CN105412036A - Brexpiprazole orally disintegrating tablets - Google Patents
Brexpiprazole orally disintegrating tablets Download PDFInfo
- Publication number
- CN105412036A CN105412036A CN201510976632.6A CN201510976632A CN105412036A CN 105412036 A CN105412036 A CN 105412036A CN 201510976632 A CN201510976632 A CN 201510976632A CN 105412036 A CN105412036 A CN 105412036A
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- CN
- China
- Prior art keywords
- piperazine azoles
- oral cavity
- disintegration tablet
- cavity disintegration
- piperazine
- 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.)
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- 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 abstract description 9
- 229960001210 brexpiprazole Drugs 0.000 title abstract 8
- 239000006191 orally-disintegrating tablet Substances 0.000 title abstract 4
- 238000002360 preparation method Methods 0.000 claims abstract description 20
- 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 abstract description 14
- 239000008101 lactose Substances 0.000 claims abstract description 14
- 239000000843 powder Substances 0.000 claims abstract description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 11
- 235000019640 taste Nutrition 0.000 claims abstract description 7
- 230000000873 masking effect Effects 0.000 claims abstract description 6
- 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 claims abstract description 4
- QPUMEZIFDXYGPG-UHFFFAOYSA-N piperazine 1H-pyrrole Chemical class N1CCNCC1.N1C=CC=C1 QPUMEZIFDXYGPG-UHFFFAOYSA-N 0.000 claims description 63
- 210000000214 mouth Anatomy 0.000 claims description 47
- 239000003795 chemical substances by application Substances 0.000 claims description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 10
- 239000000314 lubricant Substances 0.000 claims description 10
- 238000000034 method Methods 0.000 claims description 9
- 239000000945 filler Substances 0.000 claims description 8
- 239000000080 wetting agent Substances 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 7
- 239000002245 particle Substances 0.000 claims description 6
- 239000002671 adjuvant Substances 0.000 claims description 5
- 238000000643 oven drying Methods 0.000 claims description 5
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 claims description 4
- WBZFUFAFFUEMEI-UHFFFAOYSA-M Acesulfame k Chemical compound [K+].CC1=CC(=O)[N-]S(=O)(=O)O1 WBZFUFAFFUEMEI-UHFFFAOYSA-M 0.000 claims description 3
- 235000010358 acesulfame potassium Nutrition 0.000 claims description 3
- 229960004998 acesulfame potassium Drugs 0.000 claims description 3
- 239000000619 acesulfame-K Substances 0.000 claims description 3
- NOOLISFMXDJSKH-UHFFFAOYSA-N p-menthan-3-ol Chemical compound CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims description 3
- 108010011485 Aspartame Proteins 0.000 claims description 2
- 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 2
- 239000004375 Dextrin Substances 0.000 claims description 2
- 229920001353 Dextrin Polymers 0.000 claims description 2
- 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 claims description 2
- 229930195725 Mannitol Natural products 0.000 claims description 2
- 229920000168 Microcrystalline cellulose Polymers 0.000 claims description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims description 2
- 229920002472 Starch Polymers 0.000 claims description 2
- 235000021355 Stearic acid Nutrition 0.000 claims description 2
- 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 2
- 239000003125 aqueous solvent Substances 0.000 claims description 2
- 239000000605 aspartame Substances 0.000 claims description 2
- 235000010357 aspartame Nutrition 0.000 claims description 2
- 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 2
- 229960003438 aspartame Drugs 0.000 claims description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 2
- 238000004132 cross linking Methods 0.000 claims description 2
- 239000004148 curcumin Substances 0.000 claims description 2
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 2
- 235000019425 dextrin Nutrition 0.000 claims 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 claims description 2
- 238000001035 drying Methods 0.000 claims description 2
- 235000013399 edible fruits Nutrition 0.000 claims description 2
- 239000000686 essence Substances 0.000 claims description 2
- 229940031703 low substituted hydroxypropyl cellulose Drugs 0.000 claims description 2
- 235000019359 magnesium stearate Nutrition 0.000 claims description 2
- 239000000594 mannitol Substances 0.000 claims description 2
- 235000010355 mannitol Nutrition 0.000 claims description 2
- 239000008108 microcrystalline cellulose Substances 0.000 claims description 2
- 235000019813 microcrystalline cellulose Nutrition 0.000 claims description 2
- 229940016286 microcrystalline cellulose Drugs 0.000 claims description 2
- 239000011259 mixed solution Substances 0.000 claims description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 claims description 2
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 claims description 2
- 239000001253 polyvinylpolypyrrolidone Substances 0.000 claims description 2
- 235000013809 polyvinylpolypyrrolidone Nutrition 0.000 claims description 2
- 229920000523 polyvinylpolypyrrolidone Polymers 0.000 claims description 2
- 239000008213 purified water Substances 0.000 claims description 2
- 239000000741 silica gel Substances 0.000 claims description 2
- 229910002027 silica gel Inorganic materials 0.000 claims description 2
- 239000011734 sodium Substances 0.000 claims description 2
- 229910052708 sodium Inorganic materials 0.000 claims description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 claims description 2
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 claims description 2
- 239000008107 starch Substances 0.000 claims description 2
- 235000019698 starch Nutrition 0.000 claims description 2
- 239000008117 stearic acid Substances 0.000 claims description 2
- 238000004090 dissolution Methods 0.000 abstract description 10
- 239000003814 drug Substances 0.000 abstract description 8
- 239000008187 granular material Substances 0.000 abstract description 7
- 230000000694 effects Effects 0.000 abstract description 4
- 229920003134 Eudragit® polymer Polymers 0.000 abstract 2
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 abstract 2
- 235000019658 bitter taste Nutrition 0.000 abstract 2
- 239000003826 tablet Substances 0.000 abstract 1
- 239000006068 taste-masking agent Substances 0.000 abstract 1
- 239000002994 raw material Substances 0.000 description 8
- 239000003085 diluting agent Substances 0.000 description 4
- 238000007873 sieving Methods 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 102100022738 5-hydroxytryptamine receptor 1A Human genes 0.000 description 2
- 101710138638 5-hydroxytryptamine receptor 1A Proteins 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 208000024714 major depressive disease Diseases 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 239000003507 refrigerant Substances 0.000 description 2
- 102100036321 5-hydroxytryptamine receptor 2A Human genes 0.000 description 1
- 101710138091 5-hydroxytryptamine receptor 2A Proteins 0.000 description 1
- 102100039126 5-hydroxytryptamine receptor 7 Human genes 0.000 description 1
- 101710150237 5-hydroxytryptamine receptor 7 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
- 101150049660 DRD2 gene Proteins 0.000 description 1
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- UHOVQNZJYSORNB-UHFFFAOYSA-N benzene Substances C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000004108 freeze drying Methods 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 206010022437 insomnia Diseases 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 239000004570 mortar (masonry) Substances 0.000 description 1
- 210000002200 mouth mucosa Anatomy 0.000 description 1
- 239000004031 partial agonist Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 229920000768 polyamine Polymers 0.000 description 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
- 238000009790 rate-determining step (RDS) Methods 0.000 description 1
- 229940011389 rexulti Drugs 0.000 description 1
- 201000000980 schizophrenia Diseases 0.000 description 1
- 230000000698 schizophrenic effect Effects 0.000 description 1
- 230000035807 sensation Effects 0.000 description 1
- 235000019615 sensations Nutrition 0.000 description 1
- 230000014860 sensory perception of taste Effects 0.000 description 1
- 239000002400 serotonin 2A antagonist Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000126 substance Substances 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
- A61K9/2022—Organic macromolecular compounds
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- 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
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Zoology (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses brexpiprazole orally disintegrating tablets and a preparation method of the brexpiprazole orally disintegrating tablets. Bexpiprazole serves as a medicine activity component, and powder co-grinding is conducted on brexpiprazole and lactose so that the dissolution of brexpiprazole and lactose can be improved; eudragit serves as a bitter taste masking agent, a co-ground object is mixed with other auxiliaries to form granules, and finally the tablets are formed through pressing. Due to the fact that brexpiprazole is almost undissolved in water, the dissolution of brexpiprazole can be promoted by preparing the orally disintegrating tablets, and bioavailability is improved; eudragit is used for masking the bitter taste, the bitter and numb taste of brexpiprazole is effectively masked, and the medicine taking compliance of a patient is enhanced.
Description
Technical field
The present invention relates to a kind of pharmaceutical preparation of oral quick release category, particularly a kind of according to a piperazine azoles oral cavity disintegration tablet.
Background technology
According to a piperazine azoles sheet as 5-HT1A receptor and polyamine form, 5-HT2A receptor antagonist, clinically for major depressive disorder and schizoid treatment.When treating for major depressive disorder, initial dose is 0.5mg/ days or 1mg/ days, then increases to target dose 2mg, and once a day, maximum recommended dosage is 3mg/ days; When treating for schizophrenia, initial dose is 1mg/ days, and recommend target dose to be 2mg to 4mg, once a day, maximum recommended dosage is 4mg/ days.Have active widely at multiple monoamine systems according to a piperazine azoles, the partial agonist activity of d2 dopamine receptor is declined, and the affinity of specific 5-HT receptor (as 5-HT1A, 5-HT2A, 5-HT7) is improved, there is better curative effect and toleration, the untoward reaction such as patient cathisophobias, uneasy or insomnia can be reduced.
According to a piperazine azoles sheet by Japanese Otsuka Pharmaceutical Co., Ltd. and Ling Bei pharmaceutical Co. Ltd of Denmark joint development, and in July, 2015 in FDA approval listing, dosage form is tablet, and specification is 0.25mg, 0.5mg, 1mg, 2mg, 3mg and 4mg, and commodity are called: REXULTI.Chemical name is 7-[4-[4-(1-benzene [b] bithiophene-4-base) piperazine-1 base] butoxy] quinoline-2 (1H)-one, molecular formula: C25H27N302S, molecular weight: 433.57, and its structure is as follows:
Complying with a piperazine azoles is white or off-white color crystalline powder, almost insoluble in water, and disintegrate is the rate-limiting step of principal agent stripping, thus restriction bioavailability.
The advantage that oral cavity disintegration tablet has to improve rapidly the blood drug level of medicine, improves bioavailability.But one of mouthfeel parameter that to be oral cavity disintegration tablet important.Owing to self there is bitter numb excitement according to a piperazine azoles, significant sensation can be caused at oral mucosa.
Patent CN105078910A discloses a kind of according to a piperazine azoles oral cavity disintegration tablet preparation method, freeze drying technology will be adopted to be prepared into lyophilizing oral cavity disintegration tablet containing according to a piperazine azoles, and its disintegration rate be accelerated, improves stripping.But this technology is relatively loaded down with trivial details, and the preparation of preparation is easier to cracked, is unsuitable for transport, and can not gets wet when taking, improve the requirement to patient, be unfavorable for the compliance of schizophrenic patients.
Find that adding correctives is difficult to cover the excitement according to a piperazine azoles through great many of experiments simultaneously, therefore adopt the simple method of tradition to be not suitable for preparing according to a piperazine azoles oral cavity disintegration tablet.
Summary of the invention
Object of the present invention: lower according to a piperazine azoles bioavailability for solving in prior art, but according to the shortcoming of the bitter numb excitement of a piperazine azoles when being prepared into fast disintegrating preparations, the present invention proposes a kind of according to piperazine azoles oral cavity disintegration tablet and preparation method thereof, improve patient's compliance with the dissolution rate improved according to a piperazine azoles.
Technical scheme: for realizing above-mentioned goal of the invention, a piperazine azoles oral cavity disintegration tablet of complying with of the present invention is made up of the component of following weight fraction: complying with a piperazine azoles is 1 part of meter, especially strange 0.3-5 part, filler 2-5 part, disintegrating agent 0.5-3 part, lubricant 0.05-2 part, correctives 0.05-2 part.
Preferably, be made up of forming of following weight fraction according to a piperazine azoles oral cavity disintegration tablet: according to a piperazine azoles 1 part meter, especially strange 0.5-3 part, filler 3-5, disintegrating agent 0.5-2 part, lubricant 0.05-1 part, correctives 0.05-1 part.
According to a piperazine azoles oral cavity disintegration tablet, it is characterized in that, one or both that described be very especially in E100, I100, S100 combine; Described disintegrating agent be in carboxymethylstach sodium, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose and polyvinylpolypyrrolidone any one or multiple; Described filler be in microcrystalline Cellulose, mannitol, lactose, starch, dextrin any one or multiple; Described lubricant be in Pulvis Talci, stearic acid, magnesium stearate, micropowder silica gel any one or multiple; Described correctives be in the fruit essences such as aspartame, acesulfame potassium, Mentholum, Fructus Fragariae Ananssae any one or multiple.
According to the preparation method of a piperazine azoles oral cavity disintegration tablet, it is characterized in that, comprise the steps: to get 1 parts by weight according to a piperazine azoles, get 1-10 part lactose and carry out micronization processes, control according to a piperazine azoles particle diameter < 10 μm, by the especially strange mix homogeneously of common powder thing with 0.5-3 parts by weight, add in all the other and add filler and disintegrating agent, rear employing alcohol aqueous solvent is granulated as wetting agent, 24 mesh sieves are granulated, in baking oven after drying, obtain according to a piperazine azoles oral cavity disintegration tablet with additional adjuvant mixed pressuring plate.
The described preparation method according to a piperazine azoles oral cavity disintegration tablet, it is characterized in that, described wetting agent is dehydrated alcohol, purified water or both mixed solutions; The described preparation method according to a piperazine azoles oral cavity disintegration tablet, is characterized in that, taste masking powder is mixed into three-dimensional mixer or wet mixing pelletizer with what add adjuvant in all the other; The described preparation method according to a piperazine azoles oral cavity disintegration tablet, it is characterized in that, oven drying temperature is 40-80 DEG C.
A described piperazine azoles oral cavity disintegration tablet of complying with meets requirement disintegration.Intra-oral disintegration time < 1min.
The advantage that the present invention has and good effect are: compared with prior art, and the present invention by especially very and according to a piperazine azoles carrying out simply granulating carrying out taste masking, and adopts oven drying to prepare taste masking powder, improves the mouthfeel of medicine.Due to almost insoluble in water according to a piperazine azoles, be prepared into oral cavity disintegration tablet, be conducive to facilitating medicine absorption in vivo, improve the bioavailability of medicine.Be prepared into oral cavity disintegration tablet, enhance patient consumes's compliance.
Accompanying drawing explanation
According to the accumulation Dissolution profiles of external 1 hour of a piperazine azoles in the oral cavity disintegration tablet of Fig. 1 embodiment 1.
Detailed description of the invention
Below in conjunction with specific embodiment, the invention will be further described, but do not limit protection scope of the present invention.
Embodiment 1
Formulated by following component according to a piperazine azoles oral cavity disintegration tablet, by 1000 consumptions:
Its preparation method comprises the steps:
Micronization is carried out, to raw material particle size < 10 μm according to a piperazine azoles and recipe quantity lactose;
Micronization raw material and lactose altogether powder thing and recipe quantity are especially strange, mix homogeneously;
3) adopt equivalent method of progressively increasing progressively to add diluent, disintegrating agent, lubricant, after mixing of repeatedly sieving, adopt alcohol water as wetting agent, granulate, after dry, additional tabletting obtains according to a piperazine azoles oral cavity disintegration tablet.
4) oral cavity disintegration tablet prepared is detected stripping curve, within 30 minutes, should more than 85% be reached.
Result of the test
Mouthfeel: slightly bitter, but can accept.
Compressibility: good
Friability: conform with the regulations
Outward appearance: bright and clean attractive in appearance
Disintegration: conform with the regulations
Average dissolution: 89.23%
Embodiment 2
Formulated by following component according to a piperazine azoles oral cavity disintegration tablet, by 1000 consumptions:
Its preparation method comprises the steps:
1) micronization is carried out, to raw material particle size < 10 μm according to a piperazine azoles and recipe quantity lactose;
2) powder thing and recipe quantity are especially strange altogether for micronization raw material and lactose, mix homogeneously;
3) adopt equivalent method of progressively increasing progressively to add diluent, disintegrating agent, lubricant, after mixing of repeatedly sieving, adopt alcohol water as wetting agent, granulate, after dry, additional tabletting obtains according to a piperazine azoles oral cavity disintegration tablet.
4) oral cavity disintegration tablet prepared is detected stripping curve, within 30 minutes, should more than 85% be reached.
Result of the test
Mouthfeel: without bitter picotement, taste is slightly sweet, has a little refrigerant sense.
Compressibility: good
Friability: conform with the regulations
Outward appearance: bright and clean attractive in appearance
Disintegration: conform with the regulations
Average dissolution: 88.54%
Embodiment 3
Formulated by following component according to a piperazine azoles oral cavity disintegration tablet, by 1000 consumptions:
Its preparation method comprises the steps:
1) micronization is carried out, to raw material particle size < 10 μm according to a piperazine azoles and recipe quantity lactose;
2) powder thing and recipe quantity are especially strange altogether for micronization raw material and lactose, mix homogeneously;
3) adopt equivalent method of progressively increasing progressively to add diluent, disintegrating agent, lubricant, after mixing of repeatedly sieving, adopt alcohol water as wetting agent, granulate, after dry, additional tabletting obtains according to a piperazine azoles oral cavity disintegration tablet.
4) oral cavity disintegration tablet prepared is detected stripping curve, within 30 minutes, should more than 85% be reached.
Result of the test
Mouthfeel: without bitter numb excitement, refrigerant sense.
Compressibility: good
Friability: conform with the regulations
Outward appearance: bright and clean attractive in appearance
Disintegration: conform with the regulations
Average dissolution: 87.79%
Embodiment 4
Formulated by following component according to a piperazine azoles oral cavity disintegration tablet, by 1000 consumptions:
Its preparation method comprises the steps:
1) micronization is carried out, to raw material particle size < 10 μm according to a piperazine azoles and recipe quantity lactose;
2) powder thing and recipe quantity are especially strange altogether for micronization raw material and lactose, mix homogeneously;
3) adopt equivalent method of progressively increasing progressively to add diluent, disintegrating agent, lubricant, after mixing of repeatedly sieving, adopt alcohol water as wetting agent, granulate, after dry, additional tabletting obtains according to a piperazine azoles oral cavity disintegration tablet.
4) oral cavity disintegration tablet prepared is detected stripping curve, within 30 minutes, should more than 85% be reached.
Result of the test
Mouthfeel: without bitter numb excitement, Fructus Fragariae Ananssae sense of taste.
Compressibility: good
Friability: conform with the regulations
Outward appearance: bright and clean attractive in appearance
Disintegration: conform with the regulations
Average dissolution: 89.29%
Embodiment 5
Formulated by following component according to a piperazine azoles oral cavity disintegration tablet, by 1000 consumptions:
Its preparation method comprises the steps:
1) according to a piperazine azoles, and interiorly add adjuvant mix homogeneously, adopt 30% alcohol water to granulate, oven drying.After add additional materials result and obtain according to a piperazine azoles oral cavity disintegration tablet.
2) oral cavity disintegration tablet prepared is detected stripping curve, within 30 minutes, should more than 85% be reached.
Result of the test
Mouthfeel: bitter numb excitement.
Compressibility: good
Friability: conform with the regulations
Outward appearance: bright and clean attractive in appearance
Disintegration: conform with the regulations
Average dissolution: 83.29%
Embodiment 6
Formulated by following component according to a piperazine azoles oral cavity disintegration tablet, by 1000 consumptions:
Its preparation method comprises the steps:
(1) according to a piperazine azoles, and acesulfame potassium and Mentholum grind in mortar, after add in add material and adopt 30% alcohol water to granulate, oven drying.After add additional materials result and obtain according to a piperazine azoles oral cavity disintegration tablet.
(2) oral cavity disintegration tablet prepared is detected stripping curve, within 30 minutes, should more than 85% be reached.
Result of the test
Mouthfeel: bitter numb excitement.
Compressibility: good
Friability: conform with the regulations
Outward appearance: bright and clean attractive in appearance
Disintegration: conform with the regulations
Average dissolution: 82.29%
Can be found by above embodiment, the simple correctives that adopts can not be covered according to the bitter numb excitement of a piperazine azoles, and the technique of carrying out especially strange preferential mixing is carried out taste masking and is through that great many of experiments gropes.And this technique does not affect the stripping of medicine.
Embodiment 7
The analysis condition of the HPLC of the product of embodiment 6:
High performance liquid chromatograph is equipped with UV-detector
Chromatographic column: common C18 post
Determined wavelength: 254nm
Column temperature: 30 DEG C
Sample size: 10 μ l
Mobile phase: with 30% methanol solution for mobile phase A, acetonitrile is Mobile phase B, and according to the form below carries out eluting.
Flow velocity is 1.0ml per minute
The product mobile phase A of embodiment 6 is dissolved, ultrasonic 5 minutes, filters, obtains subsequent filtrate sample introduction.
| Time (minute) | Mobile phase A (%) | Mobile phase B (%) |
| 0 | 20 | 80 |
| 10 | 30 | 70 |
| 15 | 40 | 60 |
| 20 | 50 | 50 |
| 25 | 40 | 60 |
| 30 | 20 | 80 |
Above embodiments of the invention have been described in detail, but described content being only preferred embodiment of the present invention, can not being considered to for limiting practical range of the present invention.All equalizations done according to the present patent application scope change and improve, and all should still belong within patent covering scope of the present invention.
Claims (8)
1. according to a piperazine azoles oral cavity disintegration tablet, it is characterized in that, it is made up of the component of following weight fraction: complying with a piperazine azoles is 1 part of meter, especially strange 0.3-5 part, filler 2-5 part, disintegrating agent 0.5-3 part, lubricant 0.05-2 part, correctives 0.05-2 part.
2. according to claim 1, preferably, be made up of forming of following weight fraction according to a piperazine azoles oral cavity disintegration tablet: according to a piperazine azoles 1 part meter, especially strange 0.5-3 part, filler 3-5, disintegrating agent 0.5-2 part, lubricant 0.05-1 part, correctives 0.05-1 part.
3. according to claim 1 according to a piperazine azoles oral cavity disintegration tablet, it is characterized in that, one or both that described be very especially in EPO, E100, I100, S100 combine.
4. according to claim 1 according to a piperazine azoles oral cavity disintegration tablet, it is characterized in that,
Described disintegrating agent be in carboxymethylstach sodium, low-substituted hydroxypropyl cellulose, cross-linking sodium carboxymethyl cellulose and polyvinylpolypyrrolidone any one or multiple;
Described filler be in microcrystalline Cellulose, mannitol, lactose, starch, dextrin any one or multiple;
Described lubricant be in Pulvis Talci, stearic acid, magnesium stearate, micropowder silica gel any one or multiple;
Described correctives be in the fruit essences such as aspartame, acesulfame potassium, Mentholum, Fructus Fragariae Ananssae any one or multiple.
5. the preparation method according to a piperazine azoles oral cavity disintegration tablet described in claim 1, is characterized in that, comprise the steps:
That gets 1 parts by weight complies with a piperazine azoles, get 1-10 part lactose and carry out micronization processes, control according to a piperazine azoles particle diameter < 10 μm, by the especially strange mix homogeneously of common powder thing with 0.5-3 parts by weight, add in all the other and add filler and disintegrating agent, rear employing alcohol aqueous solvent is granulated as wetting agent, and 24 mesh sieves are granulated, in baking oven after drying, obtain according to a piperazine azoles oral cavity disintegration tablet with additional adjuvant mixed pressuring plate.
6. the preparation method according to a piperazine azoles oral cavity disintegration tablet according to claim 5, it is characterized in that, described wetting agent is dehydrated alcohol, purified water or both mixed solutions.
7. the preparation method according to a piperazine azoles oral cavity disintegration tablet according to claim 5, is characterized in that, taste masking powder is mixed into three-dimensional mixer or wet mixing pelletizer with what add adjuvant in all the other.
8. the preparation method according to a piperazine azoles oral cavity disintegration tablet according to claim 5, it is characterized in that, oven drying temperature is 40-80 DEG C.
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| CN106580902A (en) * | 2017-02-24 | 2017-04-26 | 佛山市弘泰药物研发有限公司 | Brexpiprazole oral disintegrating tablet and preparation method thereof |
| CN106645494A (en) * | 2016-12-29 | 2017-05-10 | 成都百裕制药股份有限公司 | Detection method of brexpiprazole starting material related substances |
| CN107349183A (en) * | 2017-02-22 | 2017-11-17 | 佛山市弘泰药物研发有限公司 | One kind is according to piperazine azoles dispersible tablet and preparation method thereof |
| CN108066301A (en) * | 2017-12-26 | 2018-05-25 | 山东鲁抗医药股份有限公司 | A kind of Dapoxetine hydrochloride oral disnitegration tablet and preparation method thereof |
| EP3545950A1 (en) * | 2018-03-26 | 2019-10-02 | Adamed sp. z o.o. | Pharmaceutical composition comprising brexpiprazole |
| CN112137994A (en) * | 2020-09-15 | 2020-12-29 | 中山大学 | Application of small molecule compound in preparation of anti-filovirus medicine |
| WO2021095779A1 (en) * | 2019-11-11 | 2021-05-20 | 大塚製薬株式会社 | Orally disintegrating tablet |
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| CN106645494B (en) * | 2016-12-29 | 2019-09-06 | 成都百裕制药股份有限公司 | According to a detection method of the piperazine azoles starting material in relation to substance |
| CN107349183A (en) * | 2017-02-22 | 2017-11-17 | 佛山市弘泰药物研发有限公司 | One kind is according to piperazine azoles dispersible tablet and preparation method thereof |
| CN106580902A (en) * | 2017-02-24 | 2017-04-26 | 佛山市弘泰药物研发有限公司 | Brexpiprazole oral disintegrating tablet and preparation method thereof |
| CN108066301A (en) * | 2017-12-26 | 2018-05-25 | 山东鲁抗医药股份有限公司 | A kind of Dapoxetine hydrochloride oral disnitegration tablet and preparation method thereof |
| WO2019185432A1 (en) | 2018-03-26 | 2019-10-03 | Adamed Pharma S.A. | Pharmaceutical composition comprising brexpiprazole |
| EP3545950A1 (en) * | 2018-03-26 | 2019-10-02 | Adamed sp. z o.o. | Pharmaceutical composition comprising brexpiprazole |
| AU2019245827B2 (en) * | 2018-03-26 | 2024-05-02 | Adamed Pharma S.A. | Pharmaceutical composition comprising brexpiprazole |
| WO2021095779A1 (en) * | 2019-11-11 | 2021-05-20 | 大塚製薬株式会社 | Orally disintegrating tablet |
| JPWO2021095779A1 (en) * | 2019-11-11 | 2021-05-20 | ||
| WO2021095092A1 (en) * | 2019-11-11 | 2021-05-20 | 大塚製薬株式会社 | Orally disintegrating tablet |
| JP7395607B2 (en) | 2019-11-11 | 2023-12-11 | 大塚製薬株式会社 | Orally disintegrating tablet |
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Application publication date: 20160323 |