CN101420982B - Dry direct compression fast disintegrating tablet - Google Patents
Dry direct compression fast disintegrating tablet Download PDFInfo
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- CN101420982B CN101420982B CN2007800132649A CN200780013264A CN101420982B CN 101420982 B CN101420982 B CN 101420982B CN 2007800132649 A CN2007800132649 A CN 2007800132649A CN 200780013264 A CN200780013264 A CN 200780013264A CN 101420982 B CN101420982 B CN 101420982B
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- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/5415—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with carbocyclic ring systems, e.g. phenothiazine, chlorpromazine, piroxicam
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth 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
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/20—Hypnotics; Sedatives
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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Abstract
It is intended to provide a method capable of producing a desired fast disintegrating tablet with good compression efficiency regardless of the kind of an active ingredient to be contained or the kind of other ingredient to be added and a fast disintegrating tablet obtained by the production method, which is a dry direct compression fast disintegrating tablet obtained by the direct compression of a mixture obtained by mixing a granulated matter obtained by mixing one or more corrigents selected from the group consisting of erythritol, xylitol, mannitol, lactose and sucrose and one or more binder powders selected from the group consisting of crystalline cellulose, crystalline cellulose carmellose sodium and carmellose potassium followed by granulating the mixture using a fluidized bed granulator while spraying an aqueous solution of reduced maltose syrup, an active ingredient, an excipient, a disintegrant, a fluidizer and a lubricant, and particularly, a dry direct compression fast disintegrating tablet containing zolpidem tartrate or meloxicam.
Description
Technical field
The present invention relates to dry direct compression fast disintegrating tablet and preparation method thereof, described method with effective ingredient and other gradation compositions particularly the powder body of particular flavours and special adhesive mix, in the aqueous solution of spraying reduction Fructus Hordei Germinatus sucrose solution maltosemalt sugar, obtain the pelletize thing then.The dry direct compression fast disintegrating tablet that is maintained immediately disintegrable and has practical tablet hardness by this combination.
Background technology
In recent years, in the medical solid preparation, because of being easy to take etc. former thereby the hope exploitation oral cavity quick disintegrating slice constantly strengthens.The condition that requires to possess as the tablet of oral cavity quick disintegrating slice for example has: (1) according to the slaking test method of Japanese Pharmacopoeia at 30 seconds with interior disintegrate; (2) 60 seconds disintegratives in the oral cavity with interior disintegrate; (3) the wear intensity test does not have obviously damaged hardness etc. under 200 commentaries on classics conditions.
As the preparation method of this oral cavity quick disintegrating slice, wet granulation and dry pelletizing method had been proposed in the past.As wet granulation, report (1) is for example arranged by with respect to containing active ingredient and as the ingredient in tablets of the saccharide of excipient, use the moisture of 0.3～7 weight %, make the particle surface of above-mentioned saccharide moistening, the mixture tabletting after drying that will contain above-mentioned active ingredient and saccharide and moisture, the method for preparing the intraoral disintegration type tablet, according to the slaking test method of record in the Japanese Pharmacopoeia the 12nd edition, the disintegration time of described disintegration-type tablet is 0.05～3.0 minute (patent documentation 1).
In addition, as dry pelletizing method, for example proposed not disperse in water before (2) administration and tablet that oral administration is used, the composite material of the micro-crystallization that will be coated in order to cover the sense of taste or the active substance of microparticle form and the mixture that contains excipient is many granules of immediately disintegrable tablet (patent documentation 2) of obtaining of compression directly.In this case, as the mixture that contains above-mentioned excipient, contain be selected from disintegrating agent and starch, producing starch or the microcrystalline Cellulose at least a, contact with water full-bodied at least a extender or at least a solubilizing agent do not take place, tablet for do not contain foaming agent and free organic acid, in the oral cavity saliva in the presence of need not chew, many granules of immediately disintegrable tablet of disintegrate in less than 60 seconds time.
Equally, as the dry type pressed disc method, the granule that for example has report (3) to have the excipient of the saccharide of highly dissoluble and swelling to make by the wet type pelletize to glassware for drinking water carries out oral cavity quick disintegrating slice (patent documentation 3) that tabletting obtains etc. with microcrystalline Cellulose.
In addition, the inventor etc. had also applied for dry direct compression fast disintegrating tablet and preparation method thereof in the past, it is characterized in that: contain (a) effective ingredient; That (b) selects in the group of being made up of the acids that is selected from citric acid, tartaric acid, malic acid, lactic acid and ascorbic acid as cosolvent or its alkali metal salt, alkali metal hydrogencarbonate and alkali carbonate is at least a; Further contain (c) excipient; (d) binding agent; (e) disintegrating agent; (f) fluidizing reagent reaches the lubricant (patent documentation 4) that (g) is made up by magnesium stearate and sucrose fatty acid ester as lubricant.
Patent documentation 1: specially permit communique No. 3069458
Patent documentation 2: specially permit communique No. 2820319
Patent documentation 3: the spy opens the 2000-16930 communique
Patent documentation 4: 2006-17401 number detailed book of special hope
But, these methods in the past, for example, in the wet granulation of above-mentioned (1), need carry out following miscellaneous processing:, use the moisture of 0.3～7 weight % with respect to the ingredient in tablets that contains active ingredient and saccharide, make the particle surface of above-mentioned saccharide moistening, drying.In addition, the dry pelletizing method of above-mentioned (2) need be carried out miscellaneous operation, when active component (effective ingredient) is in the micro-crystallization state that is coated, needs to coat micro-crystallization; When effective composition is in the microparticle state that is not coated, for example need effective ingredient by extruder grain, methods such as processing, air fluid bed are made micro-particles shapes in pot.In addition, have in the dry type pressed disc method of report (3), when granule was mismatched crystalline cellulose outward, the tendency of tabletting obstacle took place in upper punch track value height, existence.In addition, in the dry direct compression fast disintegrating tablet of (4), known particle diameter when the former powder of meloxicam is about 12 μ m when following, and the flowability of melange descends rapidly, and tabletting efficient reduces.
The dry type pressed disc method is with after mixing as compositions such as the medicine of effective ingredient and other excipient, and this mixture direct compression (vertical compression) is formed the method for tablet, is by the easy manufacture method of mixing, the tabletting two procedures just can be made tablet.But, according to the kind of medicine or be mixed into the combination that grades, there is the problem that can not prepare the tablet of wishing to get in direct pressure closing.
For example, when the flowability of the powder mixture of the composition of medicine and interpolation is low, observe that powder mixture can not flow out from the hopper of tablet machine and can't tabletting or the top split (capping) and cause that yield descends, the deviation of weight of tablet significantly becomes big.In addition, if improve the disintegrative of tablet, then there is problems such as to keep tablet hardness.
In fact, the inventor etc. find in inquiring into the process of using effective ingredient Zolpidemtar Trate or meloxicam to prepare fast disintegrating tablet by direct compression process: according to the combination of blending constituent, the flowability of the powder mixture before the tabletting descends and causes that tabletting efficient reduces, and the particle diameter of Zolpidemtar Trate or meloxicam is more little, Zolpidemtar Trate or the meloxicam dissolution rate from the tablet that obtains accelerates, but tabletting obstacles such as sticking take place easily.
Summary of the invention
Therefore, problem of the present invention provides the method for the fast disintegrating tablet of preparation, when described method prepares fast disintegrating tablet by direct compression process, no matter no matter the kind of the kind of the effective ingredient that contains, other compositions of also cooperating, all can prepare the fast disintegrating tablet of wishing to get, and the fast disintegrating tablet that obtains by this preparation method is provided with good tabletting efficient.
In order to solve above-mentioned problem; the result that the inventor etc. further investigate considers: if in each composition that adds; the composition that reduces by the flowability that will cause powder mixture before the tabletting in advance carries out granulating; make it have flowability; the outflow of powder mixture from the hopper of tablet machine improved; can prevent to push up and split generation; and the deviation of weight of tablet is diminished; and in the disintegrative that keeps tablet, can prepare fast disintegrating tablet with practical tablet hardness.
On the basis of this idea, inquire into; found that: cause that especially the mobile composition that reduces of mixed powder thing is confirmed to be the erythritol that cooperates as correctives, xylitol, mannitol etc.; with these compositions with binding agent for example crystalline cellulose carry out granulating; the composite mixed powder thing of this pelletize thing and effective ingredient and other gradation compositions; its good fluidity; can address the above problem quickly, thereby finish the present invention.
So, as a grown form of the present invention, the described invention of claim 1 is a dry direct compression fast disintegrating tablet, it is characterized in that: described dry direct compression fast disintegrating tablet uses more than one the correctives that will be selected from the group that erythritol, xylitol, mannitol, lactose, sucrose form to mix with more than one the powder body of binding agent in being selected from the group that crystalline cellulose, crystalline cellulose-sodium carboxymethyl cellulose, carboxymethyl cellulose potassium form, sprays to reduce the pelletize thing that the aqueous solution of Fructus Hordei Germinatus sucrose solution maltosemalt sugar obtains.
More specifically, the described the present invention of claim 2 is a dry direct compression fast disintegrating tablet, wherein, in the described invention of claim 1, uses fluidized bed pelletizer to carry out pelletize.
Therefore, another grown form of the present invention is a dry direct compression fast disintegrating tablet, it is characterized in that: the above-mentioned pelletize thing that obtains is mixed with effective ingredient, excipient, disintegrating agent, fluidizing reagent, lubricant and coloring agent, with the mixture direct compression that obtains.
The most concrete the present invention is to use Zolpidemtar Trate or the meloxicam above-mentioned dry direct compression fast disintegrating tablet as effective ingredient.
Further; as another form of the present invention; the described invention of claim 5 is the preparation method of dry direct compression fast disintegrating tablet; it is characterized in that: by being selected from erythritol; xylitol; mannitol; lactose; the correctives of more than one in the group that sucrose is formed be selected from crystalline cellulose; crystalline cellulose-sodium carboxymethyl cellulose; the powder body of the binding agent of more than one in the group that carboxymethyl cellulose potassium is formed mixes; in the aqueous solution of spraying reduction Fructus Hordei Germinatus sucrose solution maltosemalt sugar; use fluidized bed pelletizer to carry out pelletize; with pelletize thing and the effective ingredient that obtains; excipient; disintegrating agent; fluidizing reagent; lubricant and coloring agent mix, with this mixture direct compression.In addition, the most particularly, the described invention of claim 6 is to use Zolpidemtar Trate or the meloxicam preparation method as the above-mentioned dry direct compression fast disintegrating tablet of effective ingredient.
According to the present invention, for the powder mixture that contains the effective ingredient before the direct compression, its good fluidity, therefore, can provide the outflow of mixed powder thing from the hopper of tablet machine good, can prevent to push up and split generation, as a result of make tablet almost not have the fast disintegrating tablet of deviation of weight and adopt the preparation method of the fast disintegrating tablet of dry direct compression method.
In addition, the fast disintegrating tablet that obtains according to the present invention has desirable disintegration rate, and has practical tablet hardness, and its preparation method is inexpensive easy again.Therefore, for various effective ingredient, has the advantage that to make the fast disintegrating tablet of wishing to get.
The specific embodiment
As mentioned above; of the present invention be by causing that in advance the mobile composition that reduces of mixed powder thing before the direct compression carries out granulating at all; make it have flowability; use this pelletize thing to mix with effective ingredient and other compositions; this mixed powder thing direct compression with obtaining obtains described direct compression fast disintegrating tablet.
According to the inventor's etc. research, distinguish that the composition that the flowability that makes the mixed powder before the direct compression reduces is the composition that cooperates as correctives.
This correctives has erythritol, xylitol, mannitol, lactose, sucrose.
In addition, this correctives is the composition that uses as excipient on the other hand, and when adding as excipient, also preferably for example effective ingredient or binding agent etc. carry out pelletize in advance with these compositions and other compositions.
About the present invention, make the mobile correctives that reduces carry out granulating (pelletize) with this in advance, improve its flowability, when carrying out granulating, preferably carry out granulating with binding agent.
As this binding agent, crystalline cellulose, crystalline cellulose-sodium carboxymethyl cellulose, carboxymethyl cellulose potassium etc. are for example arranged.Wherein, especially preferably use crystalline cellulose.As this crystalline cellulose, Ceolus PH-101, Ceolus PH-302 (Asahi Chemical Corp's manufacturing) are for example arranged.
The use level of the binding agent that uses is a benchmark with the weight of final tablet, is 5～20 weight %, is preferably about 10 weight %.
Among the present invention, preferred especially by in the aqueous solution of spraying reduction Fructus Hordei Germinatus sucrose solution maltosemalt sugar, above-mentioned correctives and binding agent pelletize are carried out granulating.
The reduction Fructus Hordei Germinatus sucrose solution maltosemalt sugar that uses is that starch based is added in the water as powder reduction Fructus Hordei Germinatus sucrose solution maltosemalt sugar, reduction Fructus Hordei Germinatus sucrose solution maltosemalt sugar (another name maltose alcohol), and heating, gelatinizing add amylase, hydrolysis, the reduction of refining back, and re-refining to concentrate obtains.Odorless, it is sweet to distinguish the flavor of, and is widely used as the additive composition of various preparations at present as sweeting agent, base, correctives etc.
Among the present invention, this reduction Fructus Hordei Germinatus sucrose solution maltosemalt sugar uses with excipient as the liquor that uses when making the pelletize thing of above-mentioned correctives and binding agent.
Among the present invention; the powder body of correctives and binding agent is mixed; spraying is carried out pelletize as the aqueous solution of the reduction Fructus Hordei Germinatus sucrose solution maltosemalt sugar of excipient the time, and this pelletize for example can use fluidized bed pelletizer to carry out, and its pelletize itself also can be carried out with other original known methods.
As grown form, the present invention is a dry direct compression fast disintegrating tablet, it is characterized in that: with the correctives of binding agent with the composition that causes the mobile reduction of powder mixture, use the aqueous solution of specific reduction Fructus Hordei Germinatus sucrose solution maltosemalt sugar as excipient to carry out pelletize, improve its flowability, then with this pelletize thing and effective ingredient, excipient, disintegrating agent, fluidizing reagent and mix lubricant, with the mixture direct compression that obtains.
Can obtain having the dry direct compression fast disintegrating tablet of desirable collapsing property of speed and appropriate hardness in view of the above.
The active ingredient that uses in this case dry direct compression fast disintegrating tablet of the present invention is not particularly limited.Antimicrobial drug is for example arranged, antitubercular agent, antifungal agent, antiviral agent, anticarcinogen, vitamin agent, interenin, antiallergic agent, non-steroid antiinflammatory drug, anesthetics, the migraine medication, Rezulin, remedy for hyperlipemia, gout and hyperuricemia medication, the dysbolism medication, the sedative hypnotic, antianxiety drugs, antuepileptic, antidepressants, psychosis, the direct stimulation medicine, cardiac tonic, the beta receptor blocker, calcium-channel antagonists, anti-arrhythmic, diuretic, depressor, pressor agent, cerebral circulation and dysbolismus medication, cough medicine, expectorant, bronchodilator, the bronchial asthma medication, breathe and promote medicine, stomachic and digestant, the gastritis medication, Bendectin, the peptic ulcer medicine, diarrhea-drug for controlling intestinal function-intestinal tract disease medication, cathartic (cathartic), choleretic, parkinson disease (syndrome) medication, bone metabolism disease and osteoporosis agent (bone resorption depressant) and rheumatism and arthrosis medication (antirheumatic) etc.
As antibiotic, cefalexin is for example arranged, cefaclor, the amoxicillin, the hydrochloric acid pivmecillinam, the cefotiam hydrochloride ester, cefadroxil, cefixime, Cefditoren pivoxil Cephalosporins, cefteram pivoxil, Cefpodoxime Proxetil, cefotiam hydrochloride, cefozopran hydrochloride, Abbott 50192, cephalosporins such as cefsulodine sodium (cephem) class, the ampicillin, the ciclacillin, sulbenicillin disodium, nalidixan, synthetic antibacterial agents such as enoxacin, monocycle beta-lactams such as carumonam sodium (monobactam) class, penems and carbapenem antibiotic, paromomycin sulfate, the amoxicillin, cefaclor, cefalexin, acetylspiramycin, minocycline hydrochloride.
As antitubercular agent, isoniazid, ebutol etc. are for example arranged.
As antifungal agent, miconazole, terbinafine HCl etc. are for example arranged.
In addition, as antiviral agent, lamivudine, ribavirin, acyclovir etc. are for example arranged.
As anticarcinogen, for example there are 5-fluorouracil, uracil, mitomycin, carmofur, aclarubicin hydrochloride, cyclophosphamide, plug to replace group etc.
As the vitamin medicine, thiamine hydrochloride, thiamine mononitrate, tocopheryl acetate, cycotiamine, pyridoxal 5-phosphate, cobamamide, ascorbic acid, nicotiamide, alfacalcidol, cobamamide (Cobamyde), Vitaroxin, Riboflavin Tetrabutyrate, ascorbic acid etc. are for example arranged.
As interenin, prednisolone, triamcinolone, betamethasone etc. are for example arranged.
As antiallergic agent, diphhydramine hydrochloride, diphenhydramine tannate, triprolidine hydrochloride, promethazine hydrochloride, alimemazine tartrate, mequitazine, tea chloric acid diphenylpyraline (diphenylpyraline teoclate), d-chlorphenamine maleate, cyproheptadine hydrochloride, clemastine fumarate, ketotifen fumarate, hydrochloric acid nitrogen are for example arranged
Si Ting, oxatomide, fumaric acid emedastine, ebastine, cetirizine hydrochloride, fexofenadine hydrochloride, loratadine, Olopatadine hydrochloride, tranilast, ammonia come cluck promise, tazanolast, pranlukast hydrate, ozagrel hydrochloride etc.
As non-steroid antiinflammatory drug, aspirin, mefenamic acid, tolfenamic acid, indometacin, Indomethacin Farnesil, acemetacin, diclofenac, diclofenac sodium, amfenac sodium, etodolac, mofezolac, sulindac, nabumetone, ibuprofen, ketoprofen, loxoprofen sodium, piroxicam, ampiroxicam, meloxicam etc. are for example arranged.
As anesthetics, morphine hydrochloride, oxycodone hydrochloride, ***e hydrochloride etc. are for example arranged.
As the migraine medication, gynergen, Sumatriptan Succinate, Zomitriptan, lomerizine hydrochloride, dimetotiazine mesilate (dimetotiazine mesilate), caffeine etc. are for example arranged.
As the diabetes medication, tolbutamide, acetohexamide, chlorpropamide, glyclopyramide, glybuzole, glibenclamide, glimepiride, hydrochloric acid buformin, metformin hydrochloride, Nateglinide, acarbose, voglibose, pioglitazone hydrochloride, epalrestat etc. are for example arranged.
As remedy for hyperlipemia, pravastatin sodium, simvastatin, lovastatin, fluvastatin, atorvastatin etc. are for example arranged.
As gout therapertics, allopurinol, colchicine, benzbromarone, probenecid etc. are for example arranged.
As the sedative hypnotic, triazolam, midazolam, brotizolam, hydrochloric acid rilmazafone, lormetazepam, nimetazepam, flunitrazepam, estazolam, nitrazepam, Zolpidemtar Trate, zopiclone etc. are for example arranged.
As antianxiety drugs, flutazolam, clotiazepam, etizolam, alprazolam, lorazepam, bromazepam etc. are for example arranged.
As antuepileptic, phenytoin, ethotoin, primidone, sodium valproate, carbamazepine, clonazepam, ethosuximide, trimethadione, easypro thiazine, N-(.alpha.-ethylphenylacetyl)-N'-acetylurea etc. are for example arranged.
As antidepressants, imipramine hydrochloride, amitriptyline hydrochloride, Clomipramine Hydrochloride, psychostyl, lofepramine hydrochloride, Altapin (Marion), amoxapine, aueural, mianserin hydrochloride, trazodone hydrochloride, fluvoxamine maleate, milnacipran hydrochloride etc. are for example arranged.
As psychosis, chlorpromazine, Thioridazine Hydrochloride, periciazine, fluphenazine, Clocapramine Dihydrochloride, Tiapride Hydrchloride etc. are for example arranged.
As the direct stimulation medicine, methylphenidate hydrochloride, pemoline etc. are for example arranged.
As cardiac tonic, amrinone, Olprinone HCl, pimobendan etc. are for example arranged.
As the beta receptor blocker, labetalol hydrochloride, carvedilol, YM-09538, Arotinolol Hydrochlorid, bevantolol hydrochloride, pindolol, carteolol hydrochloride, Y-6124, propranolol hydrochloride, nadolol, Nip Luo Er, Amiodarone Hydrochloride, betaxolol hydrochloride etc. are for example arranged.
As calcium-channel antagonists, verapamil hydrochloride, diltiazem hydrochloride are for example arranged
, nifedipine, Licardipine Hydrochloride, nilvadipine, CV-4093, bepridil hydrochloride etc.
As anti-arrhythmic, Procainamide Sulphate, disopyramide phosphate etc. are for example arranged.
As diuretic, chlortalidone, tripamide etc. are for example arranged.
As depressor, minipress, E-643, terazosin hydrochloride, urapidil, cadralazine etc. are for example arranged.
As pressor agent, captopril, alacepril, lisinopril, hydrochloric acid imidapril, enalapril maleate, quinapril hydrochloride, cilazapril, delapril hydrochloride, temocapril hydrochloride, benazepril hydrochloride etc. are for example arranged.
As the brain circulatory disturbance medication, nicergoline, Ifenprodil Tartrate, Fasudic hydrochloride, sodium ozagrel etc. are for example arranged.
As cough medicine, dextromethorphan hydrobromide, cloperastine, Fominoben Hydrochloride etc. are for example arranged.
As expectorant, Bisolvon, ambroxol hydrochloride etc. are for example arranged.
As bronchodilator, ephedrine hydrochloride, salbutamol sulfate, terbutaline sulphate, Procaterol Hydrochloride etc. are for example arranged.
As the bronchial asthma medication, beclometasone, fluticasone propionate, budesonide etc. are for example arranged.
Promote medicine as breathing, dimorpholamine, doxapram hydrochloride etc. are for example arranged.
As the digestive tract medication, famotidine, ranitidine hydrochloride, cimetidine, sucralfate, sulpiride, teprenone, plaunotol, 5-aminosalicylic acid, sulfasalazine, omeprazole, lansoprazole etc. are for example arranged.
As the gastritis medication, metoclopramide, domperidone, hydrochloric acid itopride, mosapride citrate, Trimebutine Maleate, Azasetron hydrochloride, Ondansetron Hydrochloride, Granisetron Hydrochloride, Navoban (Soz), Ramosetron HCl etc. are for example arranged.
As Bendectin, metoclopramide, Ramosetron HCl, Granisetron Hydrochloride, Ondansetron Hydrochloride, Azasetron hydrochloride etc. are for example arranged.
As the peptic ulcer medicine, omeprazole, RABEPRAZOLE SODIUM, lansoprazole, cimetidine, nizatidine, famotidine, ranitidine hydrochloride, hydrochloric acid roxatidine acetate, sucralfate etc. are for example arranged.
As diarrhea-drug for controlling intestinal function-intestinal tract disease medication, loperamide hydrochloride, mesalazine, betamethasone etc. are for example arranged.
As cathartic (cathartic), bisacodyl etc. is for example arranged.
As choleretic, dehydrocholic acid, trepibutone etc. are for example arranged.
As the parkinson disease medication, levodopa, lepodopa, amantadine hydrochloride, benzhexol hydrochloride, pyrrolidine hydrochloride spit of fland in heptan etc. are for example arranged.
As the osteoporosis agent, ipriflavone etc. is for example arranged.
As antirheumatic, methotrexate, bucillamine, actarit etc. are for example arranged.
Below for example with Zolpidemtar Trate or meloxicam be effective ingredient as typical example, dry direct compression fast disintegrating tablet of the present invention is elaborated.
Zolpidemtar Trate is a white crystalline powder, odorless, bitter in the mouth, slightly water-soluble or ethanol (95%).This medicine has the character because of light slowly painted (yellow), is used for the treatment of insomnia (except the insomnia of integration dysfunction syndrome and manic-depressive psychosis) clinically.As dosage, usually, in Zolpidemtar Trate, the 5～10mg that is grown up 1 time, per os hora somni.In addition, elderly patient can suitably increase and decrease according to age, symptom, disease since 1 5mg administration, but should not surpass 10mg on the 1st.
The particle diameter of the Zolpidemtar Trate crude drug that dry direct compression fast disintegrating tablet of the present invention uses is more little, its difficult treatment, but stripping accelerates.Therefore, consider to improve the dissolubility when making tablet, can use the crude drug of appropriate particle size, preferred mean diameter is below the 100 μ m.
In addition, meloxicam is to be used for the treatment of rheumatic arthropathy, arthronosos deformans, lumbago disease, scapulohumeral periarthritis, the syndromic non-steroidal anti-inflammatory analgesics of neck shoulder wrist, and clinical consumption is oral 1 time 10mg/ days.
The particle diameter of the meloxicam crude drug that dry direct compression fast disintegrating tablet of the present invention uses is more little, its difficult treatment, but stripping accelerates.Therefore, consider to improve the dissolubility when making tablet, can use the crude drug of appropriate particle size, preferred mean diameter is below the 11 μ m, and being more preferably mean diameter is 1～11 μ m, and preferred especially mean diameter is 6～11 μ m.
Is the excipient that the medicine of typical example uses with this with Zolpidemtar Trate or meloxicam, and saccharides such as lactose, erythritol, D-mannitol, xylitol, maltose alcohol, hydroxypropyl starch sodium, crystalline cellulose, hydroxypropyl starch, calcium phosphate dibasic anhydrous, synthetic aluminium silicate, reduction Fructus Hordei Germinatus sucrose solution maltosemalt sugar etc. are for example arranged.
The excipient that cooperates is a benchmark with the weight of final tablet, is 20～70 weight %, is preferably 30～70 weight %, is more preferably about 60 weight %.
As disintegrating agent, for example can be selected from the group that polyvinylpolypyrrolidone, carboxymethyl cellulose, carboxymethylcellulose calcium, carboxymethyl starch sodium form more than one.Preferably with polyvinylpolypyrrolidone and carboxymethyl cellulose and usefulness.
The use level of disintegrating agent is a benchmark with the weight of final tablet, is 5～20 weight %, is preferably about 15 weight %.
As fluidizing reagent, for example there is light silicon dioxide (silicon dioxide) etc. silica-based.For example preferred Adsolider-101 (trade name, Freund industry (Co., Ltd.) is made).The use level of fluidizing reagent is a benchmark with the weight of final tablet, is 0.5～3 weight %, is preferably about 0.5～1.5 weight %.
In fast disintegrating tablet provided by the invention, as lubricant, magnesium stearate and sucrose fatty acid ester are arranged, and for example (use sucrose behenic acid ester as lubricant, it is broken and obtain that B-370 is carried out micropowder for sugar ester B-370F (Sugar Ester B-370F) or Surfhope J-2203F; Mitsubishi Chemical's food (Co., Ltd.) is made), preferably both also use.
The match ratio of magnesium stearate and sucrose fatty acid ester is about 1: 1～3 by weight, be preferably 1: 1～and about 2.
In addition, the use level of lubricant is a benchmark with the weight of final tablet, is 1.0～3 weight %, is preferably about 1.0～2.0 weight %.
In addition, when effective composition has bitterness,, can cooperate the odor mask of covering this bitterness according to well-established law.This odor mask for example has aspartame, Suo Matian sweeting agents such as (thaumatin) or 1-menthol, Rhizoma et radix valerianae powdered flavor (spice such as De ラ イ コ-ト), nigecose essence, Herba Menthae powdered flavor, grapefruit powdered flavor.Preferred aspartame.
The use level of these odor masks, according to the effective ingredient that contains, its consumption can suitably increase and decrease.
As coloring agent, yellow iron sesquioxide, iron sesquioxide, Black Rouge (or iron oxides), aluminum chelating agent are for example arranged.
Dry direct compression fast disintegrating tablet provided by the invention for example can be made by the preparation method of utilizing following technology.
This method roughly is made up of three process: at first make first operation of the pelletize thing comprise correctives and binding agent, with blended second operation of each composition, be the 3rd operation of carrying out tabletting then, each operation self can be carried out according to well-established law, is easy and efficient tablet manufacture method.
Its detailed process is as follows:
[first operation]
Make the aqueous solution of excipient (for example powder reduction Fructus Hordei Germinatus sucrose solution maltosemalt sugar) in advance, correctives (for example erythritol) is mixed with binding agent (for example crystalline cellulose), use the fluidized bed pelletizer pelletize, obtain the pelletize thing.Concentration of aqueous solution to above-mentioned excipient has no particular limits, and is preferred 10～20% according to the kind of the kind of the correctives that uses, consumption etc. or the binding agent that uses, consumption etc. and different, is more preferably about 15%.
Match ratio to excipient and binding agent is not particularly limited, and preferably for the correctives of per 1 part of weight, the amount of binding agent is 0.15～3.2 part a scope.The amount of binding agent for a long time, the mobile improvement, but disintegrative reduces.In addition, big if the match ratio of correctives becomes, the mobile tendency that reduces then appears.
[second operation]
To mix with effective ingredient (for example Zolpidemtar Trate or meloxicam), excipient (for example lactose), disintegrating agent (for example polyvinylpolypyrrolidone, carboxymethyl cellulose), fluidizing reagent (for example light silicon dioxide), lubricant (for example magnesium stearate, sucrose fatty acid ester), spice (for example 1-menthol), coloring agent (for example yellow iron sesquioxide, aluminum chelating agent) by the pelletize thing that above-mentioned first operation obtains, obtain powder mixture.
The mixing of this second operation can according to well-established law, for example be used mixer (trade name: BOHLE container mixer (BOHLE Container Mixer) with each composition, the effective ingredient of ormal weight; コ ト Block キ skill is ground industry (strain) manufacturing) mix.Incorporation time is not particularly limited according to the kind of the additive that uses, consumption etc. and different, preferred 5～40 minutes, is more preferably 5～30 minutes.
In addition, about lubricant, also can add in the said mixture afterwards and mix.At this moment incorporation time be so long as can make the well-mixed time of lubricant get final product, and because of consumption of said mixture etc. is subjected to special qualification, is not generally 2～10 minutes, preferred 2～4 minutes.
[the 3rd operation]
The powder mixture that above-mentioned second operation of use by such manufacturing obtains, by direct compression, the of the present invention fast disintegrating tablet that can obtain wishing to get.
The spice that fast disintegrating tablet provided by the invention uses can add in arbitrary operation of above-mentioned first operation to the second operation, preferably adds in second operation.
In addition, as requested, can also add normally used sweeting agent, cosolvents (for example sodium citrate, sodium bicarbonate) such as aspartame in the tablet of the present invention, can in arbitrary operation of above-mentioned first operation to the second operation, add.
In view of the above, the present invention can provide the dry direct compression fast disintegrating tablet of wishing to get, and the tablet that obtains keeps desirable collapsing property of speed, and has practical tablet hardness.
In addition, the form as tablet is not particularly limited, and according to well-established law, for example can make the circular plain sheet constant speed disintegrating tablet of hemocyte shape that has desirable diameter, has secant easily.
Embodiment
Enumerate embodiment below the present invention is specifically described, but these embodiment do not limit the present invention.
Embodiment 1～8
According to the cooperation of following table 1 record (use level: g), carry out the hardness that tablet is wished to get in pelletize, mixing, setting,, obtain containing the fast disintegrating tablet of Zolpidemtar Trate by powder mixture is carried out tabletting according to above-mentioned each operation.
For the tablet that obtains, measure hardness, the mensuration of tablet and test the wear intensity (%) under 200 commentaries on classics conditions according to disintegration time (second), the mensuration wear intensity of Japanese Pharmacopoeia slaking test method.
In addition, measure intraoral disintegration time (second).
Its result is shown in table 1 in the lump.
[table 1]
The preparation manipulation of representational tablet is for example shown in the cooperation prescription of embodiment 6.
[operation 1]
Mixed powder with erythritol (grind correctives, micropowder, day and change into (Co., Ltd.) manufacturing) 95.0g, crystalline cellulose (binding agent, Ceolus PH-101, Asahi Chemical Corp make) 30.0g uses fluidized bed pelletizer (trade name MP-01; Powrex (Co., Ltd.) makes), use in advance powder reduction Fructus Hordei Germinatus sucrose solution maltosemalt sugar (excipient, maltose alcohol (amalty), east and change into industry (Co., Ltd.) manufacturing) to be dissolved in 15% aqueous solution that pure water obtains to carry out pelletize, obtain the pelletize thing.
The assay value of the pelletize thing that obtains by above-mentioned method for making is as follows.
Angle of repose (°) 51.5; Specific volume (loose) 2.45mL/g; Specific volume (jolt ramming) 2.27mL/g; Moisture (%) 0.6; Mean diameter (μ m) 88.75.
[operation 2]
Add above-mentioned pelletize thing and Zolpidemtar Trate (effective ingredient) 5.0g, lactose (excipient) 105.3g, polyvinylpolypyrrolidone (disintegrating agent, polyvinylpolypyrrolidone XL, ISP makes) 33.0g, carboxymethyl cellulose (disintegrating agent, NS-300, five moral medicines (Co., Ltd.) are made) 12.0g, light silicon dioxide (fluidizing reagent, Freund industry (Co., Ltd.) is made) 3.90g, magnesium stearate (lubricant) 1.50g, sucrose fatty acid ester (lubricant, sugar ester B-370F, Mitsubishi Chemical's food (Co., Ltd.) is made) 3.0g, aspartame (sweeting agent, aspartame, aginomoto (Co., Ltd.)) 6.00g, 1-menthol (spice, Kei Kobayashi (Co., Ltd.) is made) 0.15g, yellow iron sesquioxide (coloring agent, certain herbaceous plants with big flowers changes into (Co., Ltd.) the sixth of the twelve Earthly Branches and makes) 0.15g, mixed 3 minutes.
The assay value of the powder mixture that obtains by above-mentioned mixing method is as follows.
Angle of repose (°) 39.0; Specific volume (loose) 2.45mL/g; Specific volume (jolt ramming) 1.86mL/g; Compression ratio (%) 24.1; Moisture (%) 0.8.
[operation 3]
The powder mixture that use obtains by above-mentioned operation 2 is set hardness 5Kp and is carried out tabletting, obtains dry direct compression fast disintegrating tablet (the 300mg sheet that contains the 5mg effective ingredient).
In the various embodiments described above, add the tablet of making as the 1-menthol of spice, bitterness beastly obtains relaxing.
The diameter of tablet can be selected the size that is suitable for taking, is generally about 5mm～about 20mm, is preferably about 7mm～about 15mm.
Embodiment 9
Mixed powder with erythritol (grind correctives, micropowder, day and change into (Co., Ltd.) manufacturing) 107.5g, crystalline cellulose (binding agent, Ceolus PH-101, Asahi Chemical Corp make) 17.5g uses fluidized bed pelletizer (trade name MP-01; Powrex (Co., Ltd.) makes), use in advance powder reduction Fructus Hordei Germinatus sucrose solution maltosemalt sugar (excipient, maltose alcohol, east and change into industry (Co., Ltd.) manufacturing) to be dissolved in 15% aqueous solution that pure water obtains to carry out pelletize, obtain the pelletize thing.
The above-mentioned pelletize thing that obtains shows the identical character of pelletize thing that obtains with operation 1 by embodiment 1.
Embodiment 10
Mixed powder with erythritol (grind correctives, micropowder, day and change into (Co., Ltd.) manufacturing) 30.0g, crystalline cellulose (binding agent, Ceolus PH-101, Asahi Chemical Corp make) 95.0g uses fluidized bed pelletizer (trade name MP-01; Powrex (Co., Ltd.) makes), use in advance powder reduction Fructus Hordei Germinatus sucrose solution maltosemalt sugar (excipient, maltose alcohol, east and change into industry (Co., Ltd.) manufacturing) to be dissolved in 15% aqueous solution that pure water obtains to carry out pelletize, obtain the pelletize thing.
The above-mentioned pelletize thing that obtains shows the identical physics value of pelletize thing that obtains with operation 1 by embodiment 1.
Comparative example 1
According to well-established law following each composition is mixed, make dry direct compression fast disintegrating tablet by direct compression.
The analysis of experiments value of the mixture of above-mentioned each gradation composition (moisture, specific volume, angle of repose) is as follows.
Angle of repose (°) 39.5 °; Specific volume (loose) 2.03mL/g; Specific volume (jolt ramming) 1.47mL/g; Compression ratio (%) 27.6; Ka Er index (Carr index) (%) 38.1; Moisture (%) 1.0.
The poor flow quality of the mixture that the result obtains, tabletting efficient reduces.
Comparative example 2
In the facture of above-mentioned comparative example 1, lubricant (sucrose fatty acid ester and magnesium stearate) changes Talcum (lubricant and fluidizing reagent) into, makes mixture, attempts tabletting.
The analysis of experiments value of the mixture of above-mentioned each gradation composition (moisture, specific volume, angle of repose) is as follows.
Angle of repose (°) 45.5 °; Specific volume (loose) 1.94mL/g; Specific volume (jolt ramming) 1.36mL/g; Compression ratio (%) 29.9; Ka Er index (%) 42.6; Moisture (%) 0.8.
The poor flow quality of the mixture that the result obtains, tabletting efficient reduces.
Embodiment 11～19
According to the cooperation of following table 2 record (use level: g), carry out the hardness that tablet is wished to get in pelletize, mixing, setting,, obtain containing the fast disintegrating tablet of meloxicam by powder mixture is carried out tabletting according to above-mentioned each operation.
For the tablet that obtains, measure hardness, the mensuration of tablet and test the wear intensity under 200 commentaries on classics conditions according to disintegration time (second), the mensuration wear intensity of Japanese Pharmacopoeia slaking test method.
In addition, measure intraoral disintegration time (second).
Its result is shown in table 2 in the lump.
The preparation manipulation method of representational tablet is shown in the cooperation prescription of embodiment 18.
[operation 1]
Mixed powder with erythritol (grind correctives, micropowder, day and change into (Co., Ltd.) manufacturing) 95.0g, crystalline cellulose (binding agent, Ceolus PH-101, Asahi Chemical Corp make) 30.0g uses fluidized bed pelletizer (trade name MP-01; Powrex (Co., Ltd.) makes), use in advance powder reduction Fructus Hordei Germinatus sucrose solution maltosemalt sugar (excipient, maltose alcohol, east and change into industry (Co., Ltd.) manufacturing) to be dissolved in 15% aqueous solution that pure water obtains to carry out pelletize, obtain the pelletize thing.
The assay value of the pelletize thing that obtains by above-mentioned method for making is as follows.
Angle of repose (°) 51.5; Specific volume (loose) 2.45mL/g; Specific volume (jolt ramming) 2.27mL/g; Moisture (%) 0.6; Mean diameter (μ m) 88.75.
[operation 2]
Add above-mentioned pelletize thing and meloxicam (effective ingredient, the about 8 μ m of particle diameter) 13.33g, lactose (excipient) 161.64g, polyvinylpolypyrrolidone (disintegrating agent, polyvinylpolypyrrolidone XL, ISP makes) 75.00g, sodium citrate (cosolvent, Xiao Song room chemistry (Co., Ltd.) is made), sodium bicarbonate (cosolvent, Asahi Chemical Corp makes), light silicon dioxide (fluidizing reagent, Freund industry (Co., Ltd.) is made) 6.51g, magnesium stearate (lubricant) 3.51g, sucrose fatty acid ester (lubricant, Surfhope J2203-F, Mitsubishi Chemical's food (Co., Ltd.) is made) 5.00g, aspartame (sweeting agent, aspartame, aginomoto (Co., Ltd.)) 15.00g, 1-menthol (spice, Kei Kobayashi (Co., Ltd.) is made) 0.25g, iron sesquioxide (coloring agent, certain herbaceous plants with big flowers changes into (Co., Ltd.) the sixth of the twelve Earthly Branches and makes) 0.51g, mixed 30 minutes.
The assay value of the powder mixture that obtains by above-mentioned mixing method is as follows.
Angle of repose (°) 37.5; Specific volume (loose) 2.01mL/g; Specific volume (jolt ramming) 1.61mL/g; Compression ratio (%) 24.96; Moisture (%) 0.8.
[operation 3]
The powder mixture that use obtains by above-mentioned operation 2 is set hardness 4Kp and is carried out tabletting, obtains dry direct compression fast disintegrating tablet (the 375mg sheet that contains the 10mg effective ingredient).
In the various embodiments described above, add the tablet of making as the 1-menthol of spice, bitterness beastly obtains relaxing.
The diameter of tablet can be selected the size that is suitable for taking, is generally about 5mm～about 20mm, is preferably about 7mm～about 15mm.
Comparative example 3
According to well-established law following each composition is mixed, attempt making dry direct compression fast disintegrating tablet by direct compression.
The analysis of experiments value of the mixture of above-mentioned each gradation composition (moisture, specific volume, angle of repose) is as follows.
Angle of repose (°) 39.5 °; Specific volume (loose) 1.83mL/g; Specific volume (jolt ramming) 1.37mL/g; Ka Er index (%) 33.85; Moisture (%) 0.8.
The poor flow quality of the mixture that the result obtains, tabletting efficient reduces.
Comparative example 4
According to well-established law following each composition is mixed, attempt making dry direct compression fast disintegrating tablet by direct compression.Be that employed meloxicam has carried out surface modification with light silicon dioxide in advance.
The analysis of experiments value of the mixture of above-mentioned each gradation composition (moisture, specific volume, angle of repose) is as follows.
Angle of repose (°) 40.0 °; Specific volume (loose) 1.80mL/g; Specific volume (jolt ramming) 1.34mL/g; Ka Er index (%) 34.61; Moisture (%) 0.8.
The poor flow quality of the mixture that the result obtains, tabletting efficient reduces.
From the result shown in above each table as can be known, dry direct compression fast disintegrating tablet of the present invention has good hardness, and good in intraoral disintegrative.
In addition, the foregoing description is represented is to use Zolpidemtar Trate or the meloxicam object lesson as effective ingredient, and other effective ingredient also can prepare direct compression fast disintegrating tablet equally certainly.
Industrial applicibility
As mentioned above, according to the present invention, the dry direct compression fast disintegrating tablet that keeps immediately disintegrable and have practical tablet hardness can be provided, particularly contain the direct compression fast disintegrating tablet of Zolpidemtar Trate or meloxicam, because its dissolving out capability is also good, so medical value is very big.
Claims (17)
1. dry direct compression fast disintegrating tablet, it is characterized in that: described dry direct compression fast disintegrating tablet obtains by following step: will be selected from erythritol, xylitol, mannitol, lactose, the correctives of more than one in the group that sucrose is formed be selected from crystalline cellulose, crystalline cellulose-sodium carboxymethyl cellulose, the powder body of the binding agent of more than one in the group that carboxymethyl cellulose potassium is formed mixes, the pelletize thing that the aqueous solution of spraying reduction Fructus Hordei Germinatus sucrose solution maltosemalt sugar obtains, with gained pelletize thing and effective ingredient, excipient, disintegrating agent, fluidizing reagent and mix lubricant are with the mixture direct compression that obtains; For the correctives of per 1 part of weight, the amount of binding agent is 0.15～3.2 part a scope.
2. dry direct compression fast disintegrating tablet as claimed in claim 1 wherein, carries out pelletize with fluidized bed pelletizer.
3. dry direct compression fast disintegrating tablet as claimed in claim 1 or 2, wherein, described effective ingredient is Zolpidemtar Trate or meloxicam.
4. dry direct compression fast disintegrating tablet as claimed in claim 3, wherein, it is the following Zolpidemtar Trate crude drug of 100 μ m that described Zolpidemtar Trate uses mean diameter.
5. dry direct compression fast disintegrating tablet as claimed in claim 3, wherein, it is the following meloxicam crude drug of 11 μ m that described meloxicam uses mean diameter.
6. dry direct compression fast disintegrating tablet as claimed in claim 1 or 2 wherein, is a benchmark with the weight of final tablet, and the use level of described excipient is 20～70 weight %.
7. dry direct compression fast disintegrating tablet as claimed in claim 1 or 2 wherein, is a benchmark with the weight of final tablet, and the use level of described disintegrating agent is 5～20 weight %.
8. dry direct compression fast disintegrating tablet as claimed in claim 1 or 2 wherein, is a benchmark with the weight of final tablet, and the use level of described fluidizing reagent is 0.5～3 weight %.
9. dry direct compression fast disintegrating tablet as claimed in claim 1 or 2 wherein, is a benchmark with the weight of final tablet, and the use level of described lubricant is 1.0～3 weight %.
10. the preparation method of a dry direct compression fast disintegrating tablet, it is characterized in that: by being selected from erythritol, xylitol, mannitol, lactose, the correctives of more than one in the group that sucrose is formed be selected from crystalline cellulose, crystalline cellulose-sodium carboxymethyl cellulose, the powder body of the binding agent of more than one in the group that carboxymethyl cellulose potassium is formed mixes, in the aqueous solution of spraying reduction Fructus Hordei Germinatus sucrose solution maltosemalt sugar, use fluidized bed pelletizer to carry out pelletize, with pelletize thing and the effective ingredient that obtains, excipient, disintegrating agent, fluidizing reagent and mix lubricant are with the mixture direct compression that obtains; For the correctives of per 1 part of weight, the amount of binding agent is 0.15～3.2 part a scope.
11. the preparation method of dry direct compression fast disintegrating tablet as claimed in claim 10, wherein, described effective ingredient is Zolpidemtar Trate or meloxicam.
12. it is the following Zolpidemtar Trate crude drug of 100 μ m that preparation method as claimed in claim 11, wherein said Zolpidemtar Trate are used mean diameter.
13. it is the following meloxicam crude drug of 11 μ m that preparation method as claimed in claim 11, wherein said meloxicam are used mean diameter.
14. as claim 10 or 11 described preparation methoies, wherein, be benchmark with the weight of final tablet, the use level of described excipient is 20～70 weight %.
15. as claim 10 or 11 described preparation methoies, wherein, be benchmark with the weight of final tablet, the use level of described disintegrating agent is 5～20 weight %.
16. as claim 10 or 11 described preparation methoies, wherein, be benchmark with the weight of final tablet, the use level of described fluidizing reagent is 0.5～3 weight %.
17. as claim 10 or 11 described preparation methoies, wherein, be benchmark with the weight of final tablet, the use level of described lubricant is 1.0～3 weight %.
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| Application Number | Priority Date | Filing Date | Title |
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| JP110753/2006 | 2006-04-13 | ||
| JP2006110753 | 2006-04-13 | ||
| PCT/JP2007/058095 WO2007119792A1 (en) | 2006-04-13 | 2007-04-12 | Dry direct compression fast disintegrating tablet |
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| CN101420982B true CN101420982B (en) | 2011-11-09 |
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| JP (1) | JP5215172B2 (en) |
| KR (1) | KR101400064B1 (en) |
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| TW200946142A (en) * | 2008-03-28 | 2009-11-16 | Kowa Co | Tablet |
| KR101704156B1 (en) * | 2008-11-25 | 2017-02-07 | 미쓰비시 타나베 파마 코퍼레이션 | Mixture for producing orally rapidly disintegrating tablet |
| JP5517327B2 (en) * | 2008-12-16 | 2014-06-11 | 日医工株式会社 | Composition for orally disintegrating tablets |
| CN101618026B (en) * | 2009-07-06 | 2011-03-16 | 江苏飞马药业有限公司 | Meloxicam tablet, production technology and purposes thereof |
| CN101869236A (en) * | 2010-06-09 | 2010-10-27 | 山东福田药业有限公司 | Xylitol particles capable of being directly pressed into tablets and preparation method thereof |
| KR101226271B1 (en) | 2011-01-14 | 2013-01-25 | 에스케이하이닉스 주식회사 | Programing circuit using antifuse |
| CN106913553A (en) * | 2012-04-24 | 2017-07-04 | 第三共株式会社 | Oral disnitegration tablet and its manufacture method |
| US8431155B1 (en) | 2012-04-30 | 2013-04-30 | Veroscience Llc | Bromocriptine formulations |
| CN103202817B (en) * | 2013-04-28 | 2014-10-08 | 山东天力药业有限公司 | Preparation method for mannitol grains capable of being directly pressed |
| CN103494821B (en) * | 2013-10-01 | 2018-09-25 | 迪沙药业集团有限公司 | A kind of cefixime composition |
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| CN1139878C (en) * | 2000-05-30 | 2004-02-25 | 英业达股份有限公司 | Method for formatting |
| US6740339B1 (en) * | 1999-06-18 | 2004-05-25 | Takeda Chemical Industries, Ltd. | Quickly disintegrating solid preparations |
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| JP2864737B2 (en) * | 1993-10-22 | 1999-03-08 | 株式会社ツムラ | Base for sustained release preparation, sustained release preparation and method for producing the preparation |
| EP0745382B1 (en) * | 1994-01-31 | 2003-11-12 | Yamanouchi Pharmaceutical Co. Ltd. | Intraorally soluble compressed molding and process for producing the same |
| JP4438121B2 (en) * | 1998-04-27 | 2010-03-24 | 大正製薬株式会社 | Intraoral rapidly disintegrating tablet and method for producing the same |
| JP2001058944A (en) * | 1999-06-18 | 2001-03-06 | Takeda Chem Ind Ltd | Rapidly disintegrating solid formulation |
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| US6740339B1 (en) * | 1999-06-18 | 2004-05-25 | Takeda Chemical Industries, Ltd. | Quickly disintegrating solid preparations |
| CN1139878C (en) * | 2000-05-30 | 2004-02-25 | 英业达股份有限公司 | Method for formatting |
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| JPWO2007119792A1 (en) | 2009-08-27 |
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| KR101400064B1 (en) | 2014-05-27 |
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| WO2007119792A1 (en) | 2007-10-25 |
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