WO2002092058A1 - Rapidly disintegratable solid preparation - Google Patents

Rapidly disintegratable solid preparation Download PDF

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Publication number
WO2002092058A1
WO2002092058A1 PCT/JP2002/004641 JP0204641W WO02092058A1 WO 2002092058 A1 WO2002092058 A1 WO 2002092058A1 JP 0204641 W JP0204641 W JP 0204641W WO 02092058 A1 WO02092058 A1 WO 02092058A1
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WO
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Prior art keywords
sugar
group
formulation
cellulose
active ingredient
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PCT/JP2002/004641
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French (fr)
Japanese (ja)
Inventor
Kazuhiro Ohkouchi
Hiroyoshi Koyama
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Takeda Chemical Industries, Ltd.
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/0012Galenical forms characterised by the site of application
    • A61K9/0053Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals

Abstract

A rapidly disintegratable solid preparation which comprises group (1) containing (a) an active ingredient, (b-1) a sugar and/or a sugar alcohol and (c-1) a cellulose and group (2) containing (b-2) a sugar and/or a sugar alcohol and (c-2) a cellulose, group (1) and/or group (2) containing (d) a dissolution aid. The solid preparation can be prepared by a dry method even under a low compression pressure and has a practically acceptable hardness and excellent properties necessary to drug, e.g., rapid disintegration, excellent dissolution control, and less trouble in preparation.

Description

Fast-disintegrating solid preparation technology field

The present invention is a body fluid especially rapidly disintegrate in saliva or the presence of a small amount of water in the oral cavity, useful solid preparation of the active ingredient dissolution is adjusted properly, as especially oral disintegrating to crushing solid preparation HayaKuzure壌性 on the solid formulation. BACKGROUND

Conventionally, drug patient swallowing is difficult, for the elderly or children, as taken with or combed dosage form, the development of a solid preparation which disintegrate rapidly and dissolution in the oral cavity that are underway.

For example, JP-A-6 2 1 8 0 2 8 No., Japanese Laid-Open 8-1 9 5 8 No. 9, the kneaded wet powder was filled wet-molded into a hole for tabletting, dried tablet It describes a process for preparing. The tablets obtained from to have an appropriate porosity porous, and rapid collapse 壌性 be obtained. However, this production method is to fill and compressing poor wet product fluidity, in addition to filling Paratsuki large, sometimes require special drying equipment, poor industrial productivity.

It has also been reported with the preparation of the orally disintegrating tablet of this for dry tableting method which is excellent in industrial productivity.

For example, International Publication No. WO 9 5/2 0 3 8 0, intraoral disintegrating 壌錠 of preparation by a dry tabletting method combining a low moldability saccharide with high moldability saccharides are described.

Further, International Publication No. WO 9 8 Z 0 2 1 8 5, combine erythritol tall are excipients and sugar alcohol, intraoral disintegrating by Dry tabletting method using dry or wet granulation granules 壌錠It has been described in the recipe.

Moreover, International Published No. WO 9 7/4 7 2 8 7, combines the average particle diameter of 3 0 μ πι following sugars or sugar alcohols with the active ingredient and a disintegrant, the preparation of tablets that disintegrate quickly in the oral cavity There has been described. According to the production method described in this, after milling sugar or sugar alcohols such as D- mannitol or lactose, the molded product was compression molded by adding collapse 壌剤 like, is rapid disintegration obtained is, but if the molded product using a coarse powder 碎前 sugars (lactose, average particle size 8 0 / zm) or sugar alcohol (D-mannitol, average particle diameter 6 0 mu m), forming at low tableting pressure It is difficult, so sufficient mechanical hardness can be obtained even by molding at high tableting pressures.

Commercial products containing existing active ingredients in the same component, to develop as an oral disintegrating tablet, in order maintain the efficacy and safety of the active ingredient, dissolution behavior of the active ingredient of the commercially available products and the oral disintegrating tablet it is preferable to equalize the. JP 9 one 7 1 5 2 3 No., International Publication No. WO 0 0/7 8 2 9 2, but to evaluate the collapse 壌性 in the oral cavity have been described for the elution modulating the activity Ingredient Absent. The purpose of the invention

After the tablets orally, the stomach, the gastrointestinal tract such as small intestine, dietary components, by contact with the gastrointestinal tract fluid, tablet component is contacted with various ion components, and the like. By for such work, the components of the additive in the tablet is not properly designed, elution of the basis component are affected, absorption behavior of the drug, thus, Ru may affect device expression of drug efficacy. Generally, in the case of the active ingredient of the poorly water-soluble sufficient drug efficacy expression Sarezu for elution is slow, not easy lead to excessive drug efficacy for fast elution in the case of water-soluble active ingredient.

The present invention, without the need for special formulation technology, industrial production in general equipment are possible, and have formulated such a commercial product (rapidly disintegrating solid preparation comprising the same active substance ; for example, the same dissolution profile as a tablet and the like), rapidly disintegrating solid preparation showing the absorption behavior, and in particular, to provide an orally disintegrating tablet. Summary of the Invention

The present inventors, after various investigations, containing a group containing an active ingredient and a sugar Contact Yopinomatawa sugar alcohol and cellulose, and a group containing a sugar Contact Yopi Roh or sugar alcohols and cellulose scan acids is allowed, has practically no problem hardness even at a low dry compression pressure by containing the eluted Tosuke agent to groups of one or both quick disintegration one or elution regulatory, medicament or the like excellent in manufacturability HayaKuzure 壌性 solid preparation have the excellent properties as, in particular, found that the oral disintegrating tablet can be obtained, and have completed the present invention based on these. That is, the present invention is,

(1) a) the active ingredient, b-1) sugar and / or sugar alcohol and c one 1) cellulose ethers and the group 1 comprising the b-2) sugar and / or sugar alcohol and c one 2) Cellulose rapidly disintegrating solid preparation and also contains a group 2 comprising the class, the group 1 and Z also containing d) elution auxiliaries group 2;

(2) a) the active ingredient, b-1) sugar and / or sugar alcohols, c- 1) cell opening over scan such Contact Yopi d) and the group comprising the dissolution auxiliary agent b-2) sugar and / or Ta alcohol and c one 2) rapidly disintegrating solid preparation comprising a group comprising cellulose ethers;

(3) a) the active ingredient, b-1) sugar and / or sugar alcohol and c one 1) cell group and b-2 comprising the cellulose ethers) sugar Contact Yopi Z or sugar alcohol, c one 2) rapidly disintegrating 壌性 solid preparation which comprises a group comprising cellulose ethers and d) eluting the auxiliary agent;

(4) a) active ingredient, b-1) sugar Contact Yopi Z or sugar alcohol and c one 1) cellulose ethers and the group 1 comprising the b_2) sugars and Z or sugar alcohol and c - 2) Cellulose rapidly disintegrating solid preparation and also contains a group 2 comprising a kind, containing d) elution auxiliaries groups 1 and 2;

(5) the is orally rapidly disintegrating solid preparation (1), wherein the formulation;

(6) The tablets (1), wherein the formulation;

(7) the solid preparation 1 00 parts by weight, sugar Contact Yopi Z or sugar alcohol 40-9 5 parts by weight said containing (1) according formulation;

(8) the solid preparation 1 00 parts by weight, the containing from 0.5 to 40 parts by weight of cellulose (1), wherein the formulation;

(9) said the solid preparation 1 00 parts by weight, you containing 0.0 to 5 parts by weight of elution aid (1), wherein the formulation;

(1 0) sugar glucose, fructose, lactose, wherein at least one member selected from sucrose and trehalose (1), wherein the formulation;

(1 1) wherein the sugar is lactose (1), wherein the formulation;

(12) sugar alcohol is D- mannitol, erythritol Torr, xylitol, one or the at two or more selected from Ma Ruchitoru Contact Yopi sorbitol (1), wherein the formulation;.

(13) wherein the sugar alcohol is D- mannitol (1), wherein the formulation;

(14) Average particle size of the sugar or sugar alcohol is 3 Ο μπ! Formulations of the (1), wherein the ~ 300 / in;

(1 5) D- average particle size of mannitol is 30! Wherein ~ is a 300 / zm (1 3), wherein the formulation;

(16) celluloses cellulose crystalline, powdered cellulose, 'one or more at a pre-SL selected from low substituted hydroxypropyl cellulose and carmellose (1) according formulation;

(1 7) the celluloses is low-substituted hydroxypropylcellulose (1), wherein the formulation;

(18) dissolution auxiliary agent hydroxycarboxylic cellulose, hydroxycarboxylic propyl methylation cellulose, poly Bulle pyrrolidone, gum arabic powder, gelatin, Mechiruseru loin, in one or more selected from poly Bulle alcohol and pullulan formulations of certain (1) wherein; -

(1 9) the dissolution auxiliary agent is hydroxypropyl cellulose (1) manufacturing according

20) wherein the active ingredient is manidipine hydrochloride (1), wherein the formulation;

21) wherein the active ingredient is voglibose (1), wherein the formulation;

22) wherein the active ingredient is candesartan cilexetil (1), wherein the formulation; the (23) the active ingredient is pioglitazone hydrochloride (1), wherein the formulation;

Formulations of the (1) wherein 24) group 2 further containing the active ingredient;

Formulations of the 24), wherein the active ingredient is not the same for 25) group 1 contains the active ingredient and the group 2 containing;

26) component b-1) to component b-2) and are not the same (1) preparation according; (2 7) component c one 1) to component c one 2) and are not the same (1) according formulation;

(28) said containing no collapse 壌剤 selected from crospovidone (1), wherein the formulation;

(2 9) group 1 and Z or the free has a low-substituted hydroxypropylcellulose in the group 2 (1), wherein the formulation;

(3 0) the a pharmaceutical composition for treating or preventing hypertension or diabetes (1), wherein the formulation;

(3 1) a) the active ingredient, b-1) the group and b-2 comprising the sugar and / or sugar alcohol, c one 1) cellulose ethers Contact Yopi d) eluting aid) 'sugar and / or sugar alcohol and c one 2) above, wherein the compression molding a mixture containing a group comprising the cellulose (2) method according to the formulation;

(3 2) a) the active ingredient, b-1) sugar and / or sugar alcohols and c- 1) group and b-2 comprising the cellulose) sugar Contact Yopi Z or sugar alcohols, c- 2) cellulose and d) above, wherein the compression molding a mixture containing a group comprising an elution auxiliary agent (3) preparation of a formulation according;

(3 3) (2) above for the manufacture of a description of the preparation, a) the active ingredient, b-1) sugar and / or sugar alcohols, and c one 1) celluloses Contact Yopi d) eluting adjuvant use of a group comprising a group comprising b-2) sugar and / or sugar alcohol and c _ 2) celluloses;

(34) the (3) for the manufacture of a description of the preparation, a) the active ingredient, b-1) the group and b-2 comprising a sugar Oyo Pi Z or sugar alcohol and c _ 1) celluloses ) sugar Contact Yopi Z or sugar alcohol, c one 2) use of the group comprising the cellulose and d) eluting the auxiliary agent;

It relates the like; (3 5) prevention method of treating hypertension or diabetes, which comprises administering an effective amount of the active product content using the formulation of the (1) described in the mammal. The active ingredient used in the present invention, solid, crystalline, oily, may be one several Re, such as solution form, for example, nourishing and health drugs, antipyretic analgesic antiphlogistics, psychotropic agents, anxiolytics, antidepressants , hypnotic sedative, antispasmodic drugs, central nervous system agents, cerebral metabolism improving agents, cerebral circulation improving agents, antiepileptic agents, sympathomimetic agents, gastrointestinal agents, antacids, anti-ulcer agents, 鎮晐 expectorant, antiemetic agents, respiratory accelerators, bronchodilators, antiallergic agents, dental buccal drugs, anti-histamine agents, cardiotonics, antiarrhythmic agents, diuretics, antihypertensives, vasoconstrictors, coronary vasodilators, peripheral vasodilators , hyperlipidemia for agents, Togitanzai, antibiotics, chemotherapeutic agents, antidiabetic agents, for osteoporosis agents, anti-rheumatic drugs, skeletal muscle relaxants, antispasmodic agents, hormonal agents, Al force Lloyd narcotics , sulfa drugs, gout treatment drugs, anticoagulants, anti-evil One or more components selected from such as tumor agent is use Rere.

The nourishing health drugs, such as vitamin A, vitamin D, vitamin E (acetate d-alpha - like tocopherols), vitamin B 1 (dibenzo I le thiamine, etc. Furusuruchi Amin hydrochloride), vitamin beta 2 (such as riboflavin butyrate) , vitamin beta 6 (such as hydrochloric acid pyridinium Dokishin), vitamin C (Asukorubin acid, such as L Asukorubin acid sodium), vitamins, calcium and vitamin beta 12 (acetate human mud Kiso cobalamin, etc. Shianokobaramin), magnesium, minerals such as iron, protein, amino acids, oligosaccharides, and the like herbal medicine.

The antipyretic analgesic antiphlogistics such as aspirin, § Seto § amino Fen, Etenza Mi de, ibuprofen, diphenhydramine hydrochloride, dl - maleic acid Kuronorefueyura Min, phosphoric acid dihydrazide Dorokodin, ɽ force pins, methylephedrine hydrochloride ephedrine, hydrochloric full Engineering sulfonyl propanol § Min, caffeine, anhydrous caffeine, Serape Putaze, salts I spoon lysozyme, Torufuenamu acid, Mefuenamu acid, sodium diclofenac, full Rufuenamu acid, Sarichiruami de, Aminobirin, ketoprofen, indomethacin down, Pukoromu, pentazocine and the like.

The psychotropic drug include chlorpromazine, etc. reserpine and the like. Anxiolytics, for example alprazolam, chloro-di § Ze ethoxide, etc. Jiazepa beam are exemplified.

The antidepressant, e.g. Imiburamin, maprotiline hydrochloride, etc. amphetamine are exemplified.

The hypnotic sedative include estazolam, nitrazepam, Jiazepamu, pel Lappin, such as Hue Bruno sodium barbital and the like.

The anticonvulsant agents include for example hydrobromic acid Sukoboramin, hydrochloric diphenyl m Nhidoramin, such as hydrochloric Papabe phosphorus.

The central nervous system agents, for example, citicoline and the like. The cerebral metabolism improving agents, such as hydrochloric Black Hue Niki glyphosate and the like. The cerebral circulation improving agents, such as vinpocetine and the like.

The antiepileptics include, for example Fuenitoin, Ru carbamazepine can be mentioned.

The sympathomimetic agents, such as isoproterenol hydrochloride and the like. The gastrointestinal agents, for example diastase, saccharated pepsin, scopolia extract, cellulase AP 3, lipase AP, stomachic digestive agents such Keihi oil, bell base phosphorus chloride, resistant lactic acid bacteria, and the like antiflatulent, such as bifidobacteria.

The antacid, for example magnesium carbonate, bicarbonate Natoriumu, magnesium aluminometasilicate, synthetic Hidorotarusai DOO, precipitated calcium carbonate, oxide and the like Ma Guneshiumu. .

The antiulcer agents, for example lansoprazole, Omeburazoru, Rabeburazo Le, famotidine, cimetidine, and the like ranitidine hydrochloride.

The antitussive expectorants, such as hydrochloric acid Cloperastine, hydrobromic acid Dekisutorome preparative Norefan, theophylline, force guaiacol sulfonic acid Riumu, Guaifeneshin, and the like phosphoric acid Kodin is.

The antiemetic, for example, hydrochloric Jifue two dolls, etc. Main Useful port Purami de is like et be.

The respiratory accelerators, for example, tartaric Rebarorufuan the like.

The bronchodilators, eg theophylline, sulfate and the like Saruputamoru.

The allergy drugs, amlexanox, Ru is like seratrodast.

The dental buccal drugs, for example, O alkoxy tetracycline, triamcinolone § Setonido, to a hydrochloric chloro chlorhexidine, such as Li lidocaine are exemplified.

The antihistamine, for example, hydrochloric Jifenhi Doramin, promethazine, Isochipenjiru hydrochloric acid, etc. dl- chlorpheniramine maleate and the like.

The inotropic agents, such as caffeine, digoxin and the like.

The antiarrhythmic agents include, for example, hydrochloric acid pro force In'ami de, propranolol hydrochloride, pindolol and the like.

Diuretics, for example isosorbide, Furosemi de, and etc. arsenide Dorokuro port thiazide. .

The antihypertensive agent, such as hydrochloric acid delapril, captopril, Angi O tensin converting enzyme inhibitors such as Bae Rindopuriru Erupumin, vascular dilators, such as hydralazine hydrochloride, alpha, such as hydrochloric acid labetalol, / 3-blockers, hydrochloric two Karujipin, Two Rupaji pins, - Fuejipin, hydrochloric base - adipic, diltiazem hydrochloride, two Sorujipin, nits Renjipin, hydrochloric barnidipine, efonidipine hydrochloride, amlodipine besylate, full Erojipin, cilnidipine, Aranijipin, C a antagonists such as manidipine hydrochloride, mouth Sultan, Epurosarutan , candesartan, Roh Rusarutan, telmisartan, Irubesarutan, olmesartan, Tasosanoretan, Angi O Tianjin II receptor antagonists, such as power down de Sano RETAN Sile Kisechi Norre, sympathetic central such as methyldopa depression Such as control agents, and the like.

The vasoconstrictor, such as hydrochloric phenylene Refurin the like.

The coronary vasodilator, for example hydrochloric carbocromene, molsidomine, hydrochloric acid and the like Bella Pamiru is.

The peripheral vasodilators, such as cinnarizine and the like.

The hyperlipidemia dosage, for example cerivastatin sodium, sympathizers statins, 'plug pasta Chin sodium © beam, Ru is like § atorvastatin calcium hydrate.

The choleretic agents, for example de arsenate Dorokoru acid, and the like Torepiputon. Antibiotics, for example cephalexin, cefaclor, Amokishishirin, hydrochloric Pipumeshirinamu, Kisechiru to cefotiam hydrochloride, Sefuadorokishiru, Sefikishi arm, cefditoren pivoxil, cefteram pivoxil, cefpodoxime Doki stain pro xenon cephem system, such as chill, ampicillin, Shikurashin, nalidixic acid, synthetic antibacterial agents such as Enokisashi down, Monobatatamu system such Carmo Nam sodium, Bae Nemu system 及 Pi carba Bae Nemu antibiotics and the like.

Chemotherapeutic agents, such as sulfamethizole and the like.

The antidiabetic agent, for example Toruputami de, sulfonyl Le urea drugs such Guribenkurami de, Akarubosu, Boguriposu, Miguri Torr, alpha Darukoshidaze inhibitors such Emidariteto, pioglitazone hydrochloride, Toroguridazon, etc. Insurin resistance improving drugs such as Roshiguritazo down and the like.

The osteoporosis dosage, for example, Ipurifurabon the like.

As the skeletal muscle relaxants, for example, such as the eye Tokarupamoru and the like.

The antispasmodic agent, hydrochloric Metarijin, such as dimenhydrinate and the like. Examples of the anti-Riumachi drugs, methotrexate, and the like bucillamine. The hormonal agent such as liothyronine sodium, dexamethasone sodium phosphate, prednisolone, Okisendoron, such as leuprorelin acetate can be mentioned up.

As Al force Lloyd narcotic, Ahen, morphine hydrochloride, ipecac, Okishiko de down, hydrochloric Ahen'arukaroi de, hydrochloric acid and the like cocaine.

The sulfa drug, for example Surufisomijin, such as sulfamethizole can be mentioned up.

The gout therapeutics, for example Aropurinoru, such as colchicine and the like. The anticoagulants include, for example, dicoumarol.

The antineoplastic agents such as 5-Furuorourashiru, Urashiru, like Maitomai Shin.

Among them, as the active ingredient, hydrochloric Ma - adipic, voglibose, Kandesaruta Nshirekisechiru, such as pioglitazone hydrochloride, especially salts manidipine are preferably used.

The active component generally medical, may be diluted with a diluent and the like used in the food field. Or it may be treated with masking bitterness of the active ingredient for the purpose. The amount of active ingredient mentioned above may vary depending on the type and dosage of active ingredient, example, 0.0 1-4 0 parts by weight of the solid pharmaceutical preparation 1 0 0 parts by weight of the present invention, rather preferred is 0. 0 1-2 0 parts by weight.

Examples of the sugar used in the present invention include glucose, fructose, lactose, sucrose, trehalose and the like, such as lactose are preferably used.

The sugar alcohol used in the present invention, for example D- mannitol, Ellis Lithol, xylitol, maltitol, sorbitol and the like, such as D- Ma N'nitoru is preferably used.

As for the sugar and sugar alcohols may be used in combination one kind or two or more in each, but it may also be used in combination with sugar Contact Yopi sugar alcohol.

Sugar or sugar alcohol (preferably sugar alcohol, more favorable Mashiku, D- mannitol) used in the present invention has an average particle diameter of, 1~300 / πι (e.g., lasers first diffraction type particle size distribution measuring apparatus, SYMPATEC company: HELQS a & RODOS, etc. measured by), preferably a sugar or Ta alcohols average particle size exceeds 30 mu m, an average particle size lay more preferred is 3 1 m or more sugars or sugar alcohols, especially, average particle diameter is used properly preferred sugar or sugar alcohols 35 to 200 m. Sugar or sugar alcohols such particle size, lactose granulated powder Dairakutozu scale commercial product (Freund Sangyo Co., Dairakutozu, Megureji Yapan of Taburetosu, flow rack 100, Towa Chemical mannitol S Industrial Co. and marine Christa Norre, Merck & Co., Inc. of 1.05980, CEL-STAR Japan of Mannidex, trehalose of Asahi chemical industry Co., Ltd.?, sorbitol DP- 5 0M of Towa chemical industry Co., Ltd., Amaruti MR- 50, such as pure fructose S of Kato chemical) it can be obtained as. Also, the sugar or sugar alcohol having an average particle size of. 5 to 30 im is commercially available (Megureji Yapan of Daranyurakku 230, Soruporakku 400, Towa Chemical Ma N'nitto P Industrial Co., xylylene Tonore P, Amaruti MR- 100, Japan available as Ken collar Sri Torr chemical Co. (fines), etc.), a sugar or sugar alcohol having an average particle size of 200-5 0 ° mu m are commercially available (Meggle Japan of quick shellac 80, Asahi Kasei trehalose 0 of industry Co., Ltd., it is possible to obtain xylitol XC, erythritol toll of Nikken Chemicals Co., Ltd., anhydrous crystalline glucose TD A- S of Sanei sugar spoon, as such as hydrous crystalline department etc. jar sugar TDH) .

As the sugar or sugar alcohol above the average particle diameter of 500 m, a commercial product (Meggle Japan of Prisma rack 40, pure fructose Kato Chemical, Towa Chemical flax Luthi industrial (Ltd.) MR- 20, such as sorbitol DP-1 0M) Ru can be obtained as. To obtain a sugar or sugar alcohol having an average particle size required, it can also be prepared by a method such as Kona碎. Powder stone, can be carried out using a cutter mill, a jet mill, a hammer mill.

The average particle diameter 3 0 to 9 0 Ai average particle size for the less than was the sugar or m to improve the flowability during production and sugar alcohol 9 0 m to 5 0 to the strength increase of the molded product 0 zm (preferably 9 0 zm~3 0 0 μ πι) may be used combining a sugar or sugar alcohol. The average particle diameter 3 0 to 9 0 mu less than m, (preferably an average particle diameter of 3 5 to 8 0 xm) and fine sugar or sugar alcohols mean particle size 9 0 μ m~ 5 0 0 μ ΐπ (preferably 9 0 μ m~ 3 0 0 μ m, still against preferably is used in combination with the coarse sugar or sugar alcohol having an average particle diameter of 9 0~2 0 0 im), thin paddle sugar or sugar alcohol 1 part by weight usually a coarse sugar or sugar alcohol 0. the 1 to 1 0 parts by weight, preferably 0. it is preferable to use 2 to 5 parts by weight. In particular, the active ingredient, if it is manidipine hydrochloride for fine sugar or sugar alcohol 1 part by weight, usually 0 coarse sugar or sugar alcohol. 2-3. 5 parts by weight, rather preferably is 0.3 to 2. it is preferable to use 5 parts by weight.

Also, fine when using sugars or sugar alcohols and a combination coarse sugar or a sugar alcohol, it may be used in combination one kind or two or more in each fine sugar or sugar alcohol rough and sugar or sugar alcohol also each combination are the same or different. Moreover, fine and sugar or sugar alcohol and coarse sugar or sugar alcohol, a mixture prepared by mixing a powder state is used as a raw material, but a rapidly disintegrating solid preparation of the present invention may be molded, for example, fine glycolysis or a sugar alcohol and a coarse sugar or sugar alcohol in two or more groups, after producing the granules, etc., may be molded as a rapidly disintegrating 壌性 solid preparation of the present invention. Fine Les, sugar or a sugar alcohol and coarse! /, When using a mixture of a sugar or sugar alcohol was combined mixed in a state of powder as a raw material, in a particle size distribution of the mixture is desirably exhibits a peak on the 2 or more, Further, the average particle size of the mixture is is preferably 3 0 / zm ~3 0 0 μ πι.

Preferred combinations of the fine sugar or sugar alcohols and coarse sugar or sugar alcohol, an average particle diameter of 3 0! ~ 9 0; D- mannitol Contact Yopi average particle size of less than zm is like 9 0 μ πι~3 0 0 μ πι of D- mannitol. The amount of sugar or sugar alcohol, 40 to 95 parts by weight of the solid pharmaceutical formulation 100 parts by weight, preferably 50 to 90 parts by weight.

As for the "sugar and / or sugar alcohol" "sugar and / or sugar alcohols" as component b _ 2) contained the the other group of components b-1) included in one group, and the same also, it may be different.

The celluloses, such as crystalline cellulose, powdered cellulose, low substituted hydroxycarboxylic cellulose, carmellose and the like (preferably low-substituted hydroxypropylcellulose and the like) is used, and amount thereof is 100 parts by weight of the solid pharmaceutical preparation 5-40 parts by weight 0. in contrast, preferably 1 to 20 parts by weight.

Specific examples of the crystalline cellulose, for example Seorasu KG 801, Seorasu KG 802, Avicel PH 101, PH102, PH301, PH302, PH- F 20, Avicel RC- A591 NF (manufactured by Asahi Kasei none Ltd.) and the like also include those that are referred to as microcrystalline cellulose.

Specific examples of low-substituted hydroxypropyl cellulose, for example low-substituted hydroxycarboxylic cellulose LH1 1, LH21, LH31, LH22, LH 3 2, LH20, LH30, LH32, LH33 (all manufactured by Shin-Etsu Chemical Co., ) is hydroxypropoxyl group content of such include 5-16 wt% low-substituted hydroxypropyl Le cellulose. These are possible commercially available. There have can be prepared by methods that Junzu method or to according to known methods, for example, Japanese Patent Publication 57- 53100.

The active ingredient, and the celluloses, the one or in each may be used in combination of two or more.

May contain further active ingredient is the group 2, and the active ingredient contained in the active ingredient and the other group included in one group, may be the same or different. - as the "celluloses" component c one 2) contained the the other group of "cellulose" as the component c one 1) included in the group of square, even with the same or may be different .

The elution adjuvants, may be any as long as it can adjust to regulate the dissolution of the active ingredient, for example, be one that promotes the dissolution of the slow active ingredient eluting elution fast active ingredient eluting or it may be suppressed. The elution auxiliaries, examples Ebahi Dorokishipu port Pinot receptacle Honoré loin, hydroxycarboxylic prop Honoré methylate Honoré cellulose, Po Ribinirupirori pyrrolidone, gum arabic powder, gelatin, methyl cellulose, polyvinyl alcohol, pullulan (preferably human Dorokishi use cellulose etc.) Irare, and amount thereof is 0.0 to 5 parts by weight to 1 0 0 parts by weight solid pharmaceutical formulation, preferably 0.1 to 2 parts by weight, more preferably 0.2 to 1 parts by weight.

In general, elution adjuvant has a binding force, if uniformly distributed within the tablet, tablets agent hardness increases, disintegrating in the oral cavity is bad. Therefore, a group comprising elution auxiliaries, by producing in groups that do not contain, can have the rapid oral disintegrating 壌特 properties. Further, in the example, when both groups 1 and group 2 contains the active ingredient, both of the group 1 and group 2 may also contain dissolution aids. Here, if both of the group 1 and group 2 contains a dissolution auxiliary agent, and the elution auxiliaries and elution auxiliaries that is part of the other group included in one group may be the same, or different it may be. Moreover, the dissolution if adjuvant is the same, identical content elution Tosuke agent content and the other group of dissolution aids one group included in one of the free Murrell elution auxiliaries and other group to the group even, it may be different.

Commercial products containing existing active ingredients in the same component (formulation not orally disintegrating tablet; if example embodiment, tablets, etc.), to develop as an oral disintegrating tablet, maintaining fine safety Oyo efficacy of the active ingredient for equally be Rukoto preferably the dissolution behavior of the active ingredient of the commercially available products and the oral disintegrating tablet.

Formulations Formulations of the present invention is preferably formulated containing no disintegrant gel with saliva, For example, not containing carmellose calcium, sodium carboxymethyl starch, a disintegrant selected from the cross force Rume port "scan and crospovidone , in Naka, formulations containing no crospovidone as disintegrating 壌剤 is preferred. as the formulations of the present invention is preferably a preparation containing the low-substituted hydroxypropylcellulose cell row scan in the group 1 and / or group 2, the group more preferred formulations contain low-substituted hydroxypropyl cellulose to 1 Oyopi group 2. here, even low-substituted hydroxycarboxylic cellulose of groups 1 and 2 are the same and be different good.

Also, low-substituted hydroxycarboxylic propyl cellulose if used as celluloses, in the formulation of the present invention may serve as well eluting adjuvants low-substituted hydroxypropylcellulose. Therefore, as long as the object of the present invention are achieved, it is also possible to omit the use of other solvent Detonator aid described above.

Other, formulations of the present invention, unless hinder the effects of the invention, maize starch as an excipient, potato starch, wheat starch, rice starch, partially § Strand of Denpushi, alpha Ichika starch, porous starch and the like various used in the preparation of starches and one 般製 agents additives may contain an appropriate amount. Such additives, such as excipients, acidulants, foaming agents, artificial sweeteners, flavors, lubricants, wear colorant, stabilizer, p H adjusting agent, and a surfactant.

Examples of excipients include inorganic excipients, anhydrous calcium phosphate, precipitated carbonate calcium, Kei acid Kanoreshiumu, such as light anhydrous Kei acid.

The sour agent, e.g. Kuen acid, tartaric acid, malic acid, etc. Asukorubin acid.

As the foaming agent, such as sodium bicarbonate, sodium carbonate Ru mentioned.

The sweetener include saccharin sodium, Gurichirurichi. N'nikariumu, aspartame, stevia, thaumatin, etc. acesulfame potassium cited et 'is.

The perfumes include lemon oil, orange oil, menthol, and the like. Examples of the lubricants include magnesium stearate, sucrose fatty acid esters, polyethylene da recall, talc, stearic acid, fumaric acid stearyl Luna thorium.

As the colorant, for example, Food Yellow No. 5, Food Red No. 2, Food dyes such as Food Blue No. 2, food lake dyes, and ferric oxide.

The stable 匕剤, such as sodium Edeto acid, tocopherols, Shikurodeki string and the like.

The p H adjusting agents, for example Kuen, phosphate, carbonate, tartrate, fumarate Le salts, acetate, amino acid salt and the like can be mentioned.

As the surfactant, for example Rauriru sodium sulfate, polysorbate 8 0, hard oils, polyoxyethylene (1 6 0) polyoxypropylene (3 0) glycol and the like.

There is no particular limitation on the particle diameter of used are excipients but THE variability feel less likely to occur particle size 5 0 0 μ ΐη less preferred in the oral cavity. These excipients may be used one kind may be used in combination of two or more. In producing the solid preparation of the present invention, it may be used fine granular core, the good UNA nucleus of the active ingredient, after coating with such additives, further taste 'odor masking, enteric reduction or the purpose of such sustained release, can have use coated by a known method.

As a method for producing the solid preparation of the present invention, for example,

① a) active ingredient, b-1) sugar and Z, or sugar alcohol, c one 1) celluloses Contact Yopi d) and the group 1 containing elution auxiliaries b-2) sugar and / or sugar alcohol and c - 2) were mixed group 2 containing celluloses, optionally, cellulose scan acids, fluidizing agents, lubricants, sweetening agents, such as by mixing an appropriate amount of perfume, compression molding; ② a) the active ingredient , b-1) a sugar Contact Yopi Z or sugar alcohol and c one 1) group 1 and b-2 containing cells port Ichisu acids) sugar Contact Yopi Z or sugar alcohols, c- 2) cellulose ethers and d) mixing the group 2 containing elution auxiliaries, if desired, cellulose scan acids, fluidizing agents, lubricants, sweetening agents, such as by mixing an appropriate amount of perfume, compression molding; a which method include It is.

Here, either (preferably, the group 1 containing the active ingredient) of the group 1 Oyopi group 2 is preferably from granules preferably further both are granulated.

Moreover, the solid preparation of the present invention, the group 1 to form a internal phase, group 2 may be a preparation of mononuclear such as the external phase.

Specific production methods, the active ingredient and drug substance, water is dispersed or dissolved binder, acetone, ethyl alcohol, using propyl alcohol or their mixture, the granules for tablets by wet granulation method, a method of producing granules for tablets in two or more separate groups, Koti components of group 2 water, acetone, ethyl alcohol, was dispersed in propyl alcohol or their mixture, the granules for tablets of group 1 a method of producing a single nucleus tablet granules consisting Ltd. was internal and external phases by a method of packaging and the like.

If necessary in manufacturing a 锭剤 from granules for tablets, celluloses, disintegrating agents, flow Dokazai, lubricants, perfumes, may be mixed, such as sweeteners.

Tablets, for example, single tableting machine, such as a rotary tableting machine is molded using. Pressure during the compression is usually 2. 5~3 0 kN m. The shape of the solid preparation of the present invention is not particularly limited, round, caplet, donut, shape and layered tablet such Oburongu form, it may be an nucleated tablet, more to be covered by the coating it is also possible to. Also, the mark for discrimination, characters and occasionally subjecting the split line for splitting.

Chikarabe and rapidly disintegrating solid preparation of the present invention obtained preferably orally rapidly disintegrating 壌性 solid preparation showed rapid collapse 壌性 in the oral cavity, the same as the commercial product containing the same active substance eluted It shows the behavior. Various ion component, a small influence on the dissolution of the agent components. Also it shows appropriate preparation strength. Furthermore, it exhibits excellent manufacturability.

That is, (time until the tablet with saliva in the oral cavity of healthy adult men and women are fully Kuzure壌) in orally disintegrating tablet melting in the mouth time the invention varies depending on the size and Thickness of tablet , usually 5-9 0 seconds, preferably from 5 to 6 about 0 seconds. Also, hardness (measured by a tablet hardness tester) is usually 1 0-2 0 0 1 ^, preferably about 1 0 to 1 5 ON.

Thus, orally disintegrating tablet of the present invention, the drug the patient is sufficiently masked, elderly, as easy to take tablets for pediatric, also as a safe preparation of emergency general adults, containing a pharmaceutical ingredient treatment of conventional pharmaceutical preparations as well as various diseases which can be used in the prevention, long-term storage, is excellent in stability.

Note that this formulation may or be taken without disrupting in the oral cavity, also for clothes with water. After dispersing the formulation to put the water like a cup or the like, it can also be taken. Hereinafter, by way of comparative examples further illustrate the present invention and examples which are not intended to limit the present invention.

Example, 锭剤 obtained in Reference Examples and Comparative Examples by the following test methods, to measure the tablet hardness Contact and oral disintegration time.

(1) hardness test

It was measured using a tablet hardness meter (manufactured by Toyama Sangyo Co.). Test was performed in 3 tablets or 5 tablets, it shows the average value.

(2) oral disintegration time

Tablet was measured boss by healthy adult male 3 people the time to collapse only in the saliva of the oral cavity.

(3) dissolution test

Tablets each one tablet, placed in a test solution of 90 OML adjusted to pH4 with 0. 4 mol / L phosphate monosodium hydrogen and 0. 2 Mol / L Kuen acid, rotation speed 50 r pm, 37 ° C at over time to sample, after filtration the samples, a 350 nm absorbance by a spectrophotometer was measured to calculate the eluted manidipine hydrochloride amount (n = 3). Example 1

Manidipine hydrochloride 4480 g, lactose granulated powder (Freund) 131 56 g, corn starch 660 g, low-substituted hydroxypropyl cellulose (Shin-Etsu Chemical Industry: LH- 3 1) 3300 g in a fluidized bed granulating dryer (Baurekku Co., FD- charged in S 2 type), hydroxycarboxylic cellulose (Nippon Soda) 44 O g and spraying purified water 9284 g containing yellow iron sesquioxide 44 g, granulation, granule a a drying step It was obtained. Then, power mill the granules A (Showa Chemical Machinery, P- 3 S) using, sieved through screen size (1. 2πιηιφ), to give a sized product Alpha. On the other hand, D- mannitol (Towa Kasei: Man'ni' preparative S) 86 14 g, D- Man'ni Tonore (Menoreku Corporation: 1. 05980) 4514 g, low-substituted hydroxypropyl cellulose (Shin-Etsu Chemical: LH- 1 1) 1438 g the fluidized bed granulating dryer (Paure Kkusha, FD-S 2 type) were charged into a spray D- mannitol 460 g, purified water 521 5 g containing anhydrous Kuen acid 1 44 g and yellow ferric 1 1.5 g to obtain granules B through granulation, the drying step. Next, a power mill the granules B, and sieved by screening Nsaizu (1. 2πιπιφ), to give a sized product beta.

Sieved product A1800 g, sieved product B 2376 g, crystalline cellulose 248 g, were mixed Asupa Rutemu 9. 0 g, magnesium stearate 67. 5 g. This mixed powder was tabletted with 250 mg per tablet (Kikusui Seisakusho,. Collection preparative 1 9 K AWC, tablet size 9. 5 mm, compression pressure 5. 4 kN / cm 2).

Example 2

Manidipine hydrochloride 2660 g, lactose granulated powder 1 3 1 1 1 g, corn Den flop down 559 g, low-substituted hydroxypropylcellulose (LH- 31) 1 995 g of a fluidized bed granulating dryer (Paurekku Inc.,? 0-32 charged into a mold), purified water 7727 g containing hydroxypropyl Le cellulose 266 g and yellow ferric 1 3 g and mists, granulated to obtain granules C in a drying step. Next, you have use a power mill granules C, screen size (1. 2 mm <|) and sizing in) to obtain a sized product C.

On the other hand, D- mannitol (Man'ni' preparative S) 9585 g, D- mannitol (main Rukusha: 1. 05980) 5053 g, low-substituted hydroxypropyl cellulose (Shin-Etsu Chemical: LH- 1 1) 141 8 g of fluid granulation grain dryer (Paurekku Co., FD-S 2 type) were charged to, D- mannitol 540 g, purified water 6089 g containing anhydride Kuen acid 142 g and yellow ferric 6. 8 g spray granulation to give the granules D and a drying step. Next, a power mill the granulated product D, and sieved by a screen size (1. 2πιπιφ), to give a sized product D.

Sieved product C 1 259 g, sieved product D 2233 g, crystalline cellulose 224 g, were mixed Asupa Rutemu 7. 6 g, magnesium stearate 56. 7 g.

This mixed powder was tabletted with 21 Omg per tablet (Kikusui Seisakusho, collection preparative 19K AWC, JoHitoshi (J size 9. Omikuronpaiiotapaiiotafai, compression pressure 6. 5 k N / cm 2) Q

Example 3

Hydrochloride Ma - adipic 600 g, lactose granulated powder 1644 g, toe sorghum starch 9 0 g, low-substituted hydroxypropylcellulose (LH-31) 600 g of a fluidized bed granulating dryer (Fujisangyo, FD-5 S-type) the resultant mixture was 嘖霧 purified water 1 266 g containing hydroxypropyl cellulose 60 g and yellow ferric oxide 6 g, granulation was by a drying step to obtain a granulated product E. Next, a power mill the granulated product E, and sieved by a screen support I's (0. 8πιπιφ), to give a sized product E.

On the other hand, D- mannitol (Man'ni' preparative S) 21 21 g, D- mannitol (main Rukusha: 1. 05980) 1 1 21 g, carboxymethyl cellulose (Gotoku Chemical: NS-300) 563 g of a fluidized bed granulating dryer ( Fujisangyo were charged into a FD-5 S-type), D-mannitol 1 20 g, was sprayed including purified water 1356 g of anhydrous Kuen acid 30 g and yellow ferric oxide 6 g, granulation and drying steps granulation to obtain a grain product E. Next, a power mill granules F, and sieved by a screen size (0. 8πιπιφ), to give the integer grain product F.

Sieved product E 1 0 g, sieved product F 1 3. 2 g, crystal cellulose 1. 38 g, Asuparu Thame 0. 05 g, was mixed with magnesium stearate 0. 38 g.

This mixed powder was tabletted into tablets weighing 250 mg (Universal Testing Machine, tablet size 9. 5Paiiotaiotaitafai, compression pressure 5. 3 kN / cm 2).

Reference Example 1

Using a commercially available local slot lock (2 Omg) (L ot No. 58 1), it was subjected to dissolution test.

Reference Example 2

Using a commercially available local slot lock (1 Omg) (L ot No. 559), it was subjected to an elution test.

Comparative Example 1

Manidipine hydrochloride 100 g, lactose granulated powder 21 1 g, corn starch 23. 5 g in a fluidized bed granulating dryer (Baurekku Co., LAB-:! type) to feed, purified water containing yellow ferric 1. 1 g the 201 g spray granulation to obtain granules G through drying process. - How, D_ Man - Tonore (Man'ni' door S) 10234 g, D- Man'nitonore (main Rukusha: 1 · 05980) 591 3 g, crospovidone 892 g in a fluidized bed granulating dryer (Paurekku Inc., FD- S 2 charged into a mold), D-man - tall 538 g, purified water 6074 g containing yellow ferric oxide 26. 9 g and anhydrous Kuen acid 1 34 g and mists, granulation and drying steps granulation H It was obtained. Next, you have use a power mill granules H, and sieved by a screen size (1. 2ιηιηφ), to give a sized product Eta.

Granulate G 3. 4 g., Sieved product H8. 25 g, crystalline cellulose 0. 69 g, were mixed Asuparu Thame 0. 025 g, magnesium stearate 0. 1 9 g.

This mixed powder was tabletted with 250 mg per tablet (universal testing machine, tablet size 9. 5Itaiotapaiiotafai, compression pressure 5. 4 kN / cm 2). Comparative Example 2

Manidipine hydrochloride 952 g, lactose granulated powder 1 369 g, corn starch 2 12 g, Crospovidone 302 g in a fluidized bed granulating dryer (Paurekku Co., FD-5 S-type) were charged to, hydroxypropyl cellulose 204 g and yellow three spraying purified water 4290 g dioxide containing iron 2 g, granulated to obtain granules G with a drying step. In the following, power mill the granules I (Showa Chemical Machinery Plant, P-3 S) using, sieved by screening Nsaizu (1. 2ηιπιφ), to give a sized product I.

On the other hand, D- mannitol (Towa Kasei: Mannit S) 2856 g, D- Man'ni Torr (Menoreku Corporation: 1. 05980) 1650 g, Dozo grain dryer flow crospovidone 249 g (Paurekku Inc., 0-53 type charged in), D-man - tall 1 5 0 g, spraying purified water 186 5 g containing anhydride Kuen acid 37. 5 g and yellow ferric 7. 5 g, granulation, granulation and drying process to give things J. Next, using Power Mill granules J, and sieved by a screen size (1. 2ιηιηφ), to give a sized product Eta. Sieved product I 804 g, sieved product J 1980 g, crystalline cellulose 165 g, were mixed Asuparu Thame 6. 0 g, magnesium stearate 45 g.

This mixed powder was tabletted with 250 mg per tablet (Kikusui Seisakusho, collection preparative 1 9 K, tablet size 9. 5Paiiotapaiiotafai, compression pressure 5. 2 kN / cm 2).

Example, the resulting tablets the test method in Reference Examples and Comparative Examples, the dissolution test After the start, the results showing the dissolution rate of manidipine hydrochloride eluted until the time are shown in Table 1, 2. The dissolution from tablets prepared in Example 1, 3, whereas the shows the same dissolution property as in Reference Example 1, dissolution of the tablets prepared in Comparative Example 1, 2 is lower than Reference Example 1 It showed a trend.

Dissolution from the tablets prepared in Example 2, showed similar dissolution properties as in Reference Example 2. Table 1 Shanshan real real real

施施 considered 施考 time (in minutes)

β ^ 0 10 15 30 45 60

Example 23211 1 0 22.3 32.7 46.8 54.9 62.4

Example 3 0 24.2 37.6 48.7 56.4 60.2

Reference Example 1 0 18.5 31.2 47.8 56.5 61.6

Comparative Example 1 0 8 1 1.4 19.8 27.9 36.4

Comparative Example 2 0 14 19.7 32 39.6 45.5

Table 2 hours (minutes)

0 10 20 30 45 60

Example 2 0 35.8 52.7 62.9 73.1 83.1

Reference Example 2 0 20.1 48 64.1 75.8 81

The resulting tablets the test methods in Examples and Comparative Examples, the hardness, the results of measurement between time orally disintegrating shown in Table 3. Tablet hardness which was produced in Example 1 to 3, whereas showed rapid collapse 壌性 in the oral cavity at 2 9~ 3 3 (N), the tablets of Reference Example 1, 2, collapsed in the oral cavity It did not soil. Table 3

Hardness (N) oral disintegration time (in seconds)

31.2 32.3

33.3 30

29.4 25

59 does not collapse

81.8 The availability of on the collapse and not industry

Chikarabe was rapidly disintegrating 壌性 solid preparation of the present invention obtained preferably orally rapidly disintegrating 壌性 solid preparation showed rapid disintegrability in the oral cavity, the same as the commercial product containing the same active substance eluted It shows the behavior. Various ion component, a small influence on the dissolution of the agent components. Also it shows appropriate preparation strength. Furthermore, it exhibits excellent manufacturability.

Claims

The scope of the claims
1. a) the active ingredient, b-1) sugar and / or sugar alcohols and c- 1) group 1 and b-2 comprising the cellulose ethers) sugars and Z or sugar alcohol and c one 2) celluloses the result contains a group 2 which comprises, d in the group 1 and / / or group 2) rapidly disintegrating solid preparation comprising a dissolution aid.
2. a) active ingredient, b-1) sugar and / or sugar alcohol, c one 1) cellulose scan acids and d) a group comprising a dissolution auxiliary agent b-2) bran, and / or sugar alcohol and c one 2) rapidly disintegrating 'solid preparation comprising the group comprising the cellulose.
3. a) active ingredient, b-1) sugar and / or sugar alcohols Oyopi c one 1) group and b-2 comprising the cellulose ethers) sugar Contact Yopi Z or sugar alcohol, c one 2 ) comprising a group comprising cellulose ethers and d) eluting aid quickly disintegrating solid formulation.
4. a) active ingredient, b-1) sugar and / or sugar alcohols Oyopi c _ 1) cellulose ethers and the group 1 comprising the b-2) sugar and / or sugar alcohol and c - 2) and also contains a group 2 comprising a cellulose, d in the group 1 and group 2) rapidly disintegrating solid preparation comprising a dissolution aid.
5. The formulation of claim 1 wherein the orally rapidly disintegrating 壌性 solid preparation.
6. The formulation of claim 1 wherein the tablet.
7. the solid preparation 1 00 parts by weight, sugar and / or formulation of claim 1, wherein the sugar alcohol containing 40-9 5 parts by weight.
8. Solid relative preparation 1 00 parts by weight, the formulation of claim 1, wherein you containing from 0.5 to 40 parts by weight of cellulose.
9. The solid preparation 1 00 by weight part, the formulation according to claim 1, further comprising 0.0 to 5 parts by weight of elution auxiliaries.
1 0. sugar Pudou sugar, fructose, lactose, preparation according to claim 1, wherein the one or selected from sucrose and trehalose is 2 or more.
1 1. The formulation of claim 1, wherein the sugar is lactose.
12. sugar Anorekoru is D- mannitol, erythritol tall, xylylene Tonore, one or more in preparation of claim 1 Ki载 is selected from Manore Chitoru and sorbitol.
The formulation of claim 1, wherein 13. sugar alcohol is D- mannitol.
14. sugar or preparation according to claim 1, wherein the average particle size of the sugar alcohol is 30 μ m~ 300 μ m.
1 5. The average particle diameter of D- mannitol 30 μπ! Preparation according to claim 1 3 wherein the ~ 300 At m.
16. celluloses cellulose crystalline, powdered cellulose, preparation according to claim 1, wherein the at least one selected from low substituted hydroxypropyl flop port pills cellulose and carmellose.
1 7. The formulation of claim 1 Symbol placement celluloses are low substituted hydroxypropyl cellulose.
18. Elution adjuvant hydroxycarboxylic cellulose, hydroxycarboxylic propyl methyl cellulose, poly Bulle pyrrolidone, gum arabic powder, gelatin, Mechiruseru port over scan, der one or more selected from polyvinyl alcohol and pullulan the formulation of claim 1, wherein that.
The formulation of claim 1, wherein 19. eluted aid is hydroxypropyl cellulose.
20. The formulation of claim 1, wherein the active ingredient is manidipine hydrochloride.
21. The formulation of claim 1, wherein the active ingredient is Boguriposu.
22. The formulation of claim 1, wherein the active ingredient is a force down de Sultan cilexetil.
23. The formulation of claim 1, wherein the active ingredient is pioglitazone hydrochloride.
The formulation of claim 1, wherein 24. Group 2 further containing the active ingredient.
The formulation of claim 24, wherein the active ingredient and the group 2 is not the same as the active ingredient containing the 25. group 1 contains.
26. Component b-1) and component b-2) and are not the same according to claim 1, wherein the formulation.
27. Component c one 1) to component c one 2) are not the same according to claim 1, wherein the formulation.
28. The formulation of claim 1, wherein containing no crospovidone.
Formulations according to claim 1, further comprising a low-substituted hydroxypropylcellulose to 29. Group 1 and Z or the group 2.
Preparation according to claim 1, wherein 3 is a prophylactic therapeutic agent for 0. hypertension or diabetes.
3 1. a) active ingredient, b-1) sugar and / or sugar alcohol, c _ 1) cell opening over scan acids and d) a group comprising a dissolution auxiliary agent b-2) sugar and Bruno or sugar preparation of the formulation according to claim 2, characterized by compression molding a mixture containing a group comprising one 2) celluloses § alcohol and c.
3 2. a) active ingredient, b-1) sugar and / or sugar alcohols Oyobi c one 1) the group comprising the cellulose ethers and b _ 2) sugar Contact Yopi Z or sugar alcohol, c one 2 ) the preparation of the formulation of claim 3, wherein the compression molding a mixture containing a group comprising cellulose ethers Contact Yopi d) eluting adjuvant.
3 3. for the preparation of a formulation according to claim 2, a) the active ingredient, b-1) sugar and / or sugar alcohol, c one 1) contains cellulose Contact Yopi d) eluting adjuvant that group and b _ 2) sugar Contact Yopi or sugar alcohol and c _ 2) celluloses used in the group consisting having including a.
For the preparation of claim 3, wherein the formulation 34., a) the active ingredient, b _ l) sugar and Z or sugar alcohols and c- 1) group and b-2) sugar comprising a cellulose Oyo Pinomatawa sugar alcohol ,, c _ 2) the use of cellulose Contact Yopi d) eluting capturing aid comprising a containing groups.
3 5. prophylactic treatment method for hypertension or diabetes, which comprises administering an effective amount of the active ingredient with the formulation of claim 1 wherein the mammal.
PCT/JP2002/004641 2001-05-15 2002-05-14 Rapidly disintegratable solid preparation WO2002092058A1 (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003068194A1 (en) * 2002-02-15 2003-08-21 Otsuka Pharmaceutical Co., Ltd. Tablets having improved tabletting characteristics and process for producing the same

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0839526A2 (en) * 1996-10-31 1998-05-06 Takeda Chemical Industries, Ltd. Solid pharmaceutical preparation with fast buccal disintegration or dissolution
WO1998053798A1 (en) * 1997-05-27 1998-12-03 Takeda Chemical Industries, Ltd. Solid pharmaceutical preparation
WO2000006126A1 (en) * 1998-07-28 2000-02-10 Takeda Chemical Industries, Ltd. Rapidly disintegrable solid preparation
JP2000273039A (en) * 1999-01-20 2000-10-03 Taisho Pharmaceut Co Ltd Composition disintegrable in oral cavity
JP2001058944A (en) * 1999-06-18 2001-03-06 Takeda Chem Ind Ltd Rapidly disintegrating solid formulation
JP2001139461A (en) * 1999-11-10 2001-05-22 Ohta Pharmaceut Co Ltd Quickly collapsable tablet
JP2001163770A (en) * 1999-12-08 2001-06-19 Yansen Kyowa Kk Intraorally rapid disintegration tablet and method for producing the same

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* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0839526A2 (en) * 1996-10-31 1998-05-06 Takeda Chemical Industries, Ltd. Solid pharmaceutical preparation with fast buccal disintegration or dissolution
WO1998053798A1 (en) * 1997-05-27 1998-12-03 Takeda Chemical Industries, Ltd. Solid pharmaceutical preparation
WO2000006126A1 (en) * 1998-07-28 2000-02-10 Takeda Chemical Industries, Ltd. Rapidly disintegrable solid preparation
JP2000273039A (en) * 1999-01-20 2000-10-03 Taisho Pharmaceut Co Ltd Composition disintegrable in oral cavity
JP2001058944A (en) * 1999-06-18 2001-03-06 Takeda Chem Ind Ltd Rapidly disintegrating solid formulation
JP2001139461A (en) * 1999-11-10 2001-05-22 Ohta Pharmaceut Co Ltd Quickly collapsable tablet
JP2001163770A (en) * 1999-12-08 2001-06-19 Yansen Kyowa Kk Intraorally rapid disintegration tablet and method for producing the same

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003068194A1 (en) * 2002-02-15 2003-08-21 Otsuka Pharmaceutical Co., Ltd. Tablets having improved tabletting characteristics and process for producing the same

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