JP2002308760A - Compression molding composition and use thereof - Google Patents

Abstract

PROBLEM TO BE SOLVED: To produce a molded product such as a tablet or a troche having the hardness required for carrying while having a quick disintegration property in a mouth or an aqueous solvent by a simple means. Providing technology. SOLUTION: A small amount of a compression-molding composition and a physiologically active substance containing a saccharide coated with a metasilicate aluminate and a composition containing a saccharide coated with a metasilicate aluminate, A compression molded product that disintegrates quickly even with moisture.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a composition for compression molding for pharmaceuticals and foods, and to a compression-molded preparation utilizing the composition, which can rapidly disintegrate even with a small amount of water.

[0002]

2. Description of the Related Art In recent years, in addition to the field of pharmaceuticals, health foods and nutritional foods have also been provided as oral preparations. Many of these oral preparations have been prepared as dry preparations such as tablets, capsules, granules, and powders. It is currently being provided.
However, many of these oral formulations are difficult to take for the elderly, children and patients with dysphagia.

[0003] For this reason, dry syrups which can be suspended in water to form a syrup or the like are also provided for easy taking, but in the case of powder or granules, a single dose is required. Even if it is wrapped every time, there is a risk that the contents may remain in the wrapping and a part thereof may be spilled at the time of opening, and there is a problem in taking an appropriate amount.

In recent years, tablets or lozenges which can be taken without water and disintegrate quickly in the oral cavity, and tablets which can be rapidly dissolved in aqueous solvents even when taken in water for the purpose of solving the problem of ingestion. Or lozenges are being developed.

For example, as a method for producing a tablet or a troche as described above, a method for producing an orally disintegrating tablet in which a mixture containing water to such an extent that the surface of particles is wetted (JP-A-5-27054), A method for producing an orally disintegrating tablet obtained by compressing at a low pressure, mainly comprising an amorphous saccharide, placing a tablet under humidification, moistening and drying the tablet (JP-A-11-12162 and JP-A-11-162) 3494
No. 75) is known. In addition, a rapidly disintegrating compressed composition using a composition obtained by spray-drying a suspension in which an inorganic antacid having the same mass as the saccharide is uniformly dispersed (Japanese Patent Application Laid-Open No. 2000-2000)
-86537) is also known.

[0006] In the above-mentioned prior art, although a preparation having a satisfactorily disintegrating property in an aqueous solvent and a hardness required for carrying is obtained at all, it is difficult to handle water during the manufacturing process and to obtain a preparation under high humidity. There is a possibility that there may be a problem in stability in relation to the physiologically active ingredient used, such as necessity of standing, and it is not always satisfactory from the viewpoint of production process control. Furthermore, in the case where an inorganic antacid is used, a large amount of the inorganic antacid must be used. In addition, in preparation of a pharmaceutical preparation according to the prior art, it is necessary to make pressure adjustment constant during compression molding, and setting of manufacturing conditions may be complicated.

[0007]

Therefore, by a simple means, it is possible to form tablets, troches and the like having the hardness required for carrying while maintaining the quick disintegration property in the mouth or in an aqueous solvent. The provision of manufacturing technology was required.

[0008]

DISCLOSURE OF THE INVENTION The present inventors have studied to solve the problems of the prior art, and as a result, have used a composition obtained by coating a sugar with a metasilicate aluminate as a carrier for tablets or troches. And by formulating according to the usual method, there is no wear in the distribution process,
It is possible to obtain a compression molded product that disintegrates quickly even in a small amount of water, and the compression molded product obtained by using this carrier can maintain a certain degree of hardness irrespective of the pressure at the time of compression. The present invention was also found to have both properties and completed the present invention.

That is, the present invention provides a composition for compression molding containing a saccharide coated with a metasilicate aluminate.

Another object of the present invention is to provide a compression-molded preparation obtained by compression-molding a physiologically active substance and a composition containing a saccharide coated with an aluminate metasilicate, and which rapidly disintegrates even with a small amount of water. It is.

[0011]

BEST MODE FOR CARRYING OUT THE INVENTION The saccharide used in the composition for compression molding of the present invention is not particularly limited as long as it is solid at ordinary temperature, and various saccharides are used. Examples of the types of these saccharides include monosaccharides, oligosaccharides, polysaccharides, sugar alcohols and saccharide derivatives, and specifically, for example, sucrose, coupling sugar, fructooligosaccharide, palatinose, glucose, maltose, lactose, fructose Sorbitol, xylitol, erythritol, mannitol and the like. Among them, sugar alcohols are preferred, and mannitol, trehalose, xylitol and sorbitol are particularly preferred.

As the metasilicate aluminate used for coating the saccharide, an alkali metal salt such as magnesium or an alkaline earth metal salt is used, and those having a bulk density of 4 mL / g or more are preferable. , 6
More than mL / g is more preferable. Further, this metasilicate aluminate was added in an amount of 0.001 to 1 part by weight of the saccharide.
-0.4 parts by weight, preferably 0.005-0.15 parts by weight, particularly preferably 0.01-0.1 parts by weight.

[0013] The method for coating a saccharide with an aluminate metasilicate in the composition for compression molding of the present invention may be any coating method used in the fields of medicine and food.
Although not particularly limited, a method for imparting uniformity to a coating film is preferable, and specifically, coating with various fluidized bed granulators is preferable.

[0014] The composition for compression molding of the present invention obtained as described above is used for preparing a troche or a tablet or other compression-molded preparation in the field of pharmaceuticals and foods. The use is not particularly limited. However, it can be particularly preferably used for compression-molded preparations intended for rapid disintegration in water, especially with a small amount of water.

[0015] The compression-molded preparation of the present invention may contain a physiologically active ingredient such as a pharmaceutically active ingredient, a taste ingredient and a nutritional supplement, depending on the use.

Among these physiologically active ingredients, the pharmaceutically active ingredients include, for example, nourishing tonic health drugs, antipyretic / analgesic / inflammatory drugs, psychotropic drugs, anxiolytics, antidepressants, hypnotic sedatives, antispasmodics, gastrointestinal Medicine, antacid, antitussive expectorant, dental oral medicine, antihistamine, allergy agent, inotropic agent, arrhythmia agent,
Selected from diuretics, hypotensives, vasoconstrictors, coronary vasodilators, peripheral vasodilators, cholerics, antibiotics, chemotherapeutics, diabetes, osteoporosis, skeletal muscle relaxants, etc. One or more components are used.

Nutrient tonic health drugs include, for example, vitamin A, vitamin D, vitamin E (d-α-tocopherol acetate, etc.), vitamin B ₁ (dibenzoylthiamine, fursultiamine hydrochloride, etc.), vitamin B ₂ ( Vitamins such as riboflavin butyrate, vitamin B ₆ (eg, pyridoxine hydrochloride), vitamin C (eg, ascorbic acid, sodium L-ascorbate), and vitamin B ₁₂ (eg, hydroxocobalamin acetate); minerals such as calcium, magnesium, and iron; Proteins; amino acids; oligosaccharides; crude drugs and the like.

Examples of antipyretic, analgesic and anti-inflammatory drugs include aspirin, acetaminophen, etensamide, ibuprofen, diphenhydramine hydrochloride, dl-chlorpheniramine maleate, dihydrocodeine phosphate, noscapine, methylephedrine hydrochloride, phenylpropanolamine hydrochloride, Caffeine, serrapeptase, lysozyme chloride, tolfenamic acid, mefenamic acid, diclofenac sodium, flufenamic acid, salicylamide, aminopyrine, ketoprofen, indomethacin, bucolome, pentazocine, tranexamic acid and the like.

Examples of the psychotropic drug include chlorpromazine, reserpine and the like. Examples of the anxiolytic 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. Antispasmodics include, for example, scopolamine hydrobromide, diphenhydramine hydrochloride, papaverine hydrochloride and the like.

Gastrointestinal drugs include, for example, gastrointestinal drugs such as diastase, sugar-containing pepsin, funnel extract, lipase AP, and calyx oil; intestinal drugs such as berberine chloride, resistant lactic acid bacteria and bifidobacteria; Is included. As antacids, for example, magnesium carbonate,
Examples include sodium hydrogen carbonate, magnesium metasilicate aluminate, synthetic hydrotalcite, precipitated calcium carbonate, magnesium oxide and the like. Also, gefarnate, cetraxate hydrochloride, teprenone, sofalcone,
Peptic ulcer therapeutic agents such as rebamipide, cimetidine, ranitidine hydrochloride, famotidine, nizatidine, omeprazole and lansoprazole are also included. Further, laxatives such as sodium picosulfate, senna extract and bisacodyl are also included.

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

Examples of antihistamines include diphenhydramine hydrochloride, promethazine, isotipendyl hydrochloride, dl-chlorpheniramine maleate and the like. Examples of the cardiotonic agent include, for example, ethylephrine hydrochloride and the like. Examples of the agent for allergy include oxamide, tranilast, mequitazine, ketotifen fumarate, epinastine hydrochloride, cetirizine hydrochloride and the like. Examples of the agent for arrhythmia include procainamide hydrochloride, propranolol hydrochloride, pindolol and the like. Examples of the diuretic include isosorbide, furosemide and the like. As antihypertensives, for example,
Delapril hydrochloride, captopril, hexamethonium bromide, hydralazine hydrochloride, labetalol hydrochloride, methyldopa and the like.

Examples of the vasoconstrictor include phenylephrine hydrochloride and the like. Examples of the coronary vasodilator include carbochromene hydrochloride, molsidomine, verapamil hydrochloride and the like. Examples of the peripheral vasodilator include cinnarizine and the like. As a bolus,
For example, dehydrocholic acid, trepibutone, etc. are exemplified.

Antibiotics include, for example, cephalexin,
Cephem, penem, and carbapenem antibiotics such as amoxicillin, pivmecillinam hydrochloride, and cefotiam hydrochloride are included. As chemotherapeutic agents, for example,
Sulfamethizole, thiazosulfone and the like. Examples of the antidiabetic agent include tolbutamide, voglibose and the like. Examples of the agent for osteoporosis include ipriflavone and the like. Skeletal muscle relaxants include methocarbamol and the like.

Among the above-mentioned physiologically active ingredients, the physiologically active ingredients preferably blended in the compression-molded preparation of the present invention include, for example, vitamins,
Crude drugs, antipyretic / analgesic / anti-inflammatory drugs, anxiolytics, sedative-hypnotics, gastrointestinal drugs, antitussive expectorants, antihistamines, allergies,
Antihypertensives, agents for diabetes, agents for osteoporosis, skeletal muscle relaxants and the like. Further, these active ingredients may be diluted with a diluent or the like generally used in the field of medicine, food and the like. Further, at least one of the physiologically active components in the compression-molded preparation of the present invention may be oily.

In preparing the compression-molded preparation of the present invention, the amount of the compression-molding composition and the pressure at the time of compression-molding vary depending on the other components to be added and the intended use of the compression-molded composition. The compounding amount of the composition for use is 1 to 99% by mass, preferably 20 to 95% by mass, and more preferably 30 to 90% by mass based on the total amount of the compression molded preparation.

Further, in producing the compression-molded preparation of the present invention, various additives generally used in the production of a molded preparation may be contained as long as the effects of the present invention are not hindered.

Examples of such additives include disintegrants, binders, extenders, lubricants, flavoring ingredients, fragrances, and adjuvants.

Examples of the disintegrant include starch such as corn starch and potato starch, partially pregelatinized starch, sodium carboxymethyl starch, carmellose, carmellose calcium, carmellose sodium, polyvinyl alcohol, crospovidone, low-substituted hydroxypropyl cellulose. , Crystalline cellulose, hydroxypropyl starch and the like. As the binder, for example, hydroxypropylcellulose, hydroxypropylmethylcellulose, carboxyvinyl polymer, carmellose sodium, pregelatinized starch,
Crosslinked polyvinyl pyrrolidone, gum arabic powder, gelatin, pullulan and the like can be mentioned. Examples of the bulking agent include sucrose, glucose, lactose, mannitol, maltose, sorbitol, calcium phosphate, calcium sulfate and the like.

Examples of the flavoring component include citric acid, tartaric acid, malic acid and the like. Examples of the foaming agent include baking soda. Examples of artificial sweeteners include saccharin sodium, dipotassium glycyrrhizinate, aspartame, stevia, thaumatin and the like. Examples of the masking agent include water-insoluble polymers such as ethyl cellulose, and anti-salivating gastric-soluble polymers such as methyl methacrylate / butyl methacrylate / diethylaminoethyl methacrylate copolymer.

Examples of the flavor include lemon, lemon lime, orange, menthol, peppermint oil, vanillin and the like, and powdered flavor obtained by adsorbing the same to dextrin or cyclodextrin. Examples of the lubricant include magnesium stearate, sucrose fatty acid ester, polyethylene glycol, talc, stearic acid and the like. Examples of the auxiliary include a colorant, a bioactive component stabilizer, and a solubilizing agent. For example, coloring agents include food colors such as Food Yellow No. 5, Food Red No. 3, Food Blue No. 2, etc .;
Bengara and the like. The stabilizer or the solubilizing agent varies depending on the physiologically active ingredient used.
Examples include antioxidants such as ascorbic acid and tocopherol, and surfactants such as polysorbate 80.

[0032]

The composition for compression molding of the present invention described above can be used in medicines, health foods, nutritional foods, etc., in the form of tablets, troches and the like which can be taken without water and rapidly disintegrate in the mouth. It can be advantageously used for the production of a molded preparation which is rapidly dissolved in an aqueous solvent even when taken in water.

Further, the compression-molded preparation of the present invention using the above-mentioned composition for compression molding is easily dissolved even with a small amount of water, and has sufficient strength for carrying and the like.
It can be used as tablets, lozenges and the like which rapidly disintegrate in the oral cavity.

[0034]

The present invention will be described in more detail with reference to the following examples and test examples, but the present invention is not limited to these examples.

Example 1 D-mannitol (901.45 g) was placed in a fluidized bed granulator and granulated with 375.5 mL of a 10% magnesium metasilicate aluminate (Neucillin UFL2, manufactured by Fuji Chemical) suspension. -A mannitol granulated product was obtained. This was a state in which D-mannitol was coated with magnesium aluminate metasilicate.

EXAMPLE 2 40 g of crospovidone, 5 g of aspartame and 1 g of powdered flavor were added to the whole amount of the granulated D-mannitol of Example 1, and mixed with a V-type mixer for 20 minutes. Magnesium stearate was added to this, and the tableting pressure during molding was 300 to 1
It was adjusted to 500 kgf and compression-molded at various tableting pressures to obtain a tablet of 200 mg per tablet.

Comparative Example 1 D-mannitol 901.45 g, magnesium aluminate metasilicate (Neucillin UFL2, manufactured by Fuji Chemical) 3
7.55 g and 175 mL of purified water were stirred and granulated with a stirring granulator to obtain a granulated D-mannitol. This was a state in which D-mannitol and magnesium aluminate metasilicate were dispersed in the particles.

Comparative Example 2 40 g of crospovidone, 5 g of aspartame and 1 g of powdered flavor were added to the whole amount of the D-mannitol granulated product of Comparative Example 1, and the mixture was mixed with a V-type mixer for 20 minutes. Magnesium stearate was added to this, and the tableting pressure during molding was 300 to 1
It was adjusted to 500 kgf and compression-molded at various tableting pressures to obtain a tablet of 200 mg per tablet.

Test Example 1 The tablet of Example 2 and the tablet of Comparative Example 2 were compared for their hardness and disintegration time in the oral cavity. The hardness of each tablet was measured using a TH-203 tablet breaking hardness tester manufactured by Toyama Sangyo Co., Ltd.
Tablets were measured and determined from the average. In addition, the oral disintegration time was determined by measuring the time required for disintegration in a bite state by having each tablet contained in the mouth by six persons and obtaining the average value. Table 1 shows the results.

[0040]

[Table 1]

As a result, the tablet of Example 2 exhibited a hardness of 3.0 kg / cm ² or more regardless of the molding pressure, and
All disintegrated in the oral cavity in less than 20 seconds. On the other hand, in Comparative Example 2, the disintegration time in the oral cavity exceeded 20 seconds even at a molding pressure of 500 kgf or less, and the hardness was 2.0 kg /
cm ² or less, and could not withstand normal distribution.

EXAMPLE 3 863.9 g of sucrose was put into a fluidized bed granulator, and granulated with 751 mL of a 10% magnesium aluminate metasilicate (neusilin UFL2, manufactured by Fuji Chemical) suspension to obtain a sucrose granulated product. Obtained. Crospovidone 40g in total amount of sucrose granulated product,
5 g of aspartame and 1 g of powdered flavor were added, and mixed with a V-type mixer for 20 minutes. Magnesium stearate was added thereto, and the mixture was compression-molded to obtain a tablet of 200 mg per tablet.

This had disintegration and tablet hardness almost the same as those in Example 2.

Example 4 920.225 g of lactose was placed in a fluid bed granulator, and 10% magnesium metasilicate aluminate (Neucillin UFL) was added.
2. Lactose granulated product was obtained by granulating with 187.75 mL of a suspension manufactured by Fuji Chemical. 40 g of crospovidone, 5 g of aspartame, and 1 g of powdered flavor are added to the whole lactose granulated product,
The mixture was mixed with a V-type mixer for 20 minutes. Add magnesium stearate to this and press-mold 200mg per tablet.
Tablets were obtained.

This had almost the same disintegrability and tablet hardness as those of Example 2. that's all

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) A61K 47/10 A61K 47/10 47/26 47/26 47/32 47/32 (72) Inventor Naoko Iwasaki F-term (reference) 4B018 LB10 LE01 MD01 MD27 ME14 MF02 MF08 4B035 LC04 LC06 LE05 LG01 LG07 LK08 LP26 4C076 AA37 AA49 BB01 CC01 CC03 CC04 CC22 CC40 DD27 DD38 DD67 EE41T FF41FF FF52 GG14

Claims (11)

[Claims] 1. A compression molding composition containing a saccharide coated with a metasilicate aluminate. 2. The composition for compression molding according to claim 1, wherein the saccharide is one or more of sugar or sugar alcohol. 3. The composition for compression molding according to claim 1, wherein the saccharide is a sugar alcohol. 4. The method according to claim 1, wherein 0.001 to 0.4 parts by weight of the metasilicate aluminate is used per 1 part by weight of the saccharide. The composition for compression molding according to the above. 5. A compression-molded preparation which is obtained by compression-molding a physiologically active substance and a composition containing a saccharide coated with a metasilicate aluminate, and which rapidly disintegrates even with a small amount of water. 6. The compression-molded preparation according to claim 5, wherein the physiologically active substance is a pharmaceutically active ingredient, a taste ingredient or a nutritional supplement. 7. The method according to claim 5, wherein the saccharide is one or more of sugar or sugar alcohol.
Item 8. The compression-molded preparation according to Item 1. 8. The compression-molded preparation according to any one of claims 5 to 7, wherein the saccharide is a sugar alcohol. 9. A saccharide coated with a metasilicate aluminate wherein 0.001-0.4 parts by weight of metasilicate aluminate is used per 1 part by weight of the saccharide. Item 9. The compression-molded preparation according to any one of items 8 to 10. 10. The compression-molded preparation according to any one of claims 5 to 9, wherein the amount of the saccharide coated with the aluminate metasilicate in the compression-molded composition is 1 to 99% by mass. . 11. The pressure during molding is 100 to 3,000 k.
The compression-molded preparation according to any one of claims 5 to 10, which is gf.