CN101269014B - Orally disintegrating tablet of risperidone and preparation method thereof - Google Patents
Orally disintegrating tablet of risperidone and preparation method thereof Download PDFInfo
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- CN101269014B CN101269014B CN2007100645834A CN200710064583A CN101269014B CN 101269014 B CN101269014 B CN 101269014B CN 2007100645834 A CN2007100645834 A CN 2007100645834A CN 200710064583 A CN200710064583 A CN 200710064583A CN 101269014 B CN101269014 B CN 101269014B
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- risperidone
- grittiness
- orally disintegrating
- mix homogeneously
- well
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- RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 title claims abstract description 60
- 229960001534 risperidone Drugs 0.000 title claims abstract description 60
- 239000006191 orally-disintegrating tablet Substances 0.000 title claims abstract description 24
- 238000002360 preparation method Methods 0.000 title abstract description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 28
- 239000000203 mixture Substances 0.000 claims description 27
- 239000007962 solid dispersion Substances 0.000 claims description 25
- 239000008187 granular material Substances 0.000 claims description 21
- 229920002472 Starch Polymers 0.000 claims description 15
- 239000008107 starch Substances 0.000 claims description 15
- 235000019698 starch Nutrition 0.000 claims description 15
- 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 14
- 229930195725 Mannitol Natural products 0.000 claims description 14
- 235000019359 magnesium stearate Nutrition 0.000 claims description 14
- 239000000594 mannitol Substances 0.000 claims description 14
- 235000010355 mannitol Nutrition 0.000 claims description 14
- 239000004925 Acrylic resin Substances 0.000 claims description 12
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 12
- NOOLISFMXDJSKH-UHFFFAOYSA-N p-menthan-3-ol Chemical compound CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims description 12
- 229920000178 Acrylic resin Polymers 0.000 claims description 11
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 10
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 10
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 10
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 9
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 8
- 238000005303 weighing Methods 0.000 claims description 7
- 239000001856 Ethyl cellulose Substances 0.000 claims description 6
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 6
- 229920001249 ethyl cellulose Polymers 0.000 claims description 6
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 6
- 238000007908 dry granulation Methods 0.000 claims description 5
- 239000007921 spray Substances 0.000 claims description 5
- 238000001694 spray drying Methods 0.000 claims description 5
- 239000000080 wetting agent Substances 0.000 claims description 5
- AMTWCFIAVKBGOD-UHFFFAOYSA-N dioxosilane;methoxy-dimethyl-trimethylsilyloxysilane Chemical compound O=[Si]=O.CO[Si](C)(C)O[Si](C)(C)C AMTWCFIAVKBGOD-UHFFFAOYSA-N 0.000 claims description 4
- 229940083037 simethicone Drugs 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 238000000034 method Methods 0.000 abstract description 31
- 238000005516 engineering process Methods 0.000 abstract description 9
- 239000012876 carrier material Substances 0.000 abstract description 8
- 239000000463 material Substances 0.000 abstract description 5
- 208000028017 Psychotic disease Diseases 0.000 abstract description 4
- 238000004519 manufacturing process Methods 0.000 abstract description 4
- 239000000843 powder Substances 0.000 abstract description 4
- 230000001154 acute effect Effects 0.000 abstract description 2
- 239000007787 solid Substances 0.000 abstract 2
- 206010001022 Acute psychosis Diseases 0.000 abstract 1
- 239000008188 pellet Substances 0.000 abstract 1
- 239000003814 drug Substances 0.000 description 17
- 229940079593 drug Drugs 0.000 description 15
- 239000011248 coating agent Substances 0.000 description 11
- 238000000576 coating method Methods 0.000 description 11
- 239000002671 adjuvant Substances 0.000 description 8
- 238000001035 drying Methods 0.000 description 6
- 239000000945 filler Substances 0.000 description 6
- 230000000873 masking effect Effects 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 5
- 238000012216 screening Methods 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000003826 tablet Substances 0.000 description 5
- 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 description 4
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 239000008101 lactose Substances 0.000 description 4
- 239000000314 lubricant Substances 0.000 description 4
- 239000002002 slurry Substances 0.000 description 4
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 3
- 239000001768 carboxy methyl cellulose Substances 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 210000000214 mouth Anatomy 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 238000003825 pressing Methods 0.000 description 3
- 201000000980 schizophrenia Diseases 0.000 description 3
- 239000000741 silica gel Substances 0.000 description 3
- 229910002027 silica gel Inorganic materials 0.000 description 3
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 3
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 2
- 229920002261 Corn starch Polymers 0.000 description 2
- 206010013786 Dry skin Diseases 0.000 description 2
- DOOTYTYQINUNNV-UHFFFAOYSA-N Triethyl citrate Chemical compound CCOC(=O)CC(O)(C(=O)OCC)CC(=O)OCC DOOTYTYQINUNNV-UHFFFAOYSA-N 0.000 description 2
- 230000001476 alcoholic effect Effects 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 239000011230 binding agent Substances 0.000 description 2
- NEDGUIRITORSKL-UHFFFAOYSA-N butyl 2-methylprop-2-enoate;2-(dimethylamino)ethyl 2-methylprop-2-enoate;methyl 2-methylprop-2-enoate Chemical compound COC(=O)C(C)=C.CCCCOC(=O)C(C)=C.CN(C)CCOC(=O)C(C)=C NEDGUIRITORSKL-UHFFFAOYSA-N 0.000 description 2
- 235000010980 cellulose Nutrition 0.000 description 2
- 229920002678 cellulose Polymers 0.000 description 2
- 239000001913 cellulose Substances 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 235000009508 confectionery Nutrition 0.000 description 2
- 239000008120 corn starch Substances 0.000 description 2
- 230000002950 deficient Effects 0.000 description 2
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical compound O.[Mg]=O.[Mg]=O.[Mg]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O FPAFDBFIGPHWGO-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 235000011194 food seasoning agent Nutrition 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- 239000002245 particle Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 239000001069 triethyl citrate Substances 0.000 description 2
- VMYFZRTXGLUXMZ-UHFFFAOYSA-N triethyl citrate Natural products CCOC(=O)C(O)(C(=O)OCC)C(=O)OCC VMYFZRTXGLUXMZ-UHFFFAOYSA-N 0.000 description 2
- 235000013769 triethyl citrate Nutrition 0.000 description 2
- YTLYLLTVENPWFT-UPHRSURJSA-N (Z)-3-aminoacrylic acid Chemical class N\C=C/C(O)=O YTLYLLTVENPWFT-UPHRSURJSA-N 0.000 description 1
- 108091005479 5-HT2 receptors Proteins 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- 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 description 1
- 101150049660 DRD2 gene Proteins 0.000 description 1
- 229920003149 Eudragit® E 100 Polymers 0.000 description 1
- 229920003148 Eudragit® E polymer Polymers 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 239000004354 Hydroxyethyl cellulose Substances 0.000 description 1
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 229920000881 Modified starch Polymers 0.000 description 1
- 208000003443 Unconsciousness Diseases 0.000 description 1
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000005557 antagonist Substances 0.000 description 1
- 230000000561 anti-psychotic effect Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000000903 blocking effect Effects 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000004132 cross linking Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 239000007919 dispersible tablet Substances 0.000 description 1
- 230000008451 emotion Effects 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 229960004756 ethanol Drugs 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 description 1
- 229940071826 hydroxyethyl cellulose Drugs 0.000 description 1
- -1 hydroxypropyl Chemical group 0.000 description 1
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 description 1
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 1
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
- 238000007493 shaping process Methods 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007779 soft material Substances 0.000 description 1
- 239000000600 sorbitol Substances 0.000 description 1
- 235000010356 sorbitol Nutrition 0.000 description 1
- 230000003068 static effect Effects 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
- 239000000811 xylitol Substances 0.000 description 1
- 235000010447 xylitol Nutrition 0.000 description 1
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 1
- 229960002675 xylitol Drugs 0.000 description 1
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- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an orally disintegrating tablet containing risperidone and a preparation method thereof. The orally disintegrating tablet contains solid dispersing carrier material and other accessory materials which is acceptable in pharmacy, adopts the solid dispersing technology to effectively hide the taste and is prepared by using a powder pressed disc method or pellet fabrication pressed disc method; the orally disintegrating tablet has the advantages of good mouthfeel and convenient taking, and is used for curing acute or chronic psychosis.
Description
Technical field
The present invention relates to psychotic risperidone orally disintegrating tablets of treatment acute and chronic of a kind of effective taste masking, taking convenience and preparation method thereof.
Background technology
Schizophrenia is one group of psychosis that the cause of disease is not bright, has that inharmonious and ergasia and the environment of many-sided obstacles such as perception, thinking, emotion, behavior and ergasia is inharmonious to be a kind of modal psychosis of characteristic.A lot of diseases are in person between twenty and fifty, general unconscious obstacle and disturbance of intelligence, and the course of disease is delayed more.Schizophrenia is a kind of disease with hereditary basis, and the biology in the external environment, psychological society and environmental factors all can have certain influence to morbidity, the change on part patient has the brain configuration and takes place.
Risperidone is a second filial generation antipsychotic drug, and the blocking effect of very strong 5HT2 and D2 receptor is arranged.Medicine is approaching to these two kinds of receptor affinities, can be referred to as to call DA-5HT balance antagonist, and schizoid five dimension symptoms are had curative effect, and is particularly evident to positive symptom effect, is the common drug of present clinical practice.Because compliance was relatively poor when the uncertainty of schizophrenia disease time was fallen ill with the patient, need as early as possible to patient's administration, be easy to carry, be beneficial to and take and oral cavity disintegration tablet ten minutes necessity of onset rapidly so risperidone is prepared into.But this medicine is extremely bitter, so use suitable method very important to its taste masking.
Granted publication number discloses a kind of risperidone orally disintegrating tablets and preparation method thereof in the Chinese patent of CN1274298C, the method for using granule coating risperidone orally disintegrating tablets to be carried out taste masking.Method is: with crude drug comminution by gas stream to granularity is below 5～50 μ m; Will be behind micronized crude drug and water-insoluble filler mix homogeneously; Aqueous solution with starch slurry or low-viscosity sodium carboxymethyl cellulose is processed wet granular, and the alcoholic solution moistening of the coating material that contains aminoacrylic acid esters resin, hydroxypropyl first class cellulose or hydroxyethyl-cellulose is used in dry back, the screening of dry a little back; Get No. 3 medicines and sieve the granule between No. 6 medicine sieves; Oven dry is with mixing tabletting with adjuvant with other tablettings behind the fluidized bed coating.
Have been found that there are some defectives in this taste masking method:
(1). raw material needs micronization processes, need be behind the particle drying with the alcoholic solution moistening that contains coating material, screening again after the drying a little, complex process, and the technology of " dry a little " is not easy to grasp;
(2). selecting for use of adjuvant only limits to the water-insoluble filler;
(3). get No. 3 medicines and sieve that coating can produce obvious sand type when the patient takes behind the particle drying between No. 6 medicines sieves, reduce patient's compliance.
Therefore, be necessary to provide that a kind of technology is easy, the range of choice of favorable reproducibility, adjuvant extensively, the Orally disintegrating pharmaceutical composition that contains risperidone that patient's compliance is high, overcome the defective of technical scheme that CN1274298C provides existence.
Summary of the invention
The purpose of this invention is to provide a kind of risperidone orally disintegrating tablets, not only disintegrate is rapid for it, is beneficial to absorption, and onset is faster, and mouthfeel is better, has lower production cost and simple preparation technology.
Risperidone orally disintegrating tablets provided by the invention contains the risperidone of 0.5%～1.0% weight portion and the solid dispersion carrier material of 2.5%～10.0% weight portion.
Risperidone orally disintegrating tablets provided by the invention also contains a kind of and/or several kinds of mixture in filler, binding agent, disintegrating agent, the lubricant as suitable adjuvant of the present invention.
Risperidone orally disintegrating tablets provided by the invention can be selected from a kind of and/or several kinds of mixture in lactose, mannitol, sorbitol, xylitol, starch, the microcrystalline Cellulose as suitable filler of the present invention.
Risperidone orally disintegrating tablets provided by the invention is as the optional a kind of and/or several kinds of mixture in polyvidone, sodium carboxymethyl cellulose, starch slurry, pregelatinized Starch slurry, gelatin, xanthan gum, different concentration ethanol, water of suitable binding agent of the present invention.
Risperidone orally disintegrating tablets provided by the invention can be selected from a kind of and/or several kinds of mixture in polyvinylpolypyrrolidone, carboxymethyl starch sodium, cross-linking sodium carboxymethyl cellulose, the low-substituted hydroxypropyl cellulose as suitable disintegrating agent of the present invention.
Risperidone orally disintegrating tablets provided by the invention can be selected from a kind of and/or several kinds of mixture in simethicone, magnesium stearate, micropowder silica gel, the Pulvis Talci as suitable lubricant of the present invention.
Risperidone orally disintegrating tablets provided by the invention uses solid dispersion technology to carry out taste masking.
Risperidone orally disintegrating tablets provided by the invention, its solid dispersion carrier material is selected from one or more mixtures of material of cellulose family and polyacrylic resin class.
Risperidone orally disintegrating tablets provided by the invention, described solid dispersion technology can adopt: solvent method and solvent seasoning method, concrete solid dispersion technology is following:
Solvent method: risperidone and solid dispersion carrier material are dissolved in the organic solvent jointly, granulate as wetting agent.
Solvent seasoning method: risperidone and solid dispersion carrier material are dissolved in the organic solvent jointly, solvent are removed, promptly obtain the risperidone solid dispersion through spray-dired method.
The method for preparing of risperidone orally disintegrating tablets provided by the invention can be that powder pressing method, granulating tabletting process prepare, and concrete method for making is following:
Powder pressing method: component comprises risperidone solid dispersion and other adjuvants.The percentage by weight of risperidone solid dispersion is 3.0%～11.0%, and wherein the risperidone percentage by weight is 0.5%～1.0%, and solid dispersion carrier material percentage by weight is 2.5%～10.0%, and the percentage by weight of excipient is 89.0%～97.0%.The main method step is: with risperidone solid dispersion and other adjuvant mix homogeneously, be shaped with suitable punch die tabletting.
Granulating tabletting process comprises compressing dry granulation and wet granule compression tablet method, and the step of compressing dry granulation is: component comprises risperidone solid dispersion and other adjuvants.The percentage by weight of risperidone solid dispersion is 3.0%～11.0%, and wherein the risperidone percentage by weight is 0.5%～1.0%, and solid dispersion carrier material percentage by weight is 2.5%～10.0%, and the percentage by weight of excipient is 89.0%～97.0%.The main method step is: with risperidone solid dispersion and filler, disintegrating agent mix homogeneously, behind dry granulation mechanism grain, add mix lubricant and evenly be shaped with suitable punch die tabletting the back.
The step of wet granule compression tablet method is: component comprises risperidone solid dispersion and other adjuvants.The percentage by weight of risperidone solid dispersion is 3.0%～11.0%, and wherein the risperidone percentage by weight is 0.5%～1.0%, and solid dispersion carrier material percentage by weight is 2.5%～10.0%, and the percentage by weight of excipient is 89.0%～97.0%.The main method step is: with risperidone solid dispersion and filler, disintegrating agent mix homogeneously, add suitable amount of adhesive system soft material, granulate, drying, add behind the granulate residue disintegrating agent and mix lubricant evenly the back with the punch die tabletting shaping that suits.
Use the risperidone orally disintegrating tablets of powder pressing method and granulating tabletting process preparation, the intraoral disintegration time all less than 40 seconds, the equal good mouthfeel of all components, sugariness suits, and does not have bitter, puckery and grittiness.
The specific embodiment
Below in conjunction with embodiment the present invention is done further explain, it should be understood that embodiments of the invention are to be used to explain the present invention rather than limitation of the present invention.
Embodiment 1:
Risperidone 0.67%
Acrylic resin 3.33%
Simethicone 0.02%
Mannitol 58.61%
Starch 23.31%
Ethyl cellulose 5.00%
Low-substituted hydroxypropyl cellulose 7.99%
Mentholum 0.40%
Magnesium stearate 0.67%
Method for preparing:
Take by weighing an amount of dehydrated alcohol, under stirring, add acrylic resin, be stirred to dissolving, add risperidone, simethicone, stir, put and carry out spray drying in the spray dryer.Get dried risperidone solid dispersion and ethyl cellulose, starch, mannitol and put mix homogeneously in the quick mixer granulator, add water and granulate, dry back granulate.Add Mentholum, magnesium stearate and low-substituted hydroxypropyl cellulose, mix homogeneously.With the stamping of 7mm scrobicula.The heavy 150mg of sheet, disintegration time is 30～40 seconds.
Embodiment 2:
Risperidone 0.67%
Acrylic resin 3.33%
Mannitol 58.63%
Starch 23.31%
Ethyl cellulose 5.00%
Low-substituted hydroxypropyl cellulose 7.99%
Mentholum 0.40%
Magnesium stearate 0.67%
Method for preparing:
Take by weighing an amount of dehydrated alcohol, under stirring, add acrylic resin, risperidone, be stirred to dissolving, as wetting agent.Ethyl cellulose, starch, mannitol are put mix homogeneously in the quick mixer granulator, add above-mentioned wetting agent and granulate, dry back granulate.Add Mentholum, magnesium stearate and low-substituted hydroxypropyl cellulose, mix homogeneously.With the stamping of 7mm scrobicula.The heavy 150mg of sheet, disintegration time is 30～40 seconds.
Embodiment 3:
Risperidone 0.67%
Acrylic resin 3.33%
Mannitol 58.60%
Starch 23.31%
Microcrystalline Cellulose 5.00%
Low-substituted hydroxypropyl cellulose 7.99%
Mentholum 0.40%
Magnesium stearate 0.70%
Method for preparing:
Take by weighing an amount of dehydrated alcohol, under stirring, add acrylic resin, risperidone, be stirred to dissolving, put and carry out spray drying in the spray dryer.Get dried risperidone solid dispersion and microcrystalline Cellulose, starch, mannitol and put mix homogeneously in the quick mixer granulator, dry granulation.Add Mentholum, magnesium stearate and low-substituted hydroxypropyl cellulose, mix homogeneously.With the stamping of 7mm scrobicula.The heavy 150mg of sheet, disintegration time is 20～30 seconds.
Embodiment 4:
Risperidone 0.67%
Acrylic resin 3.33%
Mannitol 43.60%
Lactose 26.30%
Microcrystalline Cellulose 20.00%
Low-substituted hydroxypropyl cellulose 8.00%
Mentholum 0.40%
Magnesium stearate 0.70%
Method for preparing:
Take by weighing an amount of dehydrated alcohol, under stirring, add acrylic resin, risperidone, be stirred to dissolving, put and carry out spray drying in the spray dryer.Get dried risperidone solid dispersion and microcrystalline Cellulose, starch, mannitol, Mentholum, magnesium stearate and low-substituted hydroxypropyl cellulose and put mix homogeneously in the quick mixer granulator.With the stamping of 7mm scrobicula.The heavy 150mg of sheet, disintegration time is 20～30 seconds.
Comparative example (CN1274298C embodiment 1 and CN1274298C embodiment 7):
1. granule prescription (CN1274298C embodiment 1):
Risperidone 200g
Corn starch 800g
Microcrystalline Cellulose 200g
2. coating fluid prescription (CN1274298C embodiment 1):
Dehydrated alcohol 10000ml
Eudragit E 100 500g
Triethyl citrate 75g
Pulvis Talci 200g
3. tabletting prescription (CN1274298C embodiment 7):
Taste masking risperidone granule 148g
Granular mannitol 730g
Lactose 550g
Microcrystalline Cellulose 120g
The sweet 18g of A Siba
Mentholum 6g
Magnesium stearate 10g
Micropowder silica gel 18g
Method for preparing:
With crude drug comminution by gas stream to granularity is below 5～50 μ m, and corn starch, microcrystalline Cellulose are crossed sieve respectively No. 6, according to granule prescription (CN1274298C embodiment 1) batching, crosses the sieve mixing No. 6, processes wet granular with 8% starch slurry.After 60 ℃ of dryings, screening is got No. 3 medicines and is sieved the granule between No. 6 medicines sieves, in coating pan with the abundant moistening of anhydrous alcohol solution that contains 10% Eudragit E 100,1.5% triethyl citrate.After 60 ℃ of dryings, screening is got No. 3 medicines and is sieved the granule between No. 6 medicines sieves once more; On fluidized-bed coating machine with the coating material coating of coating fluid prescription (CN1274298C embodiment 1) to increasing weight 8%, screening is for the third time got No. 3 medicines and is sieved the granule between No. 6 medicines sieves; According to. tabletting prescription (CN1274298C embodiment 7) is said; Earlier with granular mannitol, lactose, microcrystalline Cellulose and the sweet mix homogeneously of A Siba, again with magnesium stearate and micropowder silica gel mixing, tabletting.
The comparing result of table 1. embodiment 1, embodiment 2 and comparative example's manufacturing parameter
| Embodiment 1 | Embodiment 2 | The comparative example 3 | |
| When producing the chief engineer (hour) | 40 | 24 | 60 |
| Sheet heavy (mg) | 150 | 150 | 160 |
| Tabletting hardness (newton) | 30～40 | 30～40 | 25～30 |
| Disintegration time (second) | 30～40 | 30～40 | Not disintegrate fully |
Annotate: judge whether disintegrate fully with on August 2,2003 CDE evaluate four formulation characteristic and judgements of quality control meeting summaries about oral cavity disintegration tablet; That is: medium with water; Consumption should be less than 2ml; Temperature is 37 ℃, adopts static method, and granularity control should be less than the 710um (being equivalent to 30 mesh sieves) of dispersible tablet.
Table 2,20 health volunteers take the disintegration time that receives Orally disintegrating behind the test preparation and the comparing result of mouthfeel
| n＝20 | Embodiment 1 disintegration time (s) | Embodiment 1 mouthfeel | Embodiment 2 disintegration times (s) | Embodiment 2 mouthfeels | Comparative example's disintegration time (s) | Comparative example's mouthfeel |
| 1 | 43 | Well, no grittiness | 57 | Sticking puckery, no grittiness | 58 | Well, grittiness is arranged |
| 2 | 22 | Well, no grittiness | 25 | Sticking puckery, no grittiness | 42 | Sour and astringent, grittiness is arranged |
| 3 | 51 | Well, no grittiness | 18 | Well, no grittiness | 33 | Sour and astringent, grittiness is arranged |
| 4 | 51 | Well, no grittiness | 22 | Sticking puckery, no grittiness | 69 | Well, grittiness is arranged |
| 5 | 43 | Well, no grittiness | 57 | Sticking puckery, no grittiness | 68 | Well, grittiness is arranged |
| 6 | 28 | Well, no grittiness | 44 | Sticking puckery, no grittiness | 49 | Well, grittiness is arranged |
| 7 | 52 | Well, no grittiness | 41 | Well, no grittiness | 41 | Well, grittiness is arranged |
| 8 | 16 | Well, no grittiness | 41 | Sticking puckery, no grittiness | 41 | Well, grittiness is arranged |
| 9 | 41 | Well, no grittiness | 42 | Sticking puckery, no grittiness | 57 | Sour and astringent, grittiness is arranged |
| 10 | 20 | Well, no grittiness | 53 | Well, no grittiness | 61 | Well, grittiness is arranged |
| 11 | 43 | Well, no grittiness | 38 | Well, no grittiness | 28 | Sour and astringent, grittiness is arranged |
| 12 | 32 | Well, no grittiness | 58 | Well, no grittiness | 51 | Well, grittiness is arranged |
| 13 | 45 | Well, no grittiness | 25 | Sticking puckery, no grittiness | 42 | Sour and astringent, grittiness is arranged |
| 14 | 12 | Well, no grittiness | 55 | Well, no grittiness | 42 | Well, grittiness is arranged |
| 15 | 33 | Well, no grittiness | 18 | Well, no grittiness | 33 | Well, grittiness is arranged |
| 16 | 40 | Well, no grittiness | 47 | Well, no grittiness | 41 | Sour and astringent, grittiness is arranged |
| 17 | 52 | Well, no grittiness | 58 | Sticking puckery, no grittiness | 45 | Sour and astringent, grittiness is arranged |
| 18 | 42 | Well, no grittiness | 18 | Well, no grittiness | 40 | Well, grittiness is arranged |
| 19 | 41 | Well, no grittiness | 56 | Well, no grittiness | 48 | Sour and astringent, grittiness is arranged |
| 20 | 42 | Well, no grittiness | 50 | Sticking puckery, no grittiness | 31 | Well, grittiness is arranged |
| Maximum | 52 | — | 58 | — | 69 | — |
| Minima | 12 | — | 18 | — | 28 | — |
| Meansigma methods | 37 | — | 41 | — | 46 | — |
Therefore, can find out, use the production technology and the mouthfeel aspect of the risperidone orally disintegrating tablets of used prescription of the present invention and prepared all to be superior to disclosed risperidone orally disintegrating tablets among the CN1274298C from the result shown in the table 1.
Claims (3)
1. risperidone orally disintegrating tablets is characterized in that:
Take by weighing an amount of dehydrated alcohol, under stirring, add acrylic resin, be stirred to dissolving; Add risperidone, simethicone, stir, put and carry out spray drying in the spray dryer, get dried risperidone solid dispersion and ethyl cellulose, starch, mannitol and put mix homogeneously in the quick mixer granulator; Add water and granulate, dry back granulate adds Mentholum, magnesium stearate and low-substituted hydroxypropyl cellulose; Mix homogeneously with the stamping of 7mm scrobicula, promptly gets.
2. risperidone orally disintegrating tablets is characterized in that:
Take by weighing an amount of dehydrated alcohol, under stirring, add acrylic resin, risperidone; Be stirred to dissolving,, ethyl cellulose, starch, mannitol put mix homogeneously in the quick mixer granulator as wetting agent; Add above-mentioned wetting agent and granulate, dry back granulate adds Mentholum, magnesium stearate and low-substituted hydroxypropyl cellulose; Mix homogeneously with the stamping of 7mm scrobicula, promptly gets.
3. risperidone orally disintegrating tablets is characterized in that:
Take by weighing an amount of dehydrated alcohol, under stirring, add acrylic resin, risperidone; Be stirred to dissolving, put and carry out spray drying in the spray dryer, get dried risperidone solid dispersion and microcrystalline Cellulose, starch, mannitol and put mix homogeneously in the quick mixer granulator; Dry granulation adds Mentholum, magnesium stearate and low-substituted hydroxypropyl cellulose, mix homogeneously; With the stamping of 7mm scrobicula, promptly get.
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| CN101269014B true CN101269014B (en) | 2012-11-14 |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN101366705B (en) * | 2008-09-28 | 2010-09-08 | 浙江大学 | Risperidone percutaneous absorption paster |
| CN102440971A (en) * | 2010-10-15 | 2012-05-09 | 重庆市力扬医药开发有限公司 | Iloperidone orally disintegrating tablet |
| CN103284969B (en) * | 2013-07-01 | 2015-05-27 | 南京正宽医药科技有限公司 | Risperidone dispersible tablet and preparation method thereof |
| CN105456327A (en) * | 2015-12-29 | 2016-04-06 | 刘书玲 | Traditional Chinese medicine composition and preparation thereof for treating psychosis |
| CN107441037A (en) * | 2017-08-16 | 2017-12-08 | 南京正科医药股份有限公司 | A kind of Risperidone oral administration solution |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1478467A (en) * | 2003-06-28 | 2004-03-03 | 南昌弘益科技有限公司 | Rapid disintegrate tablet in oral and its preparation method |
| WO2005123084A1 (en) * | 2004-06-15 | 2005-12-29 | Krka, Tovarna Zdravil, D.D., Novo Mesto | Orally disintegrating pharmaceutical composition comprising risperidone |
| CN1787811A (en) * | 2003-04-16 | 2006-06-14 | 斯索恩有限公司 | Orally disintegrating tablets |
| CN1863517A (en) * | 2003-10-07 | 2006-11-15 | 安壮奇制药公司 | Rapidly disintegrating formulation |
| CN1883456A (en) * | 2005-06-20 | 2006-12-27 | 常州市第四制药厂有限公司 | Flavor-hidden pharmaceutical granule, preparation method and use thereof |
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1787811A (en) * | 2003-04-16 | 2006-06-14 | 斯索恩有限公司 | Orally disintegrating tablets |
| CN1478467A (en) * | 2003-06-28 | 2004-03-03 | 南昌弘益科技有限公司 | Rapid disintegrate tablet in oral and its preparation method |
| CN1863517A (en) * | 2003-10-07 | 2006-11-15 | 安壮奇制药公司 | Rapidly disintegrating formulation |
| WO2005123084A1 (en) * | 2004-06-15 | 2005-12-29 | Krka, Tovarna Zdravil, D.D., Novo Mesto | Orally disintegrating pharmaceutical composition comprising risperidone |
| CN1883456A (en) * | 2005-06-20 | 2006-12-27 | 常州市第四制药厂有限公司 | Flavor-hidden pharmaceutical granule, preparation method and use thereof |
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