CN106491550B - Sustained-release tablet containing quetiapine or pharmaceutically acceptable salt thereof and preparation method thereof - Google Patents
Sustained-release tablet containing quetiapine or pharmaceutically acceptable salt thereof and preparation method thereof Download PDFInfo
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Abstract
The invention belongs to the technical field of medicines, and discloses a sustained-release tablet containing quetiapine or pharmaceutically acceptable salts thereof and a preparation method thereof. The sustained-release tablet comprises: granule 1 comprising quetiapine or a pharmaceutically acceptable salt thereof, a hydrophilic gel matrix material, a pH adjusting agent and an excipient; granule 2 comprising quetiapine or a pharmaceutically acceptable salt thereof, a hydrophilic gel matrix material, a pH adjusting agent and an excipient; wherein the granules 1 and 2 are prepared by different wet granulation processes. The sustained release tablet can prevent the problems of burst release, large dissolution rate difference, poor repeatability and the like of a sustained release preparation, and improve the bioavailability of the product.
Description
Technical Field
The invention belongs to the field of pharmaceutical preparations, and particularly relates to a sustained-release tablet containing quetiapine or pharmaceutically acceptable salts thereof and a preparation method thereof.
Background
Quetiapine fumarate is a therapeutic drug for bipolar disorders including schizophrenic and depressive episodes, and for bipolar disorders including moderate to severe manic episodes, developed by the company Aslican and approved in the United states of America at 10 months 2008, and is marketed under the chemical name 11- {4- [2- (2-hydroxyethoxy) ethyl]-1-piperazinyl } dibenzo [ b, f][1,4]Sulfoazazepine
The chemical structural formula of the fumarate is shown as follows. The molecular formula is as follows: c42H50N6O4S2·C4H4O4(ii) a Molecular weight: 883.11.
quetiapine fumarate has the chemical structural general formula:
the quetiapine fumarate sustained release tablet is a hydrophilic gel skeleton sustained release tablet, is a medicinal preparation prepared by using a hydrophilic polymer as a skeleton material, generates gel when being hydrated by digestive juice after being orally taken, and releases the medicament in a diffusion or/and gel skeleton erosion way. In the oral sustained-release and controlled-release preparation, the hydrophilic gel skeleton sustained-release tablet plays an important role due to simple process, short production period, low cost and high efficiency. However, due to the limitations of the production process, the gel matrix sustained release tablet is a single release unit system, which is likely to cause the problems of burst release and great dissolution difference of the drugs, especially the water-soluble drugs. Therefore, the problem to be solved by the industry is to find a prescription or process which can control the constant-speed release and stability of the drug.
Patent document CN200780053817.3 (original drug patent: US2008287418a1) discloses a formulation comprising quetiapine or a pharmaceutically acceptable salt thereof, wherein the quetiapine content is about 9.6% to about 10.4% by weight, and wherein the formulation comprises 30% by weight of hypromellose and about 7.2% by weight of sodium citrate.
Patent document CN201110127555.9 discloses a preparation process of quetiapine fumarate sustained release tablets. The process adopts erodible slow-release auxiliary materials as retarding agents, adopts a melting method solid dispersion technology to prepare slow-release granules, and tabletting. It is a slow-release matrix tablet, and is coated with quick-release film coating process.
Patent document CN201110137879.0 discloses a sustained-release tablet of quetiapine fumarate composition, which comprises quetiapine fumarate, organic acid salt, sustained-release material and other pharmaceutic adjuvants, wherein the sustained-release material is K-type hypromellose; and the weight percentages of the components are as follows: 25-40% of quetiapine fumarate, 2-8% of organic acid salt, 5-30% of slow release material and the balance of other pharmaceutic adjuvants.
Patent document CN200810138434.2 discloses a quetiapine sustained release tablet and a preparation method thereof. The sustained release tablet contains 5 to 50 percent of sustained release framework material with pH-dependent solubility, preferably 15 to 35 percent of sustained release framework material with pH-dependent solubility according to weight percentage.
Patent document CN201010253723.4 relates to a quetiapine sustained release tablet comprising at least quetiapine or a pharmaceutically acceptable salt thereof as an active ingredient, ethylcellulose as a sustained release matrix material, and a low-viscosity water-soluble binder, wherein the average particle size of the ethylcellulose is not more than 80 μm, preferably not more than 40 μm.
The quetiapine fumarate sustained-release tablets disclosed in the patent documents all use a sustained-release material and a raw material drug which are mixed, granulated and tableted, because the production process is simple, the efficiency is high and the like. However, this production method is liable to cause large dissolution variability, poor reproducibility, and the like in the actual production process, and none of the above patent documents solves this problem.
The method for avoiding the large difference of dissolution rates and the poor reproducibility are the key points of the research on the sustained-release matrix tablets, particularly the hydrophilic gel matrix tablets, and are also the research difficulties acknowledged in the industry.
Disclosure of Invention
In view of the above-mentioned deficiencies of the prior art, the present invention aims to provide a sustained release tablet containing quetiapine or a pharmaceutically acceptable salt thereof and a preparation method thereof. The sustained release tablets containing quetiapine or pharmaceutically acceptable salts thereof have the advantages of small dissolution rate difference, good reproducibility and high bioavailability.
The invention provides a sustained-release tablet containing quetiapine or a pharmaceutically acceptable salt thereof, which comprises:
granule 1 comprising quetiapine or a pharmaceutically acceptable salt thereof, a hydrophilic gel matrix material, a pH adjusting agent and an excipient;
wherein the granules 1 and 2 are prepared by different wet granulation processes.
The inventors have found through a number of experiments that the different wet granulation processes of the granules 1 and 2 affect the formation of the granules and thus the drug release rate can be influenced and controlled.
Preferably, the wet granulation time of the granule 1 is 2-5 min, and the water addition amount is 10-28% of the total weight of the materials; the wet granulation time of the granules 2 is 6-15 min, and the water addition amount is 30-45% of the total weight of the materials.
More preferably, the wet granulation time of the granule 1 is 3-5 min; the water addition amount is 18 to 28 percent of the total weight of the materials; the wet granulation time of the granules 2 is 8-12 min; the water addition amount is 35-45% of the total weight of the materials.
The granules 1 and 2 affect the formation of granules through different wet granulation time and water addition amount, thereby controlling the drug release rate.
The granules 1 are subjected to wet granulation under the conditions, so that the early release of the sustained-release tablets can be ensured; the granules 2 are subjected to wet granulation under the conditions, so that the later release of the sustained release tablets is constant.
Namely, the sustained-release tablet of the present invention is prepared by two-step wet granulation, and then mixing the granules and tabletting.
The prepared particles 1 have loose structures, the particles 2 have compact structures, and the matrix tablet glue prepared by mixing the particles and the particles has good formability, small dissolution difference and good stability.
Preferably, the weight ratio of the particles 1 to the particles 2 is 1: 1-5, and more preferably 1: 1-3.
Preferably, in the granule 1, the weight ratio of quetiapine or pharmaceutically acceptable salt thereof, the hydrophilic gel matrix material, the pH regulator and the excipient is 1-5: 2-4: 1: 1-4; in the particles 2, the weight ratio of quetiapine or pharmaceutically acceptable salt thereof, the hydrophilic gel skeleton material, the pH regulator and the excipient is 1-5: 2-4: 1: 1-4.
More preferably, in the granule 1, the weight ratio of quetiapine or pharmaceutically acceptable salt thereof, hydrophilic gel matrix material, pH regulator and excipient is 3-4: 2-3: 1: 1-2; in the particles 2, the weight ratio of quetiapine or pharmaceutically acceptable salt thereof, the hydrophilic gel skeleton material, the pH regulator and the excipient is 3-4: 2-3: 1: 1-2.
Preferably, the hydrophilic gel matrix material comprises:
(a) hydroxypropyl methylcellulose having a viscosity of 80 to 120 mPas, and
(b) hydroxypropyl methylcellulose with viscosity of 3000-5600 mPas;
more preferably, the weight ratio of the hydroxypropyl methylcellulose with the viscosity of 80-120 mPa & s to the hydroxypropyl methylcellulose with the viscosity of 3000-5600 mPa & s is 1-6: 1.
Further preferably, the hydroxypropyl methylcellulose with the viscosity of 80-120 mPa & s is hydroxypropyl methylcellulose K100 lv; the hydroxypropyl methylcellulose with the viscosity of 3000-5600 mPa.s is hydroxypropyl methylcellulose K4M.
The present inventors have found that the use of one model of HPMC alone does not provide good control of drug release. The HPMC of two types is required to meet the proportion and proper dosage when being mixed for use. This is because when the dosage is small, a continuous gel layer cannot be formed on the surface of the tablet rapidly, so that the sustained-release tablet can be locally and rapidly hydrated and disintegrated to cause burst release.
Preferably, in the granule 1 and the granule 2, the pH regulator is sodium citrate; the excipient is selected from microcrystalline cellulose and lactose, and the weight ratio of the microcrystalline cellulose to the lactose is 3-1: 1-3; preferably 2-1: 1.
Preferably, the quetiapine or a pharmaceutically acceptable salt thereof is quetiapine fumarate.
The preparation method of the sustained release tablet containing quetiapine or pharmaceutically acceptable salt thereof provided by the invention comprises the following steps:
(1) putting the quetiapine or pharmaceutically acceptable salt thereof, hydrophilic gel skeleton material, pH regulator and excipient which are raw materials of the granules 1 into a wet granulator; atomizing water accounting for 10-28% of the total weight of the materials, adding the water into the materials for wet granulation for 2-5 min to obtain wet granules, and carrying out wet granulation, drying and dry granulation to obtain granules 1;
putting the quetiapine or pharmaceutically acceptable salt thereof, hydrophilic gel skeleton material, pH regulator and excipient which are raw materials of the granules 2 into a wet granulator; atomizing water accounting for 30-45% of the total weight of the materials, adding the water into the materials for wet granulation for 6-15 min to obtain wet granules, and carrying out wet granulation, drying and dry granulation to obtain granules 2;
(2) mixing the granules 1 and 2 with lubricant, and tabletting.
Preferably, the wet granulation time of the granule 1 is 3-5 min; the water addition amount is 18-28% of the total weight of the materials; the wet granulation time of the granules 2 is 8-12 min; the water addition amount is 35-45% of the total weight of the materials.
Preferably, the quetiapine or a pharmaceutically acceptable salt thereof, the hydrophilic gel matrix material, the pH adjusting agent and the excipient are passed through a 0.6mm mesh screen prior to use.
Preferably, the stirring speed of the wet granulator is 100-200 rpm, and the speed of the cutting knife is 1000-2500 rpm.
Preferably, the solution is added nebulized for a period of time within 3 minutes.
Preferably, the wet granulation is a 2.0mm sieve.
Preferably, the drying is carried out in an oven at 60 ℃ to a moisture content of less than 2%.
Preferably, the dry granulation is through a 1.0mm screen.
The raw material (in particular quetiapine or a pharmaceutically acceptable salt thereof) is crushed and sieved (preferably, the particle size of the quetiapine or the pharmaceutically acceptable salt thereof is less than 0.15 mm.) so as to ensure that the dissolution rate of the active ingredient is constant and the active ingredient can be completely released within a specified time.
During the preparation of the particles 1 and 2, atomization liquid adding is adopted, excessive granulation is carried out simultaneously, the particles are ensured to be loose and uniform, and no large blocks exist, so that the stability of the process is improved.
Preferably, in the step (2), the weight ratio of the particles 1 to the particles 2 is 1: 1-5, and more preferably 1: 1-3.
Preferably, in the granule 1, the weight ratio of quetiapine or pharmaceutically acceptable salt thereof, the hydrophilic gel matrix material, the pH regulator and the excipient is 1-5: 2-4: 1: 1-4; in the particles 2, the weight ratio of quetiapine or pharmaceutically acceptable salt thereof, the hydrophilic gel skeleton material, the pH regulator and the excipient is 1-5: 2-4: 1: 1-4.
More preferably, in the granule 1, the weight ratio of quetiapine or pharmaceutically acceptable salt thereof, hydrophilic gel matrix material, pH regulator and excipient is 3-4: 2-3: 1: 1-2; in the particles 2, the weight ratio of quetiapine or pharmaceutically acceptable salt thereof, the hydrophilic gel skeleton material, the pH regulator and the excipient is 3-4: 2-3: 1: 1-2.
Preferably, the hydrophilic gel matrix material comprises:
(a) hydroxypropyl methylcellulose having a viscosity of 80 to 120 mPas, and
(b) hydroxypropyl methylcellulose with viscosity of 3000-5600 mPas;
more preferably, the weight ratio of the hydroxypropyl methylcellulose with the viscosity of 80-120 mPa & s to the hydroxypropyl methylcellulose with the viscosity of 3000-5600 mPa & s is 1-6: 1;
further preferably, the hydroxypropyl methylcellulose with the viscosity of 80-120 mPa & s is hydroxypropyl methylcellulose K100 lv; the hydroxypropyl methylcellulose with the viscosity of 3000-5600 mPa.s is hydroxypropyl methylcellulose K4M.
Preferably, in the granule 1 and the granule 2, the pH regulator is sodium citrate; the excipient is selected from microcrystalline cellulose and lactose, and the weight ratio of the microcrystalline cellulose to the lactose is 3-1: 1-3; preferably 2-1: 1.
The solubility of quetiapine or a pharmaceutically acceptable salt thereof is pH dependent and decreases with increasing pH under physiological pH conditions. Therefore, the pH regulator is added, the active ingredients are mainly absorbed in the small intestine of a human body, and good bioavailability of the product can be ensured.
Preferably, the quetiapine or a pharmaceutically acceptable salt thereof is quetiapine fumarate.
The sustained release tablet prepared by the preparation method can prevent the problems of burst release, large dissolution rate difference, poor repeatability and the like of the sustained release preparation, and improve the bioavailability of the product.
Drawings
FIG. 1 is a graph showing the dissolution rate of the sustained release tablet prepared in comparative example 2 and the original drug in phosphate buffer medium at pH 6.8.
FIG. 2 is a graph showing the dissolution profiles of the sustained release tablet prepared in example 1 and the original drug in phosphate buffer medium at pH 6.8.
FIG. 3 is a graph showing the dissolution profiles of the sustained release tablet prepared in example 2 and the original drug in phosphate buffer medium at pH 6.8.
FIG. 4 is a graph showing the dissolution profiles of the sustained release tablet prepared in example 3 and the original drug in phosphate buffer medium at pH 6.8.
Detailed Description
For better understanding and clarification of the present invention, the following description is given for the sustained-release tablet containing quetiapine or a pharmaceutically acceptable salt thereof and the preparation method thereof provided in the present invention, but it should not be construed as limiting the contents of the present invention.
The equipment used in the following examples essentially included:
model G20 wet mixing granulator; BSL-25 type mixer; an FZB type crushing and granulating machine; tablet press type ZP 10A; YD-35 tablet hardness tester; RC806 dissolution apparatus.
The dissolution method comprises the following steps: release-appendix two XD first method; dissolution-appendix of two parts XC first method (chinese pharmacopoeia 2015 year edition), solution C1000 ml as solvent, basket method, rotation speed: 200rpm
Solution C: dissolving 9.459g of citric acid monohydrate, 5.08g of sodium hydroxide and 1.79g of disodium hydrogen phosphate in water, diluting to 1000ml, and mixing uniformly to obtain a solution with a pH value of 6.80;
original research drug manufacturers: astrazep, lot No.: AA0159
Comparative example 1
The recipe is shown in table 1.
Table 1: 1000 quetiapine fumarate sustained-release tablets (200 mg/tablet) prescription
Lactose, microcrystalline cellulose, sodium citrate, quetiapine fumarate, hypromellose K4M CR and hypromellose K100lv CR were sieved sequentially through a granulator with a 0.6mm circular screen according to the prescription in the above table. The materials are collected and placed in a wet mixing granulator, the stirring speed is set to be 100-200 rpm, and the cutting speed is set to be 1000-2500 rpm. After dry mixing, slowly adding purified water with an amount of 30% of the total weight of the materials within 3min for granulation, mixing for 2min after observing the particle forming property, and discharging. The granules were wet-sized through a 2.0mm circular screen.
The problems are as follows: the particles are not uniform, large lumps are more, the whole particles are difficult to complete, and the experiment can not be continued.
Comparative example 2
The recipe is shown in table 2.
Table 2: 1000 quetiapine fumarate sustained-release tablets (200 mg/tablet) prescription
| # | Material | Single dose (mg) | 1000 tablets prescription (g) |
| 1 | Quetiapine fumarate | 230.00 | 230.00 |
| 2 | Lactose | 51.68 | 51.68 |
| 3 | Microcrystalline cellulose | 51.67 | 51.67 |
| 4 | Hydroxypropyl methylcellulose K4M CR | 29.50 | 29.50 |
| 5 | Hydroxypropyl methylcellulose K100lv CR | 147.50 | 147.50 |
| 6 | Citric acid sodium salt | 70.80 | 70.80 |
| 7 | Magnesium stearate | 8.85 | 8.85 |
| Total weight of | 590 | 590 |
Lactose, microcrystalline cellulose, quetiapine fumarate, sodium citrate, hypromellose K4M CR and hypromellose K100lv CR were sieved sequentially through a granulator with a 0.6mm circular screen according to the prescription amounts in the above table. The materials are collected and placed in a wet mixing granulator, the stirring speed is set to be 100-200 rpm, and the cutting speed is set to be 1000-2500 rpm. After dry mixing, purified water with the amount of 30 percent of the total weight of the materials is atomized by a pressure pump within 3min, added for granulation, mixed for 2min after the particle formability is observed, and discharged. Wet granulating the granules through a 2.0mm circular screen, drying the wet granules in a 60 ℃ air-blast drying oven until the moisture content is less than 2%, dry granulating through a 1.0mm circular screen, sieving the magnesium stearate with a 20-mesh sieve according to the prescription amount, uniformly mixing with the granules, tabletting, and coating with a film coat.
FIG. 1 is a graph showing the dissolution profiles of the sustained-release tablet prepared in comparative example 2 and the original drug in a phosphate buffer medium at pH6.8 (the size of standard deviation is indicated by the length of the vertical line in the graph). As can be seen from FIG. 1, the vertical line is very long, the standard deviation is large, and the dissolution difference is large, which indicates that the dissolution difference between the sustained-release tablet prepared in comparative example 2 and the original drug is large and cannot meet the requirement.
Example 1
The prescription is shown in table 3:
table 3: 2000 quetiapine fumarate sustained-release tablets (200 mg/tablet) prescription
Lactose, microcrystalline cellulose, quetiapine fumarate, sodium citrate, hypromellose K4M CR and hypromellose K100lv CR were sieved sequentially through a granulator with a 0.6mm circular screen according to the prescribed amount of granule 1 in the above table. The materials are collected and placed in a wet mixing granulator, the stirring speed is set to be 100-200 rpm, and the cutting speed is set to be 1000-2500 rpm. After dry mixing, purified water with the amount of 18 percent of the total weight of the materials is atomized by a pressure pump within 3min, added for granulation, mixed for 2min after the particle formability is observed, and discharged. Wet-granulating the granules through a 2.0mm circular screen, placing the wet granules in a 60 ℃ air-blast drying oven to dry until the moisture content is less than 2%, and dry-granulating through a 1.0mm circular screen;
lactose, microcrystalline cellulose, quetiapine fumarate, sodium citrate, hypromellose K4M CR and hypromellose K100lv CR were sieved sequentially through a granulator with a 0.6mm circular screen according to the prescribed amount of granule 2 in the above table. The materials are collected and placed in a wet mixing granulator, the stirring speed is set to be 100-200 rpm, and the cutting speed is set to be 1000-2500 rpm. After dry mixing, purified water with the amount of 40 percent of the total weight of the materials is atomized by a pressure pump within 3min, added and granulated, and mixed for 2min after the granule forming is observed, and mixed for 4min again, and then discharged. Wet-granulating the granules through a 2.0mm circular screen, placing the wet granules in a 60 ℃ air-blast drying oven to dry until the moisture content is less than 2%, and dry-granulating through a 1.0mm circular screen;
mixing granule 1 and granule 2, mixing with 20 mesh magnesium stearate, tabletting, and coating.
FIG. 2 is a graph showing the dissolution profiles of the sustained release tablet prepared in example 1 and the original drug in a phosphate buffer medium at pH6.8 (the size of the standard deviation is indicated by the length of the vertical line in the graph). As can be seen from FIG. 2, the vertical line is short, the standard deviation is small, and the dissolution difference is small, which indicates that the dissolution difference between the sustained-release tablet prepared in example 1 and the original drug is small.
Example 2
The prescription is shown in table 3:
table 3: 3000 quetiapine fumarate sustained-release tablet (200 mg/tablet) prescription
Lactose, microcrystalline cellulose, quetiapine fumarate, sodium citrate, hypromellose K4M CR and hypromellose K100lv CR were sieved sequentially through a granulator with a 0.6mm circular screen according to the prescribed amount of granule 1 in the above table. The materials are collected and placed in a wet mixing granulator, the stirring speed is set to be 100-200 rpm, and the cutting speed is set to be 1000-2500 rpm. After dry mixing, purified water with the amount of 18 percent of the total weight of the materials is atomized by a pressure pump within 3min, added for granulation, mixed for 2min after the particle formability is observed, and discharged. Wet-granulating the granules through a 2.0mm circular screen, placing the wet granules in a 60 ℃ air-blast drying oven to dry until the moisture content is less than 2%, and dry-granulating through a 1.0mm circular screen;
lactose, microcrystalline cellulose, quetiapine fumarate, sodium citrate, hypromellose K4M CR and hypromellose K100lv CR were sieved sequentially through a granulator with a 0.6mm circular screen according to the prescribed amount of granule 2 in the above table. The materials are collected and placed in a wet mixing granulator, the stirring speed is set to be 100-200 rpm, and the cutting speed is set to be 1000-2500 rpm. After dry mixing, purified water with the amount of 40 percent of the total weight of the materials is atomized by a pressure pump within 3min, added and granulated, and mixed for 2min after the granule forming is observed, mixed for 1min again and discharged. Wet-granulating the granules through a 2.0mm circular screen, placing the wet granules in a 60 ℃ air-blast drying oven to dry until the moisture content is less than 2%, and dry-granulating through a 1.0mm circular screen; mixing granule 1 and granule 2, mixing with 20 mesh magnesium stearate, tabletting, and coating.
FIG. 3 is a graph showing the dissolution profiles of the sustained release tablet prepared in example 2 and the original drug in a phosphate buffer medium at pH6.8 (the size of the standard deviation is indicated by the length of the vertical line in the graph). As can be seen from fig. 3, the vertical line is short, the standard deviation is small, and the dissolution difference is small, which indicates that the dissolution difference between the sustained-release tablet prepared in example 2 and the original drug is small.
Example 3
The prescription is shown in table 3:
table 3: 3500 quetiapine fumarate sustained-release tablet (200 mg/tablet) prescription
Lactose, microcrystalline cellulose, quetiapine fumarate, sodium citrate, hypromellose K4M CR and hypromellose K100lv CR were sieved sequentially through a granulator with a 0.6mm circular screen according to the prescribed amount of granule 1 in the above table. The materials are collected and placed in a wet mixing granulator, the stirring speed is set to be 100-200 rpm, and the cutting speed is set to be 1000-2500 rpm. After dry mixing, purified water with the amount of 18 percent of the total weight of the materials is atomized by a pressure pump within 3min, added for granulation, and discharged. Wet-granulating the granules through a 2.0mm circular screen, placing the wet granules in a 60 ℃ air-blast drying oven to dry until the moisture content is less than 2%, and dry-granulating through a 1.0mm circular screen;
lactose, microcrystalline cellulose, quetiapine fumarate, sodium citrate, hypromellose K4M CR and hypromellose K100lv CR were sieved sequentially through a granulator with a 0.6mm circular screen according to the prescribed amount of granule 2 in the above table. The materials are collected and placed in a wet mixing granulator, the stirring speed is set to be 100-200 rpm, and the cutting speed is set to be 1000-2500 rpm. After dry mixing, purified water with the amount of 40 percent of the total weight of the materials is atomized by a pressure pump within 3min, added and granulated, and mixed for 2min after the granule forming is observed, and mixed for 4min again, and then discharged. Wet-granulating the granules through a 2.0mm circular screen, placing the wet granules in a 60 ℃ air-blast drying oven to dry until the moisture content is less than 2%, and dry-granulating through a 1.0mm circular screen;
mixing granule 1 and granule 2, mixing with 20 mesh magnesium stearate, tabletting, and coating.
FIG. 4 is a graph showing the dissolution profiles of the sustained release tablet prepared in example 3 and the original drug in a phosphate buffer medium at pH6.8 (the size of the standard deviation is indicated by the length of the vertical line in the graph). As can be seen from fig. 4, the vertical line is short, the standard deviation is small, and the dissolution difference is small, which indicates that the dissolution difference between the sustained-release tablet prepared in example 3 and the original drug is small.
Claims (8)
1. A sustained-release tablet comprising quetiapine or a pharmaceutically acceptable salt thereof, wherein the sustained-release tablet comprises:
granule 1 comprising quetiapine or a pharmaceutically acceptable salt thereof, a hydrophilic gel matrix material, a pH adjusting agent and an excipient; in the particles 1, the weight ratio of quetiapine or pharmaceutically acceptable salt thereof, hydrophilic gel skeleton material, pH regulator and excipient is 1-5: 2-4: 1: 1-4;
granule 2 comprising quetiapine or a pharmaceutically acceptable salt thereof, a hydrophilic gel matrix material, a pH adjusting agent and an excipient; in the particles 2, the weight ratio of quetiapine or pharmaceutically acceptable salt thereof, the hydrophilic gel skeleton material, the pH regulator and the excipient is 1-5: 2-4: 1: 1-4;
wherein the granules 1 and 2 are prepared by different wet granulation processes; the weight ratio of the particles 1 to the particles 2 is 1: 1-5;
the wet granulation time of the granules 1 is 2-5 min, and the water addition amount is 10-28% of the total weight of the materials;
the wet granulation time of the granules 2 is 6-15 min, and the water addition amount is 30-45% of the total weight of the materials;
the hydrophilic gel matrix material comprises:
(a) hydroxypropyl methylcellulose having a viscosity of 80 to 120 mPas, and
(b) hydroxypropyl methylcellulose with viscosity of 3000-5600 mPas;
the weight ratio of the hydroxypropyl methylcellulose with the viscosity of 80-120 mPa & s to the hydroxypropyl methylcellulose with the viscosity of 3000-5600 mPa & s is 1-6: 1;
in the particles 1 and 2, the pH regulator is sodium citrate; the excipient is selected from microcrystalline cellulose and lactose, and the weight ratio of the microcrystalline cellulose to the lactose is 3-1: 1-3.
2. The sustained-release tablet comprising quetiapine or a pharmaceutically acceptable salt thereof according to claim 1,
the wet granulation time of the granules 1 is 3-5 min; the water addition amount is 18 to 28 percent of the total weight of the materials;
the wet granulation time of the granules 2 is 8-12 min; the water addition amount is 35-45% of the total weight of the materials.
3. The sustained-release tablet containing quetiapine or a pharmaceutically acceptable salt thereof according to claim 1, wherein the weight ratio of the granule 1 to the granule 2 is 1: 1-3.
4. The sustained-release tablet comprising quetiapine or a pharmaceutically acceptable salt thereof according to claim 1,
in the particles 1, the weight ratio of quetiapine or pharmaceutically acceptable salt thereof, hydrophilic gel skeleton material, pH regulator and excipient is 3-4: 2-3: 1: 1-2; in the particles 2, the weight ratio of quetiapine or pharmaceutically acceptable salt thereof, the hydrophilic gel skeleton material, the pH regulator and the excipient is 3-4: 2-3: 1: 1-2.
5. The sustained-release tablet containing quetiapine or a pharmaceutically acceptable salt thereof according to claim 1, wherein the hypromellose having a viscosity of 80 to 120 mPa-s is hypromellose K100 lv; the hydroxypropyl methylcellulose with the viscosity of 3000-5600 mPa.s is hydroxypropyl methylcellulose K4M.
6. The sustained-release tablet containing quetiapine or a pharmaceutically acceptable salt thereof according to claim 1, wherein the excipient is selected from microcrystalline cellulose and lactose at a weight ratio of 2-1: 1.
7. A method for preparing a sustained-release tablet containing quetiapine or a pharmaceutically acceptable salt thereof according to any one of claims 1 to 6, comprising the steps of:
(1) putting the quetiapine or pharmaceutically acceptable salt thereof, the hydrophilic gel framework material, the pH regulator and the excipient which are raw materials of the granules 1 into a wet granulator; atomizing water accounting for 10-28% of the total weight of the materials, adding the water into the materials for wet granulation for 2-5 min to obtain wet granules, and carrying out wet granulation, drying and dry granulation to obtain granules 1;
putting the quetiapine or pharmaceutically acceptable salt thereof, the hydrophilic gel framework material, the pH regulator and the excipient which are raw materials of the granules 2 into a wet granulator; atomizing water accounting for 30-45% of the total weight of the materials, adding the water into the materials for wet granulation for 6-15 min to obtain wet granules, and carrying out wet granulation, drying and dry granulation to obtain granules 2;
(2) mixing the granules 1 and 2 with lubricant, and tabletting.
8. The method for preparing the quetiapine or pharmaceutically acceptable salt thereof sustained release tablet according to claim 7, wherein the wet granulation time of the granule 1 is 3-5 min; the water addition amount is 18-28% of the total weight of the materials; the wet granulation time of the granules 2 is 8-12 min; the water addition amount is 35-45% of the total weight of the materials; the quetiapine or a pharmaceutically acceptable salt thereof, the hydrophilic gel matrix material and the excipient are passed through a 0.6mm screen prior to use; the stirring speed of the wet granulator is 100-200 rpm, and the speed of the cutting knife is 1000-2500 rpm; the atomization adding time of the solution is within 3 minutes; the wet whole grains are screened by a 2.0mm screen; the drying is carried out in an oven at 60 ℃ to ensure that the moisture is less than 2%; the dry granulation was passed through a 1.0mm screen.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101347413A (en) * | 2008-07-22 | 2009-01-21 | 济南百诺医药科技开发有限公司 | Quetiapine sustained release tablets and method of preparing the same |
| CN102218042A (en) * | 2011-05-26 | 2011-10-19 | 青岛黄海制药有限责任公司 | Sustained release tablet of quetiapine fumarate composition and preparation method of sustained release tablet |
| CN104586805A (en) * | 2014-07-08 | 2015-05-06 | 上海中西三维药业有限公司 | Quetiapine fumarate sustained-release tablet and preparation method thereof |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
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| EP1976487A2 (en) * | 2006-01-25 | 2008-10-08 | Astron Research Limited | Sustained release dosage form of phenothiazine derivatives containing channelizer |
| WO2010082220A2 (en) * | 2009-01-05 | 2010-07-22 | Torrent Pharmaceuticals Limited | Sustained release pharmaceutical composition of quetiapine and process for preparation thereof |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101347413A (en) * | 2008-07-22 | 2009-01-21 | 济南百诺医药科技开发有限公司 | Quetiapine sustained release tablets and method of preparing the same |
| CN102218042A (en) * | 2011-05-26 | 2011-10-19 | 青岛黄海制药有限责任公司 | Sustained release tablet of quetiapine fumarate composition and preparation method of sustained release tablet |
| CN104586805A (en) * | 2014-07-08 | 2015-05-06 | 上海中西三维药业有限公司 | Quetiapine fumarate sustained-release tablet and preparation method thereof |
Non-Patent Citations (2)
| Title |
|---|
| Evaluating Scale-Up Rules of a High-Shear Wet Granulation Process;Tao Jing,et al;《Journal of Pharmaceutical Sciences》;20150525;第104卷;第2326页"Dissolution"部分第1段 * |
| 格列齐特片（II）溶出度影响因素的考察;王亚斌;《中国现代药物应用》;20140131;第8卷(第1期);第158页摘要 * |
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