CN120531692B

CN120531692B - Quetiapine fumarate sustained release tablet and preparation method thereof

Info

Publication number: CN120531692B
Application number: CN202510482318.6A
Authority: CN
Inventors: 陈良强; 纪宇; 周敏静; 彭嫒
Original assignee: Shanghai Guochuang Pharmaceutical Co ltd
Current assignee: Shanghai Guochuang Pharmaceutical Co ltd
Priority date: 2025-04-17
Filing date: 2025-04-17
Publication date: 2025-11-25
Anticipated expiration: 2045-04-17
Also published as: CN120531692A

Abstract

The invention discloses a quetiapine fumarate sustained-release tablet and a preparation method thereof, wherein the sustained-release tablet is a multilayer sustained-release tablet prepared by layering and pressing after hydrogel loaded quetiapine fumarate prepared from chitosan and carboxymethyl cellulose is dried, and comprises an outer layer, a middle layer and an inner layer, wherein the densities of the outer layer, the middle layer and the inner layer are sequentially reduced, and the sustained-release tablet comprises quetiapine fumarate, chitosan, carboxymethyl cellulose, nano silicon dioxide, lactose and microcrystalline cellulose. The above components are prepared into a sustained release tablet with excellent sustained release effect through the processes of solution preparation, multiple crosslinking, layering pressing and the like, the release time can reach 24 hours, the burst release condition in the initial release stage is obviously reduced, the release time in the first 4 hours is not more than 20%, the whole body shows stable sustained release effect, the absorption of the medicine is facilitated, and the effect of once daily administration or longer time interval administration can be realized.

Description

Quetiapine fumarate sustained release tablet and preparation method thereof

Technical Field

The invention relates to a pharmaceutical preparation, in particular to quetiapine fumarate sustained-release tablets and a preparation method thereof.

Background

Quetiapine fumarate (Quetiapine Fumarate), having the chemical name 11- [4- [2- (2-hydroxyethoxy) ethyl ] -1-piperazinyl ] dibenzo [ b, f ] [1,4] thiazepine hemifumarate, having the formula C ₄₆H₅₄N₆ O₈ S₂ and molecular weight 883.09, and having the structural formula:

Quetiapine fumarate, a tablet thereof, was first developed and successfully made by the company of aslick, ltd, FDA approved for use in 1997 under the trade name "SEROQUEL" for the treatment of various schizophrenia. The product is effective for positive symptoms of schizophrenia, negative symptoms, and relieving symptoms of emotion related to schizophrenia such as depression, anxiety and cognitive deficit. The dosage forms which are approved to be marketed worldwide at present are normal release tablets and sustained release tablets. Typical tablet sizes are 25mg, 100mg, 200mg and 300mg. The quetiapine fumarate tablet can be quickly absorbed after being orally taken, the blood concentration can reach a peak value within 2 hours, and the half life is short. Thus, the administration method generally proposed is to gradually increase after the initial dose of 25mg, reaching 300-600 mg/day by 2-3 administrations. Obviously, multiple daily administrations are inconvenient for patients and patient families, and cannot meet the requirement that people wish to take medicines once daily or for longer time intervals. In addition, the existing sustained-release tablet has huge early release amount, which leads to overlarge early blood concentration and also seriously affects the uniform absorption of the medicine.

Disclosure of Invention

The invention aims to solve the defect of unsatisfactory sustained release effect of the existing quetiapine fumarate sustained release tablet, and provides the quetiapine fumarate sustained release tablet and a preparation method thereof.

According to the technical scheme, the quetiapine fumarate sustained-release tablet is prepared by drying hydrogel loaded quetiapine fumarate prepared from chitosan and carboxymethyl cellulose, and then layering and pressing the hydrogel loaded quetiapine fumarate, wherein the sustained-release tablet comprises an outer layer, a middle layer and an inner layer, the densities of the outer layer, the middle layer and the inner layer are sequentially increased, and the sustained-release tablet comprises the following components, by mass, 0.71-1.33 parts of quetiapine fumarate, 4.21-4.85 parts of chitosan, 8.46-9.38 parts of carboxymethyl cellulose, 0.12-0.49 parts of nano silicon dioxide, 0.43-0.65 parts of lactose, 0.12-0.51 parts of microcrystalline cellulose and 0.15-0.22 parts of lubricant.

Further, the molecular weight of the chitosan is 80-90 ten thousand, and the viscosity is 200-300 mPa.s.

Further, the mass ratio of quetiapine fumarate to chitosan is 1.10:4.55.

Further, the mass ratio of the chitosan to the carboxymethyl cellulose is 4.55:8.67.

Further, the mass ratio of lactose to microcrystalline cellulose is 0.45:0.49.

Further, the lubricant is magnesium stearate or sodium lauryl sulfate.

Further, the particle size of quetiapine fumarate is 20-60 microns.

The invention also provides the quetiapine fumarate sustained-release tablet and the preparation method thereof, which are characterized by comprising the following steps:

s1, preparation of a solution:

(1) Preparing a chitosan-carboxymethyl cellulose mixed solution, namely adding chitosan and carboxymethyl cellulose into an acetic acid solution according to a proportion, and stirring until the chitosan and the carboxymethyl cellulose are completely dissolved for standby;

(2) Preparing TPP solution, namely dissolving TPP in deionized water, and stirring until the TPP is completely dissolved for later use;

(3) Preparing a medicinal solution, namely dissolving quetiapine fumarate in an ethanol-water mixed solvent for later use;

S2, preparation of hydrogel:

(1) Primary crosslinking, namely dropwise adding one half of the volume of the TPP solution in the step S1 in the stirring process of the chitosan-carboxymethyl cellulose mixed solution in the step S1, and continuing stirring after the dropwise adding is finished;

(2) Secondary crosslinking, namely adding quetiapine fumarate solution in the step S1, stirring and dispersing uniformly, adding the rest TPP solution, and stirring;

(3) Adding nano silicon dioxide, namely uniformly dispersing the nano silicon dioxide in deionized water, adding the deionized water into the hydrogel system in the step (2), and stirring;

S3, drying:

Freeze-drying the hydrogel loaded with the medicine prepared in the step S2 to obtain dried hydrogel powder;

s4, layering and tabletting:

(1) Outer layer pressing, namely uniformly mixing the dry hydrogel powder with lactose and microcrystalline cellulose, adding a lubricant, and pressing into an outer layer tablet on a tablet press;

(2) Middle-layer pressing, namely uniformly mixing the dry hydrogel powder with lactose and microcrystalline cellulose, adding a lubricant, and pressing into a middle-layer tablet on a tablet press;

(3) Inner layer pressing, namely uniformly mixing dry hydrogel powder with lactose and microcrystalline cellulose, adding a lubricant, and pressing into an inner layer sheet on a tablet press;

(4) And (3) integrating tabletting, namely sequentially placing the outer layer tablet, the middle layer tablet and the inner layer tablet into a die, and integrally pressing the die into a final sustained release tablet.

Further, the tabletting pressure during outer layer pressing is 7-9kN, the tabletting pressure during middle layer pressing is 11-14kN, and the tabletting pressure during inner layer pressing is 15-18kN.

Further, in the primary crosslinking step, the stirring temperature is 4-10 ℃ and the stirring time is 100-120min.

Compared with the prior art, the invention has the beneficial effects that:

1. According to the invention, components such as chitosan, carboxymethyl cellulose, nano silicon dioxide, lactose, microcrystalline cellulose and the like are added into the formula of the quetiapine fumarate sustained-release tablet, and the components are optimized by indexes such as particle size, viscosity, molecular weight, proportion and the like, so that a better component formula is obtained. In addition, the sustained-release tablet with the density gradient from outside to inside is prepared through the layering pressing procedure, so that the sustained-release tablet prepared by the method has excellent sustained-release effect, the release time can reach 24 hours, the abrupt release condition in the initial stage of release is obviously reduced, the release time in the first 4 hours is not more than 20%, the whole body has a stable sustained-release effect, and the absorption of the medicine is facilitated. Finally, the scientific and reasonable formula components of the invention also enable the prepared sustained release tablets to have better drug sustained release property and biocompatibility through a layering pressing process, and can realize the effect of once-daily or longer-time interval administration.

2. The carboxymethyl cellulose in the sustained-release tablet has good film forming property and sustained-release performance, is mixed with chitosan according to the mass ratio of 7:3, and can optimize the sustained-release effect while guaranteeing the adhesion of mucous membrane.

3. The nano silicon dioxide is added into the sustained release tablet, so that the porosity of the hydrogel can be increased, the diffusion of the medicine is promoted, and the excessive release resistance in the later period is prevented.

4. In the preparation process of the sustained release tablet, the crosslinking temperature is reduced to 4-10 ℃ and the crosslinking time is 100-120min, so that chitosan and TPP fully react to form a relatively stable and compact network structure.

5. In the preparation process of the sustained release tablet, the chitosan is firstly subjected to partial cross-linking to form a network, and after the medicine is added, the chitosan is subjected to secondary cross-linking to ensure that the medicine is more uniformly distributed in the network and the restraint of the medicine is enhanced.

6. In the preparation process of the sustained release tablet, a gradient tabletting technology is adopted to laminate the drug-containing layer into a multi-layer structure with different densities, the density near the outer layer is lower, the sustained release of the early-stage drug is facilitated, the density of the inner layer is higher, the sustained release of the later-stage drug is maintained, and the stable and sustained release of the drug is further maintained.

Drawings

FIG. 1 is a graph of the release results of example 1;

FIG. 2 is a graph showing the release results of comparative example 1;

FIG. 3 is a graph showing the release results of comparative example 2;

FIG. 4 is a graph showing the release results of comparative example 5;

FIG. 5 is a graph showing the release results of comparative example 7;

FIG. 6 is a graph showing the release results of comparative example 9;

FIG. 7 is a graph showing the release results of comparative example 1;

FIG. 8 is a schematic cut-away view of the product of the present invention.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the technical solutions of the present invention will be further described below.

Example 1:

The preparation process of the quetiapine fumarate sustained-release tablet of the embodiment comprises the following steps:

1. solution preparation

(1) Adding 4.55g of chitosan and 8.67g of carboxymethyl cellulose into 200mL of 1.5% acetic acid solution, stirring for 6 hours at 46 ℃ until the chitosan and the carboxymethyl cellulose are completely dissolved, wherein the molecular weight of the chitosan is 85 ten thousand, and the viscosity is 250 mPa.s;

(2) TPP solution, namely dissolving TPP in 160mL of deionized water, and stirring until the TPP is completely dissolved;

(3) Drug solution 1.10g quetiapine fumarate 45 microns was dissolved in 27mL ethanol-water mixed solvent.

2. Hydrogel preparation

(1) Primary crosslinking, namely placing the chitosan-carboxymethyl cellulose mixed solution prepared in the previous step into a constant-temperature stirrer at 8 ℃, stirring at a rotating speed of 200r/min, slowly dripping half volume of TPP solution, and continuously stirring for 110min after dripping is finished, wherein the stirring temperature is 7 ℃;

(2) Adding quetiapine fumarate solution, continuously stirring for 25min to uniformly disperse the quetiapine fumarate solution, dripping the rest TPP solution, and stirring for 95min after dripping is finished;

(3) Adding nano silicon dioxide, namely uniformly dispersing 0.32g of nano silicon dioxide in a small amount of deionized water, adding the nano silicon dioxide into the hydrogel system, and continuously stirring for 25 minutes.

3. Drying

Placing the prepared hydrogel loaded with the medicine in a freeze dryer, and freeze-drying at-70 ℃ to obtain dried hydrogel powder;

4. Gradient tabletting

(1) The outer layer pressing, namely weighing 0.5g of dry hydrogel powder, uniformly mixing the powder with 0.2g of lactose and 0.2g of microcrystalline cellulose, adding 0.18g of magnesium stearate as magnesium stearate, and pressing into an outer layer tablet on a tablet press under the pressure of 8 kN;

(2) The middle layer pressing, namely weighing 0.5g of dry hydrogel powder, uniformly mixing with 0.25g of lactose and 0.2g of microcrystalline cellulose, adding 0.18g of magnesium stearate as magnesium stearate, and pressing into a middle layer tablet on a tablet press under the pressure of 12 kN;

(3) Inner layer pressing, namely uniformly mixing the rest dry hydrogel powder with the rest lactose, microcrystalline cellulose and magnesium stearate, and pressing into an inner layer sheet on a tablet press under the pressure of 16 kN;

(4) And (3) integrating tabletting, namely sequentially placing the outer layer tablet, the middle layer tablet and the inner layer tablet into a special die, and integrally pressing the special die into a final sustained release tablet.

Example 2:

1. solution preparation

(1) Adding 4.21g of chitosan and 8.46g of carboxymethyl cellulose into 180mL of 1.5% acetic acid solution, stirring for 6 hours at 40 ℃ until the chitosan and the carboxymethyl cellulose are completely dissolved, wherein the molecular weight of the chitosan is 80 ten thousand, and the viscosity is 200 mPa.s;

(2) TPP solution, namely dissolving TPP in 100mL of deionized water, and stirring until the TPP is completely dissolved;

(3) Pharmaceutical solution 0.71g quetiapine fumarate was dissolved in 20mL ethanol-water mixture.

2. Hydrogel preparation

(1) Primary crosslinking, namely placing the chitosan-carboxymethyl cellulose mixed solution prepared in the previous step into a constant-temperature stirrer at the temperature of 5 ℃, stirring at the rotating speed of 180r/min, slowly dripping half volume of TPP solution, and continuing stirring for 100min after dripping is finished, wherein the stirring temperature is 4 ℃;

(2) Drug loading and secondary crosslinking, namely adding quetiapine fumarate solution, continuously stirring for 20min to uniformly disperse the quetiapine fumarate solution, dripping the rest TPP solution, and stirring for 90min after the dripping is finished;

(3) Adding nano silicon dioxide, namely uniformly dispersing 0.12g of nano silicon dioxide in a small amount of deionized water, adding the nano silicon dioxide into the hydrogel system, and continuously stirring for 20min.

3. Drying

4. Gradient tabletting

(1) The outer layer pressing, namely weighing 0.4g of dry hydrogel powder, uniformly mixing the powder with 0.1g of lactose and 0.1g of microcrystalline cellulose, adding 0.15g of magnesium stearate as a lubricant, and pressing into an outer layer tablet on a tablet press under the pressure of 7 kN;

(2) The middle layer pressing, namely weighing 0.4g of dry hydrogel powder, uniformly mixing the powder with 0.15g of lactose and 0.1g of microcrystalline cellulose, adding 0.15g of magnesium stearate as a lubricant, and pressing into a middle layer tablet on a tablet press under the pressure of 11 kN;

(3) Inner layer pressing, namely uniformly mixing the rest dry hydrogel powder with the rest lactose, microcrystalline cellulose and magnesium stearate, and pressing into an inner layer sheet on a tablet press at 15kN pressure;

Example 3:

1. solution preparation

(1) Adding 4.21g of chitosan and 8.46g of carboxymethyl cellulose into 180mL of 1.5% acetic acid solution, stirring for 6 hours at 40 ℃ until the chitosan and the carboxymethyl cellulose are completely dissolved, wherein the molecular weight of the chitosan is 90 ten thousand, and the viscosity is 300 mPa.s;

(2) TPP solution, namely dissolving TPP in 200mL of deionized water, and stirring until the TPP is completely dissolved;

(3) Pharmaceutical solution 1.33g quetiapine fumarate was dissolved in 30mL ethanol-water mixture.

2. Hydrogel preparation

(1) Primary crosslinking, namely placing the chitosan-carboxymethyl cellulose mixed solution prepared in the previous step into a constant-temperature stirrer at 10 ℃, stirring at a rotating speed of 250r/min, slowly dripping half volume of TPP solution, and continuously stirring for 120min after dripping is finished, wherein the stirring temperature is 10 ℃;

(2) Drug loading and secondary crosslinking, namely adding quetiapine fumarate solution, continuously stirring for 30min to uniformly disperse the quetiapine fumarate solution, dripping the rest TPP solution, and stirring for 100min after the dripping is finished;

(3) Adding nano silicon dioxide, namely uniformly dispersing 0.49g of nano silicon dioxide in a small amount of deionized water, adding the nano silicon dioxide into the hydrogel system, and continuously stirring for 30min.

3. Drying

4. Gradient tabletting

(1) The outer layer pressing, namely weighing 0.6g of dry hydrogel powder, uniformly mixing the dry hydrogel powder with 0.2g of lactose and 0.2g of microcrystalline cellulose, adding 0.22 sodium lauryl sulfate as a lubricant, and pressing into an outer layer tablet on a tablet press under the pressure of 9 kN;

(2) The middle layer pressing, namely weighing 0.6g of dry hydrogel powder, uniformly mixing the dry hydrogel powder with 0.25g of lactose and 0.2g of microcrystalline cellulose, adding 0.22 sodium lauryl sulfate as a lubricant, and pressing into a middle layer tablet on a tablet press under the pressure of 14 kN;

(3) Inner layer pressing, namely uniformly mixing the rest dry hydrogel powder with the rest lactose, microcrystalline cellulose and magnesium stearate, and pressing into an inner layer sheet on a tablet press at 18kN pressure;

(4) And (3) integrating tabletting, namely sequentially placing the outer layer tablet, the middle layer tablet and the inner layer tablet into a special die, and pressing to obtain the final sustained release tablet.

Comparative example 1:

the difference from example 1 is that the molecular weight of the chitosan is 100 ten thousand, and the other operations are the same as example 1.

Comparative example 2:

the difference from example 1 is that the molecular weight of the chitosan is 60 ten thousand, and the other operations are the same as example 1.

Comparative example 3:

The difference from example 1 is that the chitosan was 320 mPas, and the other operations were the same as in example 1.

Comparative example 4:

the difference from example 1 is that the chitosan was 180 mPas and the other procedures were as in example 1.

Comparative example 5:

the difference from example 1 is 0.75 of lactose and 0.49 of microcrystalline cellulose. The other operations are the same as in example 1.

Comparative example 6:

The difference from example 1 is that the quetiapine fumarate has a particle size of 15 microns, and the other operations are the same as in example 1.

Comparative example 7:

the difference from example 1 is that the quetiapine fumarate has a particle size of 85 microns, and the other operations are the same as in example 1.

Comparative example 8:

The difference from example 1 is that the outer-layer pressing pressure in the layered pressing is 18kN, the middle-layer pressing pressure is 14kN, and the inner-layer pressing pressure is 7kN.

Comparative example 9:

the difference from example 1 is that the temperature of stirring was 15℃and the stirring time was 110min, and the other operations were the same as in example 1.

Comparative example 10:

The difference from example 1 is that the temperature of stirring was 4℃and the stirring time was 110min, and the other operations were the same as in example 1.

Comparative example 1:

the difference from example 1 is that chitosan, carboxymethyl cellulose, nano silica, lactose and microcrystalline cellulose are not added as sustained-release components, and the other operations are the same as in example 1.

And (3) testing release effect:

The tablets prepared in each of the above examples and comparative examples were subjected to dissolution test by the method disclosed in patent CN102218042a, using 0.1M hydrochloric acid solution as a release medium, respectively. The sampling time interval was 2 hours up to 24 hours. The results are shown in Table 1 below.

TABLE 1 Release degree (%)

Note that "-" represents that the data is as before, remains stable and is no longer released.

As can be seen from the above table data and the accompanying drawings:

The release time of the sustained release tablets of examples 1-3 can last to 24 hours, and the release is slow and stable, especially in the first 4 hours, and the release is very slow, thus avoiding the abrupt release condition in the initial period. And the release amount still does not reach 50% within 14 hours, and the release amount is over 50% after 16 hours. The results of comparative example 1 show that the tablet release is faster, the release is completed within 14 hours, and the burst release condition occurs within 2 hours, since no slow release component is added. Compared with the control example, the sustained release tablets of examples 1-3 can be released continuously, avoid the abrupt release condition in the initial period, have better sustained release effect and promote the absorption of the medicine.

Comparative examples 1 and2 are for examining the influence of the molecular weight of chitosan on the sustained release effect of the drug. As can be seen from the data in the table, the release rate of comparative example 1 was slower than that of example 1 as a whole, and the release was not completed within 24 hours, indicating that the molecular weight of chitosan was not excessively large. Too high a molecular weight increases the network density of the hydrogel, affecting the diffusion of the drug. The release rate of comparative example 2 was increased compared to that of example 1 as a whole, and the release was completed in advance. It is shown that too small a molecular weight reduces the network density of the hydrogel, thereby accelerating diffusion. Therefore, the molecular weight needs to be controlled within a certain range (the molecular weight is 80-90 ten thousand), so that the density of the prepared hydrogel network structure is moderate, and the slow and continuous diffusion of the medicine is facilitated.

Comparative examples 3 and 4 are for examining the effect of chitosan viscosity on the drug release effect. As can be seen from the data in the table, the release rate of comparative example 3 was slower than that of example 1 as a whole, and the release was not completed within 24 hours, which indicates that the viscosity of chitosan was not too high, which would increase the network density of the hydrogel and affect the diffusion of the drug. Comparative example 4 showed an increased release rate compared to the whole of example 1, indicating that too small a viscosity accelerates diffusion. Therefore, the viscosity needs to be controlled within a certain range (the viscosity is 200-300 mPa.s), so that the density of the prepared hydrogel network structure is moderate, and the slow and continuous diffusion of the medicine is facilitated.

From comparative example 5, it is apparent from the results of examining the effect of the ratio of lactose amount to microcrystalline cellulose on the sustained release effect of the drug, that the increased ratio of lactose amount increases the release rate of the drug over the whole of example 1, and the release rate of the drug increases in the first 4 hours, and the release rate of the drug increases by 50% in the first 4 hours, and the release rate of the drug exceeds 60% in the first 14 hours, and the sustained release rate of the drug does not satisfy the sustained release rate of the drug for 24 hours, because the increased lactose ratio increases the hardness and toughness of the drug, which is disadvantageous for the sustained release and sustained release. Therefore, the lactose and microcrystalline cellulose are controlled within proper ranges (lactose 0.43-0.65: microcrystalline cellulose 0.12-0.51), so that the sustained-release tablet can maintain better hardness and toughness, and is beneficial to delaying drug release.

Comparative examples 6 and 7 are to examine the effect of quetiapine fumarate powder particle size on the drug release effect. As can be seen from the data in the table, the release rate of comparative example 7 is slower than that of example 1, and the release cannot be completed within 24 hours, which means that the particle size of quetiapine fumarate powder cannot be too large, and the too large particle size can reduce the contact area between the drug and the gel network, reduce the load rate, make the drug disperse unevenly in the hydrogel, cause incomplete release, and have poor release effect. The release rate of comparative example 6 was faster and completed after 20 hours compared to the overall release rate of example 1, indicating that quetiapine fumarate powder particle size cannot be too small, and would readily diffuse through the gel network for release, resulting in a fast release, a premature release, and inability to meet the daily average absorption of the drug.

Comparative example 8 is the effect of layering compression on the drug release effect, with the outer, middle and inner layers of pressure decreasing in sequence. As can be seen from the data in the table, the release rate of comparative example 8 is slower than that of example 1, and the release is incomplete, because the outer layer density of the formed sustained-release tablet is larger due to the overlarge pressure of the outer layer, the internal medicine is not easy to diffuse, the overall release is slower, the release cannot be completed within 24 hours, and the absorption of the medicine is not facilitated. Therefore, the multilayer compression preferably forms a process of gradually increasing the pressure from outside to inside, so that the lower density near the outer layer is beneficial to slow release of the early-stage medicament, and the higher density inside is beneficial to maintaining the sustained release of the later-stage medicament.

Comparative examples 9 and 10 are for examining the influence of the stirring temperature and stirring time at the time of primary crosslinking on the drug release effect. Comparative example 9 and comparative example 10 increased and decreased the stirring temperature under the predetermined stirring time conditions, respectively. As can be seen from the data in the table, the release rate of the whole of the comparative examples 9 and 10 is faster than that of the whole of the example 1, the release is finished in advance, and the continuous release cannot be realized for 24 hours, which means that the stirring temperature cannot be too high or too low, because the reaction rate is too high due to the too high temperature, so that the movement of the chitosan molecular chain and the TPP ions is relatively fast, and the chitosan molecular chain and the TPP ions do not have enough time to interact with each other to form a relatively uniform and stable crosslinked network. And the low stirring temperature can reduce the activity of chitosan and TPP, reduce the reaction rate and the crosslinking reaction, and can not form an ideal, stable and compact crosslinked network. Therefore, the stirring temperature is required to be controlled to be 4-10 ℃, and a uniform, stable and compact crosslinked network can be formed in the temperature range, so that the release of the medicine is facilitated.

The foregoing is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Any person skilled in the art will make any equivalent substitution or modification to the technical solution and technical content disclosed in the invention without departing from the scope of the technical solution of the invention, and the technical solution of the invention is not departing from the scope of the invention.

Claims

1. A quetiapine fumarate sustained release tablet is characterized in that the sustained release tablet is a multilayer sustained release tablet formed by layering and pressing after hydrogel loaded quetiapine fumarate prepared from chitosan and carboxymethyl cellulose is dried, the sustained release tablet comprises an outer layer, a middle layer and an inner layer, the densities of the outer layer, the middle layer and the inner layer are sequentially increased, the sustained release tablet comprises the following components, by mass, 0.71-1.33 parts of quetiapine fumarate, 4.21-4.85 parts of chitosan, 8.46-9.38 parts of carboxymethyl cellulose, 0.12-0.49 parts of nano silicon dioxide, 0.43-0.65 parts of lactose, 0.12-0.51 parts of microcrystalline cellulose and 0.15-0.22 parts of lubricant,

The molecular weight of the chitosan is 80-90 ten thousand, the viscosity is 200-300 mPa.s,

The particle size of quetiapine fumarate is 20-60 microns,

The preparation method of the quetiapine fumarate sustained-release tablet comprises the following steps:

s1, preparation of a solution:

S2, preparation of hydrogel:

(3) Adding nano silicon dioxide, namely uniformly dispersing the nano silicon dioxide in deionized water, adding the deionized water into a hydrogel system, and stirring;

S3, drying;

s4, layering and tabletting,

The tabletting pressure during outer layer pressing is 7-9kN, the tabletting pressure during middle layer pressing is 11-14kN, and the tabletting pressure during inner layer pressing is 15-18kN;

In the primary crosslinking step, the stirring temperature is 4-10 ℃ and the stirring time is 100-120 min.

2. The quetiapine fumarate sustained release tablet according to claim 1, wherein the mass ratio of quetiapine fumarate to chitosan is 1.10:4.55.

3. The quetiapine fumarate sustained-release tablet according to claim 1, wherein the mass ratio of the chitosan to the carboxymethyl cellulose is 4.55:8.67.

4. The quetiapine fumarate sustained-release tablet according to claim 1, wherein the mass ratio of lactose and microcrystalline cellulose is 0.45:0.49.

5. The quetiapine fumarate sustained-release tablet of claim 1, wherein said lubricant is magnesium stearate or sodium lauryl sulfate.