CN104997740B - A kind of Tandospirone dispersible tablet or coated dispersing tablet and preparation method thereof - Google Patents
A kind of Tandospirone dispersible tablet or coated dispersing tablet and preparation method thereof Download PDFInfo
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- CN104997740B CN104997740B CN201410160922.9A CN201410160922A CN104997740B CN 104997740 B CN104997740 B CN 104997740B CN 201410160922 A CN201410160922 A CN 201410160922A CN 104997740 B CN104997740 B CN 104997740B
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- Prior art keywords
- tandospirone
- dispersible tablet
- sodium
- tablet
- tablet according
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- CEIJFEGBUDEYSX-FZDBZEDMSA-N tandospirone Chemical compound O=C([C@@H]1[C@H]2CC[C@H](C2)[C@@H]1C1=O)N1CCCCN(CC1)CCN1C1=NC=CC=N1 CEIJFEGBUDEYSX-FZDBZEDMSA-N 0.000 title claims abstract description 77
- 229950000505 tandospirone Drugs 0.000 title claims abstract description 77
- 239000007919 dispersible tablet Substances 0.000 title claims abstract description 37
- 239000003826 tablet Substances 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 25
- 239000007884 disintegrant Substances 0.000 claims abstract description 12
- 239000000945 filler Substances 0.000 claims abstract description 10
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 239000011248 coating agent Substances 0.000 claims description 36
- 238000000576 coating method Methods 0.000 claims description 36
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 30
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 25
- 229930195725 Mannitol Natural products 0.000 claims description 25
- 239000000594 mannitol Substances 0.000 claims description 25
- 235000010355 mannitol Nutrition 0.000 claims description 25
- 239000000843 powder Substances 0.000 claims description 20
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 17
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- 239000008108 microcrystalline cellulose Substances 0.000 claims description 17
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 16
- 239000011734 sodium Substances 0.000 claims description 16
- 229910052708 sodium Inorganic materials 0.000 claims description 16
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- 235000011187 glycerol Nutrition 0.000 claims description 15
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 14
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 claims description 14
- 239000008101 lactose Substances 0.000 claims description 13
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 13
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 13
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 12
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- 229940037627 magnesium lauryl sulfate Drugs 0.000 claims description 11
- HBNDBUATLJAUQM-UHFFFAOYSA-L magnesium;dodecyl sulfate Chemical compound [Mg+2].CCCCCCCCCCCCOS([O-])(=O)=O.CCCCCCCCCCCCOS([O-])(=O)=O HBNDBUATLJAUQM-UHFFFAOYSA-L 0.000 claims description 11
- UNXHWFMMPAWVPI-UHFFFAOYSA-N Erythritol Natural products OCC(O)C(O)CO UNXHWFMMPAWVPI-UHFFFAOYSA-N 0.000 claims description 9
- UNXHWFMMPAWVPI-ZXZARUISSA-N erythritol Chemical compound OC[C@H](O)[C@H](O)CO UNXHWFMMPAWVPI-ZXZARUISSA-N 0.000 claims description 9
- 238000000034 method Methods 0.000 claims description 8
- 150000005846 sugar alcohols Chemical class 0.000 claims description 8
- XINCECQTMHSORG-UHFFFAOYSA-N Isoamyl isovalerate Chemical compound CC(C)CCOC(=O)CC(C)C XINCECQTMHSORG-UHFFFAOYSA-N 0.000 claims description 7
- 238000004040 coloring Methods 0.000 claims description 7
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 6
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- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 claims description 6
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- VYIRVAXUEZSDNC-TXDLOWMYSA-N (3R,3'S,5'R)-3,3'-dihydroxy-beta-kappa-caroten-6'-one Chemical compound C([C@H](O)CC=1C)C(C)(C)C=1/C=C/C(/C)=C/C=C/C(/C)=C/C=C/C=C(C)C=CC=C(C)C=CC(=O)[C@]1(C)C[C@@H](O)CC1(C)C VYIRVAXUEZSDNC-TXDLOWMYSA-N 0.000 claims description 4
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- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
- WRANYHFEXGNSND-LOFNIBRQSA-N capsanthin Natural products CC(=C/C=C/C=C(C)/C=C/C=C(C)/C=C/C1=C(C)CC(O)CC1(C)C)C=CC=C(/C)C=CC(=O)C2(C)CCC(O)C2(C)C WRANYHFEXGNSND-LOFNIBRQSA-N 0.000 claims description 4
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- MOTZDAYCYVMXPC-UHFFFAOYSA-N dodecyl hydrogen sulfate Chemical compound CCCCCCCCCCCCOS(O)(=O)=O MOTZDAYCYVMXPC-UHFFFAOYSA-N 0.000 claims description 4
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- 239000001525 mentha piperita l. herb oil Substances 0.000 claims description 4
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- 235000012658 paprika extract Nutrition 0.000 claims description 4
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- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 4
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- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 claims description 3
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- HLUCICHZHWJHLL-UHFFFAOYSA-N Haematein Natural products C12=CC=C(O)C(O)=C2OCC2(O)C1=C1C=C(O)C(=O)C=C1C2 HLUCICHZHWJHLL-UHFFFAOYSA-N 0.000 claims description 2
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- 230000000949 anxiolytic effect Effects 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 238000010241 blood sampling Methods 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 229910000019 calcium carbonate Inorganic materials 0.000 description 1
- 235000010216 calcium carbonate Nutrition 0.000 description 1
- FUFJGUQYACFECW-UHFFFAOYSA-L calcium hydrogenphosphate Chemical compound [Ca+2].OP([O-])([O-])=O FUFJGUQYACFECW-UHFFFAOYSA-L 0.000 description 1
- 235000011132 calcium sulphate Nutrition 0.000 description 1
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 1
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 239000008119 colloidal silica Substances 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 239000000470 constituent Substances 0.000 description 1
- 235000012343 cottonseed oil Nutrition 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 235000019700 dicalcium phosphate Nutrition 0.000 description 1
- 239000012738 dissolution medium Substances 0.000 description 1
- 238000007922 dissolution test Methods 0.000 description 1
- 230000005611 electricity Effects 0.000 description 1
- 230000008451 emotion Effects 0.000 description 1
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000007888 film coating Substances 0.000 description 1
- 238000009501 film coating Methods 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 239000003205 fragrance Substances 0.000 description 1
- 235000008434 ginseng Nutrition 0.000 description 1
- 229960001031 glucose Drugs 0.000 description 1
- 230000036541 health Effects 0.000 description 1
- 229960002897 heparin Drugs 0.000 description 1
- 229920000669 heparin Polymers 0.000 description 1
- 210000001320 hippocampus Anatomy 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000005554 hypnotics and sedatives Substances 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 210000000936 intestine Anatomy 0.000 description 1
- 210000003715 limbic system Anatomy 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000002075 main ingredient Substances 0.000 description 1
- 239000003595 mist Substances 0.000 description 1
- 239000011812 mixed powder Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 230000001670 myorelaxant effect Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 210000002569 neuron Anatomy 0.000 description 1
- 239000004031 partial agonist Substances 0.000 description 1
- 230000035699 permeability Effects 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 230000003518 presynaptic effect Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 230000004799 sedative–hypnotic effect Effects 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- 229940071117 starch glycolate Drugs 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229960004793 sucrose Drugs 0.000 description 1
- 125000000185 sucrose group Chemical group 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 239000007885 tablet disintegrant Substances 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
Landscapes
- Medicinal Preparation (AREA)
Abstract
The invention provides a kind of Tandospirone dispersible tablet, and it is that the supplementary material containing following percentage by weight is prepared：Tandospirone or its pharmaceutically useful salt 1%~8%, filler 65%~90%, disintegrant 4%~30%.Tandospirone dispersible tablet prepared by the present invention has disintegration rate more faster than ordinary tablet, and higher dissolution rate, can in alimentary canal efficient absorption, obtain higher bioavilability.The present invention first can also disperse to take again in water, have sweet, be more suitable for the bad crowd of oral formulations absorption, swallow the crowd having difficulties and the low the elderly of Compliance or child takes.
Description
Technical field
The present invention relates to a kind of Tandospirone dispersible tablet or coated dispersing tablet and preparation method thereof.
Background technology
Tandospirone is a kind of novel anxiolytic succeeded in developing by SUMITOMO CHEMICAL Pharmaceutical Co., Ltd, and in 1996
It is approved to list in Japan, initially enters Chinese market within 2004, the application in antianxiety field is increasingly extensive at home.
Tandospirone selectively acting is in intracerebral 5-HT1AAcceptor, site of action concentrate on the hippocampus of emotion maincenter, amygdaloid nucleus
Deng cerebral limbic system and the nuclei of median raphe of 5-HT energy nerves is projected to, by activating presynaptic 5-HT1AAcceptor, suppress neuron and put
Electricity, 5-HT synthesis is reduced, while to the 5-HT in postsynaptic1AAcceptor has partial agonist effect, is dashed forward so as to reach comprehensive adjustment
Tactile 5-HT functions, play angst resistance effect.It is long-term use of to play antidepressant effect simultaneously.With traditional hypnotic sedative agent
Compare, its angst resistance effect is special, and side effect is less, and sedative-hypnotic effect is weak, no myorelaxant effects, without according to lazyness and drug withdrawal
Withrawal symptom, in vivo without accumulation after prolonged application, had a extensive future in antianxiety field.
At present, the preparation variety that Tandospirone is commercially supplied only has two kinds of normal orals of Film coated tablets and conventional capsule
Preparation, as its clinical practice is further extensive, more requirements are proposed to the new formulation of Tandospirone.
Tandospirone, which belongs to, acts on central nervous system class medicine, and oral formulations, which need to first pass through intestines and stomach, to be absorbed into
Body circulation, IC action target spot competence exertion therapeutic action is then distributed to by blood-brain barrier.Blood-brain barrier is
One layer of defensive barrier of brain, there is strict restriction effect to the transmission of material, active constituents of medicine will be shielded by this layer
Barrier enters intracerebral, in addition to the permeability of itself, is also restricted by blood concentration.There is clinical data to show, health into
People is once after oral Tandospirone 20mg, and maximum concentration is only 2.9~3.2ng/ml in blood plasma.Generally adult is smooth using citric acid
The dosage for spending spiral shell ketone piece is oral each 10mg, and 3 times a day, and daily dosage is limited in and must not exceed 60mg.
Grain after two kinds of oral formulations of Film coated tablets and conventional capsule in the market have disintegration time long or are disintegrated
The problem of degree is big, and dissolution is slow, the absorption of medicine is have impact on, be so difficult the blood concentration after improving orally.If merely with
Increase the problem of medication dose is to overcome blood concentration low, the increased risk of adverse reaction can be brought again.So exploitation is a kind of smooth
The efficient absorption preparation of degree spiral shell ketone just becomes only choosing.
The content of the invention
It is an object of the invention to provide a kind of Tandospirone dispersible tablet or coated dispersing tablet and preparation method thereof.
The invention provides a kind of Tandospirone dispersible tablet, it be the supplementary material containing following percentage by weight prepare and
Into：
Tandospirone or its pharmaceutically useful salt 1%~8%
Filler 65%~90%
Disintegrant 4%~30%
Wherein, the pharmaceutically useful salt of Tandospirone be selected from tandospirone citrate, hydrochloric acid Tandospirone, sulfuric acid Tandospirone,
One kind in tartaric acid Tandospirone, oxalic acid Tandospirone, fumaric acid Tandospirone, maleic acid Tandospirone, preferably citric acid
Tandospirone or hydrochloric acid Tandospirone；
Filler is selected from sucrose, glucose, lactose, saccharin sodium, microcrystalline cellulose, pregelatinized starch, mannitol, sorb
One or more in sugar alcohol, antierythrite, xylitol, sodium chloride, calcium sulfate, calcium monohydrogen phosphate, calcium carbonate, colloidal silica
The group of one of combination, preferably pregelatinized starch, microcrystalline cellulose, lactose three and mannitol, D-sorbite or antierythrite
Close；
Disintegrant is selected from low-substituted hydroxypropyl cellulose, Ac-Di-Sol, PVPP, CMS
One or more combinations in sodium, sodium starch glycol, hydroxyethylmethylcellulose, methylcellulose, sodium carboxymethylcellulose,
It is preferred that low-substituted hydroxypropyl cellulose, Ac-Di-Sol, PVPP, sodium carboxymethyl starch, starch glycolate are sour
The combination of sodium, more preferably PVPP and sodium carboxymethyl starch.
Further, it is that the supplementary material containing following percentage by weight is prepared：
Tandospirone or its pharmaceutically useful salt 1%~4%
Filler 86%~89%
Disintegrant 8~10%.
Further, disintegrant percentage by weight is 9%.
Further, in the filler, lactose：Pregelatinized starch：Microcrystalline cellulose：（Mannitol, D-sorbite or
Antierythrite）=（230~250）：55：100:（40~45）.
Further, in the disintegrant, PVPP：Sodium carboxymethyl starch=10：35.
Wherein, 0.1%~2% lubricant and 0.1%~2% glidant are also contained in the dispersible tablet；
The lubricant is selected from sodium benzoate, enuatrol, sodium acetate, Macrogol 4000, Macrogol 6000, stearoyl
One in fumaric acid sodium, sldium lauryl sulfate, magnesium laurylsulfate, polyoxyethylene lauryl alcohol sodium sulphate, mono laurate sucrose ester
Kind or multiple combinations, preferably sldium lauryl sulfate or magnesium laurylsulfate；
One or more combinations of the glidant in superfine silica gel powder, talcum powder, preferably superfine silica gel powder.
Present invention also offers the preparation method of above-mentioned dispersible tablet, and it includes following operating procedure：
（1）Supplementary material is weighed by proportioning；
（2）After supplementary material is well mixed, pressed powder is directly carried out with tablet press machine and produces dispersible tablet.
Present invention also offers a kind of Tandospirone coated dispersing tablet, and it is using above-mentioned dispersible tablet as the piece heart, prepared by coating
Form.
Further, coating weight gain accounts for the 3%~4% of piece heart quality.
Further, the coating solution for being coated use is prepared by the auxiliary material of following weight proportion：
Further, the cellulose derivative is selected from hydroxypropyl cellulose, methylcellulose, carboxymethyl cellulose
One or more combination in sodium, methyl hydroxyethylcellulose, HPMC, preferably HPMC；
One or more combinations of the sugar alcohol in mannitol, D-sorbite, antierythrite, xylitol, lactitol, it is excellent
Select mannitol or D-sorbite；
Flavouring is selected from flavoring apple essence, flavoring orange essence, flavoring banana essence, mango essence, orange flavor, lemon extract, pineapple
Essence, strawberry essence, cocoanut flavour, peppermint oil, fennel oil etc. is medicinal or flavorant；
Colouring agent is selected from haematein, beet red, famille rose, capsanthin, sunset yellow, tartrazines, turmeric, carrotene, pine needle
The medicinal or food colorings such as orchid, light blue, prison are green, chlorophyll, copper chlorophyllin sodium salt.
Present invention also offers the preparation method of above-mentioned coated dispersing tablet, and it includes following operating procedure：
（1）Piece heart supplementary material is weighed by proportioning, after supplementary material is well mixed, directly pressed powder is carried out i.e. with tablet press machine
Obtain the piece heart；
（2）Coating solution supplementary material is weighed by proportioning, sugar alcohol, glycerine, flavouring and colouring agent are first added into 70~90 DEG C of heat
Dissolved in water, then HPMC is added, slowly stirring makes to be uniformly dispersed；Dispersion liquid is put into frozen water and cooled down,
Continue slowly to stir in cooling procedure, produce coating solution, it is standby；
Coating pan is first preheated to 40 ± 5 DEG C, the piece heart, which is placed in coating pan, makes piece heart thermally equivalent, controls leaving air temp
For 60 ± 5 DEG C, setting speed is 6~8 revs/min, carries out spray coating with the coating solution prepared, coating weight gain is accounted for piece heart matter
The 3%~4% of amount.
Further, step（2）In spray coating process, spray press control is in 4~6MPa.
Tandospirone dispersible tablet prepared by the present invention has disintegration rate more faster than ordinary tablet, and higher dissolution
Degree, can in alimentary canal efficient absorption, improve the bioavilability of medicine.The present invention first can also disperse to take again in water
With, be adapted to absorb oral formulations bad crowd, swallow the crowd having difficulties and the elderly that Compliance is low or
Child takes.
Tandospirone dispersible tablet composition prepared by the present invention is ingenious in design, and majority is auxiliary using economical and easily available preparation
Material, such as lactose, microcrystalline cellulose and conventional tablet disintegrant, it is surprising that the dispersible tablet tool of prescription compatibility of medicines of the present invention
There are high disintegration effect and dispersion effect, compared to the existing Tandospirone oral formulations of in the market, dissolution rate is carried significantly
It is high.
Tandospirone dispersible tablet prepared by the present invention is not only outer with allowing people to be willing to accept after special Cotton seeds
Sight and fragrance, can also effectively prevent influence of the Environmental Water to the piece heart, still with excellent disintegration effect.
Below by way of embodiment, the present invention is described in further detail, but is not intended to limit the present invention, ability
Field technique personnel are variously modified and replaced according to the present invention, without departing from the spirit of the present invention, all should belong to the present invention
Scope of the following claims.
Embodiment
Embodiment 1
The piece heart forms（1000）：
Tandospirone citrate 10g
Sucrose 240g
Mannitol 45g
Pregelatinized starch 50g
Microcrystalline cellulose 80g
Low-substituted hydroxypropyl cellulose 70g
Sldium lauryl sulfate 3g
Superfine silica gel powder 2g
Coating solution forms：
HPMC 12g
Mannitol 10g
Glycerine 12ml
Strawberry essence 2g
Capsanthin 3g
Water 600ml
Evaluation index：
Preparation technology：
The piece heart is suppressed：Tandospirone or its pharmaceutically useful salt, filler, disintegrant are crossed into 100 mesh sieves respectively, mixing is equal
It is even；Then lubricant and glidant are added, after being well mixed, the content of Tandospirone in mixed-powder is determined, calculates piece weight, use
Tablet press machine direct tablet compressing produces.
Coating solution is prepared：First sugar alcohol, glycerine, flavouring and colouring agent are added in 70~90 DEG C of hot water and dissolved, then by hydroxyl
Third methylcellulose adds, and slowly stirring makes to be uniformly dispersed；Dispersion liquid is put into frozen water and cooled down, and continues in cooling procedure slow
Slowly stir, produce coating solution, it is standby.
Coating：Coating pan is first preheated to 40 DEG C, the piece heart, which is placed in coating pan, makes piece heart thermally equivalent, controls out wind-warm syndrome
Spend for 60 DEG C or so, setting speed is 6~8 revs/min, adjusts Burners Positions, spray coating is carried out with the coating solution prepared, is sprayed
Mist Stress control makes coating weight gain account for the 3%~4% of piece heart quality in 4~6MPa.
The preparation technology of following embodiments 2~11 is the same as embodiment 1.
Embodiment 2
The piece heart forms（1000）：
Tandospirone citrate 10g
Glucose sugar 240g
Mannitol 45g
Pregelatinized starch 50g
Microcrystalline cellulose 60g
Ac-Di-Sol 90g
Sodium stearyl fumarate 3g
Superfine silica gel powder 2g
Coating solution forms：
HPMC 12g
Mannitol 10g
Glycerine 12ml
Strawberry essence 2g
Capsanthin 3g
Water 600ml
Evaluation index：
Embodiment 3
The piece heart forms（1000）：
Tandospirone citrate 10g
Saccharin sodium 240g
Mannitol 45g
Pregelatinized starch 50g
Microcrystalline cellulose 80g
PVPP 70g
Polyoxyethylene lauryl alcohol sodium sulphate 3g
Superfine silica gel powder 2g
Coating solution forms：
HPMC 12g
Mannitol 10g
Glycerine 12ml
Flavoring apple essence 2g
Pine needle orchid 5g
Water 600ml
Evaluation index：
Embodiment 4
The piece heart forms（1000）：
Tandospirone citrate 10g
Lactose 240g
Mannitol 45g
Pregelatinized starch 50g
Microcrystalline cellulose 90g
Sodium carboxymethyl starch 60g
Mono laurate sucrose ester 3g
Superfine silica gel powder 2g
Coating solution forms：
HPMC 12g
Mannitol 10g
Glycerine 12ml
Flavoring apple essence 2g
Pine needle orchid 5g
Water 600ml
Evaluation index：
Embodiment 5
The piece heart forms（1000）：
Tandospirone citrate 10g
Lactose 240g
Mannitol 45g
Pregelatinized starch 50g
Microcrystalline cellulose 60g
Sodium starch glycol 90g
Magnesium laurylsulfate 3g
Superfine silica gel powder 2g
Coating solution forms：
HPMC 12g
Mannitol 10g
Glycerine 12ml
Flavoring apple essence 2g
Pine needle orchid 5g
Water 600ml
Evaluation index：
Embodiment 6
The piece heart forms（1000）：
Tandospirone citrate 5g
Lactose 250g
Mannitol 40g
Pregelatinized starch 55g
Microcrystalline cellulose 100g
Sodium carboxymethyl starch 35g
PVPP 10g
Magnesium laurylsulfate 3g
Superfine silica gel powder 2g
Coating solution forms：
HPMC 12g
Mannitol 10g
Glycerine 12ml
Flavoring apple essence 2g
Copper chlorophyllin sodium salt 3g
Water 600ml
Evaluation index：
Embodiment 7
The piece heart forms（1000）：
Tandospirone citrate 10g
Lactose 240g
Mannitol 45g
Pregelatinized starch 55g
Microcrystalline cellulose 100g
Sodium carboxymethyl starch 35g
PVPP 10g
Magnesium laurylsulfate 3g
Superfine silica gel powder 2g
Coating solution forms：
HPMC 12g
Mannitol 10g
Glycerine 12ml
Flavoring apple essence 2g
Copper chlorophyllin sodium salt 3g
Water 600ml
Evaluation index：
Embodiment 8
The piece heart forms（1000）：
Hydrochloric acid Tandospirone 5g
Lactose 250g
D-sorbite 40g
Pregelatinized starch 55g
Microcrystalline cellulose 100g
Sodium carboxymethyl starch 35g
PVPP 10g
Magnesium laurylsulfate 3g
Superfine silica gel powder 2g
Coating solution forms：
HPMC 12g
D-sorbite 10g
Glycerine 12ml
Peppermint oil 2g
Copper chlorophyllin sodium salt 3g
Water 600ml
Evaluation index：
Embodiment 9
The piece heart forms（1000）：
Hydrochloric acid Tandospirone 10g
Lactose 240g
D-sorbite 45g
Pregelatinized starch 55g
Microcrystalline cellulose 100g
Sodium carboxymethyl starch 35g
PVPP 10g
Magnesium laurylsulfate 3g
Superfine silica gel powder 2g
Coating solution forms：
HPMC 12g
D-sorbite 10g
Glycerine 12ml
Peppermint oil 2g
Copper chlorophyllin sodium salt 3g
Water 600ml
Evaluation index：
Embodiment 10
The piece heart forms（1000）：
Tandospirone citrate 20g
Lactose 230g
Mannitol 45g
Pregelatinized starch 55g
Microcrystalline cellulose 100g
Sodium carboxymethyl starch 35g
PVPP 10g
Magnesium laurylsulfate 3g
Superfine silica gel powder 2g
Coating solution forms：
HPMC 12g
Mannitol 10g
Glycerine 12ml
Flavoring orange essence 1g
Setting sun Huang 4g
Water 600ml
Evaluation index：
Embodiment 11
The piece heart forms（1000）：
Hydrochloric acid Tandospirone 20g
Lactose 230g
Antierythrite 45g
Pregelatinized starch 55g
Microcrystalline cellulose 100g
Sodium carboxymethyl starch 35g
PVPP 10g
Magnesium laurylsulfate 3g
Superfine silica gel powder 2g
Coating solution forms：
HPMC 12g
Antierythrite 10g
Glycerine 12ml
Flavoring orange essence 1g
Setting sun Huang 4g
Water 600ml
Evaluation index：
Beneficial effects of the present invention are illustrated below by way of test example.
Test example 1
（1）Fuchsin(e)test
By the piece heart made from embodiment 1~11 and coated dispersing tablet sample be placed in temperature be 25 ± 0.5 DEG C with humidity be 75
± 2% constant temperature and humidity is tested under confined conditions, respectively at 0d, 5d, 15d, 30d measure moisture absorption weightening, is as a result listed in table 1.
Table 1
| Sample | 0d（mg） | 5d（mg） | 15d（mg） | 30d（mg） | 30d outward appearances |
| The piece heart 1 | 501 | 537 | 552 | 561 | Loose or rupture |
| Embodiment 1 | 520 | 522 | 523 | 523 | It is smooth bright and clean |
| The piece heart 2 | 500 | 533 | 553 | 567 | Loose or rupture |
| Embodiment 2 | 521 | 522 | 522 | 523 | It is smooth bright and clean |
| The piece heart 3 | 500 | 541 | 550 | 567 | Loose or rupture |
| Embodiment 3 | 522 | 523 | 523 | 524 | It is smooth bright and clean |
| The piece heart 4 | 500 | 545 | 557 | 570 | Loose or rupture |
| Embodiment 4 | 521 | 522 | 522 | 523 | It is smooth bright and clean |
| The piece heart 5 | 500 | 536 | 549 | 557 | Loose or rupture |
| Embodiment 5 | 520 | 521 | 523 | 523 | It is smooth bright and clean |
| The piece heart 6 | 500 | 539 | 545 | 569 | Loose or rupture |
| Embodiment 6 | 520 | 522 | 523 | 524 | It is smooth bright and clean |
| The piece heart 7 | 500 | 533 | 553 | 569 | Loose or rupture |
| Embodiment 7 | 521 | 522 | 522 | 523 | It is smooth bright and clean |
| The piece heart 8 | 500 | 541 | 550 | 571 | Loose or rupture |
| Embodiment 8 | 522 | 523 | 523 | 525 | It is smooth bright and clean |
| The piece heart 9 | 500 | 545 | 557 | 569 | Loose or rupture |
| Embodiment 9 | 521 | 522 | 522 | 524 | It is smooth bright and clean |
| The piece heart 10 | 500 | 536 | 549 | 557 | Loose or rupture |
| Embodiment 10 | 521 | 522 | 523 | 524 | It is smooth bright and clean |
| The piece heart 11 | 501 | 539 | 545 | 567 | Loose or rupture |
| Embodiment 11 | 521 | 522 | 523 | 524 | It is smooth bright and clean |
（2）Disintegration, dissolution test
According to sample listed by table 2, first by 2010 editions annex XA methods of Chinese Pharmacopoeia, the stainless steel shaft that hanging basket is passed through into upper end
Hang on metallic support, immerse in 1000ml beakers, and adjust when hanging basket position makes its decline screen cloth apart from beaker bottom
25mm, fills the water of 20 DEG C ± 1 DEG C of temperature in beaker, when regulation height of water level rises hanging basket screen cloth at the 15mm of underwater,
Then start disintegration tester measure disintegration time, and determine disintegration after whether all by No. 2 screen clothes of pharmacopeia, the results are shown in Table 2.
By the method for dissolution determination second in 2010 editions C of annex Ⅹ of Chinese Pharmacopoeia, with 0.1mol/L phosphate buffers
（pH6.0）900ml is dissolution medium, and rotating speed is 50 revs/min, operates in accordance with the law, after 15 minutes, takes solution appropriate, filters, takes continuous
Filtrate determines dissolution percentage, is as a result listed in table 2 as need testing solution.
Table 2
Above-described embodiment illustrates that dispersible tablet of the present invention disintegration is rapid, disintegration time limited in the 180s of States Pharmacopoeia specifications, and
Main ingredient dissolution rate can reach more than 80% in 15min.Meanwhile dispersible tablet of the present invention is handled by certain film coating, not only
Mouthfeel can be improved, prevent the influence of Environmental Water, and do not weaken disintegration and the dissolving out capability of dispersible tablet.In addition, implement
The dispersible tablet and coated dispersing tablet of 6~embodiment of example 11, disintegration time limited within 50s, and 15min dissolution rates be up to 95% with
On, show the preparation that 6~embodiment of embodiment 11 is formulated, for embodiment 1~5, more considerably improve the present invention
The disintegration of medicine and dissolving out capability.
Summary result can be seen that dispersible tablet of the present invention and coated dispersing tablet disintegration time and dissolution rate it is obvious
Quick release and quick acting effect can be reached better than States Pharmacopoeia specifications, during use, be greatly enhanced the biology profit of active component
Expenditure, the medicine for acting on central nervous system is set to play more effective therapeutic action.
（3）Bioavailability study
By 6 Beagle dogs（Numbering 1~6）2 groups are randomly divided into, every group 3, each group distinguishes oral tandospirone citrate
The tandospirone citrate dispersible tablet of ordinary tablet and embodiment 7, tested using single dose crossover, experiment the last week, which prohibits, takes it
Its medicine, and fasting 12h before administration.Blank blood is first taken before the medication of Beagle dogs, uniformly gives and drinks water after the 4h that takes medicine, respectively at
0.25,0.5,1.0,1.5,2.0,3.0,4.0,6.0,8.0,10.0,12.0,14.0,24.0h blood sampling 3ml, is placed in and is pre-coated with
In the centrifuge tube of heparin, 10min is centrifuged with 4000 turns/min immediately, draws upper plasma measure wherein Tandospirone concentration.Often
Intersect administration after being spaced one week, taken a blood sample with same method and determine Tandospirone concentration in blood plasma, finally calculate 2 kinds of preparations respectively
Pharmacokinetic parameters, the results are shown in Table 3.Compare between the pharmacokinetic parameters of each group preparation using one-way analysis of variance（One-Way
ANOVA）, with P<0.05 or P<0.01 thinks with significant difference.
Pharmacokinetics ginseng after the oral tandospirone citrate ordinary tablet of table 3Beagle dogs and tandospirone citrate dispersible tablet
Number
| Preparation/specification | Tmax(h) | Cmax(ng/ml) | AUC(ng·h/ml) | T1/2(h) |
| Commercially available/10mg（Trade name：Xi De） | 1.2±0.1 | 3.4±0.7 | 9.7±1.9 | 1.2 |
| Dispersible tablet/10mg（Embodiment 7） | 0.7±0.1# | 6.7±0.9## | 21.1±3.2## | 1.0 |
Compared with commercially available：#P<0.05,##P<0.01；
Data in table 3 show, after the oral tandospirone citrate dispersible tablet of Beagle dogs with the smooth degree spiral shell of oral citric acid
Ketone ordinary tablet compares, TmaxValue substantially reduces, CmaxValue and AUC dramatically increase.Prove the present invention dispersible tablet with it is existing
Commercial preparation is compared, and onset time substantially accelerates, and can play quick-acting effects；And bioavilability significantly improves, Ke Yifa
Wave the effect of more preferable.
Claims (16)
- A kind of 1. Tandospirone dispersible tablet, it is characterised in that：It is that the supplementary material containing following percentage by weight is prepared：Tandospirone or its pharmaceutically useful salt 1% ~ 8%Filler 65% ~ 90%Disintegrant 4% ~ 30%Wherein, the pharmaceutically useful salt of Tandospirone is selected from tandospirone citrate, hydrochloric acid Tandospirone, sulfuric acid Tandospirone, winestone One kind in sour Tandospirone, oxalic acid Tandospirone, fumaric acid Tandospirone, maleic acid Tandospirone；Filler be pregelatinized starch, microcrystalline cellulose, lactose three and selected from mannitol, D-sorbite or antierythrite it One combination；Disintegrant is the combination of PVPP and sodium carboxymethyl starch.
- 2. Tandospirone dispersible tablet according to claim 1, it is characterised in that：It is the original containing following percentage by weight Auxiliary material is prepared：Tandospirone or its pharmaceutically useful salt 1% ~ 4%Filler 86% ~ 89%Disintegrant 8 ~ 10%.
- 3. Tandospirone dispersible tablet according to claim 1, it is characterised in that：The pharmaceutically useful salt choosing of described Tandospirone From tandospirone citrate or hydrochloric acid Tandospirone.
- 4. Tandospirone dispersible tablet according to claim 2, it is characterised in that：Disintegrant percentage by weight is 9%.
- 5. Tandospirone dispersible tablet according to claim 1, it is characterised in that：In the filler, lactose：Pregelatinated forms sediment Powder：Microcrystalline cellulose：（Mannitol, D-sorbite or antierythrite）=（230~250）：55：100:（40~45）.
- 6. Tandospirone dispersible tablet according to claim 1, it is characterised in that：In the disintegrant, PVPP：Carboxylic Methyl starch sodium=10：35.
- 7. the Tandospirone dispersible tablet according to claim 1 ~ 6 any one, it is characterised in that：Also contain in the dispersible tablet There are 0.1% ~ 2% lubricant and 0.1% ~ 2% glidant；The lubricant is selected from sodium benzoate, enuatrol, sodium acetate, Macrogol 4000, Macrogol 6000, stearoyl richness horse Sour sodium, sldium lauryl sulfate, magnesium laurylsulfate, polyoxyethylene lauryl alcohol sodium sulphate, one kind in mono laurate sucrose ester or Multiple combinations；One or more combinations of the glidant in superfine silica gel powder, talcum powder.
- 8. Tandospirone dispersible tablet according to claim 7, it is characterised in that：Described lubricant is selected from laruyl alcohol sulfuric acid Sodium or magnesium laurylsulfate；Described glidant superfine silica gel powder.
- 9. the preparation method of dispersible tablet described in claim 1, it is characterised in that：It includes following operating procedure：（1）Supplementary material is weighed by proportioning；（2）After supplementary material is well mixed, pressed powder is directly carried out with tablet press machine and produces dispersible tablet.
- A kind of 10. Tandospirone coated dispersing tablet, it is characterised in that：It is with dispersible tablet described in claim 1 ~ 8 any one For the piece heart, coating is prepared.
- 11. Tandospirone coated dispersing tablet according to claim 10, it is characterised in that：Coating weight gain accounts for piece heart quality 3%~4%。
- 12. the Tandospirone coated dispersing tablet according to claim 10 or 11, it is characterised in that：It is coated the coating solution used It is prepared by the auxiliary material of following weight proportion：The g of cellulose derivative 10 ~ 60The g of sugar alcohol 5 ~ 30The ml of glycerine 10 ~ 60The g of flavouring 0.6 ~ 3.0The g of colouring agent 1 ~ 5The ml of water 600.
- 13. Tandospirone coated dispersing tablet according to claim 12, it is characterised in that：The cellulose derivative is selected from One in hydroxypropyl cellulose, methylcellulose, sodium carboxymethylcellulose, methyl hydroxyethylcellulose, HPMC Kind or several combinations；One or more combinations of the sugar alcohol in mannitol, D-sorbite, antierythrite, xylitol, lactitol；Flavouring be selected from flavoring apple essence, flavoring orange essence, flavoring banana essence, mango essence, orange flavor, lemon extract, flavoring pineapple essence, Strawberry essence, cocoanut flavour, peppermint oil, fennel oil is medicinal or flavorant；Colouring agent be selected from haematein, beet red, famille rose, capsanthin, sunset yellow, tartrazines, turmeric, carrotene, pine needle it is blue, Light blue, prison are green, chlorophyll, copper chlorophyllin sodium salt are medicinal or food coloring.
- 14. Tandospirone coated dispersing tablet according to claim 13, it is characterised in that：Described cellulose derivative is HPMC, described sugar alcohol are mannitol or D-sorbite.
- 15. the preparation method of the coated dispersing tablet of claim 12 or 13, it is characterised in that：It includes following operating procedure：（1）Piece heart supplementary material is weighed by proportioning, after supplementary material is well mixed, pressed powder is directly carried out with tablet press machine and produces piece The heart；（2）Coating solution supplementary material is weighed by proportioning, is first added sugar alcohol, glycerine, flavouring and colouring agent molten in 70 ~ 90 DEG C of hot water Solution, then HPMC is added, slowly stirring makes to be uniformly dispersed；Dispersion liquid is put into frozen water and cooled down, cooled Continue slowly to stir in journey, produce coating solution, it is standby；Coating pan is first preheated to 40 ± 5 DEG C, the piece heart, which is placed in coating pan, makes piece heart thermally equivalent, and it is 60 to control leaving air temp ± 5 DEG C, setting speed is 6 ~ 8 revs/min, carries out spray coating with the coating solution prepared, coating weight gain is accounted for piece heart quality 3%~4%。
- 16. preparation method according to claim 15, it is characterised in that：Step（2）In spray coating process, atomisation pressure Control is in 4 ~ 6 MPa.
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| CN201410160922.9A CN104997740B (en) | 2014-04-22 | 2014-04-22 | A kind of Tandospirone dispersible tablet or coated dispersing tablet and preparation method thereof |
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| US5185158A (en) * | 1992-02-27 | 1993-02-09 | Alza Corporation | Dosage form comprising succinimide drug for treating depressive disorders and composition comprising same |
| CN1915216A (en) * | 2006-08-30 | 2007-02-21 | 四川科瑞德制药有限公司 | New usage of tandospirone and its derivative, and composition containing tandospirone |
| CN101868228A (en) * | 2007-11-21 | 2010-10-20 | 大日本住友制药株式会社 | Orally disintegrating tablet |
| CN103550778A (en) * | 2013-11-18 | 2014-02-05 | 四川科瑞德制药有限公司 | Pharmaceutical composition for treating affective disorder disease |
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2014
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|---|---|---|---|---|
| US5185158A (en) * | 1992-02-27 | 1993-02-09 | Alza Corporation | Dosage form comprising succinimide drug for treating depressive disorders and composition comprising same |
| CN1915216A (en) * | 2006-08-30 | 2007-02-21 | 四川科瑞德制药有限公司 | New usage of tandospirone and its derivative, and composition containing tandospirone |
| CN101868228A (en) * | 2007-11-21 | 2010-10-20 | 大日本住友制药株式会社 | Orally disintegrating tablet |
| CN103550778A (en) * | 2013-11-18 | 2014-02-05 | 四川科瑞德制药有限公司 | Pharmaceutical composition for treating affective disorder disease |
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