JPH1133084A - Intraoral soluble type tablet and manufacture thereof - Google Patents

Abstract

PURPOSE: To provide quick collapsibility and solubility in an oral cavity and proper strength in a manufacture process and a distribution process by forming a intraoral soluble tablet of porous structure, in which inter-particle bridge formation is carried out between a medicinal constituent and sugar with polyethylene glycol. CONSTITUTION: A medicinal constituent, sugar 1, and an additive are mixed together and granulated if necessary, or alternatively, these are mixed together after granulation for each constituent is carried out. Then, particle/powder type polyethylene glycol 2 is mixed, and tableting at a low pressure and shaping are carried out, and finally, added particle type polyethylene glycol 2 is melted once by heating and the like and then hardened again by cooling. Consequently, polyethylene glycol 2 forms a bridge 3 between the medicinal constituent and the sugar particle 1 so as to contribute to adhesion between the particles 1, and hardness of the tablet can be increased as a whole.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to an orally dissolvable tablet having rapid disintegration and dissolving properties in the oral cavity and having an appropriate hardness even when compressed at a low pressure. Orally dissolvable tablets are practically sufficient disintegration by saliva without taking water in the oral cavity,
It is a tablet that has solubility. Here, practically sufficient disintegration and dissolving means disintegration or dissolution in the oral cavity in about 5 to 120 seconds.

[0002]

2. Description of the Related Art Conventionally, various pharmaceutical dosage forms for oral use have been known, but there are few dosage forms in consideration of the ease of drinking for patients.
In particular, there has been a demand for the development of a dosage form suitable for elderly people and children who have many problems in taking drugs.

For example, tablets and capsules, when taken by elderly people or children with weak swallowing power, have problems such as difficulty in swallowing and sticking to the pharynx and esophagus. In the case of powders and granules, the drug remains in the oral cavity and it is difficult to swallow, discomfort remains in the mouth, and when taken by elderly people,
In some cases, granules may enter between dentures and cause discomfort. Furthermore, since these oral preparations require water when taken, elderly people and children have problems with urination at night, and it is often difficult to prepare water. A syrup is a preferred dosage form for elderly people and children, but it is difficult to take a correct amount by measurement and it is not always suitable for elderly people and children.

[0004] In view of these circumstances, development of orally dissolving tablets has been promoted as a dosage form suitable for the elderly and children. Conventional oral dissolution type tablets include those manufactured through a freeze-drying process and those manufactured by tableting. As an example of the former, Japanese Patent Publication No. Sho 58-2441.
No. 0 publication discloses mixing the tablet contents with a solvent which is inert to the tablet contents and which is frozen at -30 to + 25 ° C.
The solvent is adjusted to 5 to 80% by weight of the total mixture, the mixture is solidified by placing the mixture in an inert cooling medium, compressed at a temperature lower than the freezing point of the solvent into tablets, and the solvent is further freeze-dried or air-dried. A method for producing a porous tablet with good disintegration by volatilization is described.

As an example of the latter, Japanese Patent Application Laid-Open No. 5-27
Japanese Patent No. 1054 discloses a porous material which has a suitable strength when it is compressed and dried when a mixture containing a medicinal ingredient, a saccharide, and water enough to moisten the surface of the saccharide particles, and which rapidly disintegrates and dissolves in the oral cavity. It is disclosed that an orally dissolving tablet having a sex structure can be obtained. Furthermore, Japanese Patent Publication No. 5-31055
No. 8 discloses that mannitol or lactose having poor moldability is mixed with sorbitol powder having a bulk specific gravity of less than 60 g / 100 ml to form other additives having high moldability, such as a cellulose compound, an acrylic acid compound, It describes that the amount of gelatin and the like can be reduced, and a solid pharmaceutical composition having excellent disintegration properties can be obtained.

[0006]

However, freeze-dried oral dissolving tablets are excellent in disintegration and dissolution in the oral cavity, but are not used in ordinary tablets due to insufficient tablet hardness. PTP (Press Through Pack) packaging etc. cannot be used, and when the product is delivered, carried or taken out for taking, etc.
Cracks were easily generated and handling was difficult. Furthermore, in the production process, a new freeze-dryer must be purchased, and the freeze-dryer cannot process a large amount of medicine at one time, and has disadvantages such as a long processing time. On the other hand, tablet-type oral dissolving tablets have solved various problems of freeze-dried oral dissolving tablets,
Disintegration and solubility in the oral cavity are not yet sufficient. In addition, a tableting preparation is usually prepared by applying granules or powder for tablet preparation to a tablet machine and obtaining a tablet having a certain hardness by pressing, usually 500 to 2000 kg / kg.
Molding is performed with high pressure using a punch. However, depending on the physicochemical properties and the amount of the medicinal ingredient and additives, there is a problem that tableting trouble such as capping may occur. The particles could be destroyed, impairing their properties.

In view of the above, these problems of freeze-dried orally dissolving type tablets and tableting orally dissolving type tablets have been solved, and rapid disintegration and solubility in the oral cavity and manufacturing process have been solved. It has been desired to develop an orally dissolvable tablet having appropriate strength in the distribution process, compatibility with the conventional production process, and the like. The present inventors have conducted various studies to develop an orally dissolving tablet having the above-mentioned properties and a method for producing the same, and obtained a tablet by mixing a medicinal ingredient and a saccharide, and powdered polyethylene glycol, Once the polyethylene glycol is melted and re-solidified,
The present inventors have found that a porous orally dissolvable tablet having rapid disintegration and dissolution in the oral cavity and having appropriate strength can be obtained, and the present invention has been completed.

[0008]

That is, according to the present invention, there is provided an orally dissolvable tablet containing a pharmaceutically active ingredient, a saccharide and polyethylene glycol, wherein the polyethylene glycol has particles between the pharmaceutically active ingredient and the saccharide. An oral dissolving tablet having a porous structure formed by forming an intercrosslink is provided.

Further, according to the present invention, a medicinal ingredient, a saccharide and polyethylene glycol are mixed, the mixture is tabletted at a low pressure, and the obtained tablet is heated to a temperature at which the polyethylene glycol melts, and then allowed to cool. The present invention provides a method for producing an orally dissolvable tablet characterized by forming a porous structure. In the present invention, it is preferable to use polyethylene glycol in the form of particles, and the tablet of the present invention comprises a disintegrant, a binder, a foaming agent,
It may contain one or more components selected from the group consisting of artificial sweeteners, flavors, lubricants and coloring agents.

[0010] Examples of the disintegrant include starch such as corn starch and potato starch, carmellose calcium and the like, and examples of the binder include gum arabic powder, gelatin and pullulan. Examples of the acidulant include citric acid, tartaric acid, and malic acid, and examples of the foaming agent include baking soda. Examples of the artificial sweetener include saccharin sodium, dipotassium glycyrrhizinate, aspartame, stevia, thaumatin and the like.

Examples of the flavor include lemon, lemon lime, orange, and menthol, and examples of the lubricant include magnesium stearate, sucrose fatty acid ester, polyethylene glycol, talc, and the like.
Stearic acid and the like are exemplified. Examples of the colorant include food colors such as Food Yellow No. 5, Food Red No. 2, Food Blue No. 2, etc .; Food Lake Dye;

[0012]

Hereinafter, the present invention will be described in detail. The orally-dissolvable tablet of the present invention has a medicinal ingredient, a saccharide and polyethylene glycol as main components, and the polyethylene glycol forms a cross-particle crosslink with the medicinal ingredient and the saccharide to form a porous structure. I have. As a form of the present invention,
When the medicinal ingredient and the saccharide form particles separately, and when the medicinal ingredient and the saccharide are mixed to form particles, the medicinal ingredient is formed as a masked particle or a sustained release particle. May be considered. Incidentally, polyethylene glycol is conventionally used as a masking agent for melting and granulating a drug having bitterness, as a plasticizer of a coating base for imparting flexibility to a coating film in a drug, and for relaxing bitterness, or As a binder for ensuring fluidity during granulation, and further, it has been used as a stabilizer for stabilizing by melt-coating a heat-stable and water-unstable drug, The present invention is the first to be used for an orally dissolving tablet.

Next, a method for producing the tablet of the present invention will be described. First, a medicinal component, a saccharide, and an additive are mixed, and if necessary, granulation is performed. Alternatively, the medicinal ingredient and the saccharide, and in some cases, the additive may be separately granulated and then mixed. Next, polyethylene glycol in the form of particles or powder is blended, and the mixture is compressed at a low pressure to adjust the shape. Finally, the added particulate polyethylene glycol is once melted by heating or the like, and then solidified by cooling.

FIG. 1 is a schematic diagram showing the inside of a tablet before and after melting polyethylene glycol particles in one embodiment of the tablet of the present invention. Represents polyethylene glycol particles or powder. Polyethylene glycol particles 2
In a stage prior to melting, the particles in the tablet are dispersed while maintaining the gaps between the particles. For this reason, unlike a normal tablet having a porous structure but having a dense particle, the tablet has no hardness and is extremely easily disintegrated. However, once the polyethylene glycol particles 2 are once melted and then re-solidified, the polyethylene glycol forms crosslinks 3 between the medicinal ingredient and the saccharide particles and contributes to the adhesion between the particles, so that the hardness of the whole tablet increases. It is. In addition, the melting of the particulate polyethylene glycol particles 2 also has the effect of increasing the porosity of the tablet. The tablet preferably has a porous structure in order to have rapid disintegration and solubility in the oral cavity, but in order to obtain a porous structure in the tablet of the present invention, polyethylene glycol is added in the form of particles. Is extremely important. In addition, since the tablet of the present invention is molded at a low pressure, tableting trouble is less likely to occur, physicochemical properties such as medicinal ingredients to be added, it is hard to be limited in the amount added, and also masking particles, sustained release particles Applicability is also a feature of the present invention.

In the production of the tablet of the present invention, a medicinal component,
Mixing of saccharides, additives and the like is performed by a method used in the production of general preparations. Specifically, a V-type mixer (manufactured by Tokuju Kousaku Co., Ltd.), a W-type mixer (manufactured by Tokuju Kousaku Co., Ltd.), a cross rotary mixer (Meiwa Kogyo Co., Ltd.)
Manufactured). The same applies when mixing polyethylene glycol with this mixture. In tableting,
An apparatus generally used for tablet molding is used, and for example, a single-shot tableting machine (manufactured by Kikusui Seisakusho Co., Ltd.), a rotary tableting machine (manufactured by Hata Iron Works, Ltd.) and the like are used. It is desirable that the molding pressure at the time of tableting be low.
The hardness is 0 kg / punch or less, preferably 200 kg / punch or less, and the hardness of the tablet after tableting is 2 kg / cm ² or less.

When powder fluidity is required at the time of tableting, the medicinal component, saccharides and additives can be granulated alone or as a mixture. For example, a fluidized bed granulator (Okawara Seisakusho) Vertical mixer (manufactured by Sanei Seisakusho Co., Ltd.), stirring granulator (Fukae Sangyo Co., Ltd.)
) Or the like and using an aqueous solution of a saccharide or a water-soluble polymer as a binder to perform granulation.

The saccharide used in the present invention is not particularly limited as long as it is water-soluble and does not adversely affect the pharmaceutically active ingredient. For example, sucrose, coupling sugar, fructooligosaccharide, palatinose, glucose, maltose, fructose ,
Examples include sugars such as lactose, isomerized lactose (lactulose), and reduced lactose (lactitol), and sugar alcohols such as sorbitol, mannitol, maltitol, xylitol, and reduced palatinose. These saccharides may be used alone or in combination of two or more.

The polyethylene glycol used in the present invention is not particularly limited as long as it is in a solid form, for example, in the form of particles, powder, or flakes, but is preferably in the form of particles. When a flaky material is used, it may be used in the form of powder by a general process such as pulverization and spray drying. Polyethylene glycol is melted in the final stage of the manufacturing process, so if the melting point is high, there is a concern that adverse effects such as the decomposition of medicinal ingredients may be adversely affected. It may cause quality deterioration such as re-melting.

Therefore, it is desirable to use polyethylene glycol having a melting point of 40 to 70 ° C., preferably 53 to 64 ° C., for example, Macrogol 1540 (melting point of 42 to 46 ° C., British Pharmacopoeia (BP) 1988). ,
Macrogol 4000 (melting point 53-57 ° C, molecular weight 26
00-3800, Japanese Pharmacopoeia XII revision), Macrogol 6000 (melting point 56-61 ° C, molecular weight 7300-93)
00, Japanese Pharmacopoeia XII revision), Macrogol 2000
0 (melting point 56-64 ° C, molecular weight 15000-2500
0, Japanese Pharmacopoeia XII).

The amount of polyethylene glycol to be added is preferably 0.5 to 25% by weight based on the total amount. Heating is generally used as a method for melting the polyethylene glycol, but a drying device such as a ventilation dryer (manufactured by Matsui Seisakusho Co., Ltd.) is used. The heating temperature and the heating time are not particularly limited as long as the polyethylene glycol can be melted.
Time.

The medicinal components applied to the preparation of the present invention are not particularly limited, and those who have difficulty swallowing tablets, the elderly,
Drugs intended for children, or drugs that can be administered without daily water, drugs that need to be administered in daily life, preparations for patients with restricted drinking water, drugs for one-time use, and the like are preferable. The following are specific examples of drugs of high utility value.

(R) -5-[(1-methyl-3-indolyl) carbonyl] -4,5,6,7-tetrahydro-
IH-benzimidazole hydrochloride and salts thereof, serotonin 5HT3 receptor antagonists such as ondansetron and granisetron, indomethacin, ibuprofen, ibufenac, alclofenac, diclofenac, mefenamic acid, flurbiprofen, flufenamic acid, ketoprofen, phenyl Non-steroidal anti-inflammatory drugs such as butazone and methyl salicylate. Steroidal anti-inflammatory agents such as cortisone, hydrocortisone, prednisolone, dexamethasone, betamethasone dipropionate, betamethasone valerate, prednisolone, triamcinolone, and fluocinoloacetonide.

Diuretics such as bendroflurothiazide commapolythiazide, methycloazide, trichlormethiazide, ticlobenzazide, pentylhydrochlorothiazide, hydrochlorothiazide, and bumetanide. Emonapride,
Antipsychotics such as diazepam, nitrazepam, flunitrazapam, lorazepam, prazepam, fludiacepam, clonazepam, chlorpromazine, reserpine, clofluberyl, trifluperidol, haloperidol, moperonpromperidol, etizolam. Barbital,
Hypnotics such as thiopental, phenobarbital, and cyclobarbital.

Etosuccinimide, sodium palproate,
Antiepileptic drugs such as acetazolamide and meprobamate. Anti-perkins agents such as chlorzoxazone and levodoba. Antiemetics such as metoclopramide and metoclopramide hydrochloride. Hormonal agents such as insulin, testosterone, methyltestosterone, progesterone, and estradiol. Analgesics, such as morphine, aspirin, codeine, acetaminophen, acetanilide, aminopyrine, and lochyliprofen; Sulfa drugs such as sulfamine, sulfamonomethoxine and sulfamethizole;

Coronary vasodilators such as nitroglycerin, isosorbide dinitrate, pentaerythritol tetranitrate, propanyl nitrate, dipyridamole and papaverine hydrochloride. H2 receptor antagonists such as famotidine, cimetidine, ranitidine hydrochloride, and loxazine acetate hydrochloride. Antiarrhythmic therapeutic agents such as ajmaline, pindolol, propranolol, quinidine, amrinone and milrinone. Cardiotonic agents such as caffeine, digoxin, digitoxin. Nicardipine hydrochloride,
Calcium antagonists such as diltiazem hydrochloride, nivadipine, nifedipine, nitredipine, nizoldipine, nimodipine and nildipine.

Antihistamines such as diphenhydramine hydrochloride, carbinoxamine, diphenylpyraline, fenbenzamine, chlorpheniramine maleate, brompheniramine maleate, diphenylimidazole, clemizole and the like. Tetracycline, oxytetracyline,
Metacycline, doxycycline, minocycline,
Antibiotics such as chloramphenicols, erythromycins, lincomycin, penicillin G, clingmycin, kanamycin, chloramphenicol, fradiomycin, streptomycin and gentamicin; Anti-neoplastic agents such as 5-fluorouracil, uracil, cytarabine, broxuridine, busulfan, actinomycin, bleomycin, and mitomycin.

Diabetes drugs such as glibenclamide and epalrestat. Gout remedies such as allopurinol, colchicine and benzbromarone. Antiallergic agents such as ketotifen fumarate, sodium cromoglycate, and amlexanox. Clonidine, atenolol, doxazosin, bilibrolol, cilazapril, lisinopril, nilvalnidipine, manidipine, isosorbide dinitrate, diltiazem,
Antihypertensive agents such as nicolarezyl, guanethidine sulfate, amosulalol hydrochloride, alacepril, delapril hydrochloride, and enalapril maleate.

Indeloxazine hydrochloride, Thiabride hydrochloride,
Central nervous system drugs such as bifemelane hydrochloride. Skeletal muscle relaxants such as dantrolene sodium. Antispasmodics such as everidine hydrochloride, tizanidine hydrochloride, butylscopolamine, methylatropine bromide. Hyperlipidemia agents such as simvastatin and bravastatin sodium. Bronchodilators such as formoterol fumarate, salbutamol sulfate, and procaterol hydrochloride.

Α-adrenergic receptor blockers such as tamsulosin hydrochloride and brazosin, hypoglycemic agents, and oral contraceptives. Analgesic and anti-inflammatory agents such as loxoprofen. Gastrointestinal motility improvers such as Dombellidone and Cisapride. Anti-gastritis and anti-gastric ulcer agents such as deprenone. Osteoporosis agents such as alfacalcidol.
Prostatic hyperplasia agents such as chlormasisone. Expectorants such as amproxol. Allergic rhinitis agents such as oxatomodo and ketotifen. Asthmatics such as azelastine, procaterol, and terfenadine. Or an animal drug having antipyretic analgesic / inflammation activity, peptic anti-ulcer activity, etc. or an animal drug for each organ such as a reproductive organ.

In addition, the present invention makes use of the properties of the present preparations, such as diagnostic drugs such as contrast agents, health foods and functional foods, oral medicines such as breath fresheners and plaque stains, as well as pharmaceuticals. It can be applied to various uses, and the range of the active ingredient is not particularly limited. The amount of the active ingredient is preferably 80% by weight or less based on the whole solid component, though it depends on its properties. In general, the active ingredients applied are preferably those which do not give an unpleasant taste when dissolved. When applied to a component exhibiting an unpleasant taste, it is preferable to perform an appropriate concealing process. Further, it is preferable that the active ingredient for which sustained release is desired is subjected to an appropriate sustained release treatment by a known method so as to obtain particles with controlled release of the active ingredient.

The preparation of the present invention has sufficient strength for handling the preparation and can be used practically like ordinary tablets.
Here, “sufficient strength for the handling of the drug product” means a strength that is at least applicable to normal PTP packaging, and if it has this strength, it can withstand other handling such as delivery and carrying. it is conceivable that.

As a measure of the strength applicable to the PTP packaging, that is, the strength at which the preparation can be extruded from the cover sheet of the ordinary PTP packaging, the hardness in the longitudinal direction of the tablet can be mentioned. The hardness varies depending on the size and shape of the tablet, for example, 1.0 kg when the diameter is about 8.0 mm
As described above, the weight is preferably 1.5 kg or more when the diameter is about 10.0 mm, and 2.0 kg or more when the diameter is about 12.0 mm. The preparation of the present invention has sufficient strength to withstand removal from the PTP package in any size. The term "rapidly disintegrating and dissolving" in the present invention means that the saliva has practically sufficient disintegrating or dissolving properties without taking water in the oral cavity. The practically sufficient disintegration or dissolution may vary depending on the individual, but usually disintegrates or dissolves in the oral cavity in about 5 to 120 seconds, preferably about 10 to 60 seconds, more preferably about 10 to 40 seconds. It indicates that

The sugar-based structure of the preparation of the present invention is rapidly weakened by saliva in the oral cavity and gradually disintegrates or dissolves. In addition, the intraoral pressure, that is, the pressure by the upper jaw and tongue Alternatively, by performing a “licking” operation or the like below, it disintegrates or dissolves in a shorter time.

For a person who has a dry or little saliva in the oral cavity, the present preparation can be applied by using water or hot water that is sufficient to moisten the mouth. In addition, the present formulation can be taken together with a small amount of water after disintegration or dissolution in the oral cavity or in a partially disintegrated or dissolved state. Ease of swallowing even in this way of taking,
Alternatively, the advantages of the preparation of the present invention, such as the use of a small amount of water, can be enjoyed. It should be noted that there is no problem even if the present preparation is taken with water as it is in the same manner as ordinary tablets. The dosage form of the present invention can be selected according to the patient's preference or according to the situation, as long as there is no restriction by the contained active ingredient.

[0035]

EXAMPLES Hereinafter, the present invention will be described in more detail with reference to examples, but the present invention is not limited to these examples. In addition, polyethylene glycol is PEG600.
0 (Sanyo Chemical Industries, Ltd.) was used.

Example 1 400 g of mannitol (manufactured by Towa Kasei Kogyo Co., Ltd.) was mixed with maltose (san malt green,
Using a maltose aqueous solution obtained by dissolving 20 g of Hayashibara Shoji Co., Ltd. in 180 g of water, granulation was performed with a fluidized bed granulator (manufactured by Okawara Seisakusho Co., Ltd.). Up to 10 g of maltose, fine particle coating is performed with a spray pressure of 3 kg / cm ² ,
Thereafter, granulation was performed at a spray pressure of 0.5 kg / cm ² . After drying the granulated product, PEG 6
000 15g, magnesium stearate 0.2g
The tablets were compounded and pressed using a rotary tableting machine (manufactured by Hata Ironworks Co., Ltd.) at a pressure of 72 kg / punch using a punch of 300 mg / φ10 mm, 10 mmR. Furthermore, the obtained tablet was air-dried at 70 ° C. for 1 hour to obtain a tablet of the present invention. The dissolution time in the mouth of the tablet was 17 seconds and the hardness was 3.3 kg.

Example 2 Maltose (San Malt S,
Hayashibara Shoji Co., Ltd.) 184.8g, PEG6000
Was mixed with 15 g of magnesium stearate and 0.2 g of magnesium stearate.
Tableting was carried out with a punch of 0 mm and 10 mmR at a pressure of 103 kg / punch. Furthermore, the tablet of the present invention was obtained by air-drying the obtained tablet at 70 ° C. for 1 hour. The dissolution time of the tablet in the oral cavity was 20 seconds and the hardness was 3.5 kg.

Example 3 154.8 g of PEG 6000 and 0.2 g of magnesium stearate were mixed with 184.8 g of lactose (Dilactose, Freund Corporation).
Using a rotary tableting machine, 1 tablet 300mg, φ10m
Tableting was performed at a pressure of 112 kg / punch with a m, 10 mmR punch. Furthermore, the tablet of the present invention was obtained by air-drying the obtained tablet at 70 ° C. for 1 hour. The dissolution time of the tablet in the oral cavity was 17 seconds and the hardness was 4.1 kg.

Example 4 Lactose (388 g) was replaced with hydroxypropylcellulose (HPC-SL, Nippon Soda) (12 g).
Was granulated with a fluidized bed granulator using an aqueous solution of HPC dissolved in 118 g of water. After drying the granulate, 184.8
15 g of PEG 6000 and 0.2 g of magnesium stearate were added to the mixture, and the mixture was mixed with a rotary tableting machine.
Tablets were pressed at a pressure of 62 kg / punch using a punch of 300 mg, φ10 mm, 10 mmR. Furthermore, the obtained tablets were
The tablet of the present invention was obtained by air drying at 0 ° C. for 1 hour. The dissolution time of the tablet in the oral cavity was 20 seconds, and the hardness was 3.0 kg.

(Example 5) Using 800 g of mannitol and 65 g of water, granulation was carried out using a vertical granulator. After drying the granules, PEG6000 was added to 184.8 g.
Was mixed with 15 g of magnesium stearate and 0.2 g of magnesium stearate.
Tableting was performed at a pressure of 195 kg / punch using a 10 mmR punch with a pressure of 195 kg. Furthermore, the obtained tablet was air-dried at 70 ° C. for 1 hour to obtain a tablet of the present invention. The dissolution time of the tablet in the oral cavity was 22 seconds and the hardness was 3.9 kg.

Example 6 500 g of mannitol was added to maltose (San malt midori, Hayashibara Shoji Co., Ltd.).
Using a maltose aqueous solution in which 3 g was dissolved in 218.7 g of water, the mixture was granulated by a fluidized bed granulator. Maltose amount 10g
Until then, fine particle coating was performed at a spray pressure of 3 kg / cm ² . Famotidine 1 was added to 485.8 g of this coated product.
7.6 g, aspartame 5.2 g, malic acid 10.5
g, and the mixture was granulated with a spray pressure of 0.5 kg / cm ² using the above maltose aqueous solution by a fluidized bed granulator.
After drying the granulated product, 11.3 g of PEG 6000 and 0.16 g of magnesium stearate were blended with 150 g, and 318 mg / tablet, Φ1 / tablet, using a rotary tableting machine.
Tableting was performed with a 0 mm and 10 mmR punch. Furthermore, the obtained tablet was air-dried at 70 ° C. for 1 hour to obtain a tablet of the present invention. The dissolution time of the tablet in the oral cavity is 20 seconds,
The hardness was 6.0 kg.

Example 7 A mixture of 396.9 g of mannitol and 3.5 g of glibenclamide was granulated by a fluid bed granulator using an aqueous maltose solution in which 21 g of maltose was dissolved in 189 g of water. Fine particle coating was performed at a spray pressure of 3 kg / cm ² up to a maltose amount of 8 g, and thereafter granulation was performed at a spray pressure of 0.6 kg / cm ² . After drying the granules, 149.8 g of PE
7.5 g of G6000 and 0.15 g of magnesium stearate were blended, and one tablet was prepared using a rotary tableting machine.
Using a 3mg, φ10mm, 10mmR punch, pressure 86
The tablet was compressed with a kg / punch. Furthermore, the tablet of the present invention was obtained by air-drying the obtained tablet at 80 ° C. for 10 minutes. The dissolution time of the tablet in the oral cavity is 30 seconds, and the hardness is 4.
It was 5 kg.

Example 8 Maltose (San Malt S,
Hayashibara Shoji Co., Ltd.) 179.8g, PEG6000
Was mixed with 20 g of magnesium stearate and 0.2 g of magnesium stearate.
Tableting was performed with a 0 mm, 10 mm R punch at a pressure of 111 kg / punch. Furthermore, the tablet of the present invention was obtained by air-drying the obtained tablet at 70 ° C. for 1 hour. The dissolution time in the mouth of the tablet was 20 seconds, and the hardness was 3.8 kg.

Example 9 20 g of PEG 6000 and 2 g of sugar ester (manufactured by Mitsubishi Kasei Food Co., Ltd.) were mixed with 178 g of glucose (Japan Food Processing Co., Ltd.), and the mixture was mixed with a rotary tableting machine. Tablets 300mg, φ1
Tableting was performed with a 0 mm, 10 mm R punch at a pressure of 157 kg / punch. Furthermore, the tablet of the present invention was obtained by air-drying the obtained tablet at 70 ° C. for 1 hour. The dissolution time of the tablet in the oral cavity was 32 seconds and the hardness was 3.8 kg.

Example 10 400 g of mannitol was added to
Maltose (San Malt Midori, Hayashibara Shoji Co., Ltd.) 20
g in water 180 g of maltose aqueous solution,
Granulation was performed with a fluid bed granulator. Fine particle coating was performed at a spray pressure of 3 kg / cm ² up to a maltose amount of 10 g, and thereafter granulation was performed at a spray pressure of 0.5 kg / cm ² . After drying the granulated product, 12 g of acetaminophen (Yoshitomi Pharmaceutical Co., Ltd.) and PEG6 were added to 18 g of the granulated product.
000 and 1.5 g each, and 30 tablets per oil press.
Tablets were punched using a 0 mg, φ10 mm, 10 mmR punch. The tablet hardness at this time was 0 on a Schleuniger tablet hardness tester.
kg. Further, the obtained tablet was air-dried at 80 ° C. for 15 minutes to obtain a tablet of the present invention. The dissolution time in the mouth of the tablet was 15 seconds, and the hardness was 5.7 kg.

[0046]

The orally-dissolvable tablet of the present invention shows rapid disintegration and dissolution in the oral cavity, and can be produced using equipment conventionally used in the production of drugs. Since it has an appropriate hardness even when pressed at a low pressure, tableting trouble can be avoided, and it can be applied to masking particles and sustained-release particles.

[Brief description of the drawings]

FIG. 1 is a schematic view showing a state inside a tablet before and after melting of polyethylene glycol particles in one embodiment of the tablet of the present invention.

[Explanation of symbols]

1 ... particles of saccharides or medicinal ingredients, 2 ... polyethylene glycol particles, 3 ... crosslinking by polyethylene glycol

Claims (5)

[Claims] 1. An orally dissolving tablet containing a pharmaceutically active ingredient, a saccharide and polyethylene glycol, and having a porous structure formed by the polyethylene glycol forming an interparticle crosslink with the pharmaceutically active ingredient and the saccharide. An orally dissolving tablet characterized by having: 2. The oral cavity according to claim 1, further comprising one or more components selected from the group consisting of disintegrants, binders, foaming agents, artificial sweeteners, flavors, lubricants and coloring agents. Dissolvable tablets. 3. A medicinal ingredient, a saccharide and polyethylene glycol are mixed, the mixture is tabletted at a low pressure, and the resulting tablet is heated to a temperature at which the polyethylene glycol melts.
Thereafter, the porous structure is formed by allowing the mixture to cool to form a porous structure. 4. The method according to claim 3, wherein said polyethylene glycol is added in the form of particles. 5. The method according to claim 3, wherein one or more components selected from the group consisting of disintegrants, binders, foaming agents, artificial sweeteners, flavors, lubricants and coloring agents are further mixed. A method for producing an oral dissolving tablet.