JPH1143429A - Solid preparation - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a solid preparation having excellent disintegrability in the oral cavity and moderate strength by including a pharmaceutical component, a water-soluble sugar alcohol and a hydroxypropyl cellulose having low substitution degree. SOLUTION: This solid preparation contains (A) 0.05-30 pts.wt. (based on 100 pts.wt. of the solid preparation) of a pharmaceutical component preferably selected from lansoprazole, voglibose, candesartan and cilexetil, (B) 5-97 pts.wt. of one or more water-soluble sugar alcohols selected from sorbitol, maltitol, saccharified product of reduced starch, xylitol, reduced palatinose and erythritol and (C) 3-50 pts.wt. of a hydroxypropyl cellulose having low substitution degree and containing 7.0-9.9 wt.% of hydroxyproxyl group. The objective preparation is useful as a preparation disintegrating in the oral cavity and preferably has a tablet form. The daily administration rate for adult is preferably 5-150 mg in terms of lansoprazole.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a solid preparation, particularly an orally disintegrable preparation having a rapid disintegration property without water in the oral cavity.

[0002]

2. Description of the Related Art At present, there is a demand for the development of orally disintegrating pharmaceutical preparations which can be taken easily by elderly people and children without water, and the following publications disclose such preparations. Things are known. JP-A-9-487
No. 26 discloses a rapidly disintegrating preparation in the oral cavity containing a drug and a substance which is moisturizable by humidification and which retains its shape by drying after molding, and as such a substance,
Sugars, sugar alcohols, and water-soluble polymer substances are exemplified. Japanese Patent Application Laid-Open No. H5-271054 discloses a method for producing a rapidly dissolving intraoral tablet containing a pharmaceutically active ingredient and a saccharide. JP-A-9-71523 discloses a tablet containing a drug, microcrystalline cellulose, low-substituted hydroxypropylcellulose and a lubricant, and which is rapidly disintegrating in the oral cavity. However, these known documents include (1) a pharmaceutical ingredient, (2) one or more water-soluble sugar alcohols selected from sorbitol, maltitol, reduced starch saccharified product, xylitol, reduced palatinose and erythritol, and (3) hydroxy. Propoxyl group content of 7.0 to 9.9
There is no description about solid preparations containing low-substituted hydroxypropylcellulose by weight.

[0003]

It is desired to develop a solid preparation having excellent disintegration properties in the oral cavity and appropriate strength (hardness) which does not cause damage in the preparation process and distribution process.

[0004]

Means for Solving the Problems The present invention provides (1) a pharmaceutical ingredient, (2) one or more water-soluble sugar alcohols selected from sorbitol, maltitol, reduced starch saccharified product, xylitol, reduced palatinose and erythritol ( (Hereinafter sometimes abbreviated as a water-soluble sugar alcohol) and (3) a solid preparation containing low-substituted hydroxypropylcellulose having a hydroxypropoxyl group content of 7.0 to 9.9% by weight; hydroxypropoxyl Group content is 7.
Use of 0 to 9.9% by weight of low-substituted hydroxypropylcellulose for preparing an orally disintegrating pharmaceutical preparation; and low-substituted hydroxypropylcellulose having a hydroxypropoxyl group content of 7.0 to 9.9% by weight And a method for improving the disintegration of a solid pharmaceutical preparation in the oral cavity.

[0005] The pharmaceutical ingredient used in the present invention is solid,
Powders, crystals, oils, solutions, etc. may be used. Specific examples thereof include, for example, nourishing tonics, antipyretics and analgesics, antipsychotics, anxiolytics, antidepressants, hypnotics and sedatives. Drugs, central nervous system drugs, brain metabolism improvers, antiepileptics, sympathomimetics, gastrointestinal drugs, antacids, antiulcers, antitussive expectorants, antiemetic, respiratory stimulants, bronchodilators, antiallergic drugs , Dental oral medicine, antihistamine, inotropic, antiarrhythmic, diuretic, antihypertensive, vasoconstrictor, coronary vasodilator, peripheral vasodilator, antihyperlipidemic, choleretic, antibiotic, chemical Therapeutic agents, antidiabetic agents, osteoporosis agents, skeletal muscle relaxants, antidiarrheals, hormonal agents, alkaloid drugs, sulfa drugs, gout drugs, anticoagulants, antineoplastic drugs, Alzheimer's disease drugs, etc. One or more components selected from And the like.

[0006] Nourishing tonic health agents include, for example, vitamin A, vitamin D, vitamin E (d-α-tocopherol acetate, etc.), vitamin B ₁ (dibenzoylthiamine, fursultiamine hydrochloride, etc.), vitamin B ₂ (butyric acid, etc.). riboflavin, etc.), vitamin B ₆ (pyridoxine hydrochloride), vitamin C (ascorbic acid, sodium L- ascorbate), vitamin vitamin B ₁₂ (such as acetic hydroxocobalamin); protein; calcium, magnesium, minerals such as iron Examples include amino acids, oligosaccharides, and crude drugs. As antipyretic analgesic and anti-inflammatory drugs,
For example, aspirin, acetaminophen, etensamide, ibuprofen, diphenhydramine hydrochloride, dl-chlorpheniramine maleate, dihydrocodeine phosphate, noscapine, methylephedrine hydrochloride, phenylpropanolamine hydrochloride, caffeine, anhydrous caffeine,
Serrapeptase, lysozyme chloride, tolfenamic acid, mefenamic acid, diclofenac sodium, flufenamic acid, salicylamide, aminopyrine, ketoprofen,
Indomethacin, bucolome, pentazocine and the like can be mentioned. Psychotropic drugs include, for example, chlorpromazine, reserpine and the like. As anxiolytics,
For example, alprazolam, chlordiazepoxide, diazepam and the like can be mentioned. Examples of the antidepressant include imipramine, maprotiline, amphetamine and the like.

[0007] Hypnotic sedatives include, for example, estazolam, nitrazepam, diazepam, perlapine, phenobarbital sodium and the like. Examples of antispasmodics include scopolamine hydrobromide, diphenhydramine hydrochloride, papaverine hydrochloride and the like. Examples of central nervous system drugs include citicoline, rothyrenine and the like. Examples of the cerebral metabolism improving agent include vinpocetine, meclofenoxate hydrochloride and the like. Antiepileptic agents include, for example, phenytoin, carbamazepine and the like. Sympathetic stimulants include, for example, isoproterenol hydrochloride and the like. Examples of the gastrointestinal drug include gastric digestive agents such as diastase, sugar-containing pepsin, funnel extract, cellulase AP3, lipase AP, and calyx oil; intestinal agents such as perperin hydrochloride, resistant lactic acid bacteria, and bifidobacteria. Examples of the antacid include magnesium carbonate, sodium bicarbonate, magnesium aluminate metasilicate, synthetic hydrotalcite, precipitated calcium carbonate, magnesium oxide and the like. Examples of the anti-ulcer agent include lansoprazole, omeprazole, rabeprazole, pantoprazole, famotidine, cimetidine, ranitidine hydrochloride and the like.

Examples of the antitussive expectorants include cloperastine hydrochloride, dextromeltophan hydrobromide, theophylline, potassium guaiacol sulfonate, guaifenesin, codeine phosphate and the like. Examples of the antiemetic include difenidol hydrochloride, metoclopramide and the like. Examples of the respiratory enhancer include levallorphan tartrate. As a bronchodilator,
Examples include theophylline and salbutanol sulfate. Antiallergic agents include, for example, amlexanox, seratrodast, and the like. Examples of the oral medicine include oxytetracycline, triamcinolone acetonide, chlorhexidine hydrochloride, lidocaine and the like. Examples of the antihistamine include diphenhydramine hydrochloride, promethazine, isotipendyl hydrochloride, dl-chlorpheniramine maleate, and the like. Examples of cardiotonic agents include caffeine, digoxin and the like. Examples of the antiarrhythmic agent include procainamide hydrochloride, propranolol hydrochloride, pindolol and the like. Diuretics include, for example, isosorbide, furosemide and the like. Examples of antihypertensive agents include delapril hydrochloride, captopril, hexamethonium bromide, hydralazine hydrochloride, labetalol hydrochloride, manidipine hydrochloride, candesartan cilexetil, methyldopa, losartan, valsartan, eprosartan,
Irbesartan, tasosartan, telmisartan, pomisartan, lipisartan, forasartan and the like.

[0009] Examples of the vasoconstrictor include phenylephrine hydrochloride. Examples of the coronary vasodilator include carbochromene hydrochloride, molsidomine, verapamil hydrochloride and the like. Peripheral vasodilators include, for example, cinnarizine and the like. As antihyperlipidemic agents,
For example, cerivastatin sodium, simvastatin,
Pravastatin sodium and the like. Bile agents include, for example, dehydrocholic acid, trepibutone, and the like. Examples of antibiotics include cephalexin, amoxicillin, pivmecillinam hydrochloride, cefotiam hydrochloride, cefozopran hydrochloride, cefmenoxime hydrochloride, ceflosin sodium and other cephem antibiotics; ampicillin, cyclacillin, sulbenicillin sodium,
Synthetic antibacterial agents such as nalidixic acid and enoxacin; monobactam antibiotics such as carmonam sodium; penem antibiotics and carbapenem antibiotics. Examples of the chemotherapeutic agent include sulfamethizole hydrochloride, thiazosulfone and the like. Examples of antidiabetic agents include tolbutamide, voglibose, pioglitazone (hydrochloride), troglitazone, 5-[[4- [2-
(Methyl-2-pyridinylamino) ethoxy] phenyl] methyl] -2,4-thiazolidinedione (BRL
-49653), acarbose, miglitol, emiglitate and the like. Examples of the agent for osteoporosis include ipriflavone and the like. Skeletal muscle relaxants include, for example, methocarbamol. Examples of the antitussive include meclizine hydrochloride, dimenhydrinate and the like.

Examples of hormonal agents include liothyronine sodium, dexamethasone sodium phosphate, prednisolone, oxendrone, leuprorelin acetate and the like. Examples of the alkaloid narcotics include opium, morphine hydrochloride, tocon, oxycodone hydrochloride, opium alkaloid hydrochloride, cocaine hydrochloride and the like. Examples of the sulfa drug include sulfamine, sulfamethizole and the like. Examples of gout remedies include allopurinol, colchicine and the like. Examples of the anticoagulant include dicoumarol and the like. Examples of the antineoplastic agent include 5-fluorouracil, uracil, and mitomycin. Examples of the drug for treating Alzheimer's disease include idebenone, vinpocetine and the like.

The pharmaceutical ingredient may be coated by a method known per se for the purpose of masking taste and odor, enteric coating or sustained release. At this time, examples of the coating agent include enteric polymers (eg, cellulose acetate phthalate, methacrylic acid copolymer L, methacrylic acid copolymer LD, methacrylic acid copolymer S, hydroxypropylmethylcellulose phthalate, hydroxypropylmethylcellulose acetate succinate, Carboxymethylethylcellulose, etc.), gastric-soluble polymers (eg, polyvinyl acetal diethylaminoacetate, aminoalkyl methacrylate copolymer, etc.),
Water-soluble polymer (eg, hydroxypropylcellulose,
Hydroxypropyl methylcellulose, etc.), poorly soluble polymers (eg, ethyl cellulose, aminoalkyl methacrylate copolymer RS, ethyl acrylate / methyl methacrylate copolymer, etc.), wax and the like.
The above-mentioned pharmaceutical ingredient is, for example, 0.01 to 70 parts by weight, preferably 0.02 to 50 parts by weight, based on 100 parts by weight of the solid preparation.
Parts by weight, more preferably 0.05 to 30 parts by weight. Among the above-mentioned pharmaceutical ingredients, nutritional tonic health drugs, antipyretic analgesics and anti-inflammatory drugs, hypnotic sedatives, central nervous system drugs, gastrointestinal drugs,
Antiulcer, antitussive expectorant, antiallergic, antiarrhythmic,
Diuretics, antihypertensives, vasoconstrictors, coronary vasodilators, antihyperlipidemics, antidiabetic agents, osteoporosis agents, skeletal muscle relaxants, antidiarrheals, and the like are preferably used. In the present invention, particularly preferably used pharmaceutical ingredients are lansoprazole, voglibose, and candesartan cilexetil.

In the present invention, the water-soluble sugar alcohol means that when 1 g of sugar alcohol is added to water and shaken vigorously every 5 minutes at 20 ° C. for 30 seconds to dissolve within 30 minutes, the amount of water required is Means a sugar alcohol that is less than 30 ml. As the water-soluble sugar alcohol, sorbitol, maltitol, reduced starch saccharified product, xylitol, reduced palatinose or erythritol may be used, and two or more of them may be used in a mixture at an appropriate ratio. The water-soluble sugar alcohol is preferably xylitol or erythritol, particularly preferably erythritol. Erythritol is usually produced by fermentation with yeast using glucose as a raw material and has a particle size of 50 mesh or less. Such erythritol can be obtained as a commercial product (a product of Niken Kagaku Co., Ltd.). The water-soluble sugar alcohol is used in an amount of 5 to 97 parts by weight, preferably 10 to 90 parts by weight, based on 100 parts by weight of the solid preparation. If the amount of the water-soluble sugar alcohol is too large, sufficient formulation strength cannot be obtained, and if it is too small, sufficient disintegration in the oral cavity cannot be obtained.

The hydroxypropoxyl group content in the low-substituted hydroxypropylcellulose of the present invention is 7.
0 to 9.9% by weight. Examples of the low-substituted hydroxypropylcellulose having a hydroxypropoxyl group content of 7.0 to 9.9% include LH-22, LH-32 and mixtures thereof, and these are commercially available products (Shin-Etsu Chemical Co., Ltd. )
). Low-substituted hydroxypropylcellulose having a hydroxypropoxyl group content of 7.0 to 9.9% is used in an amount of 3 to 50 parts by weight, preferably 5 to 40 parts by weight, based on 100 parts by weight of the solid preparation. If the amount of the low-substituted hydroxypropylcellulose is too large, sufficient disintegration in the oral cavity cannot be obtained, and if it is too small, sufficient formulation strength cannot be obtained, which is not preferable.
Thus, the hydroxypropoxyl group content is 7.0 to 7.0.
By using 9.9% of low-substituted hydroxypropylcellulose, the disintegration property in the oral cavity of a solid preparation can be improved.

The solid preparation of the present invention is particularly useful as an orally disintegrating preparation and is taken without or with water. Examples of the dosage form of the solid preparation of the present invention include tablets, granules, fine granules and the like, and among them, tablets are preferred.

The solid preparation of the present invention may contain various additives used in the manufacture of general preparations, as long as the disintegration in the oral cavity or the strength of the preparation is not hindered. Amount. Such additives include, for example, binders, sour agents, foaming agents, artificial sweeteners,
Perfumes, lubricants, coloring agents, stabilizers, disintegrants and the like can be mentioned. Examples of the binder include hydroxypropylcellulose, hydroxypropylmethylcellulose, crystalline cellulose, pregelatinized starch, polyvinylpyrrolidone, gum arabic powder, gelatin, pullulan and the like. When crystalline cellulose is used as the binder, a solid preparation having higher preparation strength can be obtained while maintaining excellent disintegration properties in the oral cavity. Here, the crystalline cellulose also includes what is called microcrystalline cellulose. Specific examples of crystalline cellulose include, for example, Ceolus KG 801, Avicel PH 101, Avicel PH 1
02, Avicel PH 301, Avicel PH 302, Avicel RC-A591NF (crystalline cellulose and carmellose sodium). Among them, CEOLUS KG 801 which is called highly moldable crystalline cellulose is preferably used. These crystalline celluloses may be used by mixing two or more kinds at an appropriate ratio. These crystalline celluloses can be obtained as commercial products (made by Asahi Kasei Corporation). In addition, crystalline cellulose is a solid preparation 100
For example, about 3 to 50 parts by weight, preferably about 5 to 40 parts by weight, and more preferably about 5 to 20 parts by weight with respect to parts by weight.

As the sour agent, for example, citric acid, tartaric acid, malic acid and the like can be mentioned. 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. As a lubricant,
For example, magnesium stearate, sucrose fatty acid ester, polyethylene glycol, talc, stearic acid and the like can be mentioned. When polyethylene glycol is used as the lubricant, it is possible to obtain a stable solid preparation in which the degradation of pharmaceutical components over time is suppressed. At this time, the polyethylene glycol is used, for example, in an amount of 0.01 to 10 parts by weight, preferably 0.1 to 5 parts by weight, based on 100 parts by weight of the solid preparation. Examples of the coloring agent include food colors such as Food Yellow No. 5, Food Red No. 2, Food Blue No. 2, etc .; As a stabilizer,
In the case of a basic pharmaceutical ingredient, a basic substance is used, and in the case of an acidic pharmaceutical ingredient, an acidic substance is used.

As disintegrants, for example, super disintegrants such as crospovidone [ISP Inc. (USA), BASF (Germany)], croscarmellose sodium (FMC-Asahi Kasei), carmellose calcium (Gotoku Yakuhin) and the like are referred to. Disintegrant; hydroxypropyl cellulose; sodium carboxymethyl starch (Matsuya Chemical Co., Ltd.);
Corn starch and the like can be mentioned, among which crospovidone is preferably used. These disintegrants may be used as a mixture of two or more kinds at an appropriate ratio. The crospovidone may be any cross-linked polymer called 1-ethenyl-2-pyrrolidinone homopolymer, and usually crospovidone having a molecular weight of 1,000,000 or more is used.
Specific examples of commercially available crospovidone include, for example, cross-linked (cross-linked) povidone, Kollidon CL [manufactured by BASF (Germany)], and polyplasdone X.
L, polyplasdone XL-10, INF-10 [ISP
Inc. (USA)], polyvinylpolypyrrolidone, PV
PP, 1-vinyl-2-pyrrolidinone homopolymer and the like. Such a disintegrant is used in an amount of, for example, 0.1 to 20 parts by weight, preferably 1 to 10 parts by weight, based on 100 parts by weight of the solid preparation.

When the drug component is an acid-labile drug component such as lansoprazole, omeprazole, rabeprazole, or pantoprazole, a basic inorganic salt may be added to stabilize the drug component in the preparation. preferable. Examples of the basic inorganic salt include basic inorganic salts of sodium, potassium, magnesium and / or calcium. These basic inorganic salts may be used as a mixture of two or more kinds at an appropriate ratio. Examples of the basic inorganic salt of sodium include sodium carbonate and sodium hydrogen carbonate. Examples of the basic inorganic salt of potassium include potassium carbonate, potassium hydrogen carbonate, sodium potassium carbonate and the like. As a basic inorganic salt of magnesium, for example, heavy magnesium carbonate,
Magnesium carbonate, magnesium oxide, magnesium hydroxide, magnesium metasilicate aluminate, magnesium silicate, magnesium silicate, magnesium aluminate, synthetic hydrotalcite [Mg ₆ Al ₂ (OH) ₁₆
.CO ₃ .4H ₂ O] and alumina hydroxide and magnesium [2.5 MgO.Al ₂ O ₃ .xH ₂ O], among which heavy magnesium carbonate, magnesium carbonate, magnesium oxide, magnesium hydroxide, etc. preferable. Examples of the basic inorganic salt of calcium include precipitated calcium carbonate and calcium hydroxide. The basic inorganic salt is preferably a basic inorganic salt of magnesium, more preferably heavy magnesium carbonate, magnesium carbonate, magnesium oxide, and magnesium hydroxide. The amount of the basic inorganic salt used may be appropriately selected depending on the type of the basic inorganic salt, and is, for example, about 0.3 to 200% by weight, preferably about 1 to 100% by weight, more preferably, about the pharmaceutical ingredient. It is about 10-50% by weight, most preferably about 20-40% by weight.

The solid preparation of the present invention is produced by a conventional method in the field of preparation. Such methods include:
For example, a medicinal ingredient, a water-soluble sugar alcohol and a low-substituted hydroxypropylcellulose having a hydroxypropoxyl group content of 7.0 to 9.9% by weight are added, if desired, mixed, molded and further optionally added with water. Drying method is mentioned. However, the solid preparation of the present invention can be produced without using water. The mixing is performed by a commonly used mixing method, for example, mixing, kneading, granulation, or the like. The mixing is performed, for example, by using a vertical granulator VG1.
0 (made by Powrex, USA), a universal kneader (manufactured by Hata Iron Works), fluidized bed granulator LAB-1, and FD-3S (made by Powrex, USA). For example, when the solid preparation is a tablet, tableting is performed at a pressure of 0.5 to ³ ton / cm ² using a single-shot tablet machine (manufactured by Kikusui Seisakusho), a rotary tableting machine (manufactured by Kikusui Seisakusho), or the like. It is performed by Drying may be performed by any method used for drying pharmaceuticals in general, such as vacuum drying and fluidized bed drying.

The solid preparation of the present invention thus obtained shows rapid disintegration or solubility in the oral cavity and moderate strength of the preparation. Oral disintegration time of the solid preparation of the present invention (time until the solid preparation is completely disintegrated in the oral saliva of healthy adult males and females) is usually about 5 to about 50 seconds,
Preferably about 5 to about 40 seconds, more preferably about 5 to about 30 seconds. The strength (measured by a tablet hardness tester) of the solid preparation of the present invention is usually about 2 to about 20 kg, preferably about 4 to about 15 kg.

The solid preparation of the present invention can be used for mammals (eg, mice, rats, rabbits, cats, dogs, cows, horses, monkeys,
To humans or the like). The dose of the solid preparation varies depending on the drug component, the administration subject, the type of disease, and the like, but may be selected from a range in which the dose as the drug component is an effective amount. For example, when the pharmaceutical ingredient is lansoprazole, the solid preparation of the present invention may be used for peptic ulcer (eg, gastric ulcer, duodenal ulcer, anastomotic ulcer, Zollinger-Ellison syndrome, etc.), gastritis, reflux esophagitis, etc. Treatment and prevention; Helicobacter pylori eradication; Control of upper gastrointestinal bleeding due to peptic ulcer, acute stress ulcer and hemorrhagic gastritis; Invasive stress (cerebrovascular disorder requiring intensive management or intensive care after surgery, head trauma Inhibition of upper gastrointestinal bleeding due to multiple organ failure and stress caused by extensive burns; Treatment and prevention of ulcers caused by nonsteroidal anti-inflammatory drugs; Treatment and prevention of hyperacidity and ulcers due to postoperative stress; Etc., and the dosage is
It is 0.5 to 1500 mg / day, preferably 5 to 150 mg / day as lansoprazole per person (60 kg body weight). Further, when the pharmaceutical ingredient is voglibose, the solid preparation of the present invention, obesity, hyperlipidemia, hyperlipidemia,
It is useful for the treatment and prevention of diabetes and the like, and its dosage is 0.01 to 30 mg / day, preferably 0.1 to 3 mg / day as voglibose per adult (60 kg body weight).
Day. The solid preparation may be administered once or twice or three times a day. Furthermore, when the pharmaceutical ingredient is candesartan cilexetil, the solid preparation of the present invention is useful for treatment and prevention of hypertension, heart disease, stroke, renal disease, and the like, and the dosage is one adult (60 kg body weight).
Per candesartan cilexetil 1-50
mg / day, preferably 2-30 mg / day.

[0022]

BEST MODE FOR CARRYING OUT THE INVENTION Hereinafter, the present invention will be described in more detail with reference to Examples and Comparative Examples, but these do not limit the present invention. The physical properties of the tablets obtained in Examples and Comparative Examples were measured by the following test methods. 1) Hardness test The hardness was measured using a tablet hardness tester (manufactured by Toyama Sangyo Co., Ltd.). The test was performed 10 times, and the average value is shown. 2) Disintegration time in oral cavity The time required for the tablet to completely disintegrate or dissolve with only saliva in the oral cavity was measured.

[0023]

EXAMPLES Example 1 0.8 g of voglibose, erythritol (Nikken Chemical Co., Ltd.)
636.8g, low-substituted hydroxypropylcellulose L
160.0 g of H-32 (hydroxypropoxyl group content: 8.8% by weight, manufactured by Shin-Etsu Chemical Co., Ltd.) is charged into a fluidized bed granulator [Powrex Co., Ltd. (USA), LAB-1] and sprayed with purified water. Granulated. After drying, magnesium stearate 2.4
g, using a rotary tableting machine, 1 tablet 400mg,
Tablets were pressed at a tableting pressure of 1.5 ton / cm ² with a 10 mmφ, corner punch. The hardness and oral disintegration time of the obtained tablet were 6.1 kg and 2 kg, respectively.
7 seconds.

Example 2 32.0 g of candesartan cilexetil, 862.8 g of erythritol (manufactured by Niken Kagaku KK), low-substituted hydroxypropylcellulose LH-32 (hydroxypropoxyl group content)
8.8% by weight, 240.0 g of Shin-Etsu Chemical Co., Ltd., 1.6 g of polyethylene glycol (manufactured by Sanyo Chemical Industries, Ltd.), and 60.0 g of crospovidone were added to a fluidized bed granulator [Powrex Co., Ltd. (USA)
LAB-1], and purified water was sprayed and granulated.
After drying, 3.6 g of magnesium stearate was blended, and the mixture was tableted using a rotary tableting machine at a tableting pressure of 1.0 ton / cm ² with a tablet of 300 mg, 10 mmφ and a corner punch. The hardness and oral disintegration time of the obtained tablet were 6.1 kg and 21 seconds, respectively. Example 3 Candesartan cilexetil 32.0 g, erythritol (manufactured by Niken Chemical Co., Ltd.) 922.8 g, low-substituted hydroxypropylcellulose LH-32 (hydroxypropoxyl group content)
8.8% by weight, 240.0 g of Shin-Etsu Chemical Co., Ltd.) and 1.6 g of polyethylene glycol (manufactured by Sanyo Chemical Industries, Ltd.) were charged into a fluidized bed granulator [Powrex Co., Ltd. (USA), FD-3SN]. Purified water was sprayed and granulated. After drying, mix 3.6 g of magnesium stearate and use a rotary tableting machine, 300 mg per tablet, 10 mmφ, tableting pressure 1.0 ton / cm with a corner punch.
^The tablet was compressed with ² . The hardness and oral disintegration time of the obtained tablet were 7.1 kg and 22 seconds, respectively.

Example 4 Candesartan cilexetil 32.0 g, erythritol (manufactured by Niken Kagaku Co., Ltd.) 924.4 g, low-substituted hydroxypropylcellulose LH-32 (hydroxypropoxyl group content)
240.0 g of 8.8% by weight (manufactured by Shin-Etsu Chemical Co., Ltd.) was charged into a fluidized bed granulator [Powrex Co., Ltd. (USA), FD-3SN] and granulated by spraying purified water. After drying, 3.6 g of magnesium stearate was blended, and using a rotary tableting machine, 300 mg per tablet, 10 mmφ, tableting pressure 1.0 ton / cm ² with a punch at the corner.
Tableting. The hardness and oral disintegration time of the obtained tablet are
8.5kg for 22 seconds each.

Example 5 (1) Production of a nucleated powder Nonpareil 105 (particle diameter: 100 to 200 μm) 300
g was placed in a tumbling fluid type coating granulator [MP-10, manufactured by Powrex (USA), and the blowing temperature was controlled at 85 ° C and the product temperature was about 28 ° C. In minutes, a previously prepared bulk liquid having the following composition was sprayed and coated. When the specified amount of the bulk liquid was sprayed, the spraying was stopped, and drying was carried out for 7 minutes. Then, the resultant was sieved with a No. 60 round sieve (250 μm) and a No. 100 round sieve (150 μm) to obtain 750 g of a nucleated powder. I got [Bulk liquid] Lansoprazole 300 g Magnesium carbonate 100 g Low-substituted hydroxypropylcellulose LH-32 50 g Hydroxypropylcellulose (type SSL) 100 g Water 1650 g (2) Production of undercoated film nucleated powder The nucleated powder 680 g is a tumbling fluid type. Put into a coating granulator [Powrex (US), MP-10], and control the blow temperature to 70 ° C and the product temperature to about 36 ° C. The powder was sprayed at a supply rate of 10 g / min to obtain 650 g of a nucleated powder with an under film. [Underhang film liquid] Hydroxypropyl methylcellulose 32g (Type 2910, viscosity 3 centistokes) Talc 8g Water 760g

(3) Production of enteric coated nucleated powder [0027] 450 g of the undercoated film nucleated powder is tumbled fluidized coating granulator [MP-10, manufactured by Powrex (USA), MP-10].
The temperature was controlled at 65 ° C. and the product temperature at about 36 ° C., and an enteric film solution having the following composition prepared in advance was sprayed at a supply rate of 17 g / min by a tangential spray method. The coated product is vacuum dried at 40 ° C. for 16 hours,
No. 42 round sieve (355 μm) and No. 80 round sieve (177 μm)
m) to obtain 950 g of enteric coated nucleated powder. [Enteric film liquid] Eudragit L30D-55 1078.3 g Eudragit NE30D 138.5 g Triethyl citrate 46.0 g Glycerin monostearate 23.1 g Talc 16.0 g Polysorbate 80 9.0 mg Yellow bengara 0.5 g Water 2038.5 g

(4) Production of granulated powder Erythritol (manufactured by Niken Kagaku Co., Ltd.) 1321.2 g, low-substituted hydroxypropylcellulose LH-32 (hydroxypropoxyl group content 8.8%, Shin-Etsu Chemical Co., Ltd.) 3)
60.0 g, citric anhydride 18.0 g, and aspartame 1.8 g were added to a fluid bed granulator [Powrex Co., Ltd. (USA)
LAB-1], and 3.6 g of polyethylene glycol (PEG-6000) was added to 896.4 mL of purified water.
Was sprayed and granulated, and dried to obtain a granulated powder. Further, 90.0 g of crospovidone and 5.4 g of magnesium stearate were added and mixed in a bag to obtain a mixed powder. (5) Preparation of Orally Disintegrating Tablets 200.0 g of the enteric coated powder and 300 powders of the mixed powder.
0 g, using an autograph, 500 mg per tablet, 11 mmφ,
Tableting was performed with a corner punch at a tableting pressure of 1.0 ton / cm ² . The hardness and oral disintegration time of the obtained tablet were 4.2 kg and 27 seconds, respectively.

Example 6 0.8 g of voglibose, erythritol (Nikken Chemical Co., Ltd.)
895.6g, low-substituted hydroxypropylcellulose L
240.0 g of H-32 (hydroxypropoxyl group content: 8.8% by weight, manufactured by Shin-Etsu Chemical Co., Ltd.) and 60.0 g of crospovidone were charged into a fluid bed granulator [LAB-1 manufactured by Powrex Co., Ltd. (USA), Purified water was sprayed and granulated. After drying, 3.6 g of magnesium stearate was blended, and using a rotary tableting machine, 300 mg per tablet, 10 mmφ, tableting pressure of 1.0 ton /
Tablets were compressed in cm ² . The hardness and oral disintegration time of the obtained tablet were 7.0 kg and 17 seconds, respectively. Example 7 0.8 g of voglibose, erythritol (Nikken Chemical Co., Ltd.)
Manufactured) 871.6 g, low-substituted hydroxypropylcellulose L
240.0 g of H-32 (hydroxypropoxyl group content: 8.8% by weight, manufactured by Shin-Etsu Chemical Co., Ltd.), 24.0 g of crospovidone, and 60.0 g of CEOLUS KG 801 (manufactured by Asahi Kasei Corporation) were mixed with a fluidized bed granulator [Pourec Co. LAB-1) (USA), and purified water was sprayed and granulated. After drying, 3.6 g of magnesium stearate was blended, and using a rotary tableting machine, 300 mg per tablet, 10 mmφ, tableting pressure 1.0 ton / cm ² with a punch at the corner.
Tableting. The hardness and oral disintegration time of the obtained tablet are
They were 10.4 kg and 24 seconds, respectively.

Comparative Example 1 Example 1 was repeated except that the low-substituted hydroxypropylcellulose LH-32 was changed to a low-substituted hydroxypropylcellulose LH-31 (hydroxypropoxyl group content: 11.0% by weight, manufactured by Shin-Etsu Chemical Co., Ltd.). Similarly, tablets were produced. The hardness of the obtained tablet and the disintegration time in the oral cavity were 8.4 kg and 7 respectively.
7 seconds. Comparative Example 2 Low-substituted hydroxypropylcellulose LH-32 was replaced with low-substituted hydroxypropylcellulose LH-30 (hydroxypropoxyl group content 14.6% by weight, manufactured by Shin-Etsu Chemical Co., Ltd.) in the same manner as in Example 1. , To produce tablets. The hardness and oral disintegration time of the obtained tablets were 6.8 kg and 5
One second.

[0031]

EFFECT OF THE INVENTION Since the solid preparation of the present invention has excellent disintegration or solubility, it can be used as an orally disintegrable preparation that can be easily taken by elderly people and children without water for treating various diseases. , Used for prevention. Further, since the solid preparation has an appropriate strength, it has excellent long-term storage stability.

Claims (11)

[Claims] (1) a pharmaceutical ingredient; (2) at least one water-soluble sugar alcohol selected from sorbitol, maltitol, reduced starch saccharified product, xylitol, reduced palatinose and erythritol, and (3) hydroxypropoxyl group content. A solid preparation comprising 7.0 to 9.9% by weight of a low-substituted hydroxypropylcellulose. 2. The solid preparation according to claim 1, wherein the water-soluble sugar alcohol is erythritol. 3. The solid preparation according to claim 1, comprising 5 to 97 parts by weight of the water-soluble sugar alcohol based on 100 parts by weight of the solid preparation. 4. A hydroxypropoxyl group content of 7.0 to 7.0.
The solid preparation according to claim 1, wherein 9.9% by weight of the low-substituted hydroxypropylcellulose is contained in an amount of 3 to 50 parts by weight based on 100 parts by weight of the solid preparation. 5. The solid preparation according to claim 1, which is an orally disintegrable preparation. 6. The solid preparation according to claim 1, which is a tablet. 7. The solid preparation according to claim 1, wherein the pharmaceutical ingredient is lansoprazole. 8. The solid preparation according to claim 1, wherein the pharmaceutical ingredient is voglibose. 9. The solid preparation according to claim 1, wherein the pharmaceutical ingredient is candesartan cilexetil. 10. A hydroxypropoxyl group content of 7.0.
Use of -9.9% by weight of low-substituted hydroxypropylcellulose for the preparation of an orally disintegrating pharmaceutical preparation. 11. A hydroxypropoxyl group content of 7.0.
A method for improving the disintegration property of a solid pharmaceutical preparation in the oral cavity, characterized in that a low-substituted hydroxypropylcellulose of about 9.9% by weight is used.