CN106667969A - Brexpiprazole sustained-release capsule and preparation method thereof - Google Patents
Brexpiprazole sustained-release capsule and preparation method thereof Download PDFInfo
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- CN106667969A CN106667969A CN201710100460.5A CN201710100460A CN106667969A CN 106667969 A CN106667969 A CN 106667969A CN 201710100460 A CN201710100460 A CN 201710100460A CN 106667969 A CN106667969 A CN 106667969A
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- coating
- coating solution
- sustained
- piperazine azoles
- isolation
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- 238000013268 sustained release Methods 0.000 title claims abstract description 44
- 239000012730 sustained-release form Substances 0.000 title claims abstract description 44
- 239000002775 capsule Substances 0.000 title claims abstract description 25
- 238000002360 preparation method Methods 0.000 title abstract description 30
- 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 14
- 229960001210 brexpiprazole Drugs 0.000 title abstract description 14
- 238000002955 isolation Methods 0.000 claims abstract description 41
- 239000011247 coating layer Substances 0.000 claims abstract description 22
- 229930006000 Sucrose Natural products 0.000 claims abstract description 21
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims abstract description 21
- 239000003814 drug Substances 0.000 claims abstract description 8
- 239000008188 pellet Substances 0.000 claims abstract description 7
- 239000000853 adhesive Substances 0.000 claims abstract description 4
- 230000001070 adhesive effect Effects 0.000 claims abstract description 3
- 238000000576 coating method Methods 0.000 claims description 209
- 239000011248 coating agent Substances 0.000 claims description 185
- QPUMEZIFDXYGPG-UHFFFAOYSA-N piperazine 1H-pyrrole Chemical class N1CCNCC1.N1C=CC=C1 QPUMEZIFDXYGPG-UHFFFAOYSA-N 0.000 claims description 40
- 239000006187 pill Substances 0.000 claims description 39
- 239000003795 chemical substances by application Substances 0.000 claims description 31
- 239000007787 solid Substances 0.000 claims description 30
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 30
- 239000008213 purified water Substances 0.000 claims description 28
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 25
- FPAFDBFIGPHWGO-UHFFFAOYSA-N dioxosilane;oxomagnesium;hydrate Chemical group 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 22
- 239000007788 liquid Substances 0.000 claims description 21
- 239000005720 sucrose Substances 0.000 claims description 20
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 claims description 18
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 claims description 18
- 229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 17
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 17
- 239000002904 solvent Substances 0.000 claims description 16
- 239000000463 material Substances 0.000 claims description 10
- 239000004372 Polyvinyl alcohol Substances 0.000 claims description 9
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 claims description 9
- 229920002689 polyvinyl acetate Polymers 0.000 claims description 9
- 229920002451 polyvinyl alcohol Polymers 0.000 claims description 9
- 235000019422 polyvinyl alcohol Nutrition 0.000 claims description 9
- 229920000058 polyacrylate Polymers 0.000 claims description 8
- 239000001267 polyvinylpyrrolidone Substances 0.000 claims description 8
- 230000003204 osmotic effect Effects 0.000 claims description 7
- 239000002994 raw material Substances 0.000 claims description 6
- 239000001856 Ethyl cellulose Substances 0.000 claims description 5
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 claims description 5
- 229920001249 ethyl cellulose Polymers 0.000 claims description 5
- 235000019325 ethyl cellulose Nutrition 0.000 claims description 5
- 238000000034 method Methods 0.000 claims description 5
- 239000000203 mixture Substances 0.000 claims description 5
- 229920002134 Carboxymethyl cellulose Polymers 0.000 claims description 4
- 239000001768 carboxy methyl cellulose Substances 0.000 claims description 4
- 235000010948 carboxy methyl cellulose Nutrition 0.000 claims description 4
- 239000008112 carboxymethyl-cellulose Substances 0.000 claims description 4
- 238000001035 drying Methods 0.000 claims description 4
- -1 hydroxypropyl Chemical group 0.000 claims description 4
- 229920003152 Eudragit® RS polymer Polymers 0.000 claims description 3
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
- FSXVSUSRJXIJHB-UHFFFAOYSA-M ethyl prop-2-enoate;methyl 2-methylprop-2-enoate;trimethyl-[2-(2-methylprop-2-enoyloxy)ethyl]azanium;chloride Chemical compound [Cl-].CCOC(=O)C=C.COC(=O)C(C)=C.CC(=C)C(=O)OCC[N+](C)(C)C FSXVSUSRJXIJHB-UHFFFAOYSA-M 0.000 claims description 3
- 229960003943 hypromellose Drugs 0.000 claims description 3
- 206010013786 Dry skin Diseases 0.000 claims description 2
- 229920003163 Eudragit® NE 30 D Polymers 0.000 claims description 2
- 229920002678 cellulose Polymers 0.000 claims description 2
- 239000001913 cellulose Substances 0.000 claims description 2
- 201000010099 disease Diseases 0.000 claims description 2
- 229940079593 drug Drugs 0.000 claims description 2
- GDCRSXZBSIRSFR-UHFFFAOYSA-N ethyl prop-2-enoate;2-methylprop-2-enoic acid Chemical compound CC(=C)C(O)=O.CCOC(=O)C=C GDCRSXZBSIRSFR-UHFFFAOYSA-N 0.000 claims description 2
- 239000002202 Polyethylene glycol Substances 0.000 claims 1
- 239000011230 binding agent Substances 0.000 claims 1
- 239000003292 glue Substances 0.000 claims 1
- 229920001223 polyethylene glycol Polymers 0.000 claims 1
- 230000000694 effects Effects 0.000 abstract description 7
- 201000000980 schizophrenia Diseases 0.000 abstract description 6
- 239000008280 blood Substances 0.000 abstract description 2
- 210000004369 blood Anatomy 0.000 abstract description 2
- 235000013681 dietary sucrose Nutrition 0.000 abstract 1
- 238000012423 maintenance Methods 0.000 abstract 1
- 230000002035 prolonged effect Effects 0.000 abstract 1
- 229960004793 sucrose Drugs 0.000 abstract 1
- 238000003756 stirring Methods 0.000 description 49
- 239000007921 spray Substances 0.000 description 25
- 238000005303 weighing Methods 0.000 description 24
- 239000000725 suspension Substances 0.000 description 21
- 239000012467 final product Substances 0.000 description 18
- 230000002572 peristaltic effect Effects 0.000 description 12
- 238000002156 mixing Methods 0.000 description 9
- TZBAVQKIEKDGFH-UHFFFAOYSA-N n-[2-(diethylamino)ethyl]-1-benzothiophene-2-carboxamide;hydrochloride Chemical compound [Cl-].C1=CC=C2SC(C(=O)NCC[NH+](CC)CC)=CC2=C1 TZBAVQKIEKDGFH-UHFFFAOYSA-N 0.000 description 9
- 238000001914 filtration Methods 0.000 description 6
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical group OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 6
- 239000010410 layer Substances 0.000 description 6
- 239000011806 microball Substances 0.000 description 6
- 208000024714 major depressive disease Diseases 0.000 description 3
- 230000035699 permeability Effects 0.000 description 3
- 239000006228 supernatant Substances 0.000 description 3
- 229920003134 Eudragit® polymer Polymers 0.000 description 2
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 0.000 description 2
- 230000008484 agonism Effects 0.000 description 2
- 230000008485 antagonism Effects 0.000 description 2
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 description 2
- 229960003638 dopamine Drugs 0.000 description 2
- 239000012530 fluid Substances 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 239000002547 new drug Substances 0.000 description 2
- 239000003361 porogen Substances 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 108020003175 receptors Proteins 0.000 description 2
- 102000005962 receptors Human genes 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 102000049773 5-HT2A Serotonin Receptor Human genes 0.000 description 1
- 102100022738 5-hydroxytryptamine receptor 1A Human genes 0.000 description 1
- 101710138638 5-hydroxytryptamine receptor 1A Proteins 0.000 description 1
- 102100036321 5-hydroxytryptamine receptor 2A Human genes 0.000 description 1
- 101710138091 5-hydroxytryptamine receptor 2A Proteins 0.000 description 1
- 239000004925 Acrylic resin Substances 0.000 description 1
- 229920000178 Acrylic resin Polymers 0.000 description 1
- 208000028698 Cognitive impairment Diseases 0.000 description 1
- 101150049660 DRD2 gene Proteins 0.000 description 1
- 102000004980 Dopamine D2 Receptors Human genes 0.000 description 1
- 108090001111 Dopamine D2 Receptors Proteins 0.000 description 1
- 101150104779 HTR2A gene Proteins 0.000 description 1
- 206010037211 Psychomotor hyperactivity Diseases 0.000 description 1
- 230000001270 agonistic effect Effects 0.000 description 1
- 229940035676 analgesics Drugs 0.000 description 1
- 239000000730 antalgic agent Substances 0.000 description 1
- 230000001430 anti-depressive effect Effects 0.000 description 1
- 230000003556 anti-epileptic effect Effects 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 238000005452 bending Methods 0.000 description 1
- 239000007767 bonding agent Substances 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 208000010877 cognitive disease Diseases 0.000 description 1
- 238000013270 controlled release Methods 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 1
- 210000002249 digestive system Anatomy 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 229940126889 dopamine receptor partial agonist Drugs 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 230000002197 limbic effect Effects 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 239000012528 membrane Substances 0.000 description 1
- 230000003340 mental effect Effects 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 238000009522 phase III clinical trial Methods 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 229920006316 polyvinylpyrrolidine Polymers 0.000 description 1
- 208000020016 psychiatric disease Diseases 0.000 description 1
- 239000000758 substrate Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 238000012795 verification Methods 0.000 description 1
Classifications
-
- 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
- A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5026—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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5005—Wall or coating material
- A61K9/5021—Organic macromolecular compounds
- A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
- A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose
- A61K9/5047—Cellulose ethers containing no ester groups, 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
- A61K9/5078—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings with drug-free core
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- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Abstract
The invention discloses a brexpiprazole sustained-release capsule as well as a preparation method and an application thereof. The brexpiprazole sustained-release capsule is prepared by filling a hollow capsule with a brexpiprazole sustained-release pellet, wherein the brexpiprazole sustained-release pellet is composed of a medicine-carrying pellet core, an isolation coating layer, a sustained-release coating layer and a protection coating layer from inside to outside; the medicine-carrying pellet core comprises the following components in percentage by weight: 3-10% of brexpiprazole, 10-30% of an adhesive and 10-60% of a saccharose blank pellet core. Through the brexpiprazole sustained-release capsule, the maintenance time of the brexpiprazole treatment concention in the body can be prolonged to 12 hours; side effects caused by excessive volatility of the medicine concentration in the blood can be reduced; moreover, the medicine taking frequency is reduced; the brexpiprazole sustained-release capsule can achieve obvious treatment effects for patients with schizophrenia and is convenient to use.
Description
Technical field
The present invention relates to technical field of medicine, and in particular to one kind is according to piperazine azoles slow releasing capsule and preparation method thereof.
Background technology
The FDA on the 25th of September in 2014 formally receives and starts what the big tomb pharmacy of examination ＆ verification company and Japan was researched and developed jointly
Brexpiprazole new drug applications（NDA）.On July 10th, 2015 is according to a piperazine azoles（Brexpiprazole）Jing FDA ratify, and can use
In schizophrenia and the auxiliary treatment of major depressive disorder.
Lundbeck submits altogether 7 II and III phase clinical researches to, wherein 3 is schizophrenia, 4 are the auxiliary of major depressive disorder
Treatment is helped, is had and is participated in more than 6000 patients.
2 III phases clinical researches of schizophrenia indication are total to be participated in more than 1200 patients.Patient is receiving treatment
Positive and Negative Symptom Scale after 6 weeks（PANSS）Fraction has greatly improved.PANSS is the evaluation of mental sickness disease
Instrument.
In terms of the auxiliary treatment of major depressive disorder, brexpiprazole is showed in II item phase III clinical trials also will
It is better than placebo.
The brexpiprazole of Lundbeck pharmacy and big tomb pharmacy joint development is that a experimental serotonin-dopamine is lived
Dynamic regulator (SDAM), may act on dopamine D 2 and 5-HT2A receptors.In dopamine D 2 receptoroid, D2 acceptor portions swash
Dynamic agent centering limbic brain path can produce functional antagonism effect, can effectively improve schizophrenia because D2 over-activities cause
The positive symptom;Centering cortex path can produce functional agonistic effect, can improve the negative disease caused by D2 hypofunctions
Shape, cognitive impairment.Brexpiprazole is a kind of curative for mental disorder of new multiple target effect mechanism
Thing, in addition to mainly possessing d2 dopamine receptor partial agonist and acting on, is also equipped with D3 acceptor portion agonisms, 5-HT1A parts
Receptor agonism and 5-HT2A partial receptor antagonisms, have while being and develop for monoamine neurotransmitter Mutiple Targets
Anti- schizophrenia and the new drug of antidepressant effect, currently carry out III clinical trial phase.
The content of the invention
It is an object of the invention to overcome existing technological deficiency, there is provided one kind is according to piperazine azoles slow releasing capsule and its a preparation side
Method and purposes, should can extend internal holding time up to 12 hours according to a piperazine azoles treatment concentration according to a piperazine azoles slow releasing capsule, reduce
The fluctuation of blood drug level.The effect is significant for antiepileptic patient is needed and it is easy to use.
The present invention is achieved through the following technical solutions the purpose：
The present invention is such a according to a piperazine azoles slow releasing capsule, the capsule by being packed into Capsuleses according to a piperazine azoles slow-release micro-pill and
It is obtained, described is from inside to outside by band pill core, isolation coatings, sustained-release coating layer, protectiveness according to a piperazine azoles slow-release micro-pill
Coatings are constituted；The principal agent coatings for including sucrose celphere and its surface with pill core, the principal agent coatings are
Jing behind sucrose celphere surface being sprayed at principal agent coating solution and being dried what is formed, the principal agent coating solution is by according to a piperazine azoles and viscous
Mixture is mixed after dissolving in a solvent；Each component percentage by weight is in band pill core：According to a piperazine azoles 1%-15%, bonding
Agent 10%-30%, sucrose celphere 10%-70%；The isolation coatings, sustained-release coating layer, protectiveness coatings
Weight summation is the 10%-100% of pellet core.
Wherein, described adhesive is by one kind in Macrogol 4000, ethyl cellulose, hypromellose or several
Kind, the solvent is one of purified water or ethanol or the two combination.
Wherein, the isolation coatings are to be sprayed to be dried with Jing after pill wicking surface by isolation coating solution to be formed；
The isolation coating solution is mixed after being dissolved in a solvent by isolation coat material and antitackiness agent；It is solid in isolation coating solution
In shape raw material, percentage by weight shared by isolation coat material is 70%-95%, and percentage by weight shared by antitackiness agent is 5%-
30%.The isolation coat material is Macrogol 4000 or carboxymethyl cellulose, and the antitackiness agent is Pulvis Talci, the solvent
It is one of purified water or ethanol or the two combination.
Wherein, the sustained-release coating layer is to be sprayed at Jing after isolation coating layer surface by sustained release coating liquid and be dried to be formed；
The sustained release coating liquid is to be dissolved in a solvent to be mixed by acrylic polymer and osmotic pressure regulator；In slow release bag
In clothing liquid solid raw material, percentage by weight shared by acrylic polymer is 20%-99%, weight shared by osmotic pressure regulator
Amount percentage ratio is 1%~80%.The acrylic polymer be Eudragit NE30D, Eudragit L30D,
One or more in Eudragit RS, the osmotic pressure regulator is hydroxypropyl methyl cellulose HPMC, polyvinylpyrrolidine
One or more in ketone PVP, PVAC polyvinylalcohol, the solvent is one of purified water or ethanol or the two combination.
Wherein, the protectiveness coatings are sprayed at Jing dryings after sustained release coating layer surface and make by protectiveness coating solution,
The protectiveness coating solution is dissolved in a solvent by blocker and fluidizer and is mixed；In protectiveness coating solution solid raw material
In, percentage by weight shared by blocker is 20%-90%, and percentage by weight shared by fluidizer is 10%~80%.The retardance
Agent is one or more in hydroxypropyl methyl cellulose HPMC, polyvinylpyrrolidone PVP, PVAC polyvinylalcohol, the fluidizer
Agent is Pulvis Talci, and the solvent is the combination of one or both of purified water or ethanol.
Further, prepare and this comprise the steps according to a method for piperazine azoles slow releasing capsule：
Step 1：Principal agent coating solution, isolation coating solution, sustained release coating liquid, protectiveness coating solution are prepared respectively；
Step 2：By sucrose celphere preheat after, in coating pan according to according to a structure of piperazine azoles slow-release micro-pill from inside to outside according to
It is secondary to carry out hydrojet coating, drying, sieve, always mix, finally it is packed in Capsuleses and obtains product.
The invention allows for it is this according to a piperazine azoles slow releasing capsule as analgesic drug product purposes.
Technical solutions according to the invention empirical tests possess following advantage and good effect：
Using acrylic polymer as slow release main material, its consumption is the principal element for determining release to the present invention.It is general
Logical sustained-release coating layer typically constitutes structure：Coating materials, sustained release substrate, porogen, gastrointestinal tract adhesive agent, and in the present invention
Using acrylic polymer, it can not be dissolved in water and Digestive system, but can expand wherein, it and hydrophilic hydroxypropyl first
Base cellulose HPMC, polyvinylpyrrolidone PVP, PVAC polyvinylalcohol share obtain slow releasing function coated preparation, it with this three
The compatibility for planting material is all preferable, and by regulation ratio different permeability can be obtained, and its principle is acrylic resin films bag
When clothing material is contacted with gastro-intestinal Fluid, the porogen of itself is met water section dissolving or is come off on film, forms countless micro- on coating membrane
Hole and bending trail, make clothing film have a permeability, and gastro-intestinal Fluid is penetrated in films by these micropores, the medicine dissolution of piece in-core to
When determining degree, medicine produces certain osmotic pressure, prevents moisture from continuing to penetrate into, and due to concentration difference inside and outside film, medicine will pass through this
Slightly hole slowly discharges to outside film, so as to reach the effect of controlled release.Compare other complicated sustained-release coating layers simplify prescription and
Technological process, and different permeability is obtained by regulation ratio and then different rate of release are obtained.
Specific embodiment
In order to deepen to present invention understanding, with reference to embodiment, the present invention is described in further detail.It is interior below
Hold such as relating to numerical value or proportionate relationship, unless otherwise noted, refer both to weight amount or part by weight.Each component in following embodiments
It is commercially available.The primary structure of the micropill being related in following examples is：Band pill core, isolation coatings, sustained release coating
Layer, protection coatings.
Embodiment 1：
Preparation with pill core
1st, principal agent coating solution is prepared：The ethyl cellulose 15g for accurately weighing is added in 60% ethanol, according to a piperazine azoles 10g, stir
After mixing uniformly, with 80 mesh sieve net filtrations gained suspension, the coating solution of solid content 55% is formed, persistently stirred during hydrojet.
2nd, 21g sucrose celphere is poured in coating pan, preheat, when sucrose celphere internal temperature reach 45 DEG C with
When upper, rotating speed is 20rpm or so in adjustment coating pan, opens peristaltic pump and spray gun starts coating, hydrojet flow-control 70~
80g/min.After having wrapped principal agent, air draft and air intake air-valve are opened, coating pan rotating speed 5rpm under dry heat temperature 50 C, is dried 5
Hour, micropill is crossed 12 mesh and 20 eye mesh screens, is obtained final product.
The preparation of isolation coat layer
1st, Macrogol 4000 3g, the Pulvis Talci 0.2g for accurately weighing is added under stirring in purified water, even suspension is stirred to obtain
Liquid, and by 80 mesh sieves, the coating solution of solid content 40% is formed, persistently stir during hydrojet.
2nd, will pour in coating pan with pill core, preheat, when band pill core internal temperature is up to more than 40 DEG C, adjust coating
Rotating speed is 20rpm or so in pot, opens peristaltic pump and spray gun starts isolation coating, and hydrojet flow-control is in 70~80g/min.
After the completion of isolation coating, coating pan rotating speed is reduced to into 5rpm, is ready for sustained release coating step.
The preparation of sustained-release coating layer
1st, hydroxypropyl methyl cellulose HPMC 1g, the Eudragit L30D30g for accurately weighing is added under stirring in purified water,
Unit for uniform suspension is stirred to obtain, and by 80 mesh sieves, forms the coating solution of solid content 60%, persistently stirred during hydrojet.
2nd, when micropill internal temperature is up to less than 35 DEG C, coating pan revolution is adjusted to into 20rpm or so, you can start spray slow
Coating solution is released, hydrojet flow-control is in 70~80g/min.After sustained release coating liquid has sprayed, micropill is set to continue in the excessively interior rotation of coating,
It is ready for protectiveness coating steps.
The preparation of protectiveness coatings
1st, PVAC polyvinylalcohol 0.6g, the Pulvis Talci 0.2g for accurately weighing is added under stirring in purified water, stirs uniformly outstanding
Supernatant liquid, and by 80 mesh sieves, the coating solution of solid content 10% is formed, persistently stir during hydrojet.
2nd, when in coating pan micropill temperature at 28~35 DEG C, relative humidity 10% or so, you can spray protectiveness coating solution,
After having wrapped clothing, air draft and air intake air-valve, heating-up temperature are opened：45 DEG C or so, under the rotating speed 5rpm of coating pan, it is dried 5 hours.It is micro-
Ball crosses 12 mesh and 20 mesh sieves, obtains final product.
Insert load weighted in coating pan according to a piperazine azoles slow-release micro-pill, adjustment coating pan rotating speed is 10 revs/min, then is added
Enter 3 ‰ Pulvis Talci of micropill amount, it is total mixed 30 minutes.Micropill after total mixing is packed in Capsuleses, is obtained final product.
Embodiment 2：
Preparation with pill core
1st, principal agent coating solution is prepared：The hypromellose 20g for accurately weighing is added in purified water, according to a piperazine azoles 15g, stirring
After uniform, with 80 mesh sieve net filtrations gained suspension, the coating solution of solid content 50% is formed, persistently stirred during hydrojet.
2nd, 21g sucrose celphere is poured in coating pan, preheat, when sucrose celphere internal temperature reach 45 DEG C with
When upper, rotating speed is 20rpm or so in adjustment coating pan, opens peristaltic pump and spray gun starts coating, hydrojet flow-control 70~
80g/min.After having wrapped principal agent, air draft and air intake air-valve are opened, coating pan rotating speed 5rpm under dry heat temperature 50 C, is dried 5
Hour, micropill is crossed 12 mesh and 20 eye mesh screens, is obtained final product.
The preparation of isolation coat layer
1st, Macrogol 4000 3g, the Pulvis Talci 0.2g for accurately weighing is added under stirring in purified water, even suspension is stirred to obtain
Liquid, and by 80 mesh sieves, the coating solution of solid content 40% is formed, persistently stir during hydrojet.
2nd, will pour in coating pan with pill core, preheat, when band pill core internal temperature is up to more than 40 DEG C, adjust coating
Rotating speed is 20rpm or so in pot, opens peristaltic pump and spray gun starts isolation coating, and hydrojet flow-control is in 70~80g/min.
After the completion of isolation coating, coating pan rotating speed is reduced to into 5rpm, is ready for sustained release coating step.
The preparation of sustained-release coating layer
1st, polyvinylpyrrolidone PVP 0.5g, the EudragitRS25g for accurately weighing is added under stirring in purified water, is stirred
Unit for uniform suspension is obtained, and by 80 mesh sieves, forms the coating solution of solid content 55%, persistently stirred during hydrojet.
2nd, when micropill internal temperature is up to less than 35 DEG C, coating pan revolution is adjusted to into 20rpm or so, you can start spray slow
Coating solution is released, hydrojet flow-control is in 70~80g/min.After sustained release coating liquid has sprayed, micropill is set to continue in the excessively interior rotation of coating,
It is ready for protectiveness coating steps.
The preparation of protectiveness coatings
1st, PVAC polyvinylalcohol 0.6g, the Pulvis Talci 0.2g for accurately weighing is added under stirring in purified water, stirs uniformly outstanding
Supernatant liquid, and by 80 mesh sieves, the coating solution of solid content 10% is formed, persistently stir during hydrojet.
2nd, when in coating pan micropill temperature at 28~35 DEG C, relative humidity 10% or so, you can spray protectiveness coating solution,
After having wrapped clothing, air draft and air intake air-valve, heating-up temperature are opened：45 DEG C or so, under the rotating speed 5rpm of coating pan, it is dried 5 hours.It is micro-
Ball crosses 12 mesh and 20 mesh sieves, obtains final product.
Insert load weighted in coating pan according to a piperazine azoles slow-release micro-pill, adjustment coating pan rotating speed is 10 revs/min, then is added
Enter 3 ‰ Pulvis Talci of micropill amount, it is total mixed 30 minutes.Micropill after total mixing is packed in Capsuleses, is obtained final product.
Embodiment 3：
Preparation with pill core
1st, principal agent coating solution is prepared：The Macrogol 4000 10g for accurately weighing is added in purified water, according to a piperazine azoles 20g, stir
After mixing uniformly, with 80 mesh sieve net filtrations gained suspension, the coating solution of solid content 45% is formed, persistently stirred during hydrojet.
2nd, 21g sucrose celphere is poured in coating pan, preheat, when sucrose celphere internal temperature reach 45 DEG C with
When upper, rotating speed is 20rpm or so in adjustment coating pan, opens peristaltic pump and spray gun starts coating, hydrojet flow-control 70~
80g/min.After having wrapped principal agent, air draft and air intake air-valve are opened, coating pan rotating speed 5rpm under dry heat temperature 50 C, is dried 5
Hour, micropill is crossed 12 mesh and 20 eye mesh screens, is obtained final product.
The preparation of isolation coat layer
1st, carboxymethyl cellulose 2g, the Pulvis Talci 0.1g for accurately weighing is added under stirring in purified water, even suspension is stirred to obtain
Liquid, and by 80 mesh sieves, the coating solution of solid content 40% is formed, persistently stir during hydrojet.
2nd, will pour in coating pan with pill core, preheat, when band pill core internal temperature is up to more than 40 DEG C, adjust coating
Rotating speed is 20rpm or so in pot, opens peristaltic pump and spray gun starts isolation coating, and hydrojet flow-control is in 70~80g/min.
After the completion of isolation coating, coating pan rotating speed is reduced to into 5rpm, is ready for sustained release coating step.
The preparation of sustained-release coating layer
1st, hydroxypropyl methyl cellulose HPMC 0.5g, the EudragitNE30D for accurately weighing is added under stirring in purified water
10g, stirs to obtain unit for uniform suspension, and by 80 mesh sieves, forms the coating solution of solid content 50%, persistently stirs during hydrojet.
2nd, when micropill internal temperature is up to less than 35 DEG C, coating pan revolution is adjusted to into 20rpm or so, you can start spray slow
Coating solution is released, hydrojet flow-control is in 70~80g/min.After sustained release coating liquid has sprayed, micropill is set to continue in the excessively interior rotation of coating,
It is ready for protectiveness coating steps.
The preparation of protectiveness coatings
1st, hydroxypropyl methyl cellulose HPMC 1g, the Pulvis Talci 0.2g for accurately weighing is added under stirring in purified water, is stirred
Unit for uniform suspension, and by 80 mesh sieves, the coating solution of solid content 10% is formed, persistently stir during hydrojet.
2nd, when in coating pan micropill temperature at 28~35 DEG C, relative humidity 10% or so, you can spray protectiveness coating solution,
After having wrapped clothing, air draft and air intake air-valve, heating-up temperature are opened：45 DEG C or so, under the rotating speed 5rpm of coating pan, it is dried 5 hours.It is micro-
Ball crosses 12 mesh and 20 mesh sieves, obtains final product.
Insert load weighted in coating pan according to a piperazine azoles slow-release micro-pill, adjustment coating pan rotating speed is 10 revs/min, then is added
Enter 3 ‰ Pulvis Talci of micropill amount, it is total mixed 30 minutes.Micropill after total mixing is packed in Capsuleses, is obtained final product.
Embodiment 4：
Preparation with pill core
1st, principal agent coating solution is prepared：Macrogol 4000 5g, the ethyl cellulose for accurately weighing is added in 60% ethanol
3g, according to a piperazine azoles 25g, after stirring, with 80 mesh sieve net filtrations gained suspension, formed solid content 50% coating solution, spray
Persistently stir during liquid.
2nd, 21g sucrose celphere is poured in coating pan, preheat, when sucrose celphere internal temperature reach 45 DEG C with
When upper, rotating speed is 20rpm or so in adjustment coating pan, opens peristaltic pump and spray gun starts coating, hydrojet flow-control 70~
80g/min.After having wrapped principal agent, air draft and air intake air-valve are opened, coating pan rotating speed 5rpm under dry heat temperature 50 C, is dried 5
Hour, micropill is crossed 12 mesh and 20 eye mesh screens, is obtained final product.
The preparation of isolation coat layer
1st, carboxymethyl cellulose 2g, the Pulvis Talci 0.2g for accurately weighing is added under stirring in 60% ethanol, stirs uniformly
Suspension, and by 80 mesh sieves, the coating solution of solid content 40% is formed, persistently stir during hydrojet.
2nd, will pour in coating pan with pill core, preheat, when band pill core internal temperature is up to more than 40 DEG C, adjust coating
Rotating speed is 20rpm or so in pot, opens peristaltic pump and spray gun starts isolation coating, and hydrojet flow-control is in 70~80g/min.
After the completion of isolation coating, coating pan rotating speed is reduced to into 5rpm, is ready for sustained release coating step.
The preparation of sustained-release coating layer
1st, polyvinylpyrrolidone PVP 0.75g, the EudragitL30D for accurately weighing is added under stirring in 60% ethanol
15g, stirs to obtain unit for uniform suspension, and by 80 mesh sieves, forms the coating solution of solid content 50%, persistently stirs during hydrojet.
2nd, when micropill internal temperature is up to less than 35 DEG C, coating pan revolution is adjusted to into 20rpm or so, you can start spray slow
Coating solution is released, hydrojet flow-control is in 70~80g/min.After sustained release coating liquid has sprayed, micropill is set to continue in the excessively interior rotation of coating,
It is ready for protectiveness coating steps.
The preparation of protectiveness coatings
1st, hydroxypropyl methyl cellulose HPMC 0.8g, the Pulvis Talci 0.3g for accurately weighing is added under stirring in purified water, is stirred
Unit for uniform suspension is obtained, and by 80 mesh sieves, forms the coating solution of solid content 10%, persistently stirred during hydrojet.
2nd, when in coating pan micropill temperature at 28~35 DEG C, relative humidity 10% or so, you can spray protectiveness coating solution,
After having wrapped clothing, air draft and air intake air-valve, heating-up temperature are opened：45 DEG C or so, under the rotating speed 5rpm of coating pan, it is dried 5 hours.It is micro-
Ball crosses 12 mesh and 20 mesh sieves, obtains final product.
Insert load weighted in coating pan according to a piperazine azoles slow-release micro-pill, adjustment coating pan rotating speed is 10 revs/min, then is added
Enter 3 ‰ Pulvis Talci of micropill amount, it is total mixed 30 minutes.Micropill after total mixing is packed in Capsuleses, is obtained final product.
Embodiment 5：
Preparation with pill core
1st, principal agent coating solution is prepared：The Macrogol 4000 10g for accurately weighing is added in purified water, according to a piperazine azoles 30g, stir
After mixing uniformly, with 80 mesh sieve net filtrations gained suspension, the coating solution of solid content 45% is formed, persistently stirred during hydrojet.
2nd, 21g sucrose celphere is poured in coating pan, preheat, when sucrose celphere internal temperature reach 45 DEG C with
When upper, rotating speed is 20rpm or so in adjustment coating pan, opens peristaltic pump and spray gun starts coating, hydrojet flow-control 70~
80g/min.After having wrapped principal agent, air draft and air intake air-valve are opened, coating pan rotating speed 5rpm under dry heat temperature 50 C, is dried 5
Hour, micropill is crossed 12 mesh and 20 eye mesh screens, is obtained final product.
The preparation of isolation coat layer
1st, Macrogol 4000 2g, the Pulvis Talci 0.2g for accurately weighing is added under stirring in purified water, even suspension is stirred to obtain
Liquid, and by 80 mesh sieves, the coating solution of solid content 40% is formed, persistently stir during hydrojet.
2nd, will pour in coating pan with pill core, preheat, when band pill core internal temperature is up to more than 40 DEG C, adjust coating
Rotating speed is 20rpm or so in pot, opens peristaltic pump and spray gun starts isolation coating, and hydrojet flow-control is in 70~80g/min.
After the completion of isolation coating, coating pan rotating speed is reduced to into 5rpm, is ready for sustained release coating step.
The preparation of sustained-release coating layer
1st, PVAC polyvinylalcohol 1.5g, the Eudragit RS 12g for accurately weighing are added under stirring in purified water, stirs
Even suspension, and by 80 mesh sieves, the coating solution of solid content 50% is formed, persistently stir during hydrojet.
2nd, when micropill internal temperature is up to less than 35 DEG C, coating pan revolution is adjusted to into 20rpm or so, you can start spray slow
Coating solution is released, hydrojet flow-control is in 70~80g/min.After sustained release coating liquid has sprayed, micropill is set to continue in the excessively interior rotation of coating,
It is ready for protectiveness coating steps.
The preparation of protectiveness coatings
1st, polyvinylpyrrolidone PVP 1g, the Pulvis Talci 0.5g for accurately weighing is added under stirring in purified water, stirs
Even suspension, and by 80 mesh sieves, the coating solution of solid content 10% is formed, persistently stir during hydrojet.
2nd, when in coating pan micropill temperature at 28~35 DEG C, relative humidity 10% or so, you can spray protectiveness coating solution,
After having wrapped clothing, air draft and air intake air-valve, heating-up temperature are opened：45 DEG C or so, under the rotating speed 5rpm of coating pan, it is dried 5 hours.It is micro-
Ball crosses 12 mesh and 20 mesh sieves, obtains final product.
Insert load weighted in coating pan according to a piperazine azoles slow-release micro-pill, adjustment coating pan rotating speed is 10 revs/min, then is added
Enter 3 ‰ Pulvis Talci of micropill amount, it is total mixed 30 minutes.Micropill after total mixing is packed in Capsuleses, is obtained final product.
Embodiment 6：
Preparation with pill core
1st, principal agent coating solution is prepared：The ethyl cellulose 10g for accurately weighing is added in purified water, according to a piperazine azoles 5g, stirring is equal
After even, with 80 mesh sieve net filtrations gained suspension, the coating solution of solid content 55% is formed, persistently stirred during hydrojet.
2nd, 21g sucrose celphere is poured in coating pan, preheat, when sucrose celphere internal temperature reach 45 DEG C with
When upper, rotating speed is 20rpm or so in adjustment coating pan, opens peristaltic pump and spray gun starts coating, hydrojet flow-control 70~
80g/min.After having wrapped principal agent, air draft and air intake air-valve are opened, coating pan rotating speed 5rpm under dry heat temperature 50 C, is dried 5
Hour, micropill is crossed 12 mesh and 20 eye mesh screens, is obtained final product.
The preparation of isolation coat layer
1st, Macrogol 4000 1.5g, the Pulvis Talci 0.2g for accurately weighing is added under stirring in purified water, stirs uniformly outstanding
Supernatant liquid, and by 80 mesh sieves, the coating solution of solid content 40% is formed, persistently stir during hydrojet.
2nd, will pour in coating pan with pill core, preheat, when band pill core internal temperature is up to more than 40 DEG C, adjust coating
Rotating speed is 20rpm or so in pot, opens peristaltic pump and spray gun starts isolation coating, and hydrojet flow-control is in 70~80g/min.
After the completion of isolation coating, coating pan rotating speed is reduced to into 5rpm, is ready for sustained release coating step.
The preparation of sustained-release coating layer
1st, PVAC polyvinylalcohol 1g, the Eudragit NE30D13g for accurately weighing is added under stirring in purified water, stirs
Even suspension, and by 80 mesh sieves, the coating solution of solid content 50% is formed, persistently stir during hydrojet.
2nd, when micropill internal temperature is up to less than 35 DEG C, coating pan revolution is adjusted to into 20rpm or so, you can start spray slow
Coating solution is released, hydrojet flow-control is in 70~80g/min.After sustained release coating liquid has sprayed, micropill is set to continue in the excessively interior rotation of coating,
It is ready for protectiveness coating steps.
The preparation of protectiveness coatings
1st, polyvinylpyrrolidone PVP 0.8g, the Pulvis Talci 0.5g for accurately weighing is added under stirring in purified water, is stirred
Unit for uniform suspension, and by 80 mesh sieves, the coating solution of solid content 10% is formed, persistently stir during hydrojet.
2nd, when in coating pan micropill temperature at 28~35 DEG C, relative humidity 10% or so, you can spray protectiveness coating solution,
After having wrapped clothing, air draft and air intake air-valve, heating-up temperature are opened：45 DEG C or so, under the rotating speed 5rpm of coating pan, it is dried 5 hours.It is micro-
Ball crosses 12 mesh and 20 mesh sieves, obtains final product.
Insert load weighted in coating pan according to a piperazine azoles slow-release micro-pill, adjustment coating pan rotating speed is 10 revs/min, then is added
Enter 3 ‰ Pulvis Talci of micropill amount, it is total mixed 30 minutes.Micropill after total mixing is packed in Capsuleses, is obtained final product.
Claims (10)
1. according to a piperazine azoles slow releasing capsule, the capsule is obtained one kind by Capsuleses are packed into according to a piperazine azoles slow-release micro-pill, and it is special
Levy and be：Described is from inside to outside by band pill core, isolation coatings, sustained-release coating layer, protection according to a piperazine azoles slow-release micro-pill
Property coatings composition；The principal agent coatings for including sucrose celphere and its surface with pill core, the principal agent coatings
Be sprayed at Jing behind sucrose celphere surface with principal agent coating solution to be dried to be formed, the principal agent coating solution by according to a piperazine azoles and
Binding agent is mixed after dissolving in a solvent；Each component percentage by weight is in band pill core：According to a piperazine azoles 1%-15%, glue
Mixture 10%-30%, sucrose celphere 10%-70%；The isolation coatings, sustained-release coating layer, protectiveness coatings
Weight summation be pellet core 10%-100%.
2. according to claim 1 according to a piperazine azoles slow releasing capsule, it is characterised in that：Described adhesive is by Polyethylene Glycol
4000th, one or more in ethyl cellulose, hypromellose, the solvent be one of purified water or ethanol or the two
Combination.
3. according to claim 1 according to a piperazine azoles slow releasing capsule, it is characterised in that：The isolation coatings are by isolating
Property coating solution be sprayed at band pill wicking surface after Jing be dried to be formed；The isolation coating solution is by isolation coat material and antitackiness agent
It is mixed after dissolving in a solvent；In isolation coating solution solid raw material, percentage by weight shared by isolation coat material
For 70%-95%, percentage by weight shared by antitackiness agent is 5%-30%.
4. according to claim 3 according to a piperazine azoles slow releasing capsule, it is characterised in that：The isolation coat material is poly- second two
Alcohol 4000 or carboxymethyl cellulose, the antitackiness agent is Pulvis Talci, and the solvent is one of purified water or ethanol or the two group
Close.
5. according to claim 1 or 4 according to a piperazine azoles slow releasing capsule, it is characterised in that：The sustained-release coating layer is by delaying
Release coating solution and be sprayed at Jing after isolation coating layer surface and be dried to be formed；The sustained release coating liquid is by acrylic polymer
Dissolve in a solvent with osmotic pressure regulator and be mixed；In sustained release coating liquid solid raw material, acrylic polymer
Shared percentage by weight is 20%-99%, and percentage by weight shared by osmotic pressure regulator is 1%~80%.
6. according to claim 5 according to a piperazine azoles slow releasing capsule, it is characterised in that：The acrylic polymer is
One or more in Eudragit NE30D, Eudragit L30D, Eudragit RS, the osmotic pressure regulator is hydroxypropyl
One or more in ylmethyl cellulose HPMC, polyvinylpyrrolidone PVP, PVAC polyvinylalcohol, the solvent is purified water
Or one of ethanol or the two combination.
7. according to claim 1 or 6 according to a piperazine azoles slow releasing capsule, it is characterised in that：The protectiveness coatings are by protecting
Shield property coating solution is sprayed at Jing dryings after sustained release coating layer surface and makes, and the protectiveness coating solution is existed by blocker and fluidizer
Dissolving in solvent is mixed；In protectiveness coating solution solid raw material, percentage by weight shared by blocker is 20%-
90%, percentage by weight shared by fluidizer is 10%~80%.
8. according to claim 7 according to a piperazine azoles slow releasing capsule, it is characterised in that：The blocker is that hydroxypropyl methyl is fine
One or more in dimension element HPMC, polyvinylpyrrolidone PVP, PVAC polyvinylalcohol, the fluidizer is Pulvis Talci, described
Solvent is the combination of one or both of purified water or ethanol.
9. it is a kind of prepare as described in any one in claim 1,2,3,4,6,8 according to a method for piperazine azoles slow releasing capsule, its
It is characterised by that the method comprises the steps：
Step 1：Principal agent coating solution, isolation coating solution, sustained release coating liquid, protectiveness coating solution are prepared respectively；
Step 2：By sucrose celphere preheat after, in coating pan according to according to a structure of piperazine azoles slow-release micro-pill from inside to outside according to
It is secondary to carry out hydrojet coating, drying, sieve, always mix, finally it is packed in Capsuleses and obtains product.
10. it is a kind of as described in any one in claim 1,2,3,4,6,8 according to a piperazine azoles slow releasing capsule as it is anti-spirit point
Split the purposes of disease drug.
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| CN201710100460.5A CN106667969A (en) | 2017-02-23 | 2017-02-23 | Brexpiprazole sustained-release capsule and preparation method thereof |
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| CN201710100460.5A CN106667969A (en) | 2017-02-23 | 2017-02-23 | Brexpiprazole sustained-release capsule and preparation method thereof |
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108066324A (en) * | 2017-12-19 | 2018-05-25 | 佛山市弘泰药物研发有限公司 | A kind of dronedarone hydrochloride spansule and preparation method thereof |
| CN108066323A (en) * | 2017-12-08 | 2018-05-25 | 佛山市弘泰药物研发有限公司 | A kind of Etoricoxib spansule and preparation method thereof |
| WO2021029020A1 (en) * | 2019-08-13 | 2021-02-18 | 大塚製薬株式会社 | Oral pharmaceutical composition |
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| CN105078910A (en) * | 2015-09-22 | 2015-11-25 | 成都欣捷高新技术开发有限公司 | Freeze-dried oral preparation containing elopiprazole and preparation method of freeze-dried oral preparation |
| CN105175401A (en) * | 2015-10-16 | 2015-12-23 | 北京康立生医药技术开发有限公司 | Preparation method of brexpiprazole |
| CN106176683A (en) * | 2016-08-31 | 2016-12-07 | 贵州益康制药有限公司 | A kind of tramadol hydrochloride slow release capsule and its production and use |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN105078910A (en) * | 2015-09-22 | 2015-11-25 | 成都欣捷高新技术开发有限公司 | Freeze-dried oral preparation containing elopiprazole and preparation method of freeze-dried oral preparation |
| CN105175401A (en) * | 2015-10-16 | 2015-12-23 | 北京康立生医药技术开发有限公司 | Preparation method of brexpiprazole |
| CN106176683A (en) * | 2016-08-31 | 2016-12-07 | 贵州益康制药有限公司 | A kind of tramadol hydrochloride slow release capsule and its production and use |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN108066323A (en) * | 2017-12-08 | 2018-05-25 | 佛山市弘泰药物研发有限公司 | A kind of Etoricoxib spansule and preparation method thereof |
| CN108066324A (en) * | 2017-12-19 | 2018-05-25 | 佛山市弘泰药物研发有限公司 | A kind of dronedarone hydrochloride spansule and preparation method thereof |
| WO2021029020A1 (en) * | 2019-08-13 | 2021-02-18 | 大塚製薬株式会社 | Oral pharmaceutical composition |
| WO2021029429A1 (en) * | 2019-08-13 | 2021-02-18 | 大塚製薬株式会社 | Oral pharmaceutical composition |
| WO2021029430A1 (en) * | 2019-08-13 | 2021-02-18 | 大塚製薬株式会社 | Oral pharmaceutical composition containing heterocyclic compound |
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Application publication date: 20170517 |