CN106491550A - A kind of slow releasing tablet containing Quetiapine or its pharmaceutically acceptable salt and preparation method thereof - Google Patents
A kind of slow releasing tablet containing Quetiapine or its pharmaceutically acceptable salt and preparation method thereof Download PDFInfo
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Abstract
The invention belongs to pharmaceutical technology field, discloses a kind of slow releasing tablet containing Quetiapine or its pharmaceutically acceptable salt and preparation method thereof.The slow releasing tablet includes：Granule 1, its include Quetiapine or its pharmaceutically acceptable salt, hydrophilic gel matrix material, pH adjusting agent and excipient；Granule 2, its include Quetiapine or its pharmaceutically acceptable salt, hydrophilic gel matrix material, pH adjusting agent and excipient；Wherein, the granule 1 and granule 2 are prepared from by different wet-granulation process.The slow releasing tablet can prevent slow releasing preparation prominent release, big dissolution difference and the problems such as poor repeatability, improve the bioavailability of product.
Description
Technical field
The invention belongs to field of pharmaceutical preparations, and in particular to a kind of slow containing Quetiapine or its pharmaceutically acceptable salt
Release piece and preparation method thereof.
Background technology
Quetiapine fumarate is a kind of manic to severe for schizophrenia, the bipolar affective disorder of paralepsy and moderate
The bipolar affective disorder medicine of outbreak, is researched and developed and got the Green Light in the U.S. in October, 2008 by Astrazeneca AB
Listing, chemical name are 11- { 4- [2- (2- hydroxyl-oxethyls) ethyl] -1- piperazinyls } dibenzo [b, f] [Isosorbide-5-Nitrae] sulfur azepine
Fumarate, chemical structural formula are as follows.Molecular formula：C42H50N6O4S2·C4H4O4；Molecular weight：883.11.
Quetiapine fumarate chemical structure of general formula：
Quetiapine Fumarate Extended-Release Tablets are hydrogel matrix slow releasing tablet, are to apply hydrophilic polymer for framework material system
Into pharmaceutical preparation, oral after meet Digestive system hydration occur and generate gel, medicine is by diffusion or/and gel skeleton corrosion
Mode release the drug.In oral sustained release controlled release preparation, hydrogel matrix slow releasing tablet is because of process is simple, with short production cycle, cost
Low, efficiency high and occupy critical role.But, due to the limitation of production technology itself, gel skeleton slow releasing tablet is single release
Cellular system, easily causes medicine, and the prominent of especially water soluble drug is released and problem that dissolution diversity is big.Therefore, find a kind of
Prescription or technique can control medicine constant release and be stably the problem for endeavouring in the industry to solve.
(original grinds medicine patent to patent documentation CN200780053817.3：US2008287418A1) disclose a kind of comprising quinoline sulfur
The preparation of flat or its available pharmaceutical salts, the content of wherein described Quetiapine are about 9.6% weight to about 10.4% weight, and its
Described in preparation comprising 30% weight hypromellose and about 7.2% weight sodium citrate.
Patent documentation CN201110127555.9 discloses a kind of preparation process of quetiapine fumarate slow release tablet.The technique is adopted
It is blocker with erodible slow-release auxiliary material, slow-releasing granules, tabletting is prepared using fusion method solid dispersion technology.Which is sustained-release matrix
Prepared by piece, outsourcing immediate release film art for coating.
Patent documentation CN201110137879.0 discloses a kind of slow releasing tablet of quetiapine fumarate compositionss, including richness
Horse acid Quetiapine, acylate, slow-release material and other pharmaceutic adjuvants, described slow-release material is K-type hypromellose；And
Each component weight percent proportioning is：Quetiapine fumarate 25%～40%, acylate 2%～8%, slow-release material 5%～
30%, other pharmaceutic adjuvants are surplus.
Patent documentation CN200810138434.2 discloses a kind of quetiapine sustained release tablet and preparation method thereof.The slow releasing tablet is pressed
Contain 5%～50% sustained-release matrix material with pH dependent solubilities according to percentage by weight meter, preferably comprise 15%～
The 35% sustained-release matrix material with pH dependent solubilities.
Patent documentation CN201010253723.4 is related to quetiapine sustained release tablet, and which includes at least the quinoline as active component
Sulfur is put down or its pharmaceutically acceptable salt, as the ethyl cellulose of sustained-release matrix material, and low viscous water soluble adhesive
The mean diameter of agent, wherein ethyl cellulose is less than 80 μm, preferred less than 40 μm.
Quetiapine Fumarate Extended-Release Tablets disclosed in above-mentioned patent documentation, using slow-release material and crude drug mixing granulation pressure
Piece, this are due to the simple production process, efficiency height etc..But it is poor that the preparation method is easily caused dissolution in actual fabrication process
Different in nature big, poor reproducibility etc., above-mentioned patent documentation does not solve this problem.
Which kind of take method to avoid dissolution diversity big, poor reproducibility is sustained-release matrix tablets, particularly hydrophilic gel
The research emphasis of matrix tablet, and the Research Challenges that industry is generally acknowledged.
Content of the invention
For above-mentioned the deficiencies in the prior art, it is an object of the invention to provide one kind contains Quetiapine or which can pharmaceutically connect
Slow releasing tablet of salt that receives and preparation method thereof.The present invention the slow releasing tablet containing Quetiapine or its pharmaceutically acceptable salt molten
Out-degree diversity is little, favorable reproducibility, bioavailability high.
The slow releasing tablet containing Quetiapine or its pharmaceutically acceptable salt that the present invention is provided, which includes：
Granule 1, its include Quetiapine or its pharmaceutically acceptable salt, hydrophilic gel matrix material, pH adjusting agent and tax
Shape agent；
Granule 2, its include Quetiapine or its pharmaceutically acceptable salt, hydrophilic gel matrix material, pH adjusting agent and tax
Shape agent；
Wherein, the granule 1 and granule 2 are prepared from by different wet-granulation process.
The present inventor has found that by many experiments the different wet-granulation process of the granule 1 and granule 2 affects granule
Molding, such that it is able to affect and Drug controlled release degree.
Preferably, the wet granulation time of the granule 1 be 2～5min, amount of water for material gross weight 10%～
28%；The wet granulation time of the granule 2 is 6～15min, and amount of water is the 30%～45% of material gross weight.
It is highly preferred that the wet granulation time of the granule 1 is 3～5min；Amount of water for material gross weight 18%～
28%；The wet granulation time of the granule 2 is 8～12min；Amount of water for material gross weight 35%～45%.
The granule 1 and granule 2 affect the molding of granule by different wet granulation time and amount of water, so as to control
Drug release rate processed.
The granule 1 carries out wet granulation by above-mentioned condition, it is ensured that the release of slow releasing tablet early stage；The granule 2
Wet granulation is carried out by above-mentioned condition, it is ensured that the release in slow releasing tablet later stage is constant.
That is, slow releasing tablet of the invention is then the tabletting after granule is mixed by two step wet granulations.
Prepared 1 structure of granule is more loose, and 2 structure consolidation of granule, both obtained matrix tablet glue after mixing
Good moldability, dissolution difference are little, good stability.
Preferably, the weight ratio of the granule 1 and granule 2 is 1:1～5, more preferably 1:1～3.
Preferably, in the granule 1, Quetiapine or its pharmaceutically acceptable salt, hydrophilic gel matrix material, pH regulator
The weight ratio of agent and excipient is 1～5:2～4:1:1～4；In the granule 2, Quetiapine or its pharmaceutically acceptable salt,
The weight ratio of hydrophilic gel matrix material, pH adjusting agent and excipient is 1～5:2～4:1:1～4.
It is highly preferred that in the granule 1, Quetiapine or its pharmaceutically acceptable salt, hydrophilic gel matrix material, pH are adjusted
The weight ratio of section agent and excipient is 3～4:2～3:1:1～2；In the granule 2, Quetiapine or which is pharmaceutically acceptable
The weight ratio of salt, hydrophilic gel matrix material, pH adjusting agent and excipient is 3～4:2～3:1:1～2.
Preferably, the hydrophilic gel matrix material includes：
(a) with the hypromellose that viscosity is 80～120mPa s, and
B () is with the hypromellose that viscosity is 3000～5600mPa s；
It is highly preferred that described with the hypromellose that viscosity is 80～120mPa s and have viscosity be 3000～
The weight ratio of the hypromellose of 5600mPa s is 1～6:1.
It is further preferred that described is hypromellose with the hypromellose that viscosity is 80～120mPa s
K100lv；It is HPMC K4M with the hypromellose that viscosity is 3000～5600mPa s.
The inventors discovered that, the release that a kind of HPMC of model cannot control medicine well is used alone.Two kinds of models
HPMC need to meet above-mentioned ratio and suitable consumption when being used in mixed way.This is due to can not be quickly in piece when consumption is less
Agent surface forms continuous gel layer, can make the rapid aquation disintegrate in slow releasing tablet local, cause prominent releasing.
Preferably, in the granule 1 and granule 2, the pH adjusting agent is sodium citrate；The excipient is selected from crystallite
Cellulose and Lactose, and both weight ratios are 3～1:1～3；Preferably 2～1:1.
Preferably, the Quetiapine or its pharmaceutically acceptable salt are quetiapine fumarate.
The present invention provide the preparation method containing Quetiapine or the slow releasing tablet of its pharmaceutically acceptable salt, it include with
Lower step：
(1) by the raw material Quetiapine of granule 1 or its pharmaceutically acceptable salt, hydrophilic gel matrix material, pH adjusting agent
With excipient as wet granulator in；The 10%～28% of above-mentioned material gross weight water atomization is added above-mentioned material wet method
2～5min of granulation obtains wet granular, and wet granulate is dried, and dry granulate obtains granule 1；
By the raw material Quetiapine of granule 2 or its pharmaceutically acceptable salt, hydrophilic gel matrix material, pH adjusting agent and tax
During shape agent is as wet granulator；The 30%～45% of above-mentioned material gross weight water atomization is added above-mentioned material wet granulation
6～15min obtains wet granular, wet granulate, dries, and dry granulate obtains granule 2；
(2) by above-mentioned granule 1 and granule 2 and mix lubricant, tabletting.
Preferably, the wet granulation time of the granule 1 is 3～5min；Amount of water for material gross weight 18～28%；
The wet granulation time of the granule 2 is 8～12min；Amount of water for material gross weight 35～45%.
Preferably, the Quetiapine or its pharmaceutically acceptable salt, hydrophilic gel matrix material, pH adjusting agent and figuration
By the screen cloth of 0.6mm before agent use.
Preferably, the mixing speed of the wet granulator is 100～200 revs/min, and cutter speed is 1000～2500
Rev/min.
Preferably, the time that the solution atomization is added is 3 minutes in.
Preferably, the wet granulate was the screen cloth of 2.0mm.
Preferably, the drying is placed in making moisture be less than 2% in 60 DEG C of baking oven.
Preferably, the dry granulate is the screen cloth by 1.0mm.
Raw material (particularly Quetiapine or its pharmaceutically acceptable salt) is crushed and process of sieving (preferably, the quinoline
Flat or its pharmaceutically acceptable salt the particle diameter of sulfur is less than 0.15mm.), it can be ensured that active component dissolution rate constant, and
Can discharge at the appointed time completely.
In the preparation of the granule 1 and granule 2, using atomization liquid feeding, while excessively being pelletized, it is ensured that granule is dredged
Loose, uniform, and without bulk, so as to improve the stability of technique.
Preferably, in step (2), the weight ratio of the granule 1 and granule 2 is 1:1～5, more preferably 1:1～3.
Preferably, in the granule 1, Quetiapine or its pharmaceutically acceptable salt, hydrophilic gel matrix material, pH regulator
The weight ratio of agent and excipient is 1～5:2～4:1:1～4；In the granule 2, Quetiapine or its pharmaceutically acceptable salt,
The weight ratio of hydrophilic gel matrix material, pH adjusting agent and excipient is 1～5:2～4:1:1～4.
It is highly preferred that in the granule 1, Quetiapine or its pharmaceutically acceptable salt, hydrophilic gel matrix material, pH are adjusted
The weight ratio of section agent and excipient is 3～4:2～3:1:1～2；In the granule 2, Quetiapine or which is pharmaceutically acceptable
The weight ratio of salt, hydrophilic gel matrix material, pH adjusting agent and excipient is 3～4:2～3:1:1～2.
Preferably, the hydrophilic gel matrix material includes：
(a) with the hypromellose that viscosity is 80～120mPa s, and
B () is with the hypromellose that viscosity is 3000～5600mPa s；
It is highly preferred that described with the hypromellose that viscosity is 80～120mPa s and have viscosity be 3000～
The weight ratio of the hypromellose of 5600mPa s is 1～6:1；
It is further preferred that described is hypromellose with the hypromellose that viscosity is 80～120mPa s
K100lv；It is HPMC K4M with the hypromellose that viscosity is 3000～5600mPa s.
Preferably, in the granule 1 and granule 2, the pH adjusting agent is sodium citrate；The excipient is fine selected from crystallite
Dimension element and Lactose, and both weight ratios are 3～1:1～3；Preferably 2～1:1.
The dissolubility of Quetiapine or its pharmaceutically acceptable salt has pH dependencies, under physiological ph conditions, with pH
Rising high-dissolvability reduces.Therefore, add pH adjusting agent, active component human body absorption mainly in small intestinal, it can be ensured that product
Good bioavailability.
Preferably, the Quetiapine or its pharmaceutically acceptable salt are quetiapine fumarate.
Slow releasing tablet prepared by the preparation method can prevent slow releasing preparation prominent release, dissolution difference is big and poor repeatability etc.
Problem, improves the bioavailability of product.
Description of the drawings
Fig. 1 grinds dissolution of the medicine in pH6.8 phosphate-buffered liquid mediums for slow releasing tablet prepared by comparative example 2 with original and writes music
Line chart.
Fig. 2 grinds dissolution of the medicine in pH6.8 phosphate-buffered liquid mediums for slow releasing tablet prepared by embodiment 1 with original and writes music
Line chart.
Fig. 3 grinds dissolution of the medicine in pH6.8 phosphate-buffered liquid mediums for slow releasing tablet prepared by embodiment 2 with original and writes music
Line chart.
Fig. 4 grinds dissolution of the medicine in pH6.8 phosphate-buffered liquid mediums for slow releasing tablet prepared by embodiment 3 with original and writes music
Line chart.
Specific embodiment
In order to be better understood from and illustrate the present invention, below just the present invention provide containing Quetiapine or its can pharmaceutically connect
Slow releasing tablet of salt that receives and preparation method thereof provides exemplary illustration, but which is understood not to the restriction to content of the invention.
In following examples, device therefor instrument mainly includes：
G20 type wet mixing pelletizers；BSL-25 type mixers；FZB type crushing and pelletizing machines；ZP10A type tablet machine；YD-
35 tablet hardness instruments；RC806 digestion instruments.
Dissolving-out method：- two the first methods of annex XD of release；- two annex XC the first method (Chinese Pharmacopoeias 2015 of dissolution
Year version), solution C 1000ml is solvent, basket method, rotating speed：200rpm
Solution C：Monohydrate potassium 9.459g, sodium hydroxide 5.08g, disodium hydrogen phosphate 1.79g is taken, is dissolved in water and dilute
Release to 1000ml, mix, obtain final product, pH6.80；
Yuan Yan medicines manufacturer：AstraZeneca, lot number：AA0159
Comparative example 1
Prescription is as shown in table 1.
Table 1：1000 Quetiapine Fumarate Extended-Release Tablets (200mg/ pieces) prescriptions
According to recipe quantity in upper table by Lactose, Microcrystalline Cellulose, sodium citrate, quetiapine fumarate, hypromellose
K4M CR and hypromellose K100lv CR pass sequentially through the pelletizing machine of 0.6mm circular screen mesh and sieve.Collection material is placed in
In wet mixing pelletizer, it is 100～200 revs/min to arrange mixing speed, and cutter speed is 1000～2500 revs/min.Dry-mixed
The purified water for being slowly added into the amount of material gross weight 30% in 3min afterwards is pelletized, and sees that grain forming remixes 2min,
Discharging.Granule is by the wet granulate of the circular screen mesh of 2.0mm.
Problem：Granule is uneven, and large crumb is more, and granulate is difficult, and experiment cannot proceed.
Comparative example 2
Prescription is as shown in table 2.
Table 2：1000 Quetiapine Fumarate Extended-Release Tablets (200mg/ pieces) prescriptions
| # | Material | Single dose (mg) | 1000 tablet recipes amount (g) |
| 1 | Quetiapine fumarate | 230.00 | 230.00 |
| 2 | Lactose | 51.68 | 51.68 |
| 3 | Microcrystalline Cellulose | 51.67 | 51.67 |
| 4 | HPMC K4M CR | 29.50 | 29.50 |
| 5 | Hypromellose K100lv CR | 147.50 | 147.50 |
| 6 | Sodium citrate | 70.80 | 70.80 |
| 7 | Magnesium stearate | 8.85 | 8.85 |
| Gross weight | 590 | 590 |
According to recipe quantity in upper table by Lactose, Microcrystalline Cellulose, quetiapine fumarate, sodium citrate, hypromellose
K4M CR and hypromellose K100lv CR pass sequentially through the pelletizing machine of 0.6mm circular screen mesh and sieve.Collection material is placed in
In wet mixing pelletizer, it is 100～200 revs/min to arrange mixing speed, and cutter speed is 1000～2500 revs/min.Dry-mixed
Add after afterwards be atomized the purified water of the amount of material gross weight 30% by compression pump and pelletized, see granule
Mouldability remixes 2min, discharging.Wet granular is placed in 60 DEG C of forced air dryings by the wet granulate of the circular screen mesh of 2.0mm by granule
Dry to moisture in case<2%, dry granulate is carried out by the circular screen mesh of 1.0mm, the magnesium stearate of recipe quantity is crossed after 20 mesh sieves
With above-mentioned granule mix homogeneously, tabletting, film coating.
Fig. 1 grinds dissolution of the medicine in pH6.8 phosphate-buffered liquid mediums for slow releasing tablet prepared by comparative example 2 with original and writes music
Line chart (size of standard deviation is represented by the length of vertical line in figure).As seen from Figure 1, vertical line is very long, and standard deviation is big, molten
Go out difference greatly, illustrate that slow releasing tablet prepared by comparative example 2 is big with the dissolution diversity that original grinds medicine, it is impossible to meet and require.
Embodiment 1
Prescription is as shown in table 3：
Table 3：2000 Quetiapine Fumarate Extended-Release Tablets (200mg/ pieces) prescriptions
Granule 1 according to recipe quantity in upper table is by Lactose, Microcrystalline Cellulose, quetiapine fumarate, sodium citrate, hydroxypropyl first
Cellulose K4M CR and hypromellose K100lv CR pass sequentially through the pelletizing machine of 0.6mm circular screen mesh and sieve.Collection material
Be placed in wet mixing pelletizer, arrange mixing speed be 100～200 revs/min, cutter speed be 1000～2500 turns/
Point.Add after after dry-mixed be atomized the purified water of the amount of material gross weight 18% by compression pump and made
Grain, sees that grain forming remixes 2min, discharges.Wet granular is placed in 60 DEG C by the wet granulate of the circular screen mesh of 2.0mm by granule
Dry to moisture in air dry oven<2%, dry granulate is carried out by the circular screen mesh of 1.0mm；
Granule 2 according to recipe quantity in upper table is by Lactose, Microcrystalline Cellulose, quetiapine fumarate, sodium citrate, hydroxypropyl first
Cellulose K4M CR and hypromellose K100lv CR pass sequentially through the pelletizing machine of 0.6mm circular screen mesh and sieve.Collection material
Be placed in wet mixing pelletizer, arrange mixing speed be 100～200 revs/min, cutter speed be 1000～2500 turns/
Point.Add after after dry-mixed be atomized the purified water of the amount of material gross weight 40% by compression pump and made
Grain, sees that grain forming remixes 2min, remixes 4min, discharges.Granule, will be wet by the wet granulate of the circular screen mesh of 2.0mm
Granule is placed in 60 DEG C of air dry ovens and dries to moisture<2%, dry granulate is carried out by the circular screen mesh of 1.0mm；
After by 2 mix homogeneously of granule 1 and granule, mix with the magnesium stearate for crossing 20 mesh sieves, tabletting, film coating.
Fig. 2 grinds dissolution of the medicine in pH6.8 phosphate-buffered liquid mediums for slow releasing tablet prepared by embodiment 1 with original and writes music
Line chart (size of standard deviation is represented by the length of vertical line in figure).As seen from Figure 2, vertical line is very short, and standard deviation is little, molten
Go out that difference is little, illustrate that slow releasing tablet prepared by embodiment 1 is little with the former dissolution diversity for grinding medicine.
Embodiment 2
Prescription is as shown in table 3：
Table 3：3000 Quetiapine Fumarate Extended-Release Tablets (200mg/ pieces) prescriptions
Granule 1 according to recipe quantity in upper table is by Lactose, Microcrystalline Cellulose, quetiapine fumarate, sodium citrate, hydroxypropyl first
Cellulose K4M CR and hypromellose K100lv CR pass sequentially through the pelletizing machine of 0.6mm circular screen mesh and sieve.Collection material
Be placed in wet mixing pelletizer, arrange mixing speed be 100～200 revs/min, cutter speed be 1000～2500 turns/
Point.Add after after dry-mixed be atomized the purified water of the amount of material gross weight 18% by compression pump and made
Grain, sees that grain forming remixes 2min, discharges.Wet granular is placed in 60 DEG C by the wet granulate of the circular screen mesh of 2.0mm by granule
Dry to moisture in air dry oven<2%, dry granulate is carried out by the circular screen mesh of 1.0mm；
Granule 2 according to recipe quantity in upper table is by Lactose, Microcrystalline Cellulose, quetiapine fumarate, sodium citrate, hydroxypropyl first
Cellulose K4M CR and hypromellose K100lv CR pass sequentially through the pelletizing machine of 0.6mm circular screen mesh and sieve.Collection material
Be placed in wet mixing pelletizer, arrange mixing speed be 100～200 revs/min, cutter speed be 1000～2500 turns/
Point.Add after after dry-mixed be atomized the purified water of the amount of material gross weight 40% by compression pump and made
Grain, sees that grain forming remixes 2min, remixes 1min, discharges.Granule, will be wet by the wet granulate of the circular screen mesh of 2.0mm
Granule is placed in 60 DEG C of air dry ovens and dries to moisture<2%, dry granulate is carried out by the circular screen mesh of 1.0mm；By granule 1
After 2 mix homogeneously of granule, mix with the magnesium stearate for crossing 20 mesh sieves, tabletting, film coating.
Fig. 3 grinds dissolution of the medicine in pH6.8 phosphate-buffered liquid mediums for slow releasing tablet prepared by embodiment 2 with original and writes music
Line chart (size of standard deviation is represented by the length of vertical line in figure).As seen from Figure 3, vertical line is very short, and standard deviation is little, molten
Go out that difference is little, illustrate that slow releasing tablet prepared by embodiment 2 is little with the former dissolution diversity for grinding medicine.
Embodiment 3
Prescription is as shown in table 3：
Table 3：3500 Quetiapine Fumarate Extended-Release Tablets (200mg/ pieces) prescriptions
Granule 1 according to recipe quantity in upper table is by Lactose, Microcrystalline Cellulose, quetiapine fumarate, sodium citrate, hydroxypropyl first
Cellulose K4M CR and hypromellose K100lv CR pass sequentially through the pelletizing machine of 0.6mm circular screen mesh and sieve.Collection material
Be placed in wet mixing pelletizer, arrange mixing speed be 100～200 revs/min, cutter speed be 1000～2500 turns/
Point.Add after after dry-mixed be atomized the purified water of the amount of material gross weight 18% by compression pump and made
Grain, discharging.Granule is placed in wet granular in 60 DEG C of air dry ovens and is dried to moisture by the wet granulate of the circular screen mesh of 2.0mm<
2%, dry granulate is carried out by the circular screen mesh of 1.0mm；
Granule 2 according to recipe quantity in upper table is by Lactose, Microcrystalline Cellulose, quetiapine fumarate, sodium citrate, hydroxypropyl first
Cellulose K4M CR and hypromellose K100lv CR pass sequentially through the pelletizing machine of 0.6mm circular screen mesh and sieve.Collection material
Be placed in wet mixing pelletizer, arrange mixing speed be 100～200 revs/min, cutter speed be 1000～2500 turns/
Point.Add after after dry-mixed be atomized the purified water of the amount of material gross weight 40% by compression pump and made
Grain, sees that grain forming remixes 2min, remixes 4min, discharges.Granule, will be wet by the wet granulate of the circular screen mesh of 2.0mm
Granule is placed in 60 DEG C of air dry ovens and dries to moisture<2%, dry granulate is carried out by the circular screen mesh of 1.0mm；
After by 2 mix homogeneously of granule 1 and granule, mix with the magnesium stearate for crossing 20 mesh sieves, tabletting, film coating.
Fig. 4 grinds dissolution of the medicine in pH6.8 phosphate-buffered liquid mediums for slow releasing tablet prepared by embodiment 3 with original and writes music
Line chart (size of standard deviation is represented by the length of vertical line in figure).As seen from Figure 4, vertical line is very short, and standard deviation is little, molten
Go out that difference is little, illustrate that slow releasing tablet prepared by embodiment 3 is little with the former dissolution diversity for grinding medicine.
Claims (10)
1. a kind of slow releasing tablet containing Quetiapine or its pharmaceutically acceptable salt, it is characterised in that the slow releasing tablet includes：
Granule 1, its include Quetiapine or its pharmaceutically acceptable salt, hydrophilic gel matrix material, pH adjusting agent and excipient；
Granule 2, its include Quetiapine or its pharmaceutically acceptable salt, hydrophilic gel matrix material, pH adjusting agent and excipient；
Wherein, the granule 1 and granule 2 are prepared from by different wet-granulation process.
2. the slow releasing tablet containing Quetiapine or its pharmaceutically acceptable salt according to claim 1, it is characterised in that
The wet granulation time of the granule 1 is 2～5min, and amount of water is the 10%～28% of material gross weight；
The wet granulation time of the granule 2 is 6～15min, and amount of water is the 30%～45% of material gross weight.
3. the slow releasing tablet containing Quetiapine or its pharmaceutically acceptable salt according to claim 1, it is characterised in that
The wet granulation time of the granule 1 is 3～5min；Amount of water for material gross weight 18%～28%；
The wet granulation time of the granule 2 is 8～12min；Amount of water for material gross weight 35%～45%.
4. the slow releasing tablet containing Quetiapine or its pharmaceutically acceptable salt according to claim 1, it is characterised in that institute
The weight ratio for stating granule 1 and granule 2 is 1:1～5, preferably 1:1～3.
5. the slow releasing tablet containing Quetiapine or its pharmaceutically acceptable salt according to claim 1, it is characterised in that
In the granule 1, Quetiapine or its pharmaceutically acceptable salt, hydrophilic gel matrix material, pH adjusting agent and excipient
Weight ratio be 1～5:2～4:1:1～4；In the granule 2, Quetiapine or its pharmaceutically acceptable salt, hydrophilic gel bone
The weight ratio of frame material, pH adjusting agent and excipient is 1～5:2～4:1:1～4；
Preferably, in the granule 1, Quetiapine or its pharmaceutically acceptable salt, hydrophilic gel matrix material, pH adjusting agent and
The weight ratio of excipient is 3～4:2～3:1:1～2；In the granule 2, Quetiapine or its pharmaceutically acceptable salt, hydrophilic
The weight ratio of gelatum skeleton material, pH adjusting agent and excipient is 3～4:2～3:1:1～2.
6. the slow releasing tablet containing Quetiapine or its pharmaceutically acceptable salt according to claim 1, it is characterised in that institute
State hydrophilic gel matrix material to include：
(a) with the hypromellose that viscosity is 80～120mPa s, and
B () is with the hypromellose that viscosity is 3000～5600mPa s；
Described with the hypromellose that viscosity is 80～120mPa s and with the hydroxyl that viscosity is 3000～5600mPa s
The weight ratio of the third methylcellulose is 1～6:1.
7. the slow releasing tablet containing Quetiapine or its pharmaceutically acceptable salt according to claim 6, it is characterised in that institute
It is hypromellose K100lv to state with the hypromellose that viscosity is 80～120mPa s；Have viscosity be 3000～
The hypromellose of 5600mPa s is HPMC K4M.
8. the slow releasing tablet containing Quetiapine or its pharmaceutically acceptable salt according to claim 1, it is characterised in that institute
State in granule 1 and granule 2, the pH adjusting agent is sodium citrate；The excipient is selected from Microcrystalline Cellulose and Lactose, and two
The weight ratio of person is 3～1:1～3；Preferably 2～1:1.
9. the slow releasing tablet containing Quetiapine or its pharmaceutically acceptable salt any one of a kind of claim 1～8
Preparation method, it is characterised in that comprise the following steps：
(1) by the raw material Quetiapine of granule 1 or its pharmaceutically acceptable salt, hydrophilic gel matrix material, pH adjusting agent and tax
During shape agent is as wet granulator；The 10%～28% of above-mentioned material gross weight water atomization is added above-mentioned material wet granulation
2～5min obtains wet granular, wet granulate, dries, and dry granulate obtains granule 1；
Raw material Quetiapine or its pharmaceutically acceptable salt, hydrophilic gel matrix material, pH adjusting agent and excipient by granule 2
In as wet granulator；By the 30%～45% of above-mentioned material gross weight water atomization add above-mentioned material wet granulation 6～
15min obtains wet granular, wet granulate, dries, and dry granulate obtains granule 2；
(2) by above-mentioned granule 1 and granule 2 and mix lubricant, tabletting.
10. the preparation method containing Quetiapine or the slow releasing tablet of its pharmaceutically acceptable salt according to claim 9, its
It is characterised by, the wet granulation time of the granule 1 is 3～5min；Amount of water for material gross weight 18～28%；Described
The wet granulation time of grain 2 is 8～12min；Amount of water for material gross weight 35～45%；The Quetiapine or its pharmaceutically
By the screen cloth of 0.6mm before acceptable salt, hydrophilic gel matrix material and excipient use；The wet granulator is stirred
Speed is mixed for 100～200 revs/min, cutter speed is 1000～2500 revs/min；The time that the solution atomization is added is 3 points
In clock；The wet granulate was the screen cloth of 2.0mm；The drying is placed in making moisture be less than 2% in 60 DEG C of baking oven；Described dry
Granulate is the screen cloth by 1.0mm.
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Address after: Haikou standard structure building 570, No. 3113, Haikou Industrial Park, Haikou, Haixin high tech Zone, Hainan Province Patentee after: Huayi Taikang Pharmaceutical Co.,Ltd. Address before: 571100 Haikou City, Hainan Province, 273 Nanhai Avenue Haikou High-tech Zone D light steel structure standard industrial plant west side Patentee before: HAINAN VISUM PHARMACEUTICAL Co.,Ltd. |