[go: up one dir, main page]

CN104546800A - Quetiapine fumarate sustained-release capsule and preparation method thereof - Google Patents

Quetiapine fumarate sustained-release capsule and preparation method thereof Download PDF

Info

Publication number
CN104546800A
CN104546800A CN201510005598.8A CN201510005598A CN104546800A CN 104546800 A CN104546800 A CN 104546800A CN 201510005598 A CN201510005598 A CN 201510005598A CN 104546800 A CN104546800 A CN 104546800A
Authority
CN
China
Prior art keywords
quetiapine fumarate
slow releasing
releasing capsule
hydroxypropyl methylcellulose
binding agent
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
Application number
CN201510005598.8A
Other languages
Chinese (zh)
Inventor
黄慧玲
刁媛媛
马苏峰
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
BEIJING D-VENTUREPHARM TECHNOLOGY DEVELOPMENT Co Ltd
Aventis Pharma Hainan Co Ltd
Original Assignee
BEIJING D-VENTUREPHARM TECHNOLOGY DEVELOPMENT Co Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by BEIJING D-VENTUREPHARM TECHNOLOGY DEVELOPMENT Co Ltd filed Critical BEIJING D-VENTUREPHARM TECHNOLOGY DEVELOPMENT Co Ltd
Priority to CN201510005598.8A priority Critical patent/CN104546800A/en
Publication of CN104546800A publication Critical patent/CN104546800A/en
Pending legal-status Critical Current

Links

Landscapes

  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

The invention discloses a matrix type sustained-release pellet capsule rich in quetiapine fumarate. The matrix type sustained-release pellet capsule has the characteristics of sustained release, long administration interval, low toxic and side effects and the like, and is used for treating schizophrenia. The invention also provides a preparation method and belongs to the technical field of medical science and pharmacy.

Description

A kind of quetiapine fumarate slow releasing capsule and preparation method thereof
Technical field
The present invention relates to the flat slow releasing capsule of a kind of fumaric acid Kui sulfur, in particular to a kind of quetiapine fumarate matrix type sustained-release micro-pill capsules agent and preparation method thereof, belong to field of pharmaceutical preparations.Described quetiapine fumarate slow releasing capsule can be used for treating schizophrenia.
Background technology
Quetiapine fumarate is a kind of atypia antipsychotic drug, and it is hexichol oxygen azatropylidene class medicine, belongs to polyceptor and does medication, have high affinity, and have stronger affinity to dopamine D 1 in brain and D2 receptor in brain to Serotonin receptor.
The flat conventional tablet specification of current fumaric acid Kui sulfur has 25mg, 100mg, 200mg and 300mg, and domestic oral routine dose is each 25mg, every day twice, increases 25mg every 1-3 day, increases to treatment accumulated dose 300-600mg gradually.The flat oral absorption of Kui sulfur is fast, and about 1 ~ 1.5h reaches peak plasma concentrations, and the elimination half-life is shorter.On the whole, patient medication is comparatively frequent, again because schizophrenic patients needs long-term prescription, brings constant and painful greatly to patient and family members.Therefore need to research and develop a kind of Kui sulfur release preparation, the release time of prolong drug, drug release is stablized, improves drug effect, reduce administration frequency.
Patent CN102614147A discloses the flat slow releasing tablet of fumaric acid Kui sulfur, and it is made up of quetiapine fumarate, modification pregelatinized Starch, filler, binding agent and lubricant, and the matrix sustained release tablet of preparation has good external sustained release performance.Patent CN102198113A discloses the flat slow releasing tablet preparation technology of fumaric acid Kui sulfur, and technique adopts erodible slow-release auxiliary material as blocker, adopts fusion method solid dispersion technology to prepare slow-releasing granules, and compress tablet coating.Compared with slow releasing tablet, slow-release micro-pill belongs to multiple agent type, has many advantages, and slow-release micro-pill is made up of the multiple piller of different release Mechanisms usually, and rate of releasing drug can reach zero level, and without time delay; Seldom by the impact of the digestive tract conveying food rhythm and pace of moving things, therefore gastric emptying rate is very little on its impact; Medicine increases at the area of gastrointestinal tract surface distributed, improves bioavailability, decreases local irritation; Slow-release micro-pill pastille percent ranges is large, can from more than 1% ~ 95%, and the maximal dose loading the slow-release micro-pill in single capsule can reach 600mg, and many other drug dosage forms are difficult to reach; Good fluidity, size is even, is easy to process; Improve medicine stability, cover adverse drug taste; Compound preparation compatibility can be applicable to.
Less about the patent of invention of the flat slow releasing capsule of fumaric acid Kui sulfur at present, CN103211794A discloses quetiapine fumarate film-controlled slow-release pellet capsule, its extended release coatings film comprises Eudragit RL 30D, plasticizer triethyl citrate and antiplastering aid Pulvis Talci composition, but its preparation process is more, complex process.The present invention relates to the agent of a kind of matrix type sustained-release micro-pill capsules, have had good sustained release effect, technique is simple, is easy to realize suitability for industrialized production.
Summary of the invention
The object of the present invention is to provide a kind of antipsychotic drug quetiapine fumarate matrix type sustained-release micro-pill capsules agent and preparation method thereof.Quetiapine fumarate slow releasing capsule prepared by the present invention daily once can ensure effective blood drug concentration in 24 hours, and reduces toxic and side effects, significantly reduces preparation differences between batches, improves the stability of sample.
The technical scheme of the present invention realizing above-mentioned purpose is as follows:
Described quetiapine fumarate matrix type sustained-release micro-pill capsules forms primarily of quetiapine fumarate, hydroxypropyl methylcellulose, filler, binding agent and lubricant, wherein according to mass ratio, quetiapine fumarate (putting down in Kui sulfur): hydroxypropyl methylcellulose: filler: binding agent: lubricant=1:(0.25 ~ 3): (0 ~ 2): (0.02 ~ 0.1): (0.01 ~ 1).
Described quetiapine fumarate slow releasing capsule content matrix type micropill comprises hydrophobic framework material, and quetiapine fumarate (putting down in Kui sulfur) in mass ratio: hydrophobic framework material=1:(0.25 ~ 2), described hydrophobic framework material is ethyl cellulose.
Described hydroxypropyl methylcellulose model is K15M.
Described filler is one or more mixture in lactose, microcrystalline Cellulose, calcium bicarbonate or sodium citrate.
Described binding agent is PVP K30, ethyl cellulose, hydroxypropyl methylcellulose, and solvent is the alcohol-water solution of water or alcohol or both arbitrary proportions.
Described lubricant is one or both in magnesium stearate, Pulvis Talci, silicon dioxide.
The preparation method of described quetiapine fumarate slow releasing capsule, comprise the following steps: (1) prepares raw material according to the proportioning of quetiapine fumarate, ethyl cellulose, hydroxypropyl methylcellulose, filler, binding agent, lubricant, quetiapine fumarate, ethyl cellulose, hydroxypropyl methylcellulose, filler and lubricant to be sieved mixing, add binding agent soft material; (2) add in extrusion spheronization machine by above-mentioned soft material, extrude with bar shaped state, extruding order number is 20 orders; (3) strip will be extruded and be placed in centrifugal spheronizator, and regulate and be applicable to rotating speed 200rpm ~ 600rpm, round as a ball; (4) fluid bed drying is 1% ~ 4% to moisture, is cooled to room temperature, screening 18-24 order micropill; (5) micropill content is measured, fill capsule.
Described quetiapine fumarate slow releasing capsule can be used for treating schizophrenia, belongs to field of pharmaceutical preparations.
Detailed description of the invention
Further illustrate the present invention by embodiment below, understand a kind of quetiapine fumarate slow releasing capsule further, but the present invention is not limited.
Slow releasing capsule prepared by following embodiment and comparative example, according to 1000 capsules amount preparations.Unless otherwise noted, all carry out with the extrusion spheronization machine of same model.
The preparation of embodiment 1 quetiapine fumarate slow releasing capsule (putting down in Kui sulfur, 50mg)
Micropill composition Consumption g
Quetiapine fumarate 58
Ethyl cellulose 20
Hydroxypropyl methylcellulose 20
Microcrystalline Cellulose 110
PVP K30 37
Pulvis Talci 5
Add up to 250
Preparation technology:
(1) get recipe quantity quetiapine fumarate, ethyl cellulose, microcrystalline Cellulose, PVP K30, Pulvis Talci mix homogeneously, cross 80 mesh sieve mixings;
(2) the hydroxypropyl methylcellulose aqueous solution preparing 3% does binding agent;
(3) appropriate (2) are added in (1), prepare soft material;
(4) add in extrusion spheronization machine by above-mentioned soft material, extrude with bar shaped state, extruding order number is 20 orders, will extrude strip in centrifugal spheronizator, regulates and is applicable to rotating speed 200rpm ~ 600rpm, round as a ball;
(5) fluid bed drying is 1% ~ 4% to moisture, is cooled to room temperature, sieves out 18 ~ 24 object micropills;
(6) micropill content is measured, fill capsule.
The preparation of embodiment 2 quetiapine fumarate slow releasing capsule (putting down in Kui sulfur, 200mg)
Micropill composition Consumption g
Quetiapine fumarate 230
Ethyl cellulose 50
Hydroxypropyl methylcellulose 16.5
Microcrystalline Cellulose 53.5
PVP K30 6
Pulvis Talci 24
Add up to 380
Preparation technology:
(1) get recipe quantity quetiapine fumarate, ethyl cellulose, hydroxypropyl methylcellulose, microcrystalline Cellulose, Pulvis Talci mix homogeneously, cross 80 mesh sieve mixings;
(2) the PVP K30 aqueous solution preparing 3% does binding agent;
(3) appropriate (2) are added in (1), prepare soft material;
(4) add in extrusion spheronization machine by above-mentioned soft material, extrude with bar shaped state, extruding order number is 20 orders, will extrude strip in centrifugal spheronizator, regulates and is applicable to rotating speed 200rpm ~ 600rpm, round as a ball;
(5) fluid bed drying is 1% ~ 4% to moisture, is cooled to room temperature, screening 18-24 object micropill;
(6) micropill content is measured, fill capsule.
The preparation of embodiment 3 quetiapine fumarate slow releasing capsule (putting down in Kui sulfur, 300mg)
Micropill composition Consumption g
Quetiapine fumarate 345
Ethyl cellulose 86.25
Hydroxypropyl methylcellulose 86.25
Microcrystalline Cellulose 103.5
PVP K30 2.1
Silicon dioxide 6.9
Add up to 630
(1) get recipe quantity quetiapine fumarate, ethyl cellulose, microcrystalline Cellulose, PVP K30, Pulvis Talci mix homogeneously, cross 80 mesh sieve mixings;
(2) the hydroxypropyl methylcellulose aqueous solution preparing 3% does binding agent;
(3) appropriate (2) are added in (1), prepare soft material;
(4) add in extrusion spheronization machine by above-mentioned soft material, extrude with bar shaped state, extruding order number is 20 orders, will extrude strip in centrifugal spheronizator, regulates and is applicable to rotating speed 200rpm ~ 600rpm, round as a ball;
(5) fluid bed drying is 1% ~ 4% to moisture, is cooled to room temperature, screening 18 ~ 24 object micropills;
(6) micropill content is measured, fill capsule.
The preparation of embodiment 4 quetiapine fumarate slow releasing capsule (putting down in Kui sulfur, 400mg)
Micropill composition Consumption g
Quetiapine fumarate 461
Ethyl cellulose 179
Hydroxypropyl methylcellulose 135
Microcrystalline Cellulose 220
Pulvis Talci 5
Add up to 1000
Preparation technology:
(1) get recipe quantity quetiapine fumarate, ethyl cellulose, hydroxypropyl methylcellulose, microcrystalline Cellulose, Pulvis Talci mix homogeneously, cross 80 mesh sieve mixings;
(2) binding agent is done with 30% alcohol-water solution;
(3) appropriate (2) are added in (1), prepare soft material;
(4) add in extrusion spheronization machine by above-mentioned soft material, extrude with bar shaped state, extruding order number is 20 orders, will extrude strip in centrifugal spheronizator, regulates and is applicable to rotating speed 200rpm ~ 600rpm, round as a ball;
(5) fluid bed drying is 1% ~ 4% to moisture, is cooled to room temperature, screening 18 ~ 24 object micropills;
(6) micropill content is measured, fill capsule.
Test example 1: stripping is investigated
According to dissolution method (Chinese Pharmacopoeia version in 2000 two annex X C first methods), respectively with 900ml, pH4.8 and pH6.6 for dissolution medium, rotating speed is 100 turns per minute.Operate, the slow releasing capsule prepared by embodiment of the present invention 1-4 carries out stripping curve detection in accordance with the law.
From above result of the test, quetiapine fumarate slow releasing capsule content is all qualified, all has obvious slow release effect.
Test example 2: study on the stability
Quetiapine fumarate slow releasing capsule in Example 1, aluminium-plastic bubble plate packing, 40 ± 2 DEG C, place under relative humidity 75 ± 5% constant temperature and humidity condition, detect related substance and content respectively at sampling in 0,1,2,3 and 6 month, testing result sees the following form.
From the above results, the quetiapine fumarate slow releasing capsule of this formula preparation places 1,2,3 and 6 month under acceleration conditions, and related substance slightly increases, and character and content inspection all conform with the regulations.Preparation should be stored under hermetically drying condition.

Claims (8)

1. quetiapine fumarate matrix type sustained-release micro-pill capsules agent, it is characterized in that: described quetiapine fumarate slow releasing capsule forms primarily of quetiapine fumarate, hydroxypropyl methylcellulose, filler, binding agent and lubricant, wherein according to mass ratio, quetiapine fumarate (putting down in Kui sulfur): hydroxypropyl methylcellulose: filler: binding agent: lubricant=1:(0.25 ~ 3): (0 ~ 2): (0.02 ~ 0.1): (0.01 ~ 1).
2. quetiapine fumarate slow releasing capsule according to claim 1, it is characterized in that: described quetiapine fumarate slow releasing capsule content matrix type micropill comprises hydrophobic framework material, and quetiapine fumarate (putting down in Kui sulfur) in mass ratio: hydrophobic framework material=1:(0.25 ~ 2), described hydrophobic framework material is ethyl cellulose.
3. quetiapine fumarate slow releasing capsule according to claim 1, it is characterized in that, described hydroxypropyl methylcellulose model is K15M.
4. quetiapine fumarate slow releasing capsule according to claim 1, is characterized in that described filler is one or more mixture in lactose, microcrystalline Cellulose, calcium bicarbonate or sodium citrate.
5. quetiapine fumarate slow releasing capsule according to claim 1, is characterized in that: described binding agent is PVP K30, ethyl cellulose, hydroxypropyl methylcellulose, and solvent is the alcohol-water solution of a kind of in water, alcohol or both arbitrary proportions.
6. quetiapine fumarate slow releasing capsule according to claim 1, is characterized in that described lubricant is one or both in magnesium stearate, Pulvis Talci, silicon dioxide.
7. the preparation method of quetiapine fumarate slow releasing capsule according to claim 1, comprise the following steps: (1) prepares raw material according to the proportioning of quetiapine fumarate, ethyl cellulose, hydroxypropyl methylcellulose, filler, binding agent, lubricant in claim 1 or 2, quetiapine fumarate, ethyl cellulose, hydroxypropyl methylcellulose, filler and lubricant to be sieved mixing, add binding agent soft material; (2) add in extrusion spheronization machine by above-mentioned soft material, extrude with bar shaped state, extruding order number is 20 orders; (3) strip will be extruded and be placed in centrifugal spheronizator, and regulate and be applicable to rotating speed 200rpm ~ 600rpm, round as a ball; (4) fluid bed drying is 1% ~ 4% to moisture, is cooled to room temperature, screening 18-24 order micropill; (5) micropill content is measured, fill capsule.
8. quetiapine fumarate slow releasing capsule according to claim 1 can be used for treating schizophrenia, belongs to field of pharmaceutical preparations.
CN201510005598.8A 2015-01-07 2015-01-07 Quetiapine fumarate sustained-release capsule and preparation method thereof Pending CN104546800A (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN201510005598.8A CN104546800A (en) 2015-01-07 2015-01-07 Quetiapine fumarate sustained-release capsule and preparation method thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN201510005598.8A CN104546800A (en) 2015-01-07 2015-01-07 Quetiapine fumarate sustained-release capsule and preparation method thereof

Publications (1)

Publication Number Publication Date
CN104546800A true CN104546800A (en) 2015-04-29

Family

ID=53064583

Family Applications (1)

Application Number Title Priority Date Filing Date
CN201510005598.8A Pending CN104546800A (en) 2015-01-07 2015-01-07 Quetiapine fumarate sustained-release capsule and preparation method thereof

Country Status (1)

Country Link
CN (1) CN104546800A (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105362252A (en) * 2015-10-09 2016-03-02 北京万全德众医药生物技术有限公司 Sustained-release capsule containing levodopa and carbidopa and preparation method of sustained-release capsule

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101002737A (en) * 2005-09-26 2007-07-25 刘凤鸣 Slow release preparation of Kui-Liu-Ping
CN101005829A (en) * 2003-10-21 2007-07-25 艾克塔维斯集团公司 Quetiapine formulations
CN101091700A (en) * 2007-07-03 2007-12-26 上海现代药物制剂工程研究中心有限公司 Composition of slow (controled) releasing preparation of Quetiadine Hemifumarate, and application
CN101912374A (en) * 2010-08-08 2010-12-15 浙江华海药业股份有限公司 Quetiapine sustained release tablet and preparation method thereof
CN102406606A (en) * 2011-11-29 2012-04-11 海南美大制药有限公司 Quetiapine fumarate liposome solid preparation

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN101005829A (en) * 2003-10-21 2007-07-25 艾克塔维斯集团公司 Quetiapine formulations
CN101002737A (en) * 2005-09-26 2007-07-25 刘凤鸣 Slow release preparation of Kui-Liu-Ping
CN101091700A (en) * 2007-07-03 2007-12-26 上海现代药物制剂工程研究中心有限公司 Composition of slow (controled) releasing preparation of Quetiadine Hemifumarate, and application
CN101912374A (en) * 2010-08-08 2010-12-15 浙江华海药业股份有限公司 Quetiapine sustained release tablet and preparation method thereof
CN102406606A (en) * 2011-11-29 2012-04-11 海南美大制药有限公司 Quetiapine fumarate liposome solid preparation

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105362252A (en) * 2015-10-09 2016-03-02 北京万全德众医药生物技术有限公司 Sustained-release capsule containing levodopa and carbidopa and preparation method of sustained-release capsule

Similar Documents

Publication Publication Date Title
CN102579381B (en) Guanidine hydrochloride sustained release preparation and preparation method thereof
CN104334169B (en) Solid composition comprising aminocarboxylate
CN108066319B (en) Tofacitinib citrate enteric sustained-release pellet and preparation method thereof
EP3498264A1 (en) Pharmaceutical preparation for oral administration with controlled dissolution rate, the preparation comprising tamsulosin hydrochloride-containing sustained-release pellets
CN111514142B (en) Pharmaceutical composition containing nitroxoline prodrug and preparation method and application thereof
WO2014104671A1 (en) Pharmaceutical composition with improved stability, containing temozolomide, and preparation method therefor
CN107669683B (en) Pharmaceutical composition containing sitagliptin and metformin
CN105982858A (en) A kind of azithromycin taste-masked dry suspension granule and preparation method thereof
CN104523695A (en) A kind of pharmaceutical composition for treating hyperproliferative diseases
CN115581686B (en) Preparation method of pregabalin capsule and pregabalin capsule
KR20160002177A (en) Pharmaceutical composition comprising oseltamivir free base
CN102552172A (en) Roxithromycin controlled-release preparation and preparation method thereof
CN113038938A (en) Fuquintinib pharmaceutical preparation and application thereof
CN105395504A (en) Flunarizine hydrochloride matrix sustained-release tablets and preparing method thereof
CN107412198A (en) Duloxetine hydrochloride enteric slow release granule and preparation method thereof
KR20160012706A (en) Sustained release formulations
CN104546800A (en) Quetiapine fumarate sustained-release capsule and preparation method thereof
CN105311635A (en) High drug-loading pharmaceutical composition with adjustable release rate and preparation method thereof
RU2727721C2 (en) Sustained-release pharmaceutical composition containing rivastigmine
CN104224728A (en) Esomeprazole enteric-coated pellets and preparation method for same
CN103565779A (en) Oxymatrine biological adhering sustained release preparation and preparation method thereof
CN104337783B (en) A kind of capecitabine tablet and preparation method thereof
KR102627892B1 (en) Rapid release drug formulation of anticoagulant and method for manufacturing same
EP3162368A1 (en) Pharmaceutical composition for oral administration
EP3622948A1 (en) Multilayered formulations with dual release rate of one or more active principles

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
RJ01 Rejection of invention patent application after publication
RJ01 Rejection of invention patent application after publication

Application publication date: 20150429