CN105395528A - Brexpiprazole oral fast dissolving film - Google Patents
Brexpiprazole oral fast dissolving film Download PDFInfo
- Publication number
- CN105395528A CN105395528A CN201510982142.7A CN201510982142A CN105395528A CN 105395528 A CN105395528 A CN 105395528A CN 201510982142 A CN201510982142 A CN 201510982142A CN 105395528 A CN105395528 A CN 105395528A
- Authority
- CN
- China
- Prior art keywords
- piperazine azoles
- combination
- brexpiprazole
- oral instant
- oral
- 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 abstract 6
- 229960001210 brexpiprazole Drugs 0.000 title abstract 6
- 238000010521 absorption reaction Methods 0.000 claims abstract description 9
- 239000003623 enhancer Substances 0.000 claims abstract description 5
- 239000004014 plasticizer Substances 0.000 claims abstract description 5
- QPUMEZIFDXYGPG-UHFFFAOYSA-N piperazine 1H-pyrrole Chemical class N1CCNCC1.N1C=CC=C1 QPUMEZIFDXYGPG-UHFFFAOYSA-N 0.000 claims description 54
- 239000012528 membrane Substances 0.000 claims description 33
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 24
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- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 9
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- 229960003943 hypromellose Drugs 0.000 claims description 9
- -1 Lac Polymers 0.000 claims description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid group Chemical group C(CC(O)(C(=O)O)CC(=O)O)(=O)O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
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- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 4
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- 239000004141 Sodium laurylsulphate Substances 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
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- 235000019282 butylated hydroxyanisole Nutrition 0.000 claims description 2
- CZBZUDVBLSSABA-UHFFFAOYSA-N butylated hydroxyanisole Chemical group COC1=CC=C(O)C(C(C)(C)C)=C1.COC1=CC=C(O)C=C1C(C)(C)C CZBZUDVBLSSABA-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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- 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
- A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
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- 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
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
-
- 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
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
- A61K9/7007—Drug-containing films, membranes or sheets
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Inorganic Chemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nutrition Science (AREA)
- Physiology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention relates to a brexpiprazole oral fast dissolving film which can be dissolved instantly in the oral cavity and is used for improving a using property of brexpiprazole, and belongs to the field of medicinal preparations. The brexpiprazole oral fast dissolving film includes a medicine active ingredient and auxiliary materials applicable to pharmacy. Brexpiprazole is adopted as the medicine active ingredient. The auxiliary materials applicable to the pharmacy include a film forming material, plasticizer, an absorption enhancer, a flavoring agent and the like. The brexpiprazole oral fast dissolving film has the advantages of being large in drug-loading capacity, small in thickness, good in mouthfeel, capable of being dissolved in the oral cavity instantly without drinking water, and high in oral absorption speed, solves the problems that severe depression patients and schizophrenia patients are poor in medicine taking compliance, hide medicine and vomit the medicine, and is particularly suitable for the patients with dysphagia.
Description
Technical field
The present invention relates to a kind of pharmaceutical preparation of oral quick release category, particularly a kind of according to piperazine azoles oral cavity disintegration tablet and preparation method thereof.
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:
.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.
Oral instant membrane (oralfastdissolvingfilms, OFDF) is a novel form in oral mucosa drug-supplying system, and compared with the oral solid formulation of other kinds, the molten film preparation of mouth has many advantages, such as novel appearance, special taste; Taking convenience; Rapid oral dissolution, not easily to spue; Absorb quick, rapid-onset; Supplementary product consumption is few, technique is simple; Swallow convenience, can not cause and suffocate etc.Many drugmakers all using rapid solution technology as a research emphasis.The preparation method of oral instant film preparation mainly contains solvent casting method and hot melt extruded method.Current said preparation product relates to food, medicine field, the topica film of existing treatment oral disease, and also have the medicine film playing general action, oral instant membrane can improve rapidly the blood drug level of medicine, improves the bioavailability of medicine.
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.Be prepared into oral instant membrane according to a piperazine azoles simultaneously and be still in blank in the prior art.
Summary of the invention
Object of the present invention: lower according to a piperazine azoles bioavailability for solving in prior art, and solve the compliance of severe depression or schizophrenic patients.The present invention proposes a kind of according to piperazine azoles oral instant membrane and preparation method thereof, comply with the dissolution rate of a piperazine azoles with raising and improve patient's compliance, buccal absorption medicine can be realized simultaneously, absorb before realizing stomach, improve drug bioavailability and reduce poisonous side effect of medicine.
Technical scheme: for realizing above-mentioned goal of the invention, the component comprising following weight according to a piperazine azoles oral instant membrane of the present invention:
According to a piperazine azoles 1mg-5mg
Filmogen 30mg-90mg
Plasticizer 2mg-15mg
Absorption enhancer 1mg-25mg
Correctives 0.1mg-10mg
Other adjuvants 0mg-25mg.
Described complies with a piperazine azoles oral instant membrane, it is characterized in that, described filmogen also comprises one in hypromellose, hydroxypropyl cellulose, polyvinyl alcohol, Lac, xanthan gum, arabic gum, tragacanth, carrageenin, guar gum, elsinan, Pullulan, agar or combination in any.
Described it is characterized in that according to a piperazine azoles oral instant membrane, described plasticizer is selected from one in Polyethylene Glycol, glycerol, mono glycerinate, diglyceride, propylene glycol, Polysorbate or combination in any.
Described it is characterized in that according to a piperazine azoles oral instant membrane, described absorption enhancer is selected from one in benzalkonium chloride, cetylpyridinium chloride, cyclodextrin, edetic acid, Polysorbate, sodium lauryl sulphate or combination in any; Described correctives is selected from one in sucralose, aspartame, stevioside, glucide, saccharin sodium, mannitol, xylitol, sorbitol, essence or combination in any.
Described complies with a piperazine azoles oral instant membrane, it is characterized in that, other adjuvants described comprise coloring agent, antioxidant, antiseptic and/or saliva stimulant, wherein said coloring agent is selected from Titanium dioxide pigment, one in color lake or its combination, antioxidant is selected from butylated hydroxyanisole, butylated hydroxytoluene, disodium edetate, vitamin C, sodium sulfite, one in sodium pyrosulfite or combination in any, antiseptic is selected from sodium benzoate, potassium sorbate, methyl hydroxybenzoate, one in ethyl hydroxybenzoate or combination in any, saliva stimulant is selected from citric acid, tartaric acid, malic acid, one in mannitol or combination in any.
Described complies with a piperazine azoles oral instant membrane, and it is characterized in that, the thickness of described membrane is 10 μm ~ 100 μm; Preferred thickness is 20 μm ~ 50 μm.
Described complies with a piperazine azoles oral instant membrane, and it is characterized in that, described membrane can dissolve completely in 30 seconds in the simulate saliva of 37 ± 1 DEG C, and release is according to a piperazine azoles.
Described complies with a piperazine azoles oral instant membrane, and it is characterized in that, described membrane can at once dissolve in oral cavity within the time being less than 10 seconds, and release is according to a piperazine azoles.
The advantage that the present invention has and good effect are: compared with prior art, and the present invention, by being prepared into oral instant membrane according to a piperazine azoles, improves the compliance of patient.Be prepared into simultaneously oral instant membrane in transportation comparatively lyophilizing oral cavity disintegration tablet more easily realize.Due to almost insoluble in water according to a piperazine azoles, be prepared into oral instant membrane, be conducive to facilitating medicine absorption in vivo, improve the bioavailability of medicine, simultaneously buccal absorption medicine, absorb before realizing stomach, greatly reduce the toxic and side effects of medicine.
Accompanying drawing explanation
Fig. 1: according to the accumulation Dissolution profiles of external 1 hour of a piperazine azoles in the oral instant membrane of embodiment 5.
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 instant membrane, by 1000 consumptions:
First the acesulfame potassium of above-mentioned amount, glycerol and polyoxyethylene sorbitan monoleate are joined in aqueous solution, after stirring and dissolving, add hypromellose, abundant stirring and dissolving obtains the blank glue of hypromellose, then adds according to a piperazine azoles and be stirred to be uniformly dispersed and obtain according to a piperazine azoles pastille glue, stir deaeration under vacuum, pastille glue scraper after deaeration is spread evenly across on polyester belt, 70 ~ 80 DEG C of heat dryings, in white after dry, toughness, intensity are slightly poor, cannot film forming.
Embodiment 2
Formulated by following component according to a piperazine azoles oral instant membrane, by 1000 consumptions:
First the acesulfame potassium of above-mentioned amount, glycerol and polyoxyethylene sorbitan monoleate are joined in aqueous solution, after stirring and dissolving, add hypromellose, abundant stirring and dissolving obtains the blank glue of hypromellose, then adds according to a piperazine azoles and be stirred to be uniformly dispersed and obtain according to a piperazine azoles pastille glue, stir deaeration under vacuum, pastille glue scraper after deaeration is spread evenly across on polyester belt, 70 ~ 80 DEG C of heat dryings, in white after dry, toughness, intensity are slightly poor, cannot film forming.
Embodiment 3
Formulated by following component according to a piperazine azoles oral instant membrane, by 1000 consumptions:
First the acesulfame potassium of above-mentioned amount, glycerol and polyoxyethylene sorbitan monoleate are joined in aqueous solution, after stirring and dissolving, add hypromellose, abundant stirring and dissolving obtains the blank glue of hypromellose, then adds according to a piperazine azoles and be stirred to be uniformly dispersed and obtain according to a piperazine azoles pastille glue, stir deaeration under vacuum, pastille glue scraper after deaeration is spread evenly across on polyester belt, 70 ~ 80 DEG C of heat dryings, in white after dry, toughness, intensity are slightly poor, cannot film forming.
Embodiment 4
Formulated by following component according to a piperazine azoles oral instant membrane, by 1000 consumptions:
First the acesulfame potassium of above-mentioned amount, glycerol and polyoxyethylene sorbitan monoleate are joined in aqueous solution, after stirring and dissolving, add gelatin, 60 ~ 70 DEG C of abundant stirring and dissolving of water-bath obtain the blank glue of gelatin, then add according to a piperazine azoles and be stirred to be uniformly dispersed and obtain, according to a piperazine azoles pastille glue, stirring deaeration under vacuum, pastille glue scraper after deaeration is spread evenly across on polyester belt, 70 ~ 80 DEG C of heat dryings, cut into certain size, must comply with a molten film of piperazine azoles mouth.This film is in yellow, and pliable and tough, be limited to 2s when dissolving, entrance dissolves at once, without thickness sense, and good mouthfeel.
Embodiment 5
Formulated by following component according to a piperazine azoles oral instant membrane, by 1000 consumptions:
First the acesulfame potassium of above-mentioned amount, glycerol and polyoxyethylene sorbitan monoleate are joined in aqueous solution, after stirring and dissolving, add gelatin, hypromellose, 60 ~ 70 DEG C of abundant stirring and dissolving of water-bath obtain the blank glue of gelatin, then add according to a piperazine azoles and be stirred to be uniformly dispersed and obtain, according to a piperazine azoles pastille glue, stirring deaeration under vacuum, pastille glue scraper after deaeration is spread evenly across on polyester belt, 70 ~ 80 DEG C of heat dryings, cut into certain size, must comply with a molten film of piperazine azoles mouth.This film is in yellow, and pliable and tough, be limited to 6s when dissolving, entrance dissolves at once, without thickness sense, and good mouthfeel.
Embodiment 6
Formulated by following component according to a piperazine azoles oral instant membrane, by 1000 consumptions:
First the acesulfame potassium of above-mentioned amount, glycerol, xanthan gum and polyoxyethylene sorbitan monoleate are joined in aqueous solution, after stirring and dissolving, add gelatin, 60 ~ 70 DEG C of abundant stirring and dissolving of water-bath obtain the blank glue of gelatin, then add according to a piperazine azoles and be stirred to be uniformly dispersed and obtain, according to a piperazine azoles pastille glue, stirring deaeration under vacuum, pastille glue scraper after deaeration is spread evenly across on polyester belt, 70 ~ 80 DEG C of heat dryings, cut into certain size, must comply with a molten film of piperazine azoles mouth.This film is in yellow, and pliable and tough, be limited to 5s when dissolving, entrance dissolves at once, without thickness sense, and good mouthfeel.
Remarks: the molten film of mouth dissolves time limit assay method
Appoint film 6 of getting it filled, get 1 at every turn, be placed in 37 ± 1 DEG C of artificial salivas gently, under static condition, observe this product consoluet time.
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 (6)
1., according to a piperazine azoles oral instant membrane, it is characterized in that, comprise the component of following weight:
Supplementary material title ratio
According to a piperazine azoles 1mg-5mg
Filmogen 30mg-90mg
Plasticizer 2mg-15mg
Absorption enhancer 1mg-25mg
Correctives 0.1mg-10mg
Other adjuvants 0mg-25mg.
2. according to claim 1 according to a piperazine azoles oral instant membrane, it is characterized in that, described filmogen also comprises one in hypromellose, hydroxypropyl cellulose, polyvinyl alcohol, Lac, xanthan gum, arabic gum, Calculus Bovis from Northwest of China late-maturing glue, carrageenin, guar gum, elsinan, Pullulan, agar or combination in any.
3. according to claim 1 according to a piperazine azoles oral instant membrane, it is characterized in that, described plasticizer is selected from one in Polyethylene Glycol, glycerol, glycerol-acid esters, diglyceride, propylene glycol, Polysorbate or combination in any.
4. according to claim 1 according to a piperazine azoles oral instant membrane, it is characterized in that, described absorption enhancer is selected from one in benzalkonium chloride, cetylpyridinium chloride, cyclodextrin, edetic acid, Polysorbate, sodium lauryl sulphate or combination in any; Described correctives is selected from one in sucralose, aspartame, stevioside, glucide, saccharin sodium, mannitol, xylitol, sorbitol, essence or combination in any.
5. according to claim 1 according to a piperazine azoles oral instant membrane, it is characterized in that, other adjuvants described comprise coloring agent, antioxidant, antiseptic and/or saliva stimulant, wherein said coloring agent is selected from Titanium dioxide pigment, one in color lake or its combination, antioxidant is selected from butylated hydroxyanisole, butylated hydroxytoluene, disodium edetate, vitamin C, sodium sulfite, one in sodium pyrosulfite or combination in any, antiseptic is selected from sodium benzoate, potassium sorbate, methyl hydroxybenzoate, one in ethyl hydroxybenzoate or combination in any, saliva stimulant is selected from citric acid, tartaric acid, malic acid, one in mannitol or combination in any.
6. according to claim 1 according to a piperazine azoles oral instant membrane, it is characterized in that, the thickness of described membrane is 10 μm ~ 100 μm; Preferred thickness is 20 μm ~ 50 μm.
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| CN201510982142.7A CN105395528A (en) | 2015-12-25 | 2015-12-25 | Brexpiprazole oral fast dissolving film |
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| 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 |
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| CN113082004A (en) * | 2021-03-30 | 2021-07-09 | 江苏谛奇医药科技有限公司 | Pharmaceutical composition containing brexpiprazole and amphiphilic polymer, and preparation method and application thereof |
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| 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 |
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| CN107823191A (en) * | 2017-11-16 | 2018-03-23 | 广州迈达康医药科技有限公司 | A kind of 9-hydroxy-risperidone orally instant film preparation and its preparation technology |
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| WO2022218356A1 (en) * | 2021-04-13 | 2022-10-20 | 上海博志研新药物技术有限公司 | Brexpiprazole oral-soluble film composition, preparation method therefor, and application thereof |
| WO2022218357A1 (en) * | 2021-04-13 | 2022-10-20 | 上海博志研新药物技术有限公司 | Brexpiprazole orally soluble film clathrate, and preparation method therefor and use thereof |
| TWI820674B (en) * | 2021-04-13 | 2023-11-01 | 大陸商上海雲晟研新生物科技有限公司 | Brexpiprazole oral film, manufacture method thereof, and use thereof |
| TWI835118B (en) * | 2021-04-13 | 2024-03-11 | 大陸商上海雲晟研新生物科技有限公司 | Brexpiprazole oral film inclusion complex, preparation method and use thereof |
| CN114767663A (en) * | 2022-04-19 | 2022-07-22 | 浙江和泽医药科技股份有限公司 | Orally dissolving film agent and preparation method thereof |
| WO2023240971A1 (en) * | 2022-06-16 | 2023-12-21 | 江苏慧聚药业股份有限公司 | Pharmaceutical composition and brexpiprazole orally dissolving film |
| CN115586272A (en) * | 2022-09-29 | 2023-01-10 | 江苏慧聚药业股份有限公司 | Detection method and application of brexpiprazole preparation dissolution |
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