CN115105504A - Brexpiprazole orally disintegrating tablet and preparation method thereof - Google Patents
Brexpiprazole orally disintegrating tablet and preparation method thereof Download PDFInfo
- Publication number
- CN115105504A CN115105504A CN202110294443.6A CN202110294443A CN115105504A CN 115105504 A CN115105504 A CN 115105504A CN 202110294443 A CN202110294443 A CN 202110294443A CN 115105504 A CN115105504 A CN 115105504A
- Authority
- CN
- China
- Prior art keywords
- brexpiprazole
- orally disintegrating
- disintegrating tablet
- cyclodextrin
- water
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- ZKIAIYBUSXZPLP-UHFFFAOYSA-N brexpiprazole Chemical compound C1=C2NC(=O)C=CC2=CC=C1OCCCCN(CC1)CCN1C1=CC=CC2=C1C=CS2 ZKIAIYBUSXZPLP-UHFFFAOYSA-N 0.000 title claims abstract description 42
- 229960001210 brexpiprazole Drugs 0.000 title claims abstract description 40
- 239000006191 orally-disintegrating tablet Substances 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title abstract description 8
- 238000000034 method Methods 0.000 claims abstract description 15
- 229920003176 water-insoluble polymer Polymers 0.000 claims abstract description 8
- 239000000945 filler Substances 0.000 claims abstract description 7
- 239000007884 disintegrant Substances 0.000 claims abstract description 6
- 239000000314 lubricant Substances 0.000 claims abstract description 6
- 239000008187 granular material Substances 0.000 claims description 16
- 229920000858 Cyclodextrin Polymers 0.000 claims description 15
- 239000003826 tablet Substances 0.000 claims description 11
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims description 9
- 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 8
- 239000001116 FEMA 4028 Substances 0.000 claims description 6
- 235000011175 beta-cyclodextrine Nutrition 0.000 claims description 6
- 229960004853 betadex Drugs 0.000 claims description 6
- 108010011485 Aspartame Proteins 0.000 claims description 5
- 239000000605 aspartame Substances 0.000 claims description 5
- IAOZJIPTCAWIRG-QWRGUYRKSA-N aspartame Chemical compound OC(=O)C[C@H](N)C(=O)N[C@H](C(=O)OC)CC1=CC=CC=C1 IAOZJIPTCAWIRG-QWRGUYRKSA-N 0.000 claims description 5
- 235000010357 aspartame Nutrition 0.000 claims description 5
- 229960003438 aspartame Drugs 0.000 claims description 5
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical compound OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 claims description 5
- 235000010355 mannitol Nutrition 0.000 claims description 5
- NOOLISFMXDJSKH-UHFFFAOYSA-N p-menthan-3-ol Chemical compound CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims description 5
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 4
- 229920000639 hydroxypropylmethylcellulose acetate succinate Polymers 0.000 claims description 4
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 4
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 4
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 4
- 238000002156 mixing Methods 0.000 claims description 4
- 229920002785 Croscarmellose sodium Polymers 0.000 claims description 3
- 229920002472 Starch Polymers 0.000 claims description 3
- 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 claims description 3
- 239000003795 chemical substances by application Substances 0.000 claims description 3
- 229960001681 croscarmellose sodium Drugs 0.000 claims description 3
- 235000010947 crosslinked sodium carboxy methyl cellulose Nutrition 0.000 claims description 3
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 3
- 239000011734 sodium Substances 0.000 claims description 3
- 229910052708 sodium Inorganic materials 0.000 claims description 3
- 239000008107 starch Substances 0.000 claims description 3
- 235000019698 starch Nutrition 0.000 claims description 3
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 claims description 2
- 229930195725 Mannitol Natural products 0.000 claims description 2
- UEDUENGHJMELGK-HYDKPPNVSA-N Stevioside Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1O[C@]12C(=C)C[C@@]3(C1)CC[C@@H]1[C@@](C)(CCC[C@]1([C@@H]3CC2)C)C(=O)O[C@H]1[C@@H]([C@@H](O)[C@H](O)[C@@H](CO)O1)O)[C@@H]1O[C@H](CO)[C@@H](O)[C@H](O)[C@H]1O UEDUENGHJMELGK-HYDKPPNVSA-N 0.000 claims description 2
- 235000009499 Vanilla fragrans Nutrition 0.000 claims description 2
- 244000263375 Vanilla tahitensis Species 0.000 claims description 2
- 235000012036 Vanilla tahitensis Nutrition 0.000 claims description 2
- 235000010358 acesulfame potassium Nutrition 0.000 claims description 2
- 229960004998 acesulfame potassium Drugs 0.000 claims description 2
- 239000000619 acesulfame-K Substances 0.000 claims description 2
- 239000000796 flavoring agent Substances 0.000 claims description 2
- 235000013355 food flavoring agent Nutrition 0.000 claims description 2
- 235000003599 food sweetener Nutrition 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 229940032147 starch Drugs 0.000 claims description 2
- 229940013618 stevioside Drugs 0.000 claims description 2
- OHHNJQXIOPOJSC-UHFFFAOYSA-N stevioside Natural products CC1(CCCC2(C)C3(C)CCC4(CC3(CCC12C)CC4=C)OC5OC(CO)C(O)C(O)C5OC6OC(CO)C(O)C(O)C6O)C(=O)OC7OC(CO)C(O)C(O)C7O OHHNJQXIOPOJSC-UHFFFAOYSA-N 0.000 claims description 2
- 235000019202 steviosides Nutrition 0.000 claims description 2
- 239000003765 sweetening agent Substances 0.000 claims description 2
- 239000001856 Ethyl cellulose Substances 0.000 claims 1
- 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 1
- 235000019325 ethyl cellulose Nutrition 0.000 claims 1
- 229920001249 ethyl cellulose Polymers 0.000 claims 1
- 229940117841 methacrylic acid copolymer Drugs 0.000 claims 1
- 229920003145 methacrylic acid copolymer Polymers 0.000 claims 1
- 238000005550 wet granulation Methods 0.000 abstract description 5
- 239000000080 wetting agent Substances 0.000 abstract description 4
- 229940079593 drug Drugs 0.000 abstract description 2
- 239000003814 drug Substances 0.000 abstract description 2
- 238000011031 large-scale manufacturing process Methods 0.000 abstract description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 10
- 238000001035 drying Methods 0.000 description 7
- 230000000052 comparative effect Effects 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 239000008213 purified water Substances 0.000 description 6
- 238000005469 granulation Methods 0.000 description 4
- 230000003179 granulation Effects 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 3
- YGCFIWIQZPHFLU-UHFFFAOYSA-N acesulfame Chemical compound CC1=CC(=O)NS(=O)(=O)O1 YGCFIWIQZPHFLU-UHFFFAOYSA-N 0.000 description 3
- 229960005164 acesulfame Drugs 0.000 description 3
- 229960000913 crospovidone Drugs 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- MVPICKVDHDWCJQ-UHFFFAOYSA-N ethyl 3-pyrrolidin-1-ylpropanoate Chemical compound CCOC(=O)CCN1CCCC1 MVPICKVDHDWCJQ-UHFFFAOYSA-N 0.000 description 3
- 235000019359 magnesium stearate Nutrition 0.000 description 3
- 229940057948 magnesium stearate Drugs 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 229940041616 menthol Drugs 0.000 description 3
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 description 3
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 description 3
- 238000004080 punching Methods 0.000 description 3
- 238000007873 sieving Methods 0.000 description 3
- 229940045902 sodium stearyl fumarate Drugs 0.000 description 3
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 2
- GWEVSGVZZGPLCZ-UHFFFAOYSA-N Titan oxide Chemical compound O=[Ti]=O GWEVSGVZZGPLCZ-UHFFFAOYSA-N 0.000 description 2
- 238000007664 blowing Methods 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 238000002347 injection Methods 0.000 description 2
- 239000007924 injection Substances 0.000 description 2
- 239000000825 pharmaceutical preparation Substances 0.000 description 2
- 150000003839 salts Chemical class 0.000 description 2
- 201000000980 schizophrenia Diseases 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- 102100022738 5-hydroxytryptamine receptor 1A Human genes 0.000 description 1
- 101710138638 5-hydroxytryptamine receptor 1A Proteins 0.000 description 1
- 102000040125 5-hydroxytryptamine receptor family Human genes 0.000 description 1
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 description 1
- 206010001540 Akathisia Diseases 0.000 description 1
- CEUORZQYGODEFX-UHFFFAOYSA-N Aripirazole Chemical compound ClC1=CC=CC(N2CCN(CCCCOC=3C=C4NC(=O)CCC4=CC=3)CC2)=C1Cl CEUORZQYGODEFX-UHFFFAOYSA-N 0.000 description 1
- 229920002261 Corn starch Polymers 0.000 description 1
- 101150049660 DRD2 gene Proteins 0.000 description 1
- 208000020401 Depressive disease Diseases 0.000 description 1
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 1
- 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 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- 208000001431 Psychomotor Agitation Diseases 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 238000007605 air drying Methods 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229960004372 aripiprazole Drugs 0.000 description 1
- 239000011230 binding agent Substances 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000003920 cognitive function Effects 0.000 description 1
- 239000003086 colorant Substances 0.000 description 1
- 239000008120 corn starch Substances 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 229960003638 dopamine Drugs 0.000 description 1
- -1 hydroxypropyl Chemical group 0.000 description 1
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 1
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 1
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 229960003943 hypromellose Drugs 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 208000024714 major depressive disease Diseases 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000013081 microcrystal Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 239000002400 serotonin 2A antagonist Substances 0.000 description 1
- 229940083542 sodium Drugs 0.000 description 1
- 235000015424 sodium Nutrition 0.000 description 1
- 238000005507 spraying Methods 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 239000004408 titanium dioxide Substances 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical class [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
- A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2013—Organic compounds, e.g. phospholipids, fats
- A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/24—Antidepressants
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Organic Chemistry (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Pain & Pain Management (AREA)
- Zoology (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to the technical field of medicines, and relates to a brexpiprazole orally disintegrating tablet and a preparation method thereof, which are characterized in that: contains brexpiprazole, and also contains filler, disintegrant, lubricant and corrective. In addition, the preparation method disclosed adopts the water-insoluble polymer as the wetting agent for wet granulation, has stable and mature technical process and simple preparation process, and is suitable for large-scale production. The brexpiprazole orally disintegrating tablet provided by the invention has the advantages of rapid disintegration, excellent taste, no gravel feeling, good compliance and the like.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and relates to a brexpiprazole orally disintegrating tablet and a preparation method thereof.
Background
Brexpiprazole is a white or off-white crystal or crystalline powder, soluble in N-methylpyrrolidone, slightly soluble in N, N-dimethylacetamide, insoluble in methanol, very insoluble in ethanol (99.5), and practically insoluble in water. The poor solubility of brexpiprazole is a key factor affecting clinical efficacy.
Brexpiprazole, for clinical use in schizophrenia and major depression, is the first dopamine D2, 5-HT1A receptor agonist and 5-HT2A receptor antagonist compound co-developed by the company danazolin north pharmaceutical and tsukamur japan. Compared with aripiprazole, the brexpiprazole has the advantages that the affinity of the brexpiprazole and a 5-HT receptor is increased, the activity of the brexpiprazole on a D2 receptor is reduced, the tolerance performance is better, the incidence rate of side effects of akathisia is lower, the curative effect on negative symptoms and cognitive functions of schizophrenia tends to be better, and the brexpiprazole has quick response when being used for adjuvant therapy of depression.
Patent application filed by Otsuka pharmaceutical Co., Ltd. publication No. CN104023750A discloses a pharmaceutical preparation comprising BETA REXPIPRAZOLE and substituted β -cyclodextrin, which is an aqueous solution after inclusion with hydroxypropyl or sulfobutyl- β -cyclodextrin, and the inclusion compound is made into an injection to obtain a lyophilized injection, in which the inclusion yield is not high, increasing the production cost.
Patent application filed by Otsuka pharmaceutical Co., Ltd, publication No. CN107397730A (reference 1) discloses a tablet containing 7- [4- (4-benzo [ b ] thiophen-4-yl-piperazin-1-yl) butoxy ] -1H-quinolin-2-one or a salt thereof, which is prepared by a wet granulation process in examples of the patent and coating after tabletting to obtain a briprazole tablet, the coating containing hypromellose, talc, titanium dioxide and a coloring agent, the plain tablet prepared containing 7- [4- (4-benzo [ b ] thiophen-4-yl-piperazin-1-yl) butoxy ] -1H-quinolin-2-one or a salt thereof as an active ingredient, and further containing: lactose, corn starch, crystalline cellulose, or other excipients; low substituted hydroxypropyl cellulose, croscarmellose sodium, sodium carboxymethyl starch, or other disintegrating agents; hydroxypropyl cellulose or other binders; and stearates or other lubricants. However, the dissolution rate was not more than 85% at 15 min.
The brexpiprazole orally disintegrating tablet has important significance for developing a brexpiprazole orally disintegrating tablet which is fast in disintegration, good in taste, good in dissolution rate, high in yield and stable in quality and a method suitable for industrial production.
The brexpiprazole is almost insoluble in water, and the dispersed brexpiprazole particles are easy to degrade when being hot melted at high temperature.
Disclosure of Invention
The invention aims to provide an orally disintegrating tablet with simple process, high dissolution speed, good patient compliance and high drug bioavailability. The invention relates to a method for accelerating the disintegration of a preparation by adding a disintegrating agent by an internal and external method so as to ensure that the patient compliance is better. The application provides a brexpiprazole orally disintegrating tablet which is characterized in that: comprises brexpiprazole, and further comprises filler, disintegrant, lubricant, water-insoluble polymer, cyclodextrin and flavoring agent.
The ratio of brexpiprazole to cyclodextrin is 1: a mass ratio of 4 to 6. The filler is one or more of mannitol, silicified microcrystalline (90), silicified microcrystalline (50), and microcrystalline cellulose PH 101. The disintegrant is one or more of sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, and croscarmellose sodium. The disintegrating dosage is 3% -10%. Which comprises 3 to 5 parts by weight of brexpiprazole, 15 to 25 parts by weight of cyclodextrin, 3 to 15 parts by weight of a water-insoluble polymer. The correctant is one or more of aspartame, Mentholum, acesulfame potassium, stevioside, herba Menthae essence, and vanilla essence.
1) Obtaining granules by mixing and granulating brexpiprazole, cyclodextrin, a water-insoluble polymer and optionally a filler;
2) mixing the obtained granules with a disintegrant and optionally a lubricant and/or a sweetener and tabletting;
example 1
(1) 13g of brexpiprazole, 65g of beta-cyclodextrin, 288.6g D-mannitol and 11.7g of hydroxypropylmethylcellulose acetate succinate (grade: HF) were mixed. Granulating while spraying purified water at 50 deg.C in fluidized bed. Drying at 35 deg.C, and sieving with 24 mesh sieve to obtain dry granule.
(2) 5.82g of the granulated granule of the above (1), 0.12g of crospovidone, 0.06g of aspartame and 0.06g of sodium stearyl fumarate were mixed to obtain a granule for tableting. The resulting granules for tableting were compressed to 303 mg per tablet weight to obtain an orally disintegrating tablet (hardness: 56N).
Example 2
(1) Mixing 0.3g of brexpiprazole, 3g of beta-cyclodextrin, 5.16g of D-mannitol and 0.27g of hydroxypropyl methyl cellulose acetate succinate (grade: HF), making soft mass, and granulating with 24 meshes. 0.5 g of purified water was added to the resulting sieved product while performing granulation, followed by drying in a circulating box type forced air drying oven at 50 ℃ for 1 hour, and then finishing with a 24-mesh sieve.
(3) 5.82g of the granulated granules of the above (1), 0.12g of crospovidone, 0.06g of aspartame and 0.06g of sodium stearyl fumarate were mixed, and the resulting granules for tableting were compressed to 303 mg per tablet weight to obtain an orally disintegrating tablet (hardness: 49N).
Example 3
(1) 0.3g of brexpiprazole, 6g of beta-cyclodextrin, 2.16g of D-mannitol and 0.27g of hydroxypropylmethylcellulose acetate succinate (grade: HF) were sieved, mixed, added to a soft mass of purified water and granulated (24 mesh). Then dried in a circulating drying oven at 50 ℃ for 1 hour, and then granulated with a 24-mesh sieve.
(4) 5.82g of the granulated granules of the above (1), 0.12g of crospovidone, 0.06g of aspartame and 0.06g of sodium stearyl fumarate were mixed and tableted (hardness: 47N).
Comparative example 1
The brexpiprazole orally disintegrating tablet is prepared from the following components in percentage by weight:
a method for preparing the brexpiprazole orally disintegrating tablet by adopting wet granulation comprises the following steps:
crushing the brexpiprazole, sieving the powder by a 200-mesh sieve, adding auxiliary materials according to the prescription amount, taking 20% of purified water as a wetting agent, granulating the powder by a 40-mesh sieve, carrying out air blast drying at 40 ℃, drying the powder to 1-3% by water, sieving the dried granules by a 30-mesh sieve, grading, weighing, converting the yield, adding silicified microcrystal (90), menthol, acesulfame and magnesium stearate, and preparing phi 6 plain punching tablets, wherein the tablet weight is 150 mg, and the hardness is 20-40N
Comparative example 2
The brexpiprazole orally disintegrating tablet is prepared from the following components in percentage by weight:
a method for preparing the brexpiprazole orally disintegrating tablet by adopting wet granulation comprises the following steps:
the brexpiprazole is crushed and sieved by a 200-mesh sieve, auxiliary materials with the amount of the prescription are added, 20% of purified water is used as a wetting agent, granulation is carried out by a 40-mesh sieve, air blowing drying is carried out at 40 ℃, moisture is dried to 1-3%, dried granules are sieved by a 30-mesh sieve, the granules are sized, weighed and converted into yield, microcrystalline cellulose (PH 101), menthol, acesulfame and magnesium stearate are added, and phi 6 plain punching tablets are 150 mg in weight and 20-40N in hardness.
Comparative example 3
The brexpiprazole orally disintegrating tablet is prepared from the following components in percentage by weight:
a method for preparing the brexpiprazole orally disintegrating tablet by adopting wet granulation comprises the following steps:
the brexpiprazole is crushed and sieved by a 200-mesh sieve, auxiliary materials with the amount of the prescription are added, 20% of purified water is used as a wetting agent, the 40-mesh sieve is used for granulation, the air blowing drying is carried out at 40 ℃, the moisture is dried to 1-3%, the dried granules are sieved by a 30-mesh sieve for granulation, the weighing and the conversion yield are achieved, microcrystalline cellulose (PH 102), menthol, acesulfame and magnesium stearate are added, and the phi 6 plain punching tablet has the weight of 150 mg and the hardness of 20-40N.
The disintegration time measuring method comprises the following steps: taking the samples of the examples and the comparative examples, the disintegration time and mouth feel of the briprazole orally disintegrating tablets prepared in the examples and the comparative examples are shown in table 1, referring to the disintegration time limit inspection method (0921, second part of chinese pharmacopoeia 2015 edition), which is an operation according to the method, and counting from the time when the tablets contact water, the time when the granules completely pass through the screen is taken as the disintegration time.
TABLE 1 disintegration time and mouth feel of briprazole orally disintegrating tablets prepared in examples and comparative examples
Through the investigation and analysis of the aspects of disintegration time, appearance, taste and the like of the samples prepared in the embodiments, the brexpiprazole orally disintegrating tablet prepared by the invention is quick in disintegration, can be completely disintegrated within 40 seconds, is good in taste, has no gravel feeling and no uncomfortable feeling, and meets the requirements of patients. And the preparation process is simple and is suitable for large-scale production.
Claims (10)
1. The brexpiprazole orally disintegrating tablet is characterized in that: comprises brexpiprazole, and further comprises filler, disintegrant, lubricant, water-insoluble polymer, cyclodextrin and flavoring agent.
2. The orally disintegrating tablet of claim 1, wherein said cyclodextrin is β -cyclodextrin.
3. The orally disintegrating tablet of claim 1, wherein said water insoluble polymer is selected from the group consisting of hydroxypropylmethylcellulose acetate succinate, methacrylic acid copolymer S, carboxymethylethylcellulose and ethylcellulose.
4. The orally disintegrating tablet of claim 1, wherein the ratio of brexpiprazole to cyclodextrin is 1: 4 to 6 in mass ratio.
5. The method of claim 1, further comprising: the filler is one or more of mannitol, silicified microcrystalline (90), silicified microcrystalline (50), and microcrystalline cellulose PH 101.
6. The method of claim 1, further comprising: the disintegrating agent is one or more of sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, and croscarmellose sodium.
7. According to claim 6, characterized in that: the disintegrating dosage is 3% -10%.
8. The orally disintegrating tablet according to claim 1, comprising 3 to 5 parts by weight of brexpiprazole, 15 to 25 parts by weight of cyclodextrin, and 3 to 15 parts by weight of a water-insoluble polymer.
9. The method of claim 1, further comprising: the correctant is one or more of aspartame, Mentholum, acesulfame potassium, stevioside, herba Menthae essence, and vanilla essence.
10. The method of claim 1, which is prepared by the following steps:
1) obtaining granules by mixing and granulating brexpiprazole, cyclodextrin, a water-insoluble polymer and optionally a filler;
2) the resulting granules are mixed with a disintegrant and optionally a lubricant and/or sweetener and compressed into tablets.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110294443.6A CN115105504A (en) | 2021-03-19 | 2021-03-19 | Brexpiprazole orally disintegrating tablet and preparation method thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202110294443.6A CN115105504A (en) | 2021-03-19 | 2021-03-19 | Brexpiprazole orally disintegrating tablet and preparation method thereof |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN115105504A true CN115105504A (en) | 2022-09-27 |
Family
ID=83323928
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202110294443.6A Pending CN115105504A (en) | 2021-03-19 | 2021-03-19 | Brexpiprazole orally disintegrating tablet and preparation method thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN115105504A (en) |
-
2021
- 2021-03-19 CN CN202110294443.6A patent/CN115105504A/en active Pending
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP4740740B2 (en) | Drug-containing particles and solid preparation containing the particles | |
| CN101129346B (en) | Ambroxol hydrochloride oral cavity disintegrating tablet and method of producing the same | |
| JP5332615B2 (en) | Orally disintegrating tablet and method for producing the same | |
| RU2466717C2 (en) | Pharmaceutical solid preparation containing benzazepin and method for preparing it | |
| EP3437646A1 (en) | Oral preparation having exceptional elutability | |
| WO2009101940A1 (en) | Tablet having improved elution properties | |
| CN105362240A (en) | Orally disintegrating tablet | |
| JP2012107049A (en) | Tablet disintegrating in the oral cavity | |
| CN103284962A (en) | Moxifloxacin dispersible tablet and preparation method thereof | |
| EP2590652A1 (en) | Pharmaceutical compositions containing vanoxerine | |
| WO2021254409A1 (en) | Pharmaceutical composition of complex and preparation method therefor | |
| JP2010202579A (en) | Acarbose-containing disintegrating preparation in oral cavity | |
| CN115105504A (en) | Brexpiprazole orally disintegrating tablet and preparation method thereof | |
| JP2020518611A (en) | Compositions with improved water solubility and bioavailability | |
| CN111228227A (en) | Salbutamol sulfate oral disintegrating tablet and preparation method thereof | |
| CN106265559B (en) | Olanzapine oral disnitegration tablet and preparation method thereof | |
| CN113440488A (en) | Rimiditan orally disintegrating tablet and preparation method thereof | |
| CN111514111A (en) | Pharmaceutical composition containing mosapride citrate and preparation method thereof | |
| CN117159484A (en) | Acetylcysteine oral preparation and preparation method thereof | |
| CN111821268A (en) | Safinamide mesylate orally disintegrating tablet and preparation method thereof | |
| WO2020253808A1 (en) | Pharmaceutical composition and preparation method therefor | |
| JP2813792B2 (en) | Preparation for oral administration of irsogladine maleate and its production method | |
| JP4393119B2 (en) | Preparation containing iodopropamide | |
| CN117797107A (en) | Sildenafil citrate medicament as well as preparation method and application thereof | |
| CN113425692A (en) | Laburnine orally disintegrating tablet and preparation method thereof |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination |