JP2008133294A - Tablet disintegrated in buccal cavity - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To easily prepare a tablet soluble in buccal cavity having appropriate disintegrating property and solubility and appropriate strength not to disintegrate during manufacturing and storage. <P>SOLUTION: This tablet is prepared by tableting under a pressure of about 3-160 Kg/cm<SP>2</SP>a mixture containing medicinal components such as a vitamin, a digestive medicine, and an antipyretic demulcent antiphlogistic agent, at least one water-soluble saccharide selected from the group consisting of xylitol and erythritol, and water to wet the surface of the saccharide, and drying. The quantity of the medicinal component is about 0.05-90 wt.% of the mixture, that of the saccharide is about 10-90 wt.% of the mixture, and the water is contained about 0.3-10 wt.% of the mixture. The tablet soluble in buccal cavity having a porous structure with a porosity of 20-80% can be obtained by the above method. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention comprises a medicinal ingredient such as vitamins, antipyretic analgesics, antihypertensive drugs, antihypertensive drugs, psychotropic drugs, diabetes drugs, and saccharides, and has moderate strength and quick solubility and disintegration in the oral cavity. The present invention relates to an orally disintegrating tablet (hereinafter sometimes referred to as an orally dissolving tablet).

  Recently, many studies have been conducted from a comprehensive point of view for the treatment of elderly patients, from physiological studies of aging to issues of medicine, pharmaceuticals, and care. Among them, according to the Silver Science Research of the Ministry of Health and Welfare, there is an interesting research report called “Study on the creation of new formulations and new packaging containers that are optimal for the elderly” (Tokyo Women's Medical University, Masayasu Sugihara et al.) Pharmaceutical Affairs Daily (issued August 22, 1989) (Non-patent Document 1). For example, a) oral dissolution type preparations, b) pasty preparations, and c) jelly type preparations are taken up as new drugs. Among them, oral dissolution type preparations and pasty preparations are both easier to take and more stable. It is a preparation that is easy for elderly people to take. In particular, in the above-mentioned oral dissolution type preparation, polyethylene glycol 1000 is selected as a base that dissolves in the oral cavity, and an oil base is selected as a base that melts at an oral temperature, and also functions such as taste and texture and moldability are also provided. In consideration, sucrose and mannit are added. Molding is carried out by cooling after filling a base of heat-melted vinyl chloride molded sheet used in PTP (Press Through Pachage). Thus, an oral dissolution type solid preparation for elderly people is obtained.

  Japanese Patent Application Laid-Open No. 52-76420 (Patent Document 1) describes a mixture or solution of an iterative mixture of 5 to 80% by weight of an inert solvent frozen at −30 ° C. to 25 ° C. After solidifying in an inert cooling medium such as liquid nitrogen, the resulting granules are compressed to below the freezing point of the solvent to form tablets, and the disintegration rate is reduced by removing the solvent by freeze drying or air drying. "A method for producing large, rapidly dissolving porous tablets" is described.

  Also, Japanese Patent Publication No. 58-24410 (Patent Document 2) states that “a solvent that freezes the tablet contents at −30 to + 25 ° C. that is inert to the tablet contents (eg, water, cyclohexane, benzene) and Mixing, where the solvent is 5-80% by weight of the total mixture, solidified by placing the mixture in an inert cooling medium, compressed into a tablet at a temperature below the freezing point of the solvent, and lyophilized or "A method for producing a porous tablet with good disintegration by volatilizing a solvent by natural drying or the like" is described.

  Furthermore, JP-A-61-15830 (Patent Document 3) discloses an antacid having a porous ultrafine crystal structure, which includes an antacid agent and a confectionery base material containing a confectionery sweetener and a plasticizer. An agent composition is described.

  On the other hand, in foreign countries, there are guidelines (USA / FDA 1983) on research on pharmaceuticals used by the elderly, and “Zydis (trade name)” by R. P Scherer, Inc. Has been commercialized. The composition of the preparation is not clear, but it is manufactured by blending medicinal ingredients, polymers, saccharides, etc., dissolving and freeze-drying (Manufacturing Chemist, Manuf. Chemist. Feb. 36 (1990)) Patent Document 2).

  However, the above-described conventional preparations are still not sufficient in terms of practicality as oral dissolution preparations in terms of storage stability, solubility, application range for drugs, and the like. For example, in the composition described in JP-A-61-15830, the components are heated and melted, so that the application range of the medicinal components is limited and the disintegration property of the preparation in the oral cavity is sufficient. Absent. Further, the above-mentioned “Zydis (trade name)” is not satisfactory for the elderly due to problems in the water solubility of medicinal ingredients, the strength of the preparation, the content of medicinal ingredients, and the like.

Furthermore, it is common that tablets with high disintegration and solubility are obtained and weak in strength. Therefore, it is necessary to develop a preparation having an appropriate strength that does not break in the preparation process and distribution process, as well as excellent disintegration and solubility in the oral cavity that are practically required.
JP 52-76420 A Japanese Patent Publication No. 58-24410 Japanese Patent Laid-Open No. 61-15830 "Study on the creation of new formulations and new packaging containers that are optimal for the elderly" (Tokyo Women's Medical University, Masayasu Sugihara, etc.), Pharmaceutical Affairs Daily, August 22, 1989 Manufacturing Chemist, Manuf. Chemist. Feb. 36 (1990)

  Accordingly, an object of the present invention is to provide an orally-dissolving tablet having moderate disintegration and solubility in the oral cavity and having an appropriate strength that does not collapse during production and storage.

  Another object of the present invention is to provide an orally-dissolving tablet that has the excellent performance as described above and can be easily obtained without going through complicated steps.

  Still another object of the present invention is to provide an orally-dissolving tablet that is practical for the elderly and children and is practical.

  In view of the circumstances as described above, the present inventors have made various studies in order to develop an intraoral dissolution type preparation, and without using the heating, melting, dissolving, and freezing means that are essential in the conventional production method. When the mixture containing a medicinal ingredient, saccharides and moisture that moisturizes the saccharide particles is tableted and dried, it has an appropriate strength that does not collapse unexpectedly in the manufacturing process, storage, and distribution process. It has been found that a porous structure that rapidly disintegrates and dissolves in the oral cavity can be obtained, and that this tablet has sufficiently satisfactory properties as an oral dissolution tablet. The present invention has been completed based on these findings.

  That is, the present invention provides an orally-dissolving tablet having a porous structure containing an effective amount of a medicinal ingredient and a water-soluble saccharide. The water-soluble saccharide is at least one selected from mannitol, xylitol, and erythritol. The tablet may have a hardness of 2 to 25 kg and a porosity of 20 to 80%.

  The present invention also provides an intraoral-dissolving tablet obtained by tableting a mixture containing a medicinal component, a saccharide, and a moisture that moistens the particle surface of the saccharide.

  Specifically, with respect to a tablet component containing a medicinal component and the water-soluble saccharide, 0.3 to 7% by weight of water is used to moisten the surface of the water-soluble saccharide particles, and the medicinal component and An orally disintegrating tablet obtained by tableting a mixture containing a water-soluble saccharide and moisture and then drying the tablet is provided.

  The oral-dissolving tablet of the present invention has excellent solubility and disintegration, so it is easy to take, and has moderate strength, so it has excellent long-term storage and stability. . Therefore, it can be suitably used for the treatment and prevention of illnesses in patients, particularly elderly or pediatric patients, applied according to the medicinal ingredients contained.

  Moreover, the intraoral dissolution type tablet which has the above outstanding performance can be manufactured very simply, without passing through a complicated process.

  The medicinal component used in the present invention may be in any form such as solid, powder, crystal, oily, solution, for example, nourishing tonic, antipyretic analgesic, antipsychotic, anxiolytic Drugs, antidepressants, hypnotic sedatives, antispasmodic drugs, gastrointestinal drugs, antacids, antitussive expectorants, dental and oral drugs, antihistamines, cardiotonic agents, arrhythmic agents, diuretics, antihypertensive agents, vasoconstrictors, coronary vessels One or more components selected from dilators, peripheral vasodilators, biliary agents, antibiotics, chemotherapeutic agents, diabetic agents, osteoporosis agents, skeletal muscle relaxants and the like are used.

For example, vitamin A, vitamin D, vitamin E (such as d-α-tocopherol acetate), vitamin B ₁ (such as dibenzoylthiamine, fursultiamine hydrochloride), vitamin B ₂ (such as riboflavin butyrate) ), Vitamin B ₆ (such as pyridoxine hydrochloride), vitamin C (such as ascorbic acid, sodium L-ascorbate), vitamin B ₁₂ (such as hydroxocobalamin acetate); minerals such as calcium, magnesium, iron; protein; amino acids Oligosaccharides; crude drugs and the like.

  Antipyretic analgesics and anti-inflammatory agents include, for example, aspirin, acetaminophen, etenzamide, ibuprofen, diphenhydramine hydrochloride, chlorpheniramine dl-maleate, dihydrocodeine phosphate, noscapine, methylephedrine hydrochloride, phenylpropanolamine hydrochloride, caffeine, serrapeptase, Examples include lysozyme chloride, tolfenamic acid, mefenamic acid, diclofenac sodium, flufenamic acid, salicylamide, aminopyrine, ketoprofen, indomethacin, bucolome, pentazocine and the like.

  Examples of the psychotropic drug include chlorpromazine, reserpine and the like. Examples of anti-anxiety drugs include chlordiazepoxide, diazepam and the like. Examples of the antidepressant include imipramine, maprotiline, amphetamine and the like. Examples of the hypnotic sedative include estazolam, nitrazepam, diazepam, phenobarbital sodium and the like. Antispasmodic agents include, for example, scopolamine hydrobromide, diphenhydramine hydrochloride, papaverine hydrochloride, and the like.

  Gastrointestinal drugs include, for example, healthy gastrointestinals such as diastase, sugar-containing pepsin, funnel extract, lipase AP, and cinnamon oil; and intestinals such as berberine chloride, resistant lactic acid bacteria, and bifidobacteria. Examples of the antacid include magnesium carbonate, sodium hydrogen carbonate, magnesium aluminate metasilicate, synthetic hydrotalcite, precipitated calcium carbonate, magnesium oxide and the like.

  Examples of the antitussive expectorant include cloperastine hydrochloride, dextromethorphan hydrobromide, theophylline, potassium guaiacol sulfonate, and guaifenesin. Examples of the dental and oral medicine include oxytetracycline, triamcinolone acetonide, chlorhexidine hydrochloride, lidocaine and the like.

  Examples of the antihistamine include diphenhydramine hydrochloride, promethazine, isothipentyl hydrochloride, dl-chlorpheniramine maleate, and the like. Examples of the cardiotonic agent include ethylephrine hydrochloride. Examples of the arrhythmic agent include procainamide hydrochloride, propranolol hydrochloride, pindolol and the like. Examples of the diuretic include isosorbide and furosemide. Examples of the blood pressure lowering agent include delapril hydrochloride, captopril, hexamethonium bromide, hydralazine hydrochloride, labetalol hydrochloride, methyldopa, and the like.

  Examples of the vasoconstrictor include phenylephrine hydrochloride. Examples of the coronary vasodilator include carbochromene hydrochloride, molsidomine, verapamil hydrochloride and the like. Examples of the peripheral vasodilator include cinnarizine and the like. Examples of the astringent include dehydrocholic acid and trepibutone.

  Antibiotics include, for example, cephem, penem and carbapenem antibiotics such as cephalexin, amoxicillin, pibmesilinum hydrochloride and cefotiam hydrochloride. Examples of the chemotherapeutic agent include sulfamethizole and thiazosulfone. Examples of the diabetic agent include tolbutamide, voglibose and the like. Examples of the osteoporosis agent include ipriflavone. Examples of skeletal muscle relaxants include metocarbamol.

  The medicinal component may be diluted with a diluent that is generally used in the fields of medicine, food, and the like. Further, at least one of the medicinal components may be oily.

  Preferable medicinal ingredients used in the present invention include, for example, the aforementioned vitamins, herbal medicines, antipyretic analgesics, anti-anxiety drugs, hypnotic sedatives, gastrointestinal drugs, antitussive expectorants, antihypertensive agents, antidiabetic agents, osteoporosis Examples include symptomatic agents and skeletal muscle relaxants.

  The content of the medicinal component in the mixture containing the medicinal component, saccharide and water varies depending on the type of medicinal component, but is usually 0.05 to 90% by weight, preferably 0.1 to 70% by weight, and more preferably. Is about 0.3 to 60% by weight.

  The saccharide used in the present invention may be any saccharide as long as it is water-soluble and does not adversely affect the medicinal component (for example, decomposition of the medicinal component). For example, sugar, starch sugar, lactose, honey, Sugar alcohol or the like is used.

  As the sugar, for example, sucrose, coupling sugar, fructooligosaccharide, palatinose and the like are used. As the starch sugar, for example, glucose, maltose, flour koji, starch syrup, isomerized sugar (fructose) and the like are used. As lactose, for example, lactose, isomerized lactose (lactulose), reduced lactose (lactitol) and the like are used. As honey, various foods generally used for food are used. Examples of the sugar alcohol include sorbitol, mannitol, reduced maltose starch syrup (maltitol), reduced starch saccharified product, xylitol, and reduced palatinose. In addition, 4-carbon sugar (for example, erythritol etc.) fermented with glucose is also used. These saccharides may be used alone or in combination of two or more.

  Preferred examples of the saccharide used in the present invention include sucrose, glucose, maltitol, xylitol, erythritol and the like.

  The average particle diameter of the saccharide is usually about 1 to 100 μm, preferably about 20 to 70 μm, and more preferably about 30 to 50 μm.

  The content of saccharides in the mixture varies depending on the type of medicinal component, but is usually about 10 to 90% by weight, preferably about 20 to 85% by weight, and more preferably about 30 to 80% by weight.

  For example, when a medicinal component with a small dosage is used and the content of the medicinal component in the mixture is 0.1 to 10% by weight, the saccharide content in the mixture is usually 30 to 90% by weight. , Preferably 50 to 85% by weight, more preferably about 60 to 85% by weight. As a medicinal component with a small dosage, diazepam and the like can be mentioned.

  In addition, when a moderate medicinal component is used and the content of the medicinal component in the mixture is 10 to 30% by weight, the saccharide content in the mixture is usually 20 to 90% by weight. It is preferably 30 to 80% by weight, more preferably about 40 to 75% by weight. Examples of the medicinal component having a medium dosage include antipyretic analgesic / anti-inflammatory agents.

  Further, when a medicinal component having a large dose is used and the content of the medicinal component in the mixture is 30 to 70% by weight, the saccharide content in the mixture is usually 10 to 70% by weight, preferably Is about 15 to 60% by weight, more preferably about 20 to 50% by weight. Vitamin C etc. are mentioned as a medicinal component with a large dosage.

  The mixture may contain various additives generally used in tablet production as long as the effects of the present invention are not hindered.

  Examples of the additive include disintegrants, binders, acidulants, foaming agents, artificial sweeteners, fragrances, lubricants, and coloring agents.

  Examples of the disintegrant include starch such as corn starch and potato starch, carmellose calcium, carmellose sodium, and polyvinyl alcohol. Examples of the binder include gum arabic powder, gelatin, pullulan and the like.

  Examples of the acidulant include citric acid, tartaric acid, malic acid and the like. Examples of the foaming agent include sodium bicarbonate. Examples of artificial sweeteners include saccharin sodium, dipotassium glycyrrhizin, aspartame, stevia, and thaumatin.

  As a fragrance | flavor, lemon, lemon lime, orange, menthol, etc. are mentioned, for example. Examples of the lubricant include magnesium stearate, sucrose fatty acid ester, polyethylene glycol, talc, stearic acid and the like. Examples of the colorant include edible pigments such as edible yellow No. 5, edible red No. 2 and edible blue No. 2; edible lake pigments;

  One or more of these additives, for example, an appropriate amount can be appropriately added at the time of mixing the medicinal ingredient and the saccharide, at the time of adding water, at the time of kneading, or before and after these steps.

  The amount of water in the mixture may be such that the saccharide particle surface contained in the mixture is moistened. In the present invention, water is added to such an extent that the surface of the saccharide particles is moistened. Therefore, when tableting and drying are performed, the saccharide particles are fused to each other, and the porous material has an appropriate porosity and hardness as an intraoral dissolution type tablet. Tablets are obtained.

  The amount of water added varies depending on the types and amounts of the medicinal ingredients, saccharides and additives, but is usually 0.3 to 10% by weight, preferably 0.3 to 7% by weight with respect to the mixture containing the medicinal ingredients and the like. %, More preferably 0.5 to 3% by weight, still more preferably 0.7 to 3% by weight, and most preferably about 1 to 3% by weight. If the amount of water added is small, the tablet strength decreases, and conversely, if it is large, medicinal ingredients and the like are likely to adhere to a molding apparatus (for example, a punch, a die, etc.) during tableting, making it difficult to produce tablets.

  More specifically, for example, in the case of using a mixture containing 20 to 40% by weight of xylitol and / or maltitol as a saccharide, the water content is usually 0.5 to 5.0% by weight, preferably Add 1.0-2.0 wt%. Moreover, when using the mixture containing 60-80 weight% of sucrose and / or glucose as saccharides, a water | moisture content is normally added 1.5-2.5 weight% with respect to the said mixture. Furthermore, when using a mixture containing 55 to 75% by weight of erythritol as a saccharide, usually 1.5 to 2.5% by weight of water is added to the mixture.

  The amount of moisture can be adjusted by adding moisture to any raw material component or a mixture thereof. The method of adding moisture is not particularly limited, and it may be added at once, or may be added dropwise or sprayed.

  In the method of the present invention, for example, water can be added to a mixture containing a medicinal component, a saccharide, and, if necessary, the additive, so that the surface of the saccharide particles contained in the mixture is moistened.

  Mixing of the medicinal component and the saccharide is performed by a mixing method generally used in the production of a preparation, for example, mixing, kneading, sieving and the like. Specifically, vertical granulator GV10 (manufactured by Paulek), universal kneader (manufactured by Hata Iron Works), fluidized bed granulator FD-5S (manufactured by Paulek), gyroscope (manufactured by Tokuju Seisakusho), etc. Can be mixed.

  A mixture containing a medicinal component, sugar and water is usually kneaded before tableting. For the kneading of the mixture containing moisture, a method generally used as a preparation means for the preparation can be used. For example, kneading can be performed using the above-described apparatus or the like used when mixing medicinal components and saccharides.

For the tableting, an apparatus generally used for tablet molding or granulation is used. For example, a single tablet machine (manufactured by Kikusui Seisakusho), a rotary tablet machine (manufactured by Kikusui Seisakusho), etc. are used. The molding pressure at the time of tableting is usually 3 to 160 kg / cm ² (2.94 × 10 ^{5 to} 1.57 × 10 ⁷ Pa), preferably ⁵ to 130 kg / cm ² (4.90 × 10 ⁵ to 1). .27 × 10 ⁷ Pa), more preferably about 8 to 50 kg / cm ² (7.84 × 10 ^{5 to} 4.90 × 10 ⁶ Pa).

  The temperature at the time of tableting is such that the saccharide particles do not dissolve or melt, and is usually room temperature (for example, about 20 to 30 ° C.), preferably about 25 ° C.

  Moreover, it is preferable to further dry the tablet obtained as described above. Drying can be performed by any method generally used in the production of pharmaceutical preparations such as vacuum drying, freeze drying, and natural drying.

  These tablets may be further coated by a coating method generally used in the production of a coated preparation to the extent that it does not adversely affect the strength and solubility of the tablet.

  The oral dissolution tablet of the present invention thus obtained has a porous structure. The porous structure referred to here usually means that the porosity is 20 to 80%, preferably 30 to 70%. Therefore, the tablet of this invention is excellent in the disintegration property and solubility in an oral cavity, and also has a strong drop strength.

  That is, in the oral-dissolving tablet of the present invention, the dissolution in the mouth (time until the tablet is completely dissolved in the saliva in the oral cavity of a healthy adult male) is usually 0.05 to 3.0 minutes, preferably 0. About 1 to 1.5 minutes, disintegration time (measurement value by disintegration test method described in Japanese Pharmacopoeia 12th revision) is usually 0.05 to 3.0 minutes, preferably 0.1 to 1. About 5 minutes, hardness (measured with a tablet hardness meter) is usually 2 to 25 kg, preferably about 3 to 20 kg, drop strength (breakage rate when a tablet is dropped on a glass plate from a height of 30 cm) Is usually about 0 to 70%, preferably about 0 to 40%.

  Therefore, the oral-dissolving tablet of the present invention can be used in various forms similar to conventional preparations containing the same medicinal ingredients as easy-to-take preparations for the elderly and children, and as safe preparations for general adults. It can be used for the treatment and prevention of illnesses and has excellent long-term storage and stability.

  In the oral-dissolving tablet of the present invention, the medicinal component is usually 0.05 to 90% by weight, preferably 0.1 to 70% by weight, more preferably about 0.3 to 60% by weight, 10 to 90% by weight, preferably 20 to 85% by weight, more preferably about 30 to 80% by weight.

  When the intraoral-dissolving tablet of the present invention contains a small amount of a medicinal ingredient, the content of the medicinal ingredient is usually about 0.1 to 10% by weight in the tablet, and the sugar content is in the tablet. The amount is usually 30 to 90% by weight, preferably 50 to 85% by weight, and more preferably about 60 to 85% by weight.

  In addition, when the intraoral-dissolving tablet of the present invention contains a moderate amount of medicinal component, the content of the medicinal component is usually about 10 to 30% by weight in the tablet, and the content of saccharide is In a tablet, it is 20 to 90 weight% normally, Preferably it is 30 to 80 weight%, More preferably, it is about 40 to 75 weight%.

  Furthermore, when the intraoral-dissolving tablet of the present invention contains a large amount of a medicinal ingredient, the content of the medicinal ingredient is usually about 30 to 70% by weight in the tablet, and the sugar content is in the tablet. Usually, it is about 10 to 70% by weight, preferably about 15 to 60% by weight, and more preferably about 20 to 50% by weight.

  The oral dissolution tablet of the present invention can be administered in the same manner as a conventional oral preparation containing the same medicinal ingredients. In general, for adults, for example, when the medicinal ingredient is diazepam, the tablet of the present invention has an amount of the medicinal ingredient of about 0 per day. It is orally administered by dividing into 1 to 3 times so as to be 0.01 mg to 100 mg, preferably 0.1 to 30 mg, more preferably 0.3 to 10 mg. In addition, for example, when orally administering the oral-dissolving tablet of the present invention containing vitamin C as a nourishing tonic for adults, the amount of vitamin C is about 2 mg to 2000 mg, preferably 100 to 2000 mg per day. The tablet of the present invention is administered.

  The present invention will be described in more detail with reference to the following examples, but these are not intended to limit the present invention.

Reference example 1
Ascorbic acid, riboflavin butyrate, d-α-tocopherol, xylitol, maltitol, corn starch, aspartame, and gum arabic powder are added to an agitation granulator (vertical granulator VG10, manufactured by Paulek) as shown in Table 1 below. And mixed for 1 minute. Next, 200 ml of water was added and kneaded. After vacuum drying using a box-type vacuum dryer (manufactured by Kashiwagi Seisakusho), magnesium stearate was added (0. 5%), and then mixed for 3 minutes with a mixer (Tumbler Mixer, Showa Chemical Machinery). About 900 tablets were obtained by tableting at a pressure of 1910 kg / cm ² (1.87 × 10 ⁸ Pa, force: 6000 kg) using a single tablet machine (manufactured by Kikusui Seisakusho) with a 20 mmφ corner plane punch. .

Reference example 2
Diazepam, sucrose, glucose, potato starch, citric acid, gelatin, and edible yellow No. 5 dye were added to a kneading machine (universal kneading machine, manufactured by Hata Iron Works) as shown in Table 2, and mixed for 2 minutes. Next, 50 ml of alcohol and 50 ml of water are added and kneaded. After vacuum drying using a box-type vacuum dryer (manufactured by Kashiwagi Seisakusho), sucrose fatty acid is granulated with a granulator (Fitzmill, Hosokawa Micron). After ester addition (0.5%), a mixer (V-type mixer, manufactured by Patterson Killy) was mixed for 1 minute. Using a rotary tablet machine (collect 19K, manufactured by Kikusui Seisakusho Co., Ltd.), about 900 pieces were tableted with a pressure of 1980 kg / cm ² (1.94 × 10 ⁸ Pa, force: 3500 kg) with a 15 mmφ corner plane punch. Tablets were obtained.

Reference example 3
Ibuprofen, caffeine, erythritol, citric acid, carmellose calcium, corn starch, stevia, and menthol were added to a fluidized bed granulator (FD-5S, manufactured by Paulek) as shown in Table 3 below, and mixed for 3 minutes. . Next, 120 ml of water is added by spraying and granulated, followed by drying, after adding 0.2% magnesium stearate and 1.8% talc as granules with a granulator (Power Mixer, Showa Chemical Machinery) , And mixed for 3 minutes with a mixer (tumbler mixer, manufactured by Showa Chemical Machinery Co., Ltd.). Using a rotary tablet machine (collect 19K, manufactured by Kikusui Seisakusho Co., Ltd.), about 900 pieces were tableted with a pressure of 1700 kg / cm ² (1.67 × 10 ⁸ Pa, force: 3000 kg) with a 15 mmφ corner plane punch. Tablets were obtained.

Reference example 4
About 900 tablets in the same manner as in Reference Example 1 except that the amount of water added was 40 ml (2%) and the pressure was 32 kg / cm ² (3.14 × 10 ⁶ Pa, force: 100 kg). Got.

Example 1
Ascorbic acid, riboflavin butyrate, d-α-tocopherol, xylitol, maltitol, corn starch, aspartame, and gum arabic powder are added to an agitation granulator (vertical granulator VG10, manufactured by Paulek) as shown in Table 1 below. And mixed for 1 minute. Next, 32 ml of water was added and kneaded, and the mixture was punched using a single tablet machine (manufactured by Kikusui Seisakusho) with a 20 mmφ corner plane punch at a pressure of 32 kg / cm ² (3.14 × 10 ⁶ Pa, force: 100 kg). About 800 tablets were obtained by tableting. Furthermore, it vacuum-dried using the box-type vacuum dryer (made by Kashiwagi Seisakusho).

Example 2
Diazepam, sucrose, glucose, potato starch, citric acid, gelatin, and food yellow No. 5 dye were added to a kneading machine (universal kneading machine, manufactured by Hata Iron Works), respectively, as shown in Table 2 below, and mixed for 2 minutes. Next, 10 ml of alcohol and 10 ml of water are added and kneaded. Using a tablet machine (single tablet machine, manufactured by Kikusui Seisakusho Co., Ltd.), the pressure is 38 kg / cm ² (3.72 × 10 ⁶ Pa) with a 10 mmφ plain surface punch. , Force: 30 kg), about 800 tablets were obtained. Furthermore, it vacuum-dried using the box-type vacuum dryer (made by the Kashiwagi Seisakusho).

Example 3
Ibuprofen, caffeine, erythritol, citric acid, carmellose calcium, corn starch, stevia, and menthol were added to a fluidized bed granulator (FD-5S, manufactured by Paulek) as shown in Table 3 below, and mixed for 3 minutes. . Next, 20 ml of water is added by spraying and granulated. Tablet machine (single tablet machine, manufactured by Kikusui Seisakusho Co., Ltd.) Pressure of 34 Kg / cm ² (3.33 × 10 ⁶ Pa, force: 60 Kg) with a 15 mmφ round corner plane punch To obtain about 800 tablets. Further, it was dried by ventilation using a mini jet oven (manufactured by Toyama Sangyo).

Example 4
About 800 tablets were obtained in the same manner as in Example 1 except that tableting was performed at a molding pressure of 10 kg / cm ² (9.80 × 10 ⁵ Pa, force: 30 kg).

Example 5
About 800 tablets were obtained in the same manner as in Example 1 except that the amount of water added was 10 ml and kneaded.

Example 6
About 800 tablets were obtained in the same manner as in Example 1 except that the amount of water added was 100 ml and kneaded.

Example 7
Using the raw material components shown in Table 4 below, except that the amount of water added was 36 ml, the same operation as in Example 1 was performed to obtain about 800 tablets.

Example 8
The same as in Example 1, except that the raw material components shown in Table 5 below were used, the amount of water added was 40 ml, and the tableting pressure was 36 kg / cm ² (3.53 × 10 ⁶ Pa, force: 110 kg). Operation was performed to obtain about 800 tablets.

Example 9
The same as in Example 2, except that the raw material components shown in Table 6 below were used, the amount of water added was 9 ml, and the tableting pressure was 101 kg / cm ² (9.90 × 10 ⁶ Pa, force: 80 kg). Operation was performed to obtain about 1600 tablets.

Example 10
The same as in Example 2, except that the raw material components shown in Table 7 below were used, the amount of water added was 11 ml, and the tableting pressure was 127 kg / cm ² (1.24 × 10 ⁷ Pa, force: 100 kg). Operation was performed to obtain about 1600 tablets.

Example 11
The same as in Example 1, except that the raw material components shown in Table 8 below were used, the amount of water added was 28 ml, and the tableting pressure was 38 kg / cm ² (3.72 × 10 ⁶ Pa, force: 120 kg). Operation was performed to obtain about 800 tablets.

Example 12
The same as in Example 1, except that the raw material components shown in Table 9 below were used, the amount of water added was 24 ml, and the tableting pressure was 35 kg / cm ² (3.43 × 10 ⁶ Pa, force: 110 kg). Operation was performed to obtain about 800 tablets.

Example 13
The same as in Example 1, except that the raw material components shown in Table 10 below were used, the amount of water added was 20 ml, and the tableting pressure was 29 kg / cm ² (2.84 × 10 ⁶ Pa, force: 90 kg). Operation was performed to obtain about 800 tablets.

Example 14
Except for using the raw material components shown in Table 11 below, the amount of water added was 24 ml, and the same operation as in Example 1 was performed to obtain about 800 tablets.

Example 15
The same as in Example 1, except that the raw material components shown in Table 12 below were used, the amount of water added was 30 ml, and the tableting pressure was 30 kg / cm ² (2.94 × 10 ⁶ Pa, force: 90 kg). Operation was performed to obtain about 800 tablets.

Example 16
Except for using the raw material components shown in Table 13 below, the amount of water added was changed to 30 ml, and the same operation as in Example 1 was performed to obtain about 800 tablets.

Example 17
The same as in Example 1, except that the raw material components shown in Table 14 below were used, the amount of water added was 40 ml, and the tableting pressure was 29 kg / cm ² (2.84 × 10 ⁶ Pa, force: 90 kg). Operation was performed to obtain about 800 tablets.

Example 18
The same as in Example 1, except that the raw material components shown in Table 15 below were used, the amount of water added was 24 ml, and the tableting pressure was 25 kg / cm ² (2.45 × 10 ⁶ Pa, force: 80 kg). Operation was performed to obtain about 800 tablets.

Example 19
The same as in Example 1, except that the raw material components shown in Table 16 below were used, the amount of water added was 10 ml, and the tableting pressure was 25 kg / cm ² (2.45 × 10 ⁶ Pa, force: 80 kg). Operation was performed to obtain about 400 tablets.

Example 20
Except for using the raw material components shown in Table 17 below, the amount of water added was 16 ml, and the same operation as in Example 1 was performed to obtain about 800 tablets.

Example 21
The same as in Example 1, except that the raw material components shown in Table 18 below were used, the amount of water added was 24 ml, and the tableting pressure was 25 kg / cm ² (2.45 × 10 ⁶ Pa, force: 80 kg). Operation was performed to obtain about 800 tablets.

Example 22
Except for using the raw material components shown in Table 19 below, the addition amounts of alcohol and water were each 6 ml, and tableting was performed with a 9 mmφ punch at a pressure of 31 kg / cm ² (3.04 × 10 ⁶ Pa, force: 20 kg). The same operation as in Example 2 was performed to obtain about 1000 300 mg tablets.

Example 23
Except for using the raw material components shown in Table 20 below, the same operation as in Example 22 was performed to obtain about 1000 300 mg tablets.

Example 24
Except for using the raw material components shown in Table 21 below, the same operation as in Example 22 was performed to obtain about 1000 300 mg tablets.

Test Example In order to explain the effects of the present invention in more detail, the following tablet characteristics were measured for the tablets obtained in the examples. The obtained results are shown in Table 22 to Table 24. Moreover, it measured similarly about the tablet obtained by the reference example as a control | contrast. The results are shown in Table 25.

(1) Porosity The porosity of the tablet was determined by the following formula.
Porosity = [{tablet volume− (tablet weight / true specific gravity of raw material components)} / tablet volume] × 100

(2) Melting in Mouth The time until the tablet was completely dissolved with the saliva in the oral cavity of a healthy adult male (age 45, height 165 cm, body weight 55 kg) was measured. The test was performed twice and the results represent the average of two times.

(3) Disintegration time It measured by the disintegration test method described in the Japanese Pharmacopoeia 12th revision. The test was performed 6 times and the results represent the average of 6 times.

(4) Hardness It was measured using a tablet hardness meter (TH-100, manufactured by Toyama Sangyo). The test was performed 10 times and the results represent an average of 10 times.

(5) Drop strength The breakage rate when the tablet was dropped onto a glass plate from a height of 30 cm was measured. The test was performed 10 times and the results represent an average of 10 times.

  Comparison between Tables 22-24 and Table 25 shows that the intraoral-dissolving tablet obtained in the present invention is excellent in solubility and disintegration, and has an appropriate strength.

Claims (15)

  An orally disintegrating tablet having a porous structure comprising an effective amount of a medicinal ingredient and at least one water-soluble saccharide selected from mannitol, xylitol and erythritol.   The orally disintegrating tablet according to claim 1 obtained by tableting.   The orally disintegrating tablet according to claim 1 or 2, having a hardness of 2 to 25 kg and a porosity of 20 to 80%.   The orally disintegrating tablet according to any one of claims 1 to 3, having a drop strength of 0 to 70%.   The orally disintegrating tablet according to any one of claims 1 to 4, comprising an effective amount of a medicinal ingredient and a water-soluble saccharide, having a hardness of 3 to 20 kg, a porosity of 30 to 70%, and a drop strength of 0 to 40%.   The orally disintegrating tablet according to any one of claims 1 to 5, comprising 0.05 to 90% by weight of a medicinal component in the tablet.   The orally disintegrating tablet according to any one of claims 1 to 6, comprising 10 to 90% by weight of a water-soluble saccharide in the tablet.   Medicinal properties are vitamins, herbal medicines, antipyretic analgesics, antipsychotics, anxiolytics, antidepressants, hypnotic sedatives, gastrointestinal drugs, antacids, antitussive expectorants, antihypertensives, antidiabetics, osteoporosis The orally disintegrating tablet according to any one of claims 1 to 7, which is a symptomatic drug or a skeletal muscle relaxant.   The orally disintegrating tablet according to any one of claims 1 to 8, wherein the water-soluble saccharide is erythritol.   The orally disintegrating tablet according to any one of claims 1 to 9, wherein the water-soluble saccharide is mannitol.   A tablet component containing a medicinal component and at least one water-soluble saccharide selected from mannitol, xylitol, and erythritol is used with 0.3 to 7% by weight of water, and the surface of the particles of the water-soluble saccharide is used. An orally disintegrating tablet obtained by moistening, tableting a mixture containing the above-mentioned medicinal ingredients, a water-soluble saccharide, and moisture, followed by drying. After moistening the surface of the water-soluble saccharide particles, a pressure of 3 to 160 kg / cm ² is applied to the mixture containing the medicinal component, saccharide and water without drying or without forming a dry granulated powder or granules. The orally disintegrating tablet according to claim 11, which is obtained by drying after tableting.   The orally disintegrating tablet according to claim 11 or 12, wherein the water-soluble saccharide has an average particle size of 1 to 100 µm.   The orally disintegrating tablet according to any one of claims 11 to 13, having a hardness of 2 to 25 kg, a porosity of 20 to 80%, and a drop strength of 0 to 70%.   A tablet component containing a medicinal component and at least one water-soluble saccharide selected from mannitol, xylitol, and erythritol is used with 0.3 to 7% by weight of water, and the surface of the particles of the water-soluble saccharide is used. A method of improving the orally disintegrating property of a tablet by moistening, tableting a mixture containing the medicinal component, a water-soluble saccharide and water, and then drying.