ingredient into the body after a predetermined time has elapsed after ingestion of the solid preparation.

[0014] In a solid preparation containing an active ingredient in the inner layer portion, the dissolution time until 20% by mass of the active ingredient is dissolved is preferably 1 hour or more. The lower limit is more preferably 2 hours or more, even more preferably 3 hours or more, and particularly preferably 4 hours or more. The upper limit is preferably 20 hours or less, more preferably 15 hours or less, even more preferably 12 hours or less, and particularly preferably 9 hours or less. The dissolution time of the active ingredient in the inner layer portion can be controlled by adjusting the solubility and disintegration property of the outer layer portion. By controlling the dissolution time until 20% by mass of the active ingredient is dissolved, it is possible to obtain, for example, a preparation that passes through the stomach and disintegrates in the intestine, or a preparation that disintegrates after a predetermined set time such as sleep time has elapsed.

[0015] In addition, in a solid preparation containing an active ingredient in the inner layer portion, the difference between the dissolution time until 20% by mass of the active ingredient is dissolved (hereinafter referred to as "20% dissolution time") and the dissolution time until 80% by mass of the active ingredient is dissolved (hereinafter referred to as "80% dissolution time") (hereinafter referred to as "dissolution time difference") is preferably 3 hours or less. The dissolution time difference is "80% dissolution time - 20% dissolution time". The upper limit of the dissolution time difference is more preferably 2 hours or less, even more preferably 1 hour or less, and particularly preferably 30 minutes or less. By reducing the dissolution time difference, it is possible to provide a solid preparation in which the active ingredient is rapidly released from the inner layer portion.

[0016] The dissolution time is measured by the dissolution test method (paddle method) specified in the Japanese Pharmacopoeia, 17th Edition. The dissolution test is performed using 900 mL of purified water as the test liquid, with the paddle rotation speed at 50 rpm and the test liquid temperature at 37°C. The amount of the dissolved active ingredient is quantified by sampling the test liquid at predetermined time intervals and measuring the content of the active ingredient. The test liquid may be selected from purified water, the first liquid (pH 1.2) or the second liquid (pH 6.8) of the Japanese Pharmacopoeia, 17th Edition dissolution test, or diluted McIlvaine's buffer solution (pH 5.0) depending on the application of the solid preparation.

[0017] The dosage form of the solid preparation of the present invention is not particularly limited as long as it is acceptable for use in pharmaceuticals, quasi-drugs, cosmetics, food, animal medicines, feed, etc., but is preferably a tablet or capsule. Examples of tablets include dry-coated tablets (inner layer: inner core tablet, outer layer: outer layer), film-coated tablets (inner layer: tablet, outer layer: film coat layer), and sugar-coated tablets (inner layer: tablet, outer layer: film coat layer and / or sugar coat layer). Examples of capsules include hard capsule preparations (inner layer: filling, outer layer: hard capsule), and soft capsule preparations (inner layer: filling, outer layer: soft capsule). Among these, tablets are preferred from the viewpoint of easy control of disintegration time, and dry-coated tablets are more preferred.

[0018] The inner layer and the outer layer constituting the solid preparation of the present invention will be described in detail below. [Inner layer of solid formulation] The solid preparation of the present invention has an inner layer made of a foamable composition. When the inner layer comes into contact with water due to dissolution of the outer layer, the foamable composition in the inner layer foams in the presence of water in a living body, causing the inner layer to rapidly disintegrate. This allows the active ingredient in the inner layer to be rapidly dissolved.

[0019] The foamable composition used in the inner layer portion of the present invention is a composition that generates gas when it comes into contact with water, and although there are no particular limitations, it preferably contains a foaming component and a foaming assistant. The foamable composition is substantially free of moisture, where "substantially free" means, for example, less than 5% by volume.

[0020] (Foaming ingredient) The foaming component contained in the foamable composition is one that reacts with a foaming assistant in the presence of water to generate carbon dioxide gas, and is not particularly limited as long as it is acceptable for use in pharmaceuticals, quasi-drugs, cosmetics, foods, veterinary medicines, feeds, etc. Examples of the foaming component include alkali metal carbonates, alkali metal hydrogen carbonates, ammonium carbonate, etc. Specific examples of the foaming component include sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, and ammonium carbonate. A preferred foaming component is sodium hydrogen carbonate from the viewpoint of versatility. These foaming components may be blended alone or in combination of two or more.

[0021] The content of the foaming component in the foamable composition is not particularly limited. The content of the foaming component is, for example, 20% by mass or more and 80% by mass or less. The lower limit is more preferably 30% by mass or more, even more preferably 40% by mass or more, and particularly preferably 50% by mass or more. On the other hand, the upper limit is more preferably 70% by mass or less, even more preferably 65% ​​by mass or less, and particularly preferably 60% by mass or less. By setting the content of the foaming component within the above range, the foamability of the foamable composition can be improved.

[0022] (foaming aid) The foaming assistant contained in the foamable composition is a substance that reacts with the foaming component to generate carbon dioxide gas, and is not particularly limited as long as it is acceptable for use in pharmaceuticals, quasi-drugs, cosmetics, foods, veterinary medicines, feed, etc. Examples of the foaming assistant include organic acids having 2 to 6 carbon atoms. Specific examples of the foaming aid include citric acid, tartaric acid, malic acid, lactic acid, gluconic acid, succinic acid, fumaric acid, oxalic acid, and ascorbic acid. A preferred foaming aid is citric acid from the viewpoint of versatility. These foaming aids may be used alone or in combination of two or more.

[0023] The content of the foaming auxiliary in the foamable composition is not particularly limited. The content of the foaming auxiliary in the foamable composition is, for example, 10% by mass or more and 70% by mass or less. The lower limit is more preferably 20% by mass or more, even more preferably 30% by mass or more, and particularly preferably 40% by mass or more. On the other hand, the upper limit is more preferably 60% by mass or less, even more preferably 55% by mass or less, and particularly preferably 50% by mass or less. In addition, the ratio of the content of the foaming auxiliary to the content of the foaming component in the foamable composition is not particularly limited. The ratio of the content of the foaming auxiliary to the content of the foaming component is, for example, 0.1 or more and 2.0 or less. The lower limit is more preferably 0.3 or more, even more preferably 0.4 or more, and particularly preferably 0.5 or more. On the other hand, the upper limit is more preferably 1.7 or less, even more preferably 1.6 or less, and particularly preferably 1.5 or less. By setting the content of the foaming assistant in the above range, the foamability of the foamable composition can be improved.

[0024] The total amount of the foaming component and the foaming auxiliary in the foamable composition of the present invention is not particularly limited, but is preferably 30 to 99% by mass. From the viewpoint of foamability, the lower limit is more preferably 50% by mass or more, even more preferably 70% by mass or more, and particularly preferably 80% by mass or more. From the viewpoint of the amount of the active ingredient, the upper limit is more preferably 95% by mass or less, and even more preferably 90% by mass or less.

[0025] (Calcium Citrate) The foamable composition of the present invention preferably contains calcium citrate in addition to the foaming component and the foaming assistant. The calcium citrate is intended to inhibit the reaction between the foaming component and the foaming assistant. The calcium citrate inhibits the reaction between the foaming component and the foaming assistant, so that a foamable composition having improved storage stability can be efficiently produced. The calcium citrate is preferably used to coat the foaming assistant in order to further inhibit the reaction between the foaming component and the foaming assistant.

[0026] The content of calcium citrate is not particularly limited. The content of calcium citrate is, for example, 0.2% by mass or more and 9.0% by mass or less. The lower limit is more preferably 1.0% by mass or more, and even more preferably 1.5% by mass or more. On the other hand, the upper limit is more preferably 6.0% by mass or less, even more preferably 4.0% by mass or less, and particularly preferably 3.0% by mass or less. In addition, the ratio of the content of calcium citrate to the content of the foaming assistant is not particularly limited. The ratio of the content of calcium citrate to the content of the foaming assistant is, for example, 0.01 or more and 0.11 or less. The lower limit is more preferably 0.02 or more, even more preferably 0.03 or more, and particularly preferably 0.04 or more. On the other hand, the upper limit is more preferably 0.09 or less, even more preferably 0.07 or less, and particularly preferably 0.06 or less. By setting the content of calcium citrate within the above range, the foaming power (increase in foaming amount) and storage stability of the foamable composition can be improved.

[0027] (Binding Agent) The foamable composition may be granulated with a binder to form foamable granules. The binder enhances the binding strength of the composition, and is not particularly limited as long as it is acceptable for use in pharmaceuticals, quasi-drugs, cosmetics, food, veterinary medicines, feed, etc. Examples of binders include celluloses, synthetic resins, sugars, polyethers, waxes, etc. Specific examples of binders include hydroxypropyl cellulose, hydroxyethyl cellulose, low-substituted hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl methyl cellulose, carboxymethyl cellulose, carboxymethyl ethyl cellulose, croscarmellose, polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid, polymethacrylic acid, glucose, sucrose, lactose, maltose, dextrin, sorbitol, mannitol, polyethylene glycol, paraffin, gum arabic, gelatin, agar, starch, pullulan, shellac, and zein. Preferred binders are hydroxypropyl cellulose, shellac, and zein from the viewpoints of improving the foaming power and storage stability of the foamable composition and moldability. These binders may be blended alone or in combination of two or more. By forming the foamable composition into effervescent granules, the foaming power (increase in foaming amount) and storage stability of the foamable composition can be further improved, and the processing suitability for tableting is also improved.

[0028] (Coating of foaming components and foaming assistants with a film material) Other means for inhibiting the reaction between the foaming component and the foaming assistant include, for example, coating one or both of the foaming component and the foaming assistant with a coating material, such as hydroxypropyl cellulose, hydroxypropyl methyl cellulose, pullulan, gelatin, shellac, zein, and hardened fats and oils. The storage stability of the foamable composition can be improved by coating either or both of the foaming component and the foaming assistant with a coating material.

[0029] The method for coating the foaming component and the foaming assistant with the coating material is not particularly limited as long as it is a method commonly used in the art, and examples of the coating method include granulation coating, pan coating, rolling coating, fluidized bed coating, and dry coating.

[0030] The particle size of the foaming component and foaming assistant is not particularly limited, but is, for example, 10 μm or more and 1 mm or less. The lower limit is more preferably 50 μm or more, and further preferably 100 μm or more. The upper limit is more preferably 500 μm or less. By making the particle size of the foaming component and foaming assistant 10μm or more, the surface area is reduced, which improves the coating performance of the coating material. Also, by making the particle size 1mm or less, it is excellent in processing suitability such as tableting.

[0031] (Active ingredient) The active ingredient is not particularly limited as long as it exhibits efficacy and effect and is acceptable for use in medicines, foods, veterinary medicines, feeds, and the like. Examples of the active ingredient include medicinal ingredients and functional ingredients used in medicines, quasi-drugs, OTC medicines, Chinese herbal medicines, herbal medicines, cosmetics, cosmetic materials, health foods, supplements, veterinary medicines, feeds, and the like. Specific examples of medicinal ingredients and functional ingredients include vitamin A, vitamin D, vitamin E, vitamin B1, vitamin B2, vitamin B6, vitamin B12, vitamin C, folic acid, biotin, niacin, pantothenic acid, iron, copper, zinc, manganese, selenium, chromium, molybdenum, polyglutamic acid, wisteria tea polyphenols, caffeine, lipid regulators, antidiabetic agents, appetite suppressants, antihypertensive agents, vasodilators, β-adrenergic receptor blockers, cardiac ion channel agents, arrhythmia treatments, anticoagulants, central nervous system function improvers, sympathomimetics, parasympathomimetics, antimuscarinic agonists, dopaminergic agents, tranquilizers, antidepressants, and antiepileptic agents. Examples of the medicinal and functional ingredients include antianxiety agents, hypnotics, stimulants, animal-derived substances, plant-derived substances, lapizin, nobiletin, sulforaphane, ampelopsin, curcumins, resveratrols, geraniol, osajin, isoliquiritigenin, hydroxytyrosol, 25-hydroxycholecalciferol, S-adenosylmethionine, anthocyanin, ascorbic acid 2-glucoside, proteoglycan, N-acetylglucosamine, collagen, bilberry extract, carrot powder, gokahi, licorice, peony root, cinnamon bark, fennel, scutellaria, bifidobacteria, lactic acid bacteria, yeast, and dietary fibers such as polydextrose. These medicinal ingredients and functional ingredients may be blended alone or in combination of two or more.

[0032] (Other Ingredients) In addition to the above-mentioned foaming components, foaming assistants, binders, and active ingredients, the foamable composition of the present invention may contain additives, as necessary, that are used in applications such as medicines, quasi-drugs, cosmetics, foods, veterinary medicines, feeds, etc. Specific examples of additives include excipients, sweeteners, acidulants, flavorings, and colorants.

[0033] The excipient adjusts the bulk of the component composition of the granules, and is not particularly limited as long as it is acceptable for use in pharmaceuticals, quasi-drugs, cosmetics, food, veterinary medicines, feed, etc. Examples of excipients include dextrin, starch, sugars, sugar alcohols, cellulose, crystalline cellulose, etc. These excipients may be used alone or in combination of two or more.

[0034] [Outer layer of solid dosage form] The solid preparation of the present invention has at least one outer layer. The outer layer is not particularly limited as long as it can protect the inner layer from water outside and inside the body and is acceptable for use in medicines, quasi-drugs, cosmetics, food, veterinary medicines, feed, etc. For example, the outer layer may be obtained by tableting a powder composition, such as the outer layer of a dry-coated tablet, a coating such as a film coating or sugar coating, or a capsule such as a hard capsule or a soft capsule. The outer layer is preferably one having properties such as enteric properties and sustained release properties. The solid preparation of the present invention may have one or more of these outer layers. The outer layer may be at least one layer, or may have two or more layers.

[0035] When the outer layer portion is obtained by tableting a powder composition, the powder composition is not particularly limited, but preferably contains an oily component, a binder, and the like. The dissolution time of the outer layer part can be controlled by adjusting the amount of oily component added to the outer layer part. The oily component is not particularly limited as long as it is acceptable for use in pharmaceuticals, quasi-drugs, cosmetics, food, veterinary medicines, feed, etc. Examples of the oily component include natural waxes, higher fatty acids, paraffins, oils and fats, and higher alcohols. Among these, oils and fats are preferred, hydrogenated oils are more preferred, and hydrogenated rapeseed oil is particularly preferred.

[0036] The binder improves the binding force of the powder composition and can control the dissolution time more accurately. The binder is not particularly limited as long as it is acceptable for use in medicines, quasi-drugs, cosmetics, food, veterinary medicines, feed, etc. Examples of the binder include celluloses, synthetic resins, sugars, polyethers, etc. Specific examples of binders include hydroxypropyl cellulose, hydroxyethyl cellulose, low-substituted hydroxypropyl cellulose, hydroxypropyl methyl cellulose, hydroxyethyl methyl cellulose, carboxymethyl cellulose, carboxymethyl ethyl cellulose, croscarmellose, polyvinylpyrrolidone, polyvinyl alcohol, polyacrylic acid, polymethacrylic acid, glucose, sucrose, lactose, maltose, dextrin, sorbitol, mannitol, polyethylene glycol, gum arabic, gelatin, agar, starch, pullulan, shellac, and zein. From the viewpoint of improving sustained release and moldability, hydroxypropyl cellulose is preferred. In addition, these binders may be blended alone or in combination of two or more.

[0037] In addition to the oily component and the binder, the powder composition may contain additives, as necessary, that are used in applications such as medicines, quasi-drugs, cosmetics, foods, veterinary medicines, feed, etc. Specific examples of additives include excipients, sweeteners, acidulants, flavorings, colorants, etc.

[0038] When a coating is used for the outer layer, an enteric coating, a sustained release coating, a film coating, a sugar coating, etc. are used. An enteric coating or a sustained release coating is preferred.

[0039] Examples of enteric coating compositions include cellulose, hydroxypropyl cellulose phthalate, cellulose acetate phthalate, ethyl cellulose, hydroxypropyl cellulose, hypromellose, methyl cellulose, and carboxymethyl cellulose.

[0040] Examples of the composition of the sustained release coating include cellulose, hydroxypropyl cellulose phthalate, cellulose acetate phthalate, ethyl cellulose, hydroxypropyl cellulose, hypromellose, methyl cellulose, and carboxymethyl cellulose.

[0041] Sugar coatings include monosaccharides, disaccharides, sugar alcohols, etc., such as glucose, sucrose, lactose, sorbitol, mannitol, xylitol, erythritol, maltitol, etc. These sugars may be blended alone or in combination of two or more.

[0042] The film coating includes a film coating agent such as a synthetic resin, a polysaccharide, etc., for example, polyvinyl alcohol, polyvinylpyrrolidone, methylcellulose, pullulan, zein, shellac, yeastrap, etc. Furthermore, these film coating agents may be blended alone or in combination of two or more kinds.

[0043] The above coating bases may be used by mixing two or more of them in an appropriate ratio. If necessary, suitable pharmacologically acceptable additives such as plasticizers, excipients, lubricants, masking agents, colorants, and preservatives may be further added. EXAMPLES

[0044] Although examples of the present invention will be described below, the present invention is not limited to these examples, and various modifications are possible within the technical concept of the present invention.

[0045] Experiment 1. Preparation of solid formulations As the solid preparation of the present invention, dry-coated tablets having an inner layer and an outer layer made of an effervescent composition were produced, and the changes in dissolution time and dissolution rate were observed.

[0046] (Manufacturing of inner layer) An inner core tablet having the composition shown in Table 1 was produced as the inner layer of the dry coated tablet. The inner layer 1 was produced by mixing effervescent granules obtained by granulating sodium bicarbonate (foaming agent) and citric acid coated with calcium citrate (foaming assistant) with hydroxypropyl cellulose, fine silicon dioxide (Silopege 720, Fuji Silysia Chemical), calcium stearate, and vitamin B2 (active ingredient) to prepare a powder for tableting. Comparative Example 1 was produced by replacing the effervescent granules of the inner layer 1 with crystalline cellulose (Ceolas FD-101, Asahi Kasei).

[0047] [Table 1]

[0048] (Outer layer manufacturing) A powder composition having the composition shown in Table 2 was produced as the outer layer of the dry coated tablets. The outer layer was manufactured by mixing hydroxypropyl methylcellulose (Metolose NE-4000, manufactured by Shin-Etsu Chemical Co., Ltd.), dextrin (Pinex #2, manufactured by Matsutani Chemical Industry Co., Ltd.), crystalline cellulose (Ceolas FD-101, manufactured by Asahi Kasei Corporation), hardened rapeseed oil (Lubriwax 102H, manufactured by Freund Corporation), fine silica (Silopage 720, manufactured by Fuji Silysia Chemical Ltd.), and calcium stearate to obtain a powder composition.

[0049] The dry-coated tablets were produced using a tablet compression machine (N-30E single punch tablet machine, manufactured by Okada Seiko Co., Ltd.). The inner layer powder was tableted at 1000 kgf to obtain inner core tablets with a flat punch diameter of 5 mm and a particle weight of 75 mg. The powder composition that would become the outer layer and the inner core were compressed into tablets to obtain dry-coated tablets having a diameter of 9 mm and a final particle weight of 300 mg.

[0050] [Table 2]

[0051] (Dissolution test) The manufactured dry coated tablets were subjected to a dissolution test of vitamin B2 using the paddle method of the Japanese Pharmacopoeia general test dissolution test method. The amount of test solution (purified water) was 900 mL, and the paddle rotation speed was 50 rpm. The dissolution rate (%) was measured at 0 minutes, 1 hour, and 4 to 9 hours after the start of the test by ultraviolet-visible absorbance measurement. Each test was performed three times. The results are shown in Figure 1.

[0052] As a result of the experiment, as shown in the graph of FIG. 1, in the dry coated tablet (with effervescence) using the inner layer portion 1, rapid dissolution of vitamin B2 from the inner layer portion was observed about 7 hours after the start of the test. The dissolution time, that is, the time at which the dissolution rate of vitamin B2 from the inner layer portion reached 20%, was 6.5 to 7.5 hours after the start of the test. The difference in dissolution time (80% dissolution time-20% dissolution time) was about 20 minutes. On the other hand, in the dry coated tablet (without effervescence) of Comparative Example 1, almost no dissolution of vitamin B2 was observed even after 8 hours.

[0053] Experiment 2. Examination of the composition of the inner layer Using the inner layer shown in Table 3, inner core tablets were produced in the same manner as in Experiment 1. The partially pregelatinized starch used was (PCS-FC-30, manufactured by Asahi Kasei Corporation).

[0054] (Hardness of the inner core tablet) The hardness of the core tablets was measured using a tablet hardness tester (New Speed ​​Checker TS-75N, manufactured by Okada Seiko Co., Ltd.).

[0055] (Evaluation of the collapsibility of the inner layer) The disintegration properties of the inner core tablets produced in Experiment 2 were evaluated using the disintegration test method of the Japanese Pharmacopoeia General Test Method. Purified water was used as the test liquid. The time from when the outer layer dissolved and the inner core tablet started to dissolve until it disintegrated was measured. The results are shown in Table 3 under "Disintegration Time."

[0056] [Table 3]

[0057] The experimental results show that the inner layer made of the effervescent composition disintegrates rapidly when the inner core tablet starts to dissolve. Furthermore, the inner core tablet having the inner layer made of the effervescent composition exhibited superior disintegration properties compared to the inner core tablet containing a disintegrant (partially pregelatinized starch). In addition, the hardness of the inner core tablet was 10.0 kgf or less, and excellent disintegrability was observed.

[0058] Experiment 3. Examination of the composition of the outer layer Dry-coated tablets were produced in the same manner as in Experiment 1 using the outer layer shown in Table 4 (the inner core tablet was inner layer 1).

[0059] (Evaluation of sustained release properties of outer layer) The disintegration properties of the dry-coated tablets produced in Experiment 3 were evaluated using the disintegration test method of the Japanese Pharmacopoeia General Test Method. Purified water was used as the test liquid. The time from when the outer layer dissolved until when the core tablet started to dissolve was measured. The results are shown in Table 4 under "Time when the core tablet started to dissolve (min)".

[0060] [Table 4]

[0061] The results of Experiment 3 show that the sustained release properties of the outer layer can be controlled by adjusting the formulation of the outer layer. Comparing outer layers 3 to 5, it was found that the inclusion of dextrin and crystalline cellulose improved the sustained release properties of the outer layer. Furthermore, comparing outer layers 1 and 2, or outer layers 6 to 9, it was shown that the dissolution time can be controlled by adjusting the content of fats and oils. [Industrial Applicability]

[0062] The present invention can provide a solid preparation in which the release rate of the component from the inner layer is improved. As a result, the present invention can provide medicines, quasi-drugs, cosmetic preparations, health foods (nutritional supplements, functional foods, foods for the sick, foods for specified health uses, foods with functional claims, etc.), supplements, feeds, etc. in which the release rate of the component from the inner layer is improved.

[0063] According to the present invention, a solid preparation with controlled release of an active ingredient can be provided. For example, a solid preparation for promoting wakefulness can be provided by using caffeine as an active ingredient and adjusting the time until the inner layer starts to dissolve to about 6 hours. When this solid preparation for promoting wakefulness is taken before going to bed, caffeine is rapidly released about 6 hours later, promoting wakefulness.

Claims

1. A dry coated tablet having at least one outer layer and an inner layer made of an effervescent composition, The outer layer portion contains dextrin, and hydroxypropyl methylcellulose or crystalline cellulose, A solid formulation comprising an active ingredient in the inner layer portion, the active ingredient being dissolved in 20% by mass of the dry-coated tablet in 1 hour or more when the dry-coated tablet is immersed in purified water.

2. The solid formulation according to claim 1 , wherein the outer layer contains a hardened oil.

3. 3. The solid formulation according to claim 1, wherein the difference between the dissolution time required for 20% by mass of the active ingredient to be dissolved and the dissolution time required for 80% by mass of the active ingredient to be dissolved is 3 hours or less.

4. The solid formulation according to any one of claims 1 to 3, wherein the foamable composition contains a foaming component and a foaming assistant.

5. The solid formulation according to any one of claims 1 to 4, characterized in that the active ingredient is caffeine.

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