JP5054966B2 - Solid preparation - Google Patents

Description

  The present invention relates to a solid preparation with significantly improved pharmacological disintegration.

  In order for a solid preparation to exert its medicinal effects, it is generally necessary for the active ingredient contained therein to be absorbed from the digestive tract, and as a previous step, the solid preparation must disintegrate and dissolve. Therefore, in tablets that do not disintegrate in vivo after taking or tablets that take time to disintegrate, the availability of active ingredients in the living body is low. Therefore, it is very important to enhance disintegration pharmacologically in order to sufficiently exhibit the medicinal effect of the solid preparation.

  Until now, various attempts have been made to improve the disintegration property of solid preparations. The most commonly practiced method is to incorporate a swelling substance such as starch into the preparation as a disintegrant. Such a swellable substance increases the volume by swelling with water, destroys the internal structure of the solid preparation, and promotes disintegration. As such a disintegrant, for example, corn starch, potato starch, corn starch, hydroxypropyl starch, sodium carboxymethyl starch, crystalline cellulose, hydroxypropyl cellulose, carmellose, carmellose calcium and the like are generally used (non-patented). Reference 1).

  It is also known that a surfactant is used as a disintegration accelerator. Surfactants are considered to promote the swelling of swellable substances such as the above-mentioned starch by enhancing the wettability of the solid preparation in water, thereby enhancing the disintegration of the solid preparation (Non-Patent Document). 2).

  However, the pharmacological disintegration achieved by the prior art as described above is still not fully satisfactory, and further useful techniques are developed to achieve higher pharmacological disintegration of solid preparations. Was desired.

Supervised by Toshio Minamihara, Mix Pharmaceutical Series 4 Pharmaceutical Sciences, Mix Co., Ltd., April 2, 1999, first edition 1 published, page 37 Nanzan-do Medical University Dictionary, Nanzan-do Co., Ltd., February 1, 1996, 17th edition, 7th edition, 1805 pages

  In view of such conventional problems, an object of the present invention is to provide a solid preparation with significantly improved pharmacological disintegration.

  As a result of diligent studies to solve the above problems, the present inventors have found that three components, a medium-chain fatty acid triglyceride having a very low freezing point of −30 ° C. to 15 ° C., a nonionic surfactant, and a sugar alcohol. When combined and blended into a solid preparation, it has been found that the action of these three components can be combined to achieve extremely high pharmacological disintegration, and the present invention has been completed.

Accordingly, the present invention provides the following.
(1) A solid preparation containing (A) a medium-chain fatty acid triglyceride having a freezing point of −30 ° C. to 15 ° C., (B) a nonionic surfactant, and (C) a sugar alcohol.
(2) The solid preparation according to item (1), wherein the (B) nonionic surfactant is a polyoxyethylene sorbitan fatty acid ester.
(3) The solid preparation according to item (1) or (2), wherein the critical relative humidity at 37 ° C. of (C) sugar alcohol is 70% or more.
(4) Any one of Items (1) to (3), wherein (C) the sugar alcohol is at least one selected from the group consisting of D-mannitol, xylitol, erythritol, maltitol, lactitol, and reduced palatinose. The solid preparation according to item.
(5) The solid preparation according to any one of items (1) to (4), which is a tablet.

  According to the present invention, there is provided a solid preparation having a remarkably enhanced pharmaceutical disintegration property that it disintegrates very rapidly when it is in contact with water at the time of administration (during administration). In the present invention, it is very advantageous in that a solid preparation having such extremely high pharmaceutical disintegrability can be obtained by a very simple operation of blending the above-mentioned three components.

  Hereinafter, the present invention will be described in detail. It should be understood that the terms used in the present specification are used in the meaning normally used in the art unless otherwise specified.

The term “medium chain fatty acid” used in the present specification refers to a saturated fatty acid represented by CH ₃ (CH ₂ ) _n COOH, wherein n = 4 to 10, preferably n = 6 to 8. Means things.

  The “medium chain fatty acid triglyceride” used in the present invention is also simply referred to as MCT (short for Medium Chain Acid Triglyceride), and is a triglyceride in which at least one of three fatty acids ester-bonded to glycerin is a medium chain fatty acid. Preferably, it refers to a triglyceride in which at least two of the three fatty acids ester-linked to glycerin are medium chain fatty acids, most preferably a triglyceride in which all three of the fatty acids ester-linked to glycerin are medium chain fatty acids.

  The present invention includes a triglyceride having only one kind of medium chain fatty acid ester-linked to glycerin (for example, caprylic acid triglyceride in which the medium-chain fatty acid ester-bonded to glycerin is only caprylic acid, capric acid only in capric acid. Triglycerides and the like may be used, and triglycerides (for example, medium chain fatty acids ester-bonded to glycerin are caprylic acid and capric acid). Caprylic acid / capric acid) triglyceride and caprylic acid, capric acid and lauric acid (caprylic acid / capric acid / lauric acid) triglyceride, etc.) may be used. As the medium chain fatty acid triglyceride of the present invention, only one kind of medium chain fatty acid triglyceride may be used, or a mixture of plural kinds of medium chain fatty acid triglycerides may be used.

  The medium-chain fatty acid triglyceride used in the present invention may be an extract from a natural product or a synthetic product. Commercially available products are also available for the medium-chain fatty acid triglycerides used in the present invention. For example, Kao Corporation (trade name: Coconut), Nisshin Science Co., Ltd. (trade name: ODO-L), Mitsuba Trading Co., Ltd. (Trade name: Miglyol), Nippon Oil & Fat Co., Ltd. (trade name: Panaceto), Higher Alcohol Industry Co., Ltd. (trade name: TCG-M), or Riken Vitamin Co., Ltd. (trade name: Actor) is there.

  The term “freezing point” refers to the temperature at which solidification of a liquid or gas begins, as can be generally understood by those skilled in the art. For example, it is easily measured by those skilled in the art by the freezing point measurement method described in the 15th revision Japanese Pharmacopoeia. Can be done. In the case of impurities and mixtures, the freezing point changes during the solidification process, so the melting point and the freezing point do not match, and it is generally known that the freezing point of a mixture or the like is slightly lower than the freezing point of a pure substance. In the case of a pure substance, the freezing point coincides with the melting point.

  The medium chain fatty acid triglyceride used in the present invention has a freezing point of -30 ° C to 15 ° C. More preferably, the medium chain fatty acid triglyceride used in the present invention has a freezing point of −20 ° C. to 10 ° C., more preferably −15 ° C. to 5 ° C., and particularly preferably −10 ° C. to 0 °. It has a freezing point of ° C., most preferably a freezing point of −8 ° C. to −2 ° C.

  The content ratio of the medium chain fatty acid triglyceride in the solid preparation of the present invention is not particularly limited as long as the effect of the present invention can be achieved, and can be appropriately changed by those skilled in the art from the kind and property of the medium chain fatty acid triglyceride used. However, in order to obtain a higher effect of the present application, it is usually 0.01 to 20% by weight, preferably 0.1 to 15% by weight, more preferably 0.1 to 12% by weight, particularly preferably based on the whole solid preparation. Is preferably 0.4 to 10% by weight.

  The “nonionic surfactant” used in the present invention refers to a surfactant having a nonionic hydrophilic group, as generally understood by those skilled in the art. Any nonionic surfactant can be used in the present invention. For example, polyoxyethylene sorbitan fatty acid ester, sucrose fatty acid ester, polyoxyethylene hydrogenated castor oil and the like can be used, but are not limited thereto. . Especially, in order to acquire the effect of this application more reliably, polyoxyethylene sorbitan fatty acid ester is used for this invention. Examples of the polyoxyethylene sorbitan fatty acid ester include polysorbate 20 (also known as polyoxyethylene sorbitan monolaurate (20E.O.)), polysorbate 21 (also known as polyoxyethylene sorbitan monolaurate (4E.O.)), and polysorbate. 40 (alias: polyoxyethylene sorbitan monopalmitate (20E.O.)), polysorbate 60 (alias: polyoxyethylene sorbitan monostearate (20E.O.)), polysorbate 61 (alias: polyoxyethylene monostearate) Sorbitan (4E.O.)), polysorbate 65 (also known as polyoxyethylene sorbitan tristearate (20E.O.)), polysorbate 80 (also known as polyoxyethylene sorbitan monooleate (20E.O.)), polysorbate 81 (alias: monooleic acid Polyoxyethylene sorbitan (5E.O.)), polysorbate 85 (also known as polyoxyethylene sorbitan trioleate (20E.O.)), polysorbate 120 (also known as polyoxyethylene sorbitan monoisostearate (20E.O.)) ) And the like, but is not limited thereto.

  In the solid preparation of the present invention, only one kind of nonionic surfactants as described above may be used, or two or more kinds may be used in combination.

  Commercially available products can also be used as the nonionic surfactant used in the present invention. For example, Nikko Chemicals Co., Ltd., Nippon Surfactant Co., Ltd., ADEKA Co., Ltd., Cognis Japan Co., Ltd., Daiichi Kogyo Seiyaku Co., Ltd. It can be obtained from Co., Ltd., Takemoto Yushi Co., Ltd., Nippon Yushi Co., Ltd., Kao Co., Ltd., Sanyo Chemical Industries Co., Ltd.

  The content ratio of the nonionic surfactant in the solid preparation of the present invention is not particularly limited as long as the effect of the present invention can be achieved, and may be appropriately changed by those skilled in the art depending on the type and properties of the nonionic surfactant used. obtain. However, in order to obtain a higher effect of the present application, it is usually 0.01 to 10% by weight, preferably 0.09 to 5% by weight, more preferably 0.4 to 3% by weight based on the whole solid preparation. Is good.

  Further, the ratio of the total amount of the medium chain fatty acid triglyceride and the nonionic surfactant in the solid preparation of the present invention is not particularly limited as long as the effect of the present application can be achieved, and from the types and properties of both components used. It can be appropriately varied by those skilled in the art. Usually, however, the ratio of the total amount of both components to the total amount of the solid preparation is 0.02 to 20% by weight, preferably 0.05 to 15% by weight, more preferably 0.5 to 12% by weight, particularly preferably. It is good to set it as 0.9 to 10 weight%.

  Further, the mixing ratio of the medium chain fatty acid triglyceride and the nonionic surfactant in the solid preparation of the present invention is not particularly limited as long as the effect of the present invention can be obtained, and the medium chain fatty acid triglyceride and the nonionic interface to be used are not limited. It can be appropriately varied by those skilled in the art based on the type and nature of the active agent. However, from the viewpoint of obtaining the effect of the present application more surely, preferably, the nonionic surfactant is 0.01 to 20 parts by weight, more preferably 0.1 to 15 parts by weight with respect to 1 part by weight of the medium chain fatty acid triglyceride. Parts, particularly preferably 0.1 to 10 parts by weight.

  The “sugar alcohol” used in the present invention refers to any polyhydric alcohol obtained by reducing the carbonyl group of a sugar molecule, and may be either D-form, L-form or DL-form. For example, the sugar alcohol can be mannitol, xylitol, erythritol, maltitol, lactitol, reduced palatinose (palatinite), sorbitol, and the like.

  In addition, it is known that D-mannitol, which is a sugar alcohol used in Examples, has a relatively high critical relative humidity at 37 ° C. and is about 70% or more. Therefore, preferably, the present invention uses a high alcohol having a critical relative humidity at 37 ° C. that exhibits the same properties as D-mannitol, specifically, a sugar alcohol having a critical relative humidity at 37 ° C. of 70% or more. . The term “critical relative humidity” is a hygroscopic parameter well known in the art, also referred to as critical specific humidity, and indicates the inherent hygroscopicity of the substance of interest. A low critical relative humidity means that the substance has a property of easily absorbing moisture, and conversely, a high critical relative humidity means that the substance has a property of hardly absorbing moisture. Examples of sugar alcohols having a critical relative humidity at 37 ° C. of 70% or more include erythritol, xylitol, D-mannitol, maltitol, lactitol, and reduced palatinose. In the present invention, these sugar alcohols are preferably used. Can be used. More preferably, the sugar alcohol used in the present invention is erythritol, xylitol, D-mannitol, and / or lactitol.

  In the solid preparation of the present invention, only one kind of sugar alcohols as described above may be used, or two or more kinds may be used in combination.

  The sugar alcohol used in the present invention may be an extract from a natural product, a synthetic product, or a commercially available product. For example, commercially available sugar alcohols include Mitsubishi Chemical (trade name: erythritol), Towa Kasei Kogyo (trade name: Xylit, Mannit, Sorbit, Amarti, Resis, Milchen, etc.), Kao Corporation (trade name: Nippon Pharmacy) Higashi Mannitol Kao), Nikken Kasei Co., Ltd. (trade name: Lactitol Nikken), and the like.

  The content ratio of the sugar alcohol in the solid preparation of the present invention is not particularly limited as long as the effect of the present application can be obtained, and can be appropriately changed by those skilled in the art from the type and properties of the sugar alcohol used. However, in order to obtain a higher effect of the present application, it is usually 30 to 97% by weight, preferably 40 to 90% by weight, particularly preferably 50 to 75% by weight based on the whole solid preparation.

  The mixing ratio of the medium chain fatty acid triglyceride and the sugar alcohol in the solid preparation of the present invention is not particularly limited as long as the effects of the present invention can be achieved, and is based on the type and properties of the medium chain fatty acid triglyceride and the sugar alcohol used. It can be appropriately changed by a trader. However, the sugar alcohol is usually 1.5 to 9700 parts by weight, preferably 2 to 900 parts by weight, and more preferably 5 to 150 parts by weight with respect to 1 part by weight of the medium chain fatty acid triglyceride.

  In addition, the mixing ratio of the nonionic surfactant and the sugar alcohol in the solid preparation of the present invention is not particularly limited as long as the effects of the present invention can be achieved, and the types of the nonionic surfactant and the sugar alcohol used are not limited. It can be appropriately changed by those skilled in the art based on the properties and the like. However, the sugar alcohol is usually 3 to 9700 parts by weight, preferably 8 to 900 parts by weight, and more preferably 15 to 750 parts by weight with respect to 1 part by weight of the nonionic surfactant.

  According to the use, you may mix | blend other arbitrary active ingredients with the solid formulation of this invention. Examples of such other active ingredients include, but are not limited to, the ingredients listed below. Other optional active ingredients as listed below may also be in the form of their physiologically or pharmaceutically acceptable salts. Other optional active ingredients such as these may be blended singly or in combination of two or more.

  Examples of other optional active ingredients that can be blended include medicinal ingredients (physiologically active ingredients, pharmacologically active ingredients, or active ingredients). These components are not particularly limited, and include, for example, antipyretic analgesic components (aspirin, salicylic acid derivatives such as methyl salicylate; acetaminophen, sazapyrine, ethenamide, isopropylantipyrine, indomethacin, ibuprofen, etc.), sedative hypnotic components (bromvalerylurea, Allyl isopropyl acetylurea), anti-inflammatory components (celecoxib, lysozyme, azulene sulfonic acid, etc.), antihistamine components (chlorpheniramine, mequitazine, diphenhydramine, etc.), antiallergic components (emedastine, etc.), expectorant components (potassium guaiacol sulfonate) , L-ethylcysteine hydrochloride, potassium cresol sulfonate, bromhexine hydrochloride, ambroxol hydrochloride, guaifenesin, etc., antitussive ingredients (Maou, Nantenjitsu) Any herbal medicine), bronchodilators (such as xanthine derivatives such as caffeine), parasympatholytic agents (such as belladonna alkaloids, belladonna total alkaloids), bactericidal ingredients (such as cetylpyridinium chloride, decalinium chloride, chlorhexidine hydrochloride), vasopressors (such as Phenylephrine hydrochloride, etc.), healthy stomach components (anise, aloe and other herbal medicines; parasympathomimetic agents such as carnitine; anti-dopamine drugs such as metoclopramide; trimebutine, menthol, glutamic acid, etc.), antacid components (magnesium carbonate, precipitated magnesium carbonate) , Dry aluminum hydroxide gel, histamine H2 receptor antagonist (such as cimetidine), proton pump inhibitor (such as lansoprazole), mucosal repair component (such as glycyrrhizic acid or its salt), digestive enzyme (diastase, Creatine, such as pepsin), cell-activating component (retinal, retinol, etc.), herbal components, vitamins, amino acids, such as minerals may be exemplified.

  The blending ratio of any active ingredient as described above can be appropriately selected depending on the size and use of the solid preparation, and is, for example, 0.001 to 80% by weight, preferably 0.001 to 30% by weight based on the whole solid preparation. More preferably, it may be 0.001 to 10% by weight.

  The solid preparation of the present invention can also be used as a component other than the above-described conventional components used in quasi drugs, pharmaceuticals, foods, etc., for example, sweeteners, flavoring agents, lubricants, binders, and excipients. Agent, preservative, chelating agent, antioxidant, cooling agent, coating agent, stabilizer, suspending agent, fluidizing agent, emulsifier, thickener, solubilizer, thickener, buffer, fragrance , Colorants, dispersants, adsorbents, wetting agents, moisture-proofing agents, antistatic agents, foaming agents, plasticizers, sweeteners, solvents, pH adjusters, antifoaming agents, etc. An agent may be further contained. Specific examples of conventional components that can be arbitrarily blended are shown below, but the components used in the present invention are not limited thereto.

  Disintegrants: starches (corn starch, potato starch, corn starch, hydroxypropyl starch, sodium carboxymethyl starch, partially pregelatinized starch, etc.), celluloses (carboxymethylcellulose calcium, crystalline cellulose, hydroxypropylcellulose, low substituted hydroxypropylcellulose) , Carmellose, carmellose calcium, croscarmellose sodium, etc.) and plasma silicic acid. In the present invention, corn starch, hydroxypropyl cellulose, crystalline cellulose, light anhydrous silicic acid and the like are preferably used.

  Excipients: Sugars such as glucose, sucrose, lactose, fructose, crystalline cellulose, carmellose sodium, calcium hydrogen phosphate, wheat starch, rice starch, corn starch, potato starch, dextrin, β-cyclodextrin, light anhydrous silicic acid , Titanium oxide, magnesium aluminate metasilicate, talc, kaolin, etc.

  Binders: Cellulose derivatives such as methylcellulose, ethylcellulose, hydroxypropylcellulose, hydroxypropylmethylcellulose, polyvinylpyrrolidone, polyvinyl alcohol, acrylic polymer, gelatin, gum arabic, pullulan, pregelatinized starch, agar, tragacanth, sodium alginate, alginic acid Propylene glycol ester etc.

Lubricant: stearic acid, magnesium stearate, calcium stearate, polyoxyl stearate, cetanol, talc, hydrogenated oil, sucrose fatty acid ester, dimethylpolysiloxane, beeswax, beeswax, etc.
Antioxidants: Dibutylhydroxytoluene (BHT), propyl gallate, butylhydroxyanisole (BHA), tocopherol, citric acid and the like.

  Coating agent: Hydroxypropyl methylcellulose, hydroxypropylcellulose, methylcellulose, ethylcellulose, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, carboxymethylethylcellulose, cellulose acetate phthalate, polyvinyl acetal diethylaminoacetate, aminoalkyl methacrylate copolymer, hydroxypropylmethylcellulose Acetate succinate, methacrylic acid copolymer, polyvinyl acetate diethylaminoacetate, shellac, etc.

Colorant: Food Red No. 2, Food Red No. 3, Food Red No. 102, Food Yellow No. 4, Food Yellow No. 5, Food Blue No. 1, Food Yellow No. 4, Metal Lake, Copper Chlorofin Sodium, Riboflavin, Turmeric Extract Carotene solution.
Flavoring agents: aspartame, ascorbic acid, stevia, menthol, licorice crude extract, simple syrup, etc.

Plasticizer: Triethyl citrate, polyethylene glycol, triacetin, cetanol and the like.
Sweetener: Natural or synthetic sweeteners such as sucrose and aspartame.
Fragrance: Menthol, camphor, borneol, cinnamaldehyde, etc.

  Solvent: water, ethanol, isopropanol, lauryl alcohol, cetanol, stearyl alcohol, oleyl alcohol, lanolin alcohol, behenyl alcohol, 2-hexyl decanol, isostearyl alcohol, 2-octyldodecanol and the like.

pH adjuster: citric acid, malic acid, sodium hydrogen phosphate, dipotassium phosphate, etc.
Cooling agents: l-menthol, mint water, etc.
Suspending agents: kaolin, carmellose sodium, xanthan gum, methylcellulose, tragacanth, etc.
Antifoaming agent: dimethylpolysiloxane, silicon antifoaming agent, etc.
Thickener: xanthan gum, tragacanth, methylcellulose, dextrin, etc.
Solubilizer: ethanol, sucrose fatty acid ester, macrogol, etc.

  The blending ratio of the conventional ingredients as described above can be appropriately selected depending on the size and use of the solid preparation, and is, for example, 0.001 to 97% by weight, preferably 0.01 to 90% by weight, based on the whole solid preparation. possible.

  The solid preparation of the present invention can be a preparation of any dosage form that is required to enhance pharmacological disintegration. For example, the solid preparation of the present invention can be in a dosage form such as a tablet, hard capsule, granule, powder, dry syrup, pill, troche, or suppository. Preferably, the solid preparation of the present invention is a tablet, hard capsule, granule, powder or dry syrup, in which higher disintegration is generally desired, and the pharmaceutical composition disintegration is improved due to the small specific surface area. Tablets that are particularly strongly desired to be applied are particularly preferred. As shown in the examples described later, according to the present invention, it has been demonstrated that even in the form of a tablet, high pharmaceutical disintegrability can be exhibited. The tablet may be an uncoated tablet, or may be coated with a film coat base or sugar.

  The tablet may be in any dosage form, but is preferably a tablet that can be swallowed in the oral cavity by chewing and disintegrating or dissolving if necessary (this form is referred to as “chewable tablet” in this specification). It is said). Examples of chewable tablets include, but are not limited to, chewable tablets, intraoral quick disintegrating tablets, and intraoral quick dissolving tablets.

  In particular, since the tablet of the present invention is very excellent in pharmacological disintegration, even a small amount of saliva in the mouth can exhibit good pharmacological disintegration. Therefore, the tablet of the present invention can be suitably used as a tablet that can be taken without water without taking water from the outside.

  The solid preparation of the present invention can be produced by applying a conventional method in the field of pharmaceutics as it is or appropriately. For example, taking the case of a tablet as an example, the tablet of the present invention may be prepared by a compression molding method, or may be prepared by a method of pouring into a certain mold and molding. Preferably, however, the tablets of the present invention are produced by a compression molding process.

  When the compression molding method is used, the tablet of the present invention specifically includes medium chain fatty acid triglycerides, nonionic surfactants, sugar alcohols, and other optional ingredients blended as necessary (for example, After mixing and mixing the compounding ingredients such as excipients blended to adjust the shape of the tablet, but not limited to this, the mixture is directly compression-molded (direct compression) Or the mixture obtained as described above is granulated to produce a granulated product, and if necessary, the granulated product is granulated to form a granulated product. Or it manufactures by compressing a granule (indirect compression method).

  As a method for mixing the blending components, any method known in the art that can mix each blending component stably and uniformly can be used. Most simply, for example, mixing can be performed using a mixer such as a container rotating mixer or a container fixed mixer.

  As needed, before performing a compression molding process, the mixture obtained in this way is granulated, and a granulated material is manufactured, or a granule is further processed and a granule is manufactured. Examples of the granulation treatment method that can be performed to obtain the solid preparation of the present invention include, for example, extrusion granulation method, fluidized bed granulation method, tumbling granulation method, high-speed stirring granulation method, spray drying method, and emulsion granulation method. Examples thereof include, but are not limited to, a grain method. Examples of the sizing treatment method that can be performed to obtain the tablet of the present invention include, but are not limited to, a wet pulverization sizing method, a dry pulverization sizing method, and a roll pulverization method.

  In order to compression-mold the mixture, granulated product or granule obtained as described above, any compression molding apparatus known in the art can be used. Examples of the compression molding apparatus include, but are not limited to, a rotary tableting machine and a single-shot tableting machine. Preferably, compression molding is performed using a rotary tableting machine.

  The shape of the tablet is not particularly limited as long as the effect of the present invention can be achieved, and can be appropriately selected by those skilled in the art depending on the application. For example, the tablet shape is a horizontal, flat surface according to a conventional method, and the shape when viewed from the top surface is a circle, ellipse, polygon (triangle, quadrangle, pentagon, etc.), star, animal, plant, donut, etc. However, it is not limited to these. However, it is particularly preferable that the shape of the tablet when viewed as described above is circular or elliptical.

  The size of the tablet is not particularly limited as long as the effect of the present application can be obtained, and can be appropriately selected by those skilled in the art according to the use. However, in order to obtain a higher effect of the present application that is suitable for ingestion, the diameter of the circumscribed circle when viewed from above is usually about 6 to 30 mm, preferably 6 It is good that it is about ˜18 mm, more preferably it is about 6 to 15 mm, and particularly preferably about 6 to 10 mm. Further, the thickness of the tablet is usually about 2.0 to 6.0 mm, preferably about 2.5 to 5.0 mm, and particularly preferably about 3.0 to 4.5 mm. It is good to become.

  The solid preparation of the present invention includes pharmaceuticals, quasi drugs, foods (for example, foods for the elderly, foods for special use, foods for specific health use, foods for conditional health use, nutritional functional foods, functional foods, health supplements, (Supplements, health foods, confectionery, confectionery, animal food, pet food, feed). As a pharmaceutical, for example, the solid preparation of the present invention can be used for any pharmaceutical use such as rhinitis drug, motion sickness drug, gastrointestinal drug, diarrhea drug and the like.

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

Example 1 :
(Preparation of test tablets)
The test tablet of Example 1 was prepared by the following method.
First, 170 parts by weight of corn starch, 634 parts by weight of D-mannitol, and 30 parts by weight of hydroxypropyl cellulose are mixed in advance, kneaded with an appropriate amount of ethanol, and medium chain fatty acid triglyceride ((caprylic acid / capric acid) Triglyceride, freezing point: about −5 ° C.) After dispersion with 24 parts by weight and 12 parts by weight of polysorbate 80, granulation was performed by an extrusion granulation method. This granulated product is sized to give granules, and then 30 parts by weight of light anhydrous silicic acid, 20 parts by weight of crystalline cellulose, and 25 parts by weight of magnesium stearate are added to the granules. And mixed for 15 minutes. This mixture was tableted with a rotary tableting machine (collect 19, manufactured by Kikusui Seisakusho Co., Ltd.) at a main pressure of 15 kN / 杵 (preload 2 kN / 杵), and circular chewable tablets (diameter 9.5 mm, thickness) 4.0 mm, one tablet 315 mg).

  On the other hand, a test tablet of Comparative Example 1 was prepared in the same manner as above except that polysorbate 80 (nonionic surfactant) was changed to sodium lauryl sulfate (ionic surfactant).

  Subsequently, the disintegration property of the tablets was examined according to the following disintegration test method for the test tablets of Example 1 and Comparative Example 1 obtained as described above.

(Pharmaceutical disintegration test for tablets)
The disintegration properties of these test tablets were tested according to a general formulation disintegration test method (general test method Japanese Pharmacopoeia 15th revision). Specifically, each test tablet and test liquid (using water) is put in a glass tester (n = 6), and the temperature of the test liquid is kept at 37 ° C. ± 2 ° C., and the reciprocation is 29-32 times per minute. Smoothly moved up and down with an amplitude of 53 to 57 mm. The time until no tablet residue was found in the tester was measured. It can be said that the shorter the time until disappearance, the higher the pharmacological disintegration property, that is, the superior pharmacological disintegration property of disintegrating very rapidly when exposed to water at the time of administration (during administration).
The results of this test are shown in the bottom column of Table 1 below.

  As shown from this result, the disintegration time is remarkably shortened by using a nonionic surfactant (polysorbate 80), compared with the case of using an ionic surfactant (sodium lauryl sulfate), and the preparation is disintegrated. It was observed that the property was significantly improved.

Example 2 :
The test tablet of Example 2 was prepared by the following method.
First, 170 parts by weight of corn starch, 634 parts by weight of D-mannitol, and 30 parts by weight of hydroxypropyl cellulose are mixed in advance, kneaded with an appropriate amount of ethanol, and medium chain fatty acid triglyceride ((caprylic acid / capric acid) Triglyceride, freezing point: about −5 ° C.) After dispersion with 24 parts by weight and 12 parts by weight of polysorbate 80, granulation was performed by an extrusion granulation method. This granulated product is sized to give granules, and then 30 parts by weight of light anhydrous silicic acid, 20 parts by weight of crystalline cellulose, and 25 parts by weight of magnesium stearate are added to the granules. And mixed for 15 minutes. This mixture was tableted with a rotary tableting machine (collect 19, manufactured by Kikusui Seisakusho Co., Ltd.) at a main pressure of 15 kN / 杵 (preload 2 kN / 杵), and circular chewable tablets (diameter 9.5 mm, thickness) 4.0 mm, one tablet 315 mg).

  On the other hand, a test tablet of Comparative Example 2 was prepared in the same manner as above except that medium-chain fatty acid triglyceride was not blended and the amount of D-mannitol was increased instead.

  Subsequently, the disintegration property of the tablets was examined according to the disintegration test method described in Example 1 for the test tablets of Example 2 and Comparative Example 2 obtained as described above. The results are shown in the bottom column of Table 2 below.

  As shown from this result, the disintegration time is remarkably shortened by blending the medium chain triglyceride with the nonionic surfactant (polysorbate 80) and the sugar alcohol as compared with the case where the medium chain triglyceride is not blended together. It was confirmed that the disintegration property of the preparation was remarkably improved.

Example 3 :
The test tablet of Example 3 was prepared by the following method.
First, 170 parts by weight of corn starch, 634 parts by weight of D-mannitol, and 30 parts by weight of hydroxypropyl cellulose are mixed in advance, kneaded with an appropriate amount of ethanol, and medium chain fatty acid triglyceride ((caprylic acid / capric acid) Triglyceride, freezing point: about −5 ° C.) After dispersion with 24 parts by weight and 12 parts by weight of polysorbate 80, granulation was performed by an extrusion granulation method. This granulated product is sized to give granules, and then 30 parts by weight of light anhydrous silicic acid, 20 parts by weight of crystalline cellulose, and 25 parts by weight of magnesium stearate are added to the granules. And mixed for 15 minutes. This mixture was tableted with a rotary tableting machine (collect 19, manufactured by Kikusui Seisakusho Co., Ltd.) at a main pressure of 15 kN / 杵 (preload 2 kN / 杵), and circular chewable tablets (diameter 9.5 mm, thickness) 4.0 mm, one tablet 315 mg).

  On the other hand, the same as above except that medium-chain fatty acid triglyceride (freezing point: about −5 ° C.) is not blended, and instead, salami beeswax (melting point: about 60-67 ° C.) which is a solid oily substance at room temperature is blended. Thus, a test tablet of Comparative Example 3 was prepared (note that white beeswax was a solid at room temperature, so it was used after being heated to 100 ° C. and dissolved).

  Subsequently, the disintegration property of the tablets was examined according to the disintegration test method described in Example 1 for the test tablets of Example 3 and Comparative Example 3 obtained as described above. The results are shown in the bottom column of Table 3 below.

  As shown from this result, by adding medium chain fatty acid triglyceride (freezing point: about −5 ° C.) together with nonionic surfactant (polysorbate 80) and sugar alcohol, white beeswax (melting point: about 60-67 ° C.). ) Was significantly shortened compared with the case of blending together, and the disintegration property of the preparation was significantly improved.

Example 4 :
The test tablet of Example 4 was prepared by the following method.
First, 170 parts by weight of corn starch, 634 parts by weight of D-mannitol, and 30 parts by weight of hydroxypropyl cellulose are mixed in advance, kneaded with an appropriate amount of ethanol, and medium chain fatty acid triglyceride ((caprylic acid / capric acid) Triglyceride, freezing point: about −5 ° C.) After dispersion with 24 parts by weight and 12 parts by weight of polysorbate 80, granulation was performed by an extrusion granulation method. This granulated product is sized to give granules, and then 30 parts by weight of light anhydrous silicic acid, 20 parts by weight of crystalline cellulose, and 25 parts by weight of magnesium stearate are added to the granules. And mixed for 15 minutes. This mixture was tableted with a rotary tableting machine (collect 19, manufactured by Kikusui Seisakusho Co., Ltd.) at a main pressure of 15 kN / 杵 (preload 2 kN / 杵), and circular chewable tablets (diameter 9.5 mm, thickness) 4.0 mm, one tablet 315 mg).

  On the other hand, test tablets were prepared in the same manner as described above except that D-mannitol used for granulation was changed to lactose (Comparative Example 4-1) or crystalline cellulose (Comparative Example 4-2).

  Next, the disintegration property of the tablets was examined according to the disintegration test method described in Example 1 for the test tablets of Example 4, Comparative Example 4-1 and Comparative Example 4-2 obtained as described above. The results are shown in the bottom column of Table 4 below.

  As shown by this result, the disintegration time is remarkably shortened by blending sugar alcohol with nonionic surfactant (polysorbate 80) and medium-chain fatty acid triglyceride as compared with blending lactose and crystalline cellulose together. It was confirmed that the disintegration property of the preparation was remarkably improved.

Examples 5-7 :
The test tablet of Example 5 was prepared by the following method.
First, 170 parts by weight of corn starch, 634 parts by weight of D-mannitol, and 30 parts by weight of hydroxypropyl cellulose are mixed in advance, kneaded with an appropriate amount of ethanol, and medium chain fatty acid triglyceride ((caprylic acid / capric acid) Triglyceride, freezing point: about −5 ° C.) After dispersion with 24 parts by weight and 12 parts by weight of polysorbate 80, granulation was performed by an extrusion granulation method. This granulated product is sized to give granules, and then 30 parts by weight of light anhydrous silicic acid, 20 parts by weight of crystalline cellulose, and 25 parts by weight of magnesium stearate are added to the granules. And mixed for 15 minutes. This mixture was tableted with a rotary tableting machine (collect 19, manufactured by Kikusui Seisakusho Co., Ltd.) at a main pressure of 15 kN / 杵 (preload 2 kN / 杵), and circular chewable tablets (diameter 9.5 mm, thickness) 4.0 mm, one tablet 315 mg).

  On the other hand, test tablets were prepared in the same manner as described above except that polysorbate 80 was changed to polysorbate 60 (Example 6) or polysorbate 20 (Example 7).

  Subsequently, the disintegration property of the tablets was examined according to the disintegration test method described in Example 1 for the test tablets of Examples 5 to 7 obtained as described above. The results are shown in the bottom column of Table 5 below.

  As shown from this result, it is recognized that the disintegration property of the preparation is remarkably improved not only when polysorbate 80 is used as the nonionic surfactant but also when polysorbate 60 or polysorbate 20 is used. It has been found that various nonionic surfactants can be used in the present invention.

Examples 8-9 :
The test tablet of Example 8 was prepared by the following method.
First, 170 parts by weight of corn starch, 646 parts by weight of D-mannitol, and 30 parts by weight of hydroxypropylcellulose are mixed in advance, kneaded with an appropriate amount of ethanol, and medium chain fatty acid triglyceride ((caprylic acid / capric acid) Triglyceride, freezing point: about −5 ° C.) After dispersion with 4.5 parts by weight and 4.5 parts by weight of polysorbate 80, granulation was performed by an extrusion granulation method. This granulated product is granulated into granules, and then 30 parts by weight of light anhydrous silicic acid, 30 parts by weight of crystalline cellulose, and 30 parts by weight of magnesium stearate are added to the granules. And mixed for 15 minutes. This mixture was tableted with a rotary tableting machine (Collect 19, manufactured by Kikusui Seisakusho Co., Ltd.) at a main pressure of 5 kN / 杵 (preload 2 kN / 杵), and a circular chewable tablet (diameter 9.5 mm, thickness) 4.1 mm, one tablet 315 mg).

  On the other hand, a test tablet of Example 9 was prepared in the same manner as described above except that the content of the nonionic surfactant was further reduced and the amount of D-mannitol was increased accordingly.

  Subsequently, the disintegration property of the tablets was examined according to the disintegration test method described in Example 1 for the test tablets of Examples 8 to 9 obtained as described above. The results are shown in the bottom column of Table 6 below.

  As shown from this result, even when the amount of medium chain fatty acid triglyceride and nonionic surfactant is very small to the extent shown in this example, the disintegration of the preparation is remarkably improved. It was recognized that it was possible to

  Formulation examples are given below, but the present invention is not limited to these examples.

Formulation Example 1 (Tablet: diameter 10 mm, thickness 3.7 mm):
d-Chlorpheniramine maleate 6.0 parts by weight Belladonna total alkaloid 0.4 parts by weight Caffeine anhydride 60.0 parts by weight Phenylephrine hydrochloride 15.0 parts by weight Sucralose 21.0 parts by weight Light silicic anhydride 75.0 parts by weight Corn starch 190.0 parts by weight Hydroxypropylcellulose 27.0 parts by weight Medium chain fatty acid triglyceride (freezing point: about -5 ° C) 36.0 parts by weight Polysorbate 80 12.0 parts by weight Magnesium stearate 30.0 parts by weight
D-mannitol remaining
Total 1050.0 parts by weight

Formulation Example 2 (tablet: diameter 10 mm, thickness 4.2 mm):
Scopolamine hydrobromide 0.5 parts by weight Pyridoxine hydrochloride 12.0 parts by weight Phenylephrine hydrochloride 15.0 parts by weight Medium chain fatty acid triglyceride (freezing point: about −5 ° C.) 43.2 parts by weight
HCO-60 (polyoxyethylene hydrogenated castor oil) 21.6 parts by weight Light anhydrous silicic acid 70.0 parts by weight Corn starch 250.0 parts by weight Hydroxypropylcellulose 36.0 parts by weight Aspartame 30.0 parts by weight Magnesium stearate 40 .0 parts by weight perfume
Xylitol balance
1440.0 parts by weight in total

Claims (6)

(A) Medicinal component, (B) Medium chain fatty acid triglyceride 0.01 to 20% by weight of saturated fatty acid (CH ₃ (CH ₂ ) _n COOH: n = 4 to 10) having a freezing point of −30 ° C. to 15 ° C. (C) polyoxyethylene sorbitan fatty acid ester 0.01 to 10% by weight , ( D) sugar alcohol 30 to 97% by weight having a critical relative humidity at 37 ° C. of 70% or more , and (E) a disintegrant , A solid preparation consisting of conventional ingredients whose fraction can be blended into a normal solid preparation.   (D) The solid preparation according to claim 1, wherein the sugar alcohol is at least one selected from the group consisting of D-mannitol, xylitol, erythritol, maltitol, lactitol, and reduced palatinose.   (D) The solid preparation according to claim 1, wherein the sugar alcohol is D-mannitol.   (A) Medicinal component is antipyretic analgesic component, sedative hypnotic component, anti-inflammatory component, antihistamine component, antiallergic component, expectorant component, antitussive component, bronchodilator, parasympathetic nerve blocker, bactericidal component, pressor, healthy stomach It is one or more types selected from the group consisting of components, antacid components, mucosal repair components, digestive enzymes, cell activation components, herbal medicine components, vitamins, amino acids, and minerals. The solid preparation according to item.   Medicinal ingredients are aspirin, acetaminophen, sazapyrine, etenzamide, isopropylantipyrine, indomethacin, ibuprofen, bromvalerylurea, allylisopropylacetylurea, celecoxib, lysozyme, azulene sulfonic acid, chlorpheniramine, mequitazine, diphenhydramine, emedastine, potassium guaiacol sulfonate L-ethylcysteine hydrochloride, potassium cresolsulfonate, bromhexine hydrochloride, ambroxol hydrochloride, guaifenesin, maou, nantenjitsu, caffeine, belladonna alkaloids, belladonna total alkaloids, cetylpyridinium chloride, decalinium chloride, chlorhexidine hydrochloride, phenylephrine hydrochloride, anise Fruit, aloe, carnitine, metoclopramide, trimebutine Menthol, glutamic acid, magnesium carbonate, precipitated magnesium carbonate, dry aluminum hydroxide gel, cimetidine, lansoprazole, glycyrrhizic acid or a salt thereof, diastase, pancreatin, pepsin, retinal, retinol, or at least one selected from the group The solid formulation as described in any one of Claims 1-3.   The solid preparation according to any one of claims 1 to 5, which is a tablet.