CN203227048U - Dry-coated tablet as anti-tumor agent - Google Patents
Dry-coated tablet as anti-tumor agent Download PDFInfo
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- CN203227048U CN203227048U CN 201220364549 CN201220364549U CN203227048U CN 203227048 U CN203227048 U CN 203227048U CN 201220364549 CN201220364549 CN 201220364549 CN 201220364549 U CN201220364549 U CN 201220364549U CN 203227048 U CN203227048 U CN 203227048U
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Abstract
The utility model provides a dry-coated tablet which is characterized by being an anti-tumor agent composed of an inner core and a shell, wherein the diameter phi of the inner core ranges from 3mm to 24mm, the thickness of the shell ranges from 0.2mm to 2mm, and the height of the agent ranges from 1mm to 10mm.
Description
Technical field
This utility model relates to a kind of dry-pressing coated tablet for oral use that contains ftorafur (Tegafur), Ji Meilaxi (Gimeracil) and Oteracil Potassium (Oteracil potassium).
Background technology
Ftorafur, Ji Meilaxi and Oteracil Potassium compounding ingredient are a kind of antitumor agent, it is characterized in that: by in as the ftorafur of the prodrug of fluorouracil (5-FU), cooperating as the Ji Meilaxi of the decomposing inhibitor of 5-FU with as the Oteracil Potassium of phosphorylation inhibitor, can improve antitumous effect and alleviate Alimentary toxicity, as tumor chemical therapy medicine that can be oral, extensive use clinically (patent documentation 1).
Now, ftorafur, Ji Meilaxi and Oteracil Potassium compounding ingredient, with ftorafur: Ji Meilaxi: the mol ratio of Oteracil Potassium is the content of 1:0.4:1, so that the title of " TS-1 capsule-containing " is commercially available capsule arranged, and so that the title of " TS-1 cooperates granule " is commercially available granule (patent documentation 2) arranged.But capsule or granule are difficult to swallow sometimes for the old people that function of deglutition reduces, and are seeking a kind of Orally disintegrating tablet, even this disintegrating tablet clinically dysphagia person also can take disintegrate rapidly in the oral cavity easily.
On the other hand, generally speaking, the active component of many demonstration antitumous effects more is classified as dangerous drug, and then pharmacologically active is more high, and ftorafur also is one of them, and its action need is given one's full attention to.Be the state that exposes or during because of the breaking of preparation, the damaged state that disperses, not only medical personnel but also the patient who takes or the care-giver that takes medicine also might be subjected to the influence of drug exposure at the active component of anticarcinogen.Usually, in order to reduce drug exposure.Can use and medicament enclosed in the capsule that is made of gelatin etc. or medicament be made tablet and with the method for coatings such as sugar, macromolecule etc.But, because these methods postpone the disintegrate of preparation, therefore, can't expect in intraoral rapid disintegrate.
In addition, in order to improve the disintegrative of Orally disintegrating tablet, become the low preparation of its corresponding intensity more.At this moment, the process that can't tolerate manufacturing, circulation maybe can't tolerate utilization makes the height of medicament from about the 1m fall and to making up a prescription that its automatic minute chartered plane that carries out subpackage carries out usually, in preparation, produce break, damaged, worry medical personnel's etc. medicament exposure hazard is increased.
For the preparation that is combined with ftorafur, Ji Meilaxi and Oteracil Potassium.Cooperate preparation even for example in patent documentation 3, disclose a kind of ftorafur, Ji Meilaxi and Oteracil Potassium of under humidified condition, also stablizing and can be oral.But this cooperates preparation to improve as stability of formulation as purpose, does not consider the patient's etc. of dysphagia taking.In addition, in order to improve the functions such as disintegrative of tablet, and with stable saccharide and with and add the instabilityization that disintegrating agent etc. can cause effective ingredient.In addition, the intraoral disintegration tablet that is combined with ftorafur, Ji Meilaxi and Oteracil Potassium is disclosed in patent documentation 4.But, for this patent, although this medicine is highly active anticarcinogen, do not have the countermeasure for medical personnel, care-giver's etc. pharmacy exposure.
The prior art document
Patent documentation
Patent documentation 1: No. 2614164 communiques of Japan Patent
Patent documentation 2: international 2009/084216 pamphlet that discloses
Patent documentation 3: TOHKEMY 2010-235539 communique,
Patent documentation 4: the open CN1660105A communique of Chinese patent
Summary of the invention
The problem that invention will solve
As mentioned above, known up to now ftorafur, Ji Meilaxi and Oteracil Potassium are cooperated preparation, wish to obtain the danger of a kind of abundant reduction drug exposure and have sufficient tablet strength, when taking, also can not cause the preparation that drug compliance reduces.
The purpose of this utility model is to provide a kind of reduction that realizes drug exposure danger, disintegrative and the dry-pressing coated tablet that is combined with ftorafur, Ji Meilaxi and Oteracil Potassium of tablet strength fully rapidly.Particularly, the purpose of this utility model is to provide a kind of dry-pressing coated tablet, it is the shell that formability is good and disintegrative is good and the combination that contains the kernel of effective ingredient, has sufficient mechanical, even reduced the dangerous of drug exposure and also disintegrate rapidly in the oral cavity.
Be used for solving the method for problem
Inventor of the present utility model has attempted making the various tablets that are combined with ftorafur, Ji Meilaxi and Oteracil Potassium that can be oral in order to solve above-mentioned problem.
Its result, by making the kernel that contains ftorafur, Ji Meilaxi and Oteracil Potassium and the dry-pressing coated tablet that is combined by the formability shell good and that disintegrative is good that specific additive constitutes, even discovery has sufficient mechanical, reduced the dangerous of drug exposure and in the oral cavity the also preparation of disintegrate rapidly, thereby finished this utility model.
That is, this utility model provides following dry-pressing coated tablet.
(1) a kind of dry-pressing coated tablet, its by contain (a) ftorafur, (b) Ji Meilaxi and (c) Oteracil Potassium constitute as kernel and the shell of effective ingredient.
(2) according to (1) described dry-pressing coated tablet, it contains (a) ftorafur, (b) Ji Meilaxi and (c) Oteracil Potassium with mol ratio 1:0.4:1.
(3) according to (1) or (2) described dry-pressing coated tablet, wherein, the 50 quality %～100 quality % of nuclear composition in by (a) ftorafur, (b) Ji Meilaxi and (c) effective ingredient that constitutes of Oteracil Potassium accounts for.
(4) according to each described dry-pressing coated tablet in (1)～(3), wherein, the 70 quality %～99 quality % of nuclear composition in by (a) ftorafur, (b) Ji Meilaxi and (c) effective ingredient that constitutes of Oteracil Potassium accounts for.
(5) according to each described dry-pressing coated tablet in (1)～(4), wherein, the total content of the effective ingredient in the dry-pressing coated tablet (a)～(c) is 10～60 quality %.
(6) according to each described dry-pressing coated tablet in (1)～(5), wherein, shell contains a kind, 2 kinds or 3 kinds in lactose, crystalline cellulose, the hydroxypropyl cellulose.
(7) according to (6) described dry-pressing coated tablet, wherein, shell contains a kind or 2 kinds in lactose, the crystalline cellulose.
(8) according to (7) described dry-pressing coated tablet, wherein, shell contains lactose and crystalline cellulose.
(9) according to (6), (7) or (8) described dry-pressing coated tablet, wherein, in shell, also contain disintegrating agent.
(10) according to (9) described dry-pressing coated tablet, wherein, disintegrating agent is selected from crospovidone (Crospovidone), carboxymethyl cellulose, corn starch, low degree of substitution hydroxypropyl cellulose, part alphalysed starch.
(11) according to (10) described dry-pressing coated tablet, wherein, disintegrating agent is crospovidone and/or part alphalysed starch.
(12) according to each described dry-pressing coated tablet in (1)～(11), wherein, shell contains the lactose of 30～65 quality %.
(13) according to each described dry-pressing coated tablet in (1)～(12), wherein, shell contains the crystalline cellulose of 30～50 quality %.
(14) according to each described dry-pressing coated tablet in (1)～(13), wherein, shell contains the crospovidone of 2.5～15 quality %.
(15) according to each described dry-pressing coated tablet in (1)～(14), wherein, shell contains the part alphalysed starch of 2～7.5 quality %.
(16) according to each described dry-pressing coated tablet in (1)～(15), it is characterized in that, friability with the dry-pressing coated tablet when accumulation revolution 100 changes is below 0.3% and at the shell that does not crack in fact from the shatter test of height 1m, and the disintegration time of utilizing Pharmacopeia of Japan ordinary test method slaking test method to obtain is below 120 seconds.
(17) according to each described dry-pressing coated tablet in (1)～(16), it is characterized in that, friability with the dry-pressing coated tablet when accumulation revolution 100 changes is below 0.2%, and at the shell that does not crack in fact from the shatter test of height 1m, the disintegration time of utilizing Pharmacopeia of Japan ordinary test method slaking test method to obtain is below 95 seconds.
(18) according to each described dry-pressing coated tablet in (1)～(17), wherein, kernel is
The thickness of shell is 0.2～2mm, and the height of preparation is 1～10mm.
(19) according to (18) described dry-pressing coated tablet, wherein, kernel is
The thickness of shell is 0.5～1.5mm, and the height of preparation is 1.5～7mm.
(20) according to each described dry-pressing coated tablet in (1)～(19), wherein, be shaped as circle or ellipse.
(21) according to each described dry-pressing coated tablet in (1)～(20), it is made by compression-molding apparatus, described extrusion forming device has pestle in two directions up and down of mortar, at least go up pestle and be made of the dual structure of center pestle with the outer pestle of the periphery of surrounding this center pestle, this center pestle and outer pestle can grind and can carry out squeeze operation.
The effect of invention
According to this utility model, by making the dry-pressing coated tablet and medicine being enclosed kernel, there is not effective ingredient on the surface of tablet, can reduce the medical personnel greatly and wait the danger that is exposed to medicine, can also realize tablet strength and the disintegrate rapidly of appropriateness.And then, by being divided into kernel and shell, can reducing and promote contacting of additive that effective ingredient decomposes, therefore can suppress to decompose.
Description of drawings
Fig. 1 is the related sketch map of section of expression dry-pressing coated tablet.
The specific embodiment
In this utility model, the mol ratio of ftorafur, Ji Meilaxi and Oteracil Potassium can suitably be selected, but preferably is respectively the compounding ingredient of 1:0.4:1.Amount as ftorafur, Ji Meilaxi and the Oteracil Potassium of the effective ingredient in this utility model dry-pressing coated tablet changes according to dosage form, drug dosage schedule etc., be not particularly limited, suitably select to get final product, but preferably the total content with 3 effective ingredient in the dry-pressing coated tablet is made as about 10～60 quality %, more preferably be made as 20～50 quality %, especially preferably be made as 25～35 quality %.
The preferred dry-pressing coated tablet of this utility model for have friability (accumulation revolution 100 change) be below 0.3% shell, more preferably have a dry-pressing coated tablet that friability is the shell below 0.1%.Wherein, " friability " is employed implication in the technical field of common preparation, namely, be in order to learn whether tablet through molding can tolerate vibration or the impact in coating, printing, packing or the market-circulation as subsequent handling, and the parameter that the reduction of the tablet weight that obtains with the friability testing machine that utilize to use rotary drum is estimated is the index of tablet strength.Particularly, (revolution of internal diameter 287 ± 4mm) for example is adjusted to rotation in 1 minute 24～26 to be changeed will to have the drum of motor based on the reference information " the friability test method(s) of tablet " of Pharmacopeia of Japan the 15th revised edition, measure certain postrotational tablet weight, the percentage rate of the reduction of tablet weight is worth as friability with this when calculating it with respect to beginning.In this manual, expression will be accumulated revolution and be made as 100 friabilities when changeing, utilize 25rpm, 4 minutes tablet weight to calculate.The friability that accumulation revolution 100 is changeed is that the situation below 0.3% is defined as the tablet strength height.It is low to be defined as tablet strength greater than 0.3% situation on the contrary.Effective ingredient contained in this utility model is also referred to as anticarcinogen sometimes, in order further to reduce exposure hazard, also needs to improve tablet strength than general medicament, therefore, compares with common preparation, more wishes to preestablish friability lower.
The preferred dry-pressing coated tablet of this utility model is the dry-pressing coated tablet with the shell that does not crack in fact from the shatter test of height 1m, preferably has the dry-pressing coated tablet of the shell that does not crack in fact from the shatter test of height 2m.Wherein, " shatter test " be whether can tolerate manufacturing in order to learn-circulation waits or utilizes vibration or the impact that divides automatically in the making up a prescription that chartered plane carries out, and employed test in the technical field of preparation usually.Particularly, tablet is fallen on the corrosion resistant plate naturally from the height of 1m～2m, confirm the crackle of tablet and the rate of mass reduction before and after the test.In addition, in this utility model, " not cracking in fact " refers to 5 tablets are being carried out not cracking fully under the situation of shatter test, and the rate of mass reduction in 5 tablets is lower than 0.1% degree.
The preferred dry-pressing coated tablet of this utility model is that the disintegration time of dry-pressing coated tablet integral body is in 120 seconds.Particularly, when this dry-pressing coated tablet is the slaking test of implementation basis Pharmacopeia of Japan the 15th revised edition ordinary test method slaking test method, its disintegration time be 120 seconds with interior dry-pressing coated tablet.This disintegration time was preferably in 95 seconds, more preferably in 80 seconds.In making the oral cavity under the situation of fast disintegrative dry-pressing coated tablet, actual identical or faster than it with disintegration time in the above-mentioned slaking test method owing to applied the motion of intraoral friction, tongue sometimes in intraoral dissolving-disintegration time.In addition, summarize above-mentioned slaking test method simply, as described below.Exerciser is installed on bearing, puts into beaker, be adjusted to 1 minute reciprocal 29～32 times, amplitude 53～57mm and move up and down smoothly.Be made as exerciser when dropping to the below, the wire side of bottom apart from beaker at the bottom of 25mm, when the amount that adds the water of beaker was made as below exerciser drops to, the upper surface of exerciser was surperficial consistent with liquid.The temperature of liquid is remained on 37 ± 2 ℃.Put into a slice sample in the glass tubing of exerciser, experimental liquid makes water, puts into bracket panel, moves up and down.Measure the time till the residue of sample unconfirmed in the glass tubing, as disintegration time.
The disintegrate of tablet depends on the small frictional force of a spot of moisture, tongue and the maxillary of saliva degree greatly in the oral cavity.Therefore, in the employed various slaking tests of common tablet (Japanese pharmacy the 14th revised edition ordinary test method slaking test method), reflection is unactual in intraoral disintegrate.Therefore, as the Orally disintegrating tablet exerciser, exploitation and sale have ODT-101(Fushan Mountain industry system) and field, TRICORPTESTER(ridge Seiko system), by using them, and the dependency of the data of consideration and people's sense evaluation test, just can there be the individual difference, repeatability is good, and measure (list of references: Narazaki R. easily, Harada T., et al., Chem.Pharm.Bull., 52,704-707(2004)).Utilize in preferred 20 seconds of the disintegration time that the Orally disintegrating tablet exerciser ODT-101 of dry-pressing coated tablet of the present utility model measures, more preferably in 16 seconds, in preferred especially 14 seconds.
The preferred dry-pressing coated tablet of this utility model preferably utilizes Pharmacopeia of Japan ordinary test method dissolution test method the 2nd method (50min
-1, experimental liquid water 900mL) and the dissolution rate (CDHP, 15 minutes values) that records is more than 90%, and is more preferably more than 95%, preferred more than 97% especially.
Particularly preferred dry-pressing coated tablet of the present utility model, the friability (accumulation revolution 100 changes) with dry-pressing coated tablet is the shell below 0.3%, the disintegration time of utilizing Pharmacopeia of Japan ordinary test method slaking test method to obtain is below 120 seconds; The dry-pressing coated tablet that is more preferably, the friability (accumulation revolution 100 changes) with dry-pressing coated tablet is the shell below 0.2%, the disintegration time of utilizing Pharmacopeia of Japan ordinary test method slaking test method to obtain is below 95 seconds;
Further preferred dry-pressing coated tablet, friability (accumulation revolution 100 changes) with dry-pressing coated tablet is below 0.2% and at the shell that does not crack in fact from the shatter test of height 1m, and the disintegration time of utilizing Pharmacopeia of Japan ordinary test method slaking test method to obtain is below 95 seconds; Further preferred dry-pressing coated tablet, friability (accumulation revolution 100 changes) with dry-pressing coated tablet is below 0.2% and at the shell that does not crack in fact from the shatter test of height 2m, and the disintegration time of utilizing Pharmacopeia of Japan ordinary test method slaking test method to obtain is below 95 seconds;
Further preferred dry-pressing coated tablet, friability (accumulation revolution 100 changes) with dry-pressing coated tablet is below 0.2% and at the shell that does not crack in fact from the shatter test of height 2m, the disintegration time of utilizing Pharmacopeia of Japan ordinary test method slaking test method to obtain is below 95 seconds, the disintegration time of utilizing Orally disintegrating tablet exerciser ODT-101 to record is in 20 seconds, utilizes Pharmacopeia of Japan ordinary test method dissolution test method the 2nd method (50min
-1, experimental liquid water 900mL) and the dissolution rate (CDHP, 15 minutes values) that records is more than 90%; Particularly preferred dry-pressing coated tablet, friability (accumulation revolution 100 changes) with dry-pressing coated tablet is below 0.2% and at the shell that does not crack in fact from the shatter test of height 2m, the disintegration time of utilizing Pharmacopeia of Japan ordinary test method slaking test method to obtain is below 95 seconds, the disintegration time of utilizing Orally disintegrating tablet exerciser ODT-101 to record is in 16 seconds, utilizes Pharmacopeia of Japan ordinary test method dissolution test method the 2nd method (50min
-1, experimental liquid water 900mL) and the dissolution rate (CDHP, 15 minutes values) that records is more than 95%.
In addition, " hardness " can be measured based on the method TABLET BREAKING FORCE of USP record for estimating an index of tablet strength.That is, when circular piece, between 2 parallel pressing plates, pressurize the load when measuring the tablet fracture along diametric(al) with certain speed (20N/ below second or 3.5mm/ below second).As the hardness of this utility model dry-pressing coated tablet, in view of with the balance of disintegrative, be preferably 30N～60N, more preferably 35N～55N.
The additive that contains in the shell as this utility model dry-pressing coated tablet, in order to improve tablet strength, for example can enumerate: crystalline cellulose, lactose, hydroxypropyl cellulose etc., be preferably crystalline cellulose, lactose or their mixture, more preferably the mixture of crystalline cellulose and lactose.And then, in order to improve disintegrative, stripping property, preferably contain disintegrating agent, for example contain crospovidone, part alphalysed starch, carboxymethyl cellulose, corn starch, low degree of substitution hydroxypropyl cellulose etc., more preferably crospovidone and/or part alphalysed starch.
In this utility model, as the amount of employed lactose in the outer shell component, preferably use 30～65 quality %, more preferably 40～60 quality % are preferably 45～55 quality % especially.Under the situation of amount less than 30 quality % of lactose, the trend of disintegrative variation is arranged, under the situation greater than 65 quality %, the trend that has friability to increase.As the amount of crystalline cellulose, preferably use 30～50 quality %, more preferably 35～45 quality %, under the situation of amount less than 30 quality % of crystalline cellulose, the trend that has friability to increase under the situation greater than 50 quality %, has the trend of disintegrative variation and taste deterioration.In addition, for the amount ratio of lactose and crystalline cellulose, if consider tablet hardness, disintegrative, take the balance of sense, more preferably by quality ratio the amount of lactose and the amount of crystalline cellulose are made as 1:0.5～1.5, especially preferably be made as 1:0.8～1.3.As the amount of crospovidone, preferably use 2.5～15 quality %, more preferably 2.5～7.5 quality %.As the amount of part alphalysed starch, preferably use with 2～7.5 quality %, more preferably use with 2.5～5 quality %.
For the kernel of this utility model dry-pressing coated tablet, also can only be constituted by the effective ingredient that comprises ftorafur, Ji Meilaxi and Oteracil Potassium.As the use level of effective ingredient, the 50 quality %～100 quality % of nuclear composition preferably account for 70 quality %～99 quality % in can accounting for.And then, for tablet strength and the disintegrative of appropriateness are provided, also can add pharmaceutically acceptable binding agent and/or the disintegrating agent of appropriate amount.As this binding agent, so long as employed binding agent just is not particularly limited in the pharmaceutical preparation, for example can enumerate: gelatinized corn starch liquid, methylcellulose, hydroxypropyl cellulose (HPC-SSL, HPC-SL, HPC-L etc.), hydroxypropyl emthylcellulose, sodium carboxymethyl cellulose (carmethose), arabic gum, gelatin, agar, Tragacanth, sodium alginate, pulullan polysaccharide, polyvinyl pyrrolidone, polyvinyl alcohol, Polyethylene Glycol etc., they can use a kind of or make up two or more uses, are preferably hydroxypropyl cellulose.The content of binding agent can add 0.1～2.0 quality % with respect to the total amount of ftorafur, Ji Meilaxi and Oteracil Potassium, more preferably is made as 0.4～1.0 quality %.In addition, as disintegrating agent, for example can enumerate: carmellose, carboxymethylcellulose calcium, cross-linked carboxymethyl cellulose sodium, corn starch, part alphalysed starch, crystalline cellulose, low degree of substitution hydroxypropyl cellulose, crospovidone etc., they can use a kind of or make up two or more uses, are preferably part alphalysed starch, crospovidone.The content of disintegrating agent is preferably 3～15 quality % with respect to the total amount of ftorafur, Ji Meilaxi and Oteracil Potassium.
And then, can in kernel, add a small amount of disintegrate auxiliary agent, as the disintegrate auxiliary agent, for example can enumerate: carmellose, carboxymethylcellulose calcium, carmethose, cross-linked carboxymethyl cellulose sodium, low degree of substitution hydroxypropyl cellulose, carboxymethyl starch sodium, corn starch, potato starch, alphalysed starch, the part alphalysed starch, hydroxypropyl starch, crospovidone, sodium lauryl sulphate, polysorbate, the polyethylene glycol oxide polyoxypropyleneglycol, sorbitan monooleate, propylene glycolmonostearate, the mono laurate macrogol ester, they can use a kind of or make up two or more uses.
In dry-pressing coated tablet of the present utility model, except aforesaid additive, in the scope that does not hinder effect of the present utility model, can contain employed various preparation additives usually.As the preparation additive, so long as common employed additive just is not particularly limited, for example can enumerate lubricant, coloring agent, flavour enhancer and correctives etc.As lubricant, can enumerate: magnesium stearate, calcium stearate, stearic acid, sodium stearyl fumarate, Talcum and sucrose fatty acid ester etc.As coloring agent, can enumerate: edible yellow No. 5 pigments, edible red No. 2 pigments, edible blue No. 2 pigments, edible color lake pigment, yellow iron sesquioxide and titanium oxide etc.As flavour enhancer, can enumerate: Fructus Citri tangerinae, the various spice of Fructus Citri Limoniae etc.As correctives, can enumerate: L-menthol, Camphora, Herba Menthae etc.
It is made that this utility model dry-pressing coated tablet for example can use tablet machine LIBRA2DC(chrysanthemum water to make), the AP-MS-C type has the nuclear sheet tablet machine (field ferrum steel made) wait the sheet of examining tablet machine is arranged, can also use Autograph AG-E50k(Shimadzu Seisakusho Ltd. system) etc. make.That is, as its general method for making, roughly be made of the quadravalence section, can make as follows: (i) the outer shell component with a part is supplied in the mortar; The kernel that (ii) will carry out tabletting in advance is supplied in mortar; (iii) remaining outer shell component is supplied in mortar; (iv) in mortar, carry out press molding between pestle up and down.In addition, also can use international open 2003-28706 pamphlet, J.Jpn. Soc.Pharm.Mach.﹠Eng.14(4), 12-21(2005) wait in the tablet machine of the method for record and rotary compression molding press (three and chemical research made) make, from the tablet with dual structure of kernel and shell can being considered with high production rate and the aspect of easily carrying out molding, also preferred this manufacture method.Namely, dry-pressing coated tablet of the present utility model can easily be made by compression-molding apparatus, described extrusion forming device has pestle in two directions up and down of mortar, at least go up pestle and be made of the dual structure of center pestle with the outer pestle of the periphery of surrounding this center pestle, this center pestle and outer pestle all can grind and can carry out squeeze operation.Like this, dry-pressing coated tablet of the present utility model can be made by enough 1 tablet machine once, therefore need not implement described numerous and diverse technology, operation in the past, can make effectively.Therefore, do not have the position deviation of the nuclear as dry-pressing coated tablet in the past, shell can be made as thin as a wafer.Particularly the thickness of shell can be made below the 1mm.The thin layerization of this shell also helps the improvement of the disintegrative of dry-pressing coated tablet.
The shape of this utility model dry-pressing coated tablet is so long as take easily or do not have the shape of sense of discomfort when taking, and its shape just is not particularly limited, but preferred and general pharmaceuticals are similarly made circular or oval-shaped preparation.In addition, its size is so long as can insert in the oral cavity in and chew and do not follow difficult degree to get final product.For example, if circular piece, as long as then be
Following degree gets final product, and is preferably designed for
More preferably be designed to
Be more preferably and be designed to
The height of preparation is preferably designed for 1.5～7mm as long as for the following degree of 10mm, can be designed as 1～10mm, further is preferably designed for 2～5mm.
The shape of kernel depends on the pestle front end shape of employed pestle, but based on the shape of above-mentioned dry-pressing coated tablet.The size of kernel depends on the size of dry-pressing coated tablet integral body more, and is for the molding procedure that makes kernel is successfully carried out, preferably not too small.In addition, in order to improve the disintegrative of dry-pressing coated tablet, preferably in the scope that molding of shell is not caused obstruction, increase kernel with respect to shell.Therefore, for kernel, if circular piece, as long as then be
Following degree gets final product, and can be designed as
Be preferably designed for
More preferably be designed to
In addition, kernel also can be divided into a plurality of parts as required.
The thickness of shell is according to the size of kernel, is set at that abrasiveness is low, the shape of dry-pressing coated tablet can get final product by the thickness that shell keeps, and is suitably in the scope of 0.2～2mm to design.In order to improve intraoral fast disintegrative, the tablet strength of preferred raising housing parts within reason.Therefore, the thickness of shell namely can keep making thinly as much as possible in the scope of shape of dry-pressing coated tablet preferably in the scope of the problem that does not have abrasiveness, is preferably set to 0.5～1.5mm in reality.
As this utility model dry-pressing coated tablet, preferred kernel is
The thickness of shell is that the height of 0.2～2mm, preparation is the dry-pressing coated tablet of 1～10mm, and more preferably kernel is
The thickness of shell is that the height of 0.5～1.5mm, preparation is the dry-pressing coated tablet of 1.5～7mm, is more preferably kernel and is
The thickness of shell is that the height of 0.5～1.5mm, preparation is the dry-pressing coated tablet of 2～5mm.
[embodiment]
Below, enumerate reference example, embodiment and test example this utility model is described in further detail, but this utility model is not limited to these examples.Need to prove that employed ftorafur and Ji Meilaxi are roc pharmaceutical industries corporate system among this embodiment, Oteracil Potassium is Sumitomo Chemical Co. Ltd.'s system.In addition, hydroxypropyl cellulose (HPC) is Japanese Cao Da corporate system, part alphalysed starch and crystalline cellulose are chemical company of Asahi Chemical Industry system, magnesium stearate is peaceful chemical company system, and crospovidone is BASF AG's system.
The preparation 1 of nuclear composition in the reference example 1()
Use fluidized bed pelletizer Multiplex MP-01(Powrex corporate system); in the mixture of ftorafur 66.1g, Ji Meilaxi 19.15g, Oteracil Potassium 64.75g and lactose (Borculo Domo Ingredients corporate system) 150g; 200.0g sprays with water; and carry out pelletize, nuclear composition in preparing.
The preparation 2 of nuclear composition in the reference example 2()
By the method same with reference example 1, in the mixture of ftorafur 66.1g, Ji Meilaxi 19.15g, Oteracil Potassium 64.75g and lactose (Borculo Domo Ingredients corporate system) 150g, to be dissolved with the liquid that HPC1.0g forms in water 199.0g sprays, and carry out pelletize, nuclear composition in preparing.
The preparation 3 of nuclear composition in the reference example 3()
By the method same with reference example 1, in the mixture of ftorafur 132.2g, Ji Meilaxi 38.3g and Oteracil Potassium 129.5g, 200g sprays with water, and carries out pelletize, nuclear composition in the preparation.
The preparation 4 of nuclear composition in the reference example 4()
By the method same with reference example 1, in the mixture of ftorafur 132.2g, Ji Meilaxi 38.3g and Oteracil Potassium 129.5g, will in water 199.7g, be dissolved with the liquid that HPC 0.3g forms and spray, and carry out pelletize, nuclear composition in the preparation.
The preparation 5 of nuclear composition in the reference example 5()
By the method same with reference example 1, in the mixture of ftorafur 132.2g, Ji Meilaxi 38.3g and Oteracil Potassium 129.5g, will in water 198.5g, be dissolved with the liquid that HPC 1.5g forms and spray, and carry out pelletize, nuclear composition in the preparation.
The preparation 6 of nuclear composition in the reference example 6()
By the method same with reference example 1, in the mixture of ftorafur 132.2g, Ji Meilaxi 38.3g and Oteracil Potassium 129.5g, will in water 197.0g, be dissolved with the liquid that HPC 3.0g forms and spray, and carry out pelletize, nuclear composition in the preparation.
The preparation 7 of nuclear composition in the reference example 7()
By the method same with reference example 1, in the mixture of ftorafur 132.2g, Ji Meilaxi 38.3g and Oteracil Potassium 129.5g, will in water 195.5g, be dissolved with the liquid that HPC 4.5g forms and spray, and carry out pelletize, nuclear composition in the preparation.
The preparation 8 of nuclear composition in the reference example 8()
By the method same with reference example 1, in the mixture of ftorafur 132.2g, Ji Meilaxi 38.3g and Oteracil Potassium 129.5g, will in water 194.0g, be dissolved with the liquid that HPC 6.0g forms and spray, and carry out pelletize, nuclear composition in the preparation.
The preparation 9 of nuclear composition in the reference example 9()
By the method same with reference example 1, in the mixture of ftorafur 200g, Ji Meilaxi 58g and Oteracil Potassium 196g and part alphalysed starch (chemical company of Asahi Chemical Industry system) 14g, to in water 396g, be dissolved with the liquid that HPC 4g forms and spray, and carry out pelletize, nuclear composition in the preparation.
The preparation 10 of nuclear composition in the reference example 10(＞
By the method same with reference example 1, in the mixture of ftorafur 200g, Ji Meilaxi 58g and Oteracil Potassium 196g, will in water 396g, be dissolved with the liquid that HPC 4g forms and spray, and carry out pelletize, nuclear composition in the preparation.
Embodiment 1
Use Autograph AG-E50k(Shimadzu Seisakusho Ltd. system), to mix lactose (MEGGLE Excipients﹠Technology corporate system) 59.88mg, the mixture that crystalline cellulose 60mg and magnesium stearate 0.12mg form is as shell, to be 25mg at the pelletize thing 57mg(of reference example 5 ftorafur) in add mixture that part alphalysed starch 2.84mg and magnesium stearate 0.28mg form as kernel, according to shell ground floor 30mg, kernel 60.12mg, and then the order of shell second layer 60mg fills, and prepares the dry-pressing coated tablet of tablet external diameter 8mm with tabletting pressure 5kN.Related the illustrating in Fig. 1 of section with the dry-pressing coated tablet that obtains.The interior nuclear diameter of the dry-pressing coated tablet that obtains is 6mm, and the thickness of shell (a) is 1mm.
Embodiment 2
Use Autograph AG-E50k(Shimadzu Seisakusho Ltd. system), similarly to Example 1 will be with lactose 53.76mg(MEGGLE Excipients﹠Technology corporate system), crystalline cellulose 60mg, the mixture that the ratio of crospovidone 6mg and magnesium stearate 0.24mg mixes is as shell, to be 25mg at the pelletize thing 57mg(of reference example 5 ftorafur) in add mixture that part alphalysed starch 2.84mg and magnesium stearate 0.28mg form as kernel, at shell 120mg, kernel 60.12mg, preparation contains the dry-pressing coated tablet of ftorafur 25mg under the condition of tabletting pressure 5kN.The external diameter of the dry-pressing coated tablet that obtains is 8mm, and interior nuclear diameter is 6mm, and the thickness of shell is 1mm.
Embodiment 3
Use Autograph AG-E50k(Shimadzu Seisakusho Ltd. system), use the interior nuclear composition of reference example 1～4 and 6～10, in addition, the preparation method by similarly to Example 1 prepares desired dry-pressing coated tablet.
Embodiment 4
Use the rotary compression molding press put down in writing in the international open 2003-28706 pamphlet (three and chemical research made), the mixture that will mix with the ratio shown in the table 1 is as shell, to be 25mg in the pelletize thing 57.25mg(of reference example 10 ftorafur amount) in add crospovidone 1.5mg, part alphalysed starch 1.5mg, correctives 1.5mg, the mixture that magnesium stearate 0.25mg forms is as interior nuclear composition, according to the shell ground floor, kernel 62mg, and then the order of the shell second layer is filled the (amount of shell ground floor: the amount of the shell second layer=35:85), prepare the dry-pressing coated tablet 1～4 of tablet external diameter 8mm with tabletting pressure 4kN.
Test example 1
For the dry-pressing coated tablet 1～4 that obtains among the embodiment 4, implement hardness, friability, intraoral disintegration test and dissolution test.Show the result in table 1.The result, consider from the viewpoint of hardness, friability, intraoral disintegration and stripping property, for outer shell component, confirmed when direct compression lactose 34～64 quality %, crystalline cellulose 30～50 quality % and crospovidone 5～15 quality %, to be the dry-pressing coated tablet of excellence.
(experimental condition)
Hardness tablet hardness tester TABLET TESTER 8M, the Shleuniger system
Friability tablet friability exerciser 100 changes (25rpm, 4 minutes)
Slaking test Pharmacopeia of Japan ordinary test method slaking test method experimental liquid water
Intraoral disintegration test intraoral disintegration exerciser ODT-101, Fushan Mountain chemistry counterweight processed
Rotating speed 75rpm, experimental liquid water
Dissolution test Pharmacopeia of Japan ordinary test method dissolution test method the 2nd method (50min
-1), experimental liquid water 900mL
[table 1]
Embodiment 5
Use similarly to Example 4 rotary compression molding press (three and chemical research made), the mixture that will mix with the ratio shown in the table 2 is as shell, by nuclear composition in the preparation method preparation similarly to Example 4, order according to shell ground floor, kernel 60mg and then the shell second layer is filled the (amount of shell ground floor: the amount of the shell second layer=35:85), prepare the dry-pressing coated tablet 5～8 of tablet external diameter 8mm with tabletting pressure 4kN.
Test example 2
For the dry-pressing coated tablet 5～8 that obtains among the embodiment 5, implement hardness, friability, intraoral disintegration test and dissolution test.Show the result in table 2.The result, consider from the viewpoint of hardness, friability, intraoral disintegration and stripping property, confirmed when direct compression lactose 39～59 quality %, crystalline cellulose 30～50 quality %, crospovidone 2.5～7.5 quality % and part alphalysed starch 2.5～7.5 quality %, to be the dry-pressing coated tablet of excellence.
(experimental condition)
Hardness tablet hardness tester TABLET TESTER 8M, the Schleuniger system
Friability tablet friability exerciser PTF30ERA, PharmaTest Apparatebau system 100 is changeed (25rpm, 4 minutes)
Slaking test Pharmacopeia of Japan ordinary test method slaking test method experimental liquid water
Intraoral disintegration test intraoral disintegration exerciser ODT-101, Fushan Mountain chemistry counterweight processed
Rotating speed 75rpm, experimental liquid water
Dissolution test Pharmacopeia of Japan ordinary test method dissolution test method the 2nd method (50min
-1), experimental liquid water 900mL
[table 2]
Embodiment 6
Use similarly to Example 4 rotary compression molding press (three and chemical research made), the mixture that will mix with the ratio shown in the table 3 is as shell, to be 20mg in the pelletize thing 45.8mg(of reference example 10 ftorafur amount) in add crospovidone 2mg, part alphalysed starch 0.4mg, correctives 1.2mg, the mixture that magnesium stearate 0.2mg forms is as interior nuclear composition, according to the shell ground floor, kernel 49.6mg, and then the order of the shell second layer is filled the (amount of shell ground floor: the amount of the shell second layer=30:66), prepare the dry-pressing coated tablet 9～12 of tablet external diameter 8mm with tabletting pressure 4kN.
Test example 3
For the dry-pressing coated tablet 9～12 that obtains among the embodiment 6, implement hardness, friability, intraoral disintegration test and dissolution test.Show the result in table 3.The result, consider from the viewpoint of hardness, friability, intraoral disintegration and stripping property, confirmed when direct compression lactose 39～59 quality %, crystalline cellulose 30～50 quality %, crospovidone 2.5～7.5 quality % and part alphalysed starch 2.5～7.5 quality %, to be the dry-pressing coated tablet of excellence.
[table 3]
Test example 4
For the dry-pressing coated tablet 6～8 that obtains among the embodiment 5 and commercially available Orally disintegrating tablet (A company, B company, C company, D company, E company), implement to make its height from 1m to fall tablet shatter test on corrosion resistant plate naturally.Show the result in table 4 and table 5.As a result, having confirmed that dry-pressing coated tablet 5～8 compares with commercially available Orally disintegrating tablet, is all excellent dry-pressing coated tablet of crackle and rate of mass reduction.
(experimental condition)
Tablet shatter test corrosion resistant plate, 1m(5 of height)
[table 4]
[table 5]
Comparative example
Claims (6)
1. dry-pressing coated tablet is characterized in that:
Its antitumor agent for being made of kernel and shell, described kernel is
The thickness of shell is 0.2～2mm, and the height of preparation is 1～10mm.
2. dry-pressing coated tablet as claimed in claim 1 is characterized in that:
Described antitumor agent is the TS-1 compounding chemicals.
3. dry-pressing coated tablet as claimed in claim 1 is characterized in that:
Friability with the dry-pressing coated tablet when accumulation revolution 100 changes is the shell below 0.3%, and the disintegration time of utilizing Pharmacopeia of Japan ordinary test method slaking test method to obtain is below 120 seconds.
4. dry-pressing coated tablet as claimed in claim 1 is characterized in that:
Friability with the dry-pressing coated tablet when accumulation revolution 100 changes is below 0.2% and at the shell that does not crack in fact from the shatter test of height 1m, and the disintegration time of utilizing Pharmacopeia of Japan ordinary test method slaking test method to obtain is below 95 seconds.
5. dry-pressing coated tablet as claimed in claim 1 is characterized in that:
Kernel is
The thickness of shell is 0.5～1.5mm, and the height of preparation is 1.5～7mm.
6. dry-pressing coated tablet as claimed in claim 1 is characterized in that:
Be shaped as circle or ellipse.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 201220364549 CN203227048U (en) | 2011-07-25 | 2012-07-25 | Dry-coated tablet as anti-tumor agent |
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201110208402.7 | 2011-07-25 | ||
| CN201110208402 | 2011-07-25 | ||
| CN 201220364549 CN203227048U (en) | 2011-07-25 | 2012-07-25 | Dry-coated tablet as anti-tumor agent |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN203227048U true CN203227048U (en) | 2013-10-09 |
Family
ID=47567900
Family Applications (3)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 201220364549 Expired - Fee Related CN203227048U (en) | 2011-07-25 | 2012-07-25 | Dry-coated tablet as anti-tumor agent |
| CN201510178161.4A Pending CN104873517A (en) | 2011-07-25 | 2012-07-25 | Dry-pressed coated tablet containing tegafur, gimeracil and oteracil potassium |
| CN201210260323.5A Expired - Fee Related CN102895212B (en) | 2011-07-25 | 2012-07-25 | Dry coated tablet containing ftorafur, gimeracil, Oteracil Potassium |
Family Applications After (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201510178161.4A Pending CN104873517A (en) | 2011-07-25 | 2012-07-25 | Dry-pressed coated tablet containing tegafur, gimeracil and oteracil potassium |
| CN201210260323.5A Expired - Fee Related CN102895212B (en) | 2011-07-25 | 2012-07-25 | Dry coated tablet containing ftorafur, gimeracil, Oteracil Potassium |
Country Status (2)
| Country | Link |
|---|---|
| CN (3) | CN203227048U (en) |
| HK (2) | HK1180584A1 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104840464A (en) * | 2014-08-22 | 2015-08-19 | 山东新时代药业有限公司 | Oral disintegrating preparation containing tegafur, gimeracil and potassium oxonate |
| CN106581001B (en) * | 2016-11-03 | 2018-12-21 | 江苏恒瑞医药股份有限公司 | A kind of preparation method of tegafur, gimeracil and oteracil potassium composition |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPWO2003028706A1 (en) * | 2001-09-28 | 2005-01-13 | 株式会社三和化学研究所 | Nucleated fast-disintegrating molded product |
| CN100333726C (en) * | 2004-12-23 | 2007-08-29 | 鲁南制药集团股份有限公司 | Disintegration piece taken through oral cavity containing Gimeracil and Oteracil Potassium with fluorine being added |
| CN101380327B (en) * | 2008-10-09 | 2011-01-26 | 北京恒瑞康达医药科技发展有限公司 | Anti-cancer composite sustained-release composition and preparation method thereof |
| CN102458475B (en) * | 2009-05-20 | 2016-03-30 | 大日本住友制药株式会社 | The oral cavity disintegration tablet of pressed coated |
| CN101711765B (en) * | 2009-10-31 | 2011-03-23 | 山东新时代药业有限公司 | Dispersing tablet containing tegafur, gimeracil and oteracil potassium |
-
2012
- 2012-07-25 CN CN 201220364549 patent/CN203227048U/en not_active Expired - Fee Related
- 2012-07-25 CN CN201510178161.4A patent/CN104873517A/en active Pending
- 2012-07-25 CN CN201210260323.5A patent/CN102895212B/en not_active Expired - Fee Related
-
2013
- 2013-07-03 HK HK13107789.5A patent/HK1180584A1/en not_active IP Right Cessation
-
2015
- 2015-12-15 HK HK15112304.9A patent/HK1211481A1/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| HK1180584A1 (en) | 2013-10-25 |
| CN104873517A (en) | 2015-09-02 |
| CN102895212B (en) | 2015-09-30 |
| HK1211481A1 (en) | 2016-05-27 |
| CN102895212A (en) | 2013-01-30 |
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