WO2023040173A1

WO2023040173A1 - Pentoxifylline sustained-release tablet and preparation method therefor

Info

Publication number: WO2023040173A1
Application number: PCT/CN2022/075613
Authority: WO
Inventors: 孙立杰; 李磊; 程彦超; 董伟昌; 丁立秀; 左悦; 赵文鹤
Original assignee: 石家庄四药有限公司
Priority date: 2021-09-18
Filing date: 2022-02-09
Publication date: 2023-03-23
Also published as: CN113813239B; CN113813239A

Abstract

A pentoxifylline sustained-release tablet, which comprises the following components: 370-420 parts pentoxifylline, 120-160 parts sustained-release material, 10-16 parts adhesive, 5-10 parts lubricant, and 150-300 parts wetting agent; the sustained-release material is a mixture of carrageenan and xanthan gum or a mixture of carrageenan and konjac gum; the wetting agent is purified water. The pentoxifylline sustained-release tablet is prepared by means of a wet granulation process based on atomization dispersion, using a complex of carrageenan and xanthan or a complex of carrageenan and konjac glucomannan as the sustained-release material and purified water as the wetting agent, thereby improving the problems of unstable sustained-release of pentoxifylline, poor dissolution consistency in an original preparation, and high pentoxifylline viscosity.

Description

A kind of pentoxifylline sustained-release tablet and preparation method thereof

This patent application claims the priority of Chinese Patent Application No. CN202111112218.2 filed on September 18, 2021. The disclosure of the prior application is incorporated by reference in its entirety into this application.

technical field

The application relates to the technical field of pharmaceutical preparations, in particular to a pentoxifylline sustained-release tablet and a preparation method thereof.

Background technique

The chemical name of pentoxifylline is 3,7-dihydro-3,7-dimethyl-1-(5-oxohexyl)-1H-purine-2,6-dione, and the molecular formula is C ₁₃ H ₁₈ N ₄ O ₃ , is a methylxanthine derivative, in the form of white needle crystals. Pentoxifylline can reduce blood viscosity, improve blood fluidity, promote microcirculation of ischemic tissue, increase oxygen supply of special organs, and increase intracellular adenosine triphosphate content by inhibiting phosphodiesterase, thereby improving The deformability of red blood cells. In addition, pentoxifylline also has the effect of reducing fibrinogen and inhibiting the aggregation of red blood cells and platelets. Clinically, pentoxifylline is often used in the treatment of cerebrovascular disorders, sequelae caused by stroke, ischemic cerebrovascular diseases and other diseases.

Because pentoxifylline is administered orally, it has a strong first-pass effect, fast drug metabolism, short half-life, and low bioavailability, resulting in poor clinical oral application effect of the current common dosage form. Compared with other conventional oral preparations, Pentoxifylline Sustained-release Tablets can prolong drug release and eliminate the peak and valley phenomenon of blood drug concentration, thereby prolonging the duration of therapeutic effect, reducing toxic and side effects, and reducing the number of medications. Therefore, it has been favored by doctors and doctors in recent years. widespread concern of patients.

However, the dissolution rate of the pentoxifylline sustained-release tablet product reported in the literature is poorly consistent with the original research product, and the sustained-release effect is unstable; In order to reduce the viscosity of granulation, there are problems such as explosion protection in the workshop and solvent residue. Therefore, it is of great significance to develop a pentoxifylline sustained-release tablet with good consistency with the original research product, high production safety and low cost.

technical problem

The application provides a pentoxifylline sustained-release tablet and its preparation method. The application uses a compound (i.e. a mixture) of carrageenan and xanthan gum or a compound of carrageenan and konjac gum as a sustained-release material, Effectively improved the problem of unstable sustained-release effect of pentoxifylline and poor dissolution consistency with the original research product. In the preparation process, purified water was used as the wetting agent in the granulation process, and the purified water was atomized and dispersed for wet granulation. The method not only solves the problem of high viscosity of pentoxifylline granulation, but also improves the safety of the process and reduces the production cost, and the prepared pentoxifylline sustained-release tablet product has no organic solvent residue.

technical solution

In order to solve the problems of the technologies described above, the technical solution provided by the application is:

A pentoxifylline sustained-release tablet, comprising the following raw material components in parts by weight: 370-420 parts of pentoxifylline, 120-160 parts of sustained-release material, 10-16 parts of adhesive, 5-10 parts of lubricant parts and wetting agent 150-300 parts;

Wherein, the slow-release material is a mixture of carrageenan and xanthan gum, or a mixture of carrageenan and konjac gum; the wetting agent is purified water.

It can be understood that the parts by weight of each component can be any value within the above range.

In one embodiment, the slow-release material is a mixture of carrageenan and xanthan gum at a mass ratio of 0.75-1.0:1.

Further preferably, the slow-release material is a mixture of carrageenan and xanthan gum with a mass ratio of 1:1.

In one embodiment, the slow-release material is a mixture of carrageenan and konjac gum with a mass ratio of 1.6-3.0:1.

Further preferably, the slow-release material is a mixture of carrageenan and konjac gum with a mass ratio of 3:1.

The inventor found in the research and development process that the sustained-release effect of pentoxifylline sustained-release tablets prepared by selecting existing hydroxypropyl cellulose, sodium alginate, chitosan, etc. as sustained-release materials is unstable, and cannot achieve the same level as the original research. The dissolution curve of the preparation is highly consistent, the in vitro dissolution data is quite different from that of the original preparation, the sustained release effect is unstable, and the reproducibility of the in vitro dissolution data is poor.

The present application selects a mixture of carrageenan and xanthan gum, or carrageenan and konjac gum in a specific ratio as the slow-release material, and utilizes the synergistic slow-release effect of the two, not only can effectively regulate the release rate of pentoxifylline, and achieve a good At the same time, it can also improve the uniformity of pentoxifylline sustained-release tablets, so that the reproducibility of the in vitro dissolution data of pentoxifylline is good, so as to achieve a high degree of consistency with the in vitro dissolution data of the original preparation, and improve the safety of clinical medication It can effectively replace the original preparation.

In one of the embodiments, the adhesive is povidone K25.

In one of the embodiments, the lubricant is magnesium stearate.

The present application preferred magnesium stearate as a lubricant, which can improve the compressibility in tablet production, and besides, it can also improve the hardness and smoothness of the prepared tablet.

In one of the embodiments, the pentoxifylline sustained-release tablet includes the following raw material components in parts by weight: 400 parts of pentoxifylline, 70 parts of carrageenan, 70 parts of xanthan gum, and 10 parts of adhesive , 10 parts of lubricant and 220 parts of wetting agent.

In one of the embodiments, the pentoxifylline sustained-release tablet includes the following raw material components in parts by weight: 400 parts of pentoxifylline, 105 parts of carrageenan, 35 parts of konjac gum, 10 parts of binder, 8 parts of lubricant and 260 parts of wetting agent.

The formulations of the pentoxifylline sustained-release tablets in the above two examples can make the prepared pentoxifylline sustained-release tablets reach the same height as the dissolution curve of the original preparation, which is more conducive to exerting the drug effect of pentoxifylline and improving the clinical drug safety. The application also provides a preparation method for the above-mentioned pentoxifylline sustained-release tablets, comprising the following steps:

Step a, premixing process: weighing each component according to the designed proportion, adding pentoxifylline, binder and slow-release material into a granulator for premixing to obtain a premix;

Step b, granulation process: atomize and spray a wetting agent into the premix to granulate, granulate, dry, and obtain granules;

In step c, the granules and the lubricant are uniformly mixed, compressed into tablets, and coated to obtain pentoxifylline sustained-release tablets.

In step a, said weighing each component according to the designed ratio specifically refers to weighing each component according to the parts by weight of the raw material components of the pentoxifylline sustained-release tablet.

Exemplarily, the pentoxifylline is weighed after passing through a 30-mesh sieve, and then mixed with other materials, the other materials being adhesives and slow-release materials.

In one embodiment, in step a, in the premixing process, the stirring speed is 100-150 rpm, the granulating knife rotational speed is 200-300 rpm, and the premixing time is 5-10 min.

In one embodiment, in step b, in the granulation process, the stirring speed is 300-500 rpm, and the granulation knife rotational speed is 500-700 rpm.

The granulation time in this application is: after the wetting agent (purified water) is atomized and sprayed, continue granulation for 1-3 minutes.

In one embodiment, in step b, the injection flow rate of the wetting agent is 25-50 g/min.

The spray gun is driven by the peristaltic pump to realize atomized spraying of the wetting agent (purified water). By controlling the speed of the peristaltic pump to adjust the spraying flow of the wetting agent, and by adjusting the pressure of the spray gun, the atomized and dispersed state of the purified water can be controlled. Optionally, the pressure of the control spray gun is 0.35MPa.

By controlling the injection flow rate of purified water to 25-50g/min, the viscosity of the material can be effectively controlled, which solves the problem that the current pentoxifylline granulation material has a high viscosity and is easy to form agglomerates, and realizes the need not to add ethanol solvent to adjust the viscosity. The purpose is to effectively improve the safety of the process and reduce the production cost.

In one embodiment, in step b, the granulation is to pass the granulated primary granules through a 20-24 mesh sieve.

Exemplarily, in step b, the drying temperature is 50-60°C.

In one embodiment, in step c, the core hardness of the compressed tablet is 60-120N.

The hardness of the tablet core in this range is beneficial to improve the consistency of the dissolution rate of the pentoxifylline sustained-release tablet and the original preparation.

Exemplarily, in step c, the mixing speed of the particles and the lubricant is 10-15 rpm, and the mixing time is 5-10 min.

Exemplarily, in step c, when coating, the Opadry coating solution with a mass concentration of 10%-12% is selected, and the weight gain of the coating is 2%-3% of the total weight of the tablet core.

It can be understood that the numerical range disclosed in the present application can be any value in the range interval; the disclosed numerical value is only a better choice. Certainly, in other embodiments, other numerical values may also be used, and are not limited thereto.

Beneficial effect

Compared with the prior art, the applicant chooses a mixture of carrageenan and xanthan gum or carrageenan and konjac gum with good biocompatibility and biodegradability as the slow-release material. The effective control of the release rate of ketoxifylline makes the dissolution curve of the prepared pentoxifylline sustained-release tablet highly consistent with the dissolution curve of the original preparation, which can more stably exert the drug effect of the pentoxifylline tablet, and also improves the The product uniformity of pentoxifylline sustained-release tablets can better ensure the consistency of product quality and improve the efficacy and safety of the drug; in addition, the choice of purified water as a wetting agent improves the safety of the process and the production cost is reduced, and there is no organic solvent residue in the prepared pentoxifylline sustained-release tablet, which further improves the safety of the drug.

The preparation method of the pentoxifylline sustained-release tablet provided by the application, cooperates with the specific formula of the application, uses the mixture of carrageenan and xanthan gum, or carrageenan and konjac gum as the slow-release material, and controls the amount of the slow-release material , and in combination with the process of spraying purified water as a wetting agent in the wet granulation process, it solves the problem of high viscosity and easy agglomeration of the material during wet granulation of pentoxifylline, which leads to unstable product quality and slow-release The problem of unstable effect and the large difference between the in vitro dissolution curve and the original preparation, at the same time greatly improved the safety of the process, reduced the production cost, and avoided the problem of organic solvent residue in the product, thus ensuring the safety of the product. It is conducive to improving the bioequivalence between the product and the original research preparation, and realizing a good replacement for the original research product.

The Pentoxifylline Sustained-release Tablets provided by this application have a simple formula, simple and easy preparation process and high safety, and the dissolution curve in vitro is highly consistent with that of the original preparation. The dissolution rate of tablets at different times: the cumulative release rate can reach 19-23% in 2 hours, 39%-46% in 6 hours, 63%-73% in 12 hours, and 63%-73% in 16 hours. 76%-86%, showing a good sustained-release effect, and the test of high-temperature factors has proved that after being placed under high-temperature conditions, the dissolution rate of the pentoxifylline sustained-release tablets prepared by the application has no obvious change, and the dissolution property is stable , effectively improving the stability of the pentoxifylline sustained-release tablet, thereby helping to improve the safety of its clinical application, and having broad application prospects.

Embodiment of this application

In order to make the purpose, technical solution and advantages of the present application clearer, the present application will be further described in detail below in conjunction with the embodiments. It should be understood that the specific embodiments described here are only used to explain the present application, and are not intended to limit the present application.

In order to better illustrate the present application, the following examples are used for further illustration.

Example 1

The present embodiment provides a kind of pentoxifylline sustained-release tablet, and the prescription quantity of 1000 pentoxifylline sustained-release tablets is shown in the following table:

The preparation method of above-mentioned pentoxifylline sustained-release tablet is as follows:

Step 1, passing the pentoxifylline raw material through a 30-mesh sieve for subsequent use;

Step 2, each component is weighed respectively according to the prescription amount, and the weighed pentoxifylline, carrageenan, xanthan gum and povidone K25 are added into the granulator for stirring and premixing, and the stirring paddle in the granulator is The rotating speed is 106 rev/min, the rotating speed of the granulating knife is 300 rev/min, and the premixing time is 8min to obtain the premix;

Step 3. Adjust the pressure of the spray gun to 0.35MPa, adjust the speed of the peristaltic pump, and spray purified water into the above premixed material through the spray gun at a flow rate of 30g/min for wet granulation. The stirring speed of the granulation process is 300 rpm , the rotation speed of the granulation knife is 500 rpm, continue to granulate for 2 minutes after adding the purified water, discharge the material, then pass through a 24-mesh sieve for granulation, and then transfer to the boiling dryer for drying, the air inlet temperature is 60°C, Get particles;

Step 4, add the magnesium stearate of recipe quantity to above-mentioned granule, mix evenly, mixing rotating speed is 15 revolutions/min, and mixing time is 5min, and the intermediate content of the mixed material is detected, and the sheet weight is determined according to the intermediate content, Put the intermediate material into the hopper of the tablet press, press the tablet, and control the tablet core hardness to 70-110N;

Step 5: Coating with Opadry coating solution with a mass concentration of 12%, the weight gain of the coating is 2.5% of the total mass of the tablet core, to obtain pentoxifylline sustained-release tablets.

Example 2

Step 2, each component is weighed respectively according to the prescription amount, and the weighed pentoxifylline, carrageenan, xanthan gum and povidone K25 are added into the granulator for stirring and premixing, and the stirring paddle in the granulator is The rotating speed is 120 revs/min, the rotating speed of the granulating knife is 300 revs/min, and the premixing time is 5min to obtain the premix;

Step 3. Adjust the pressure of the spray gun to 0.35MPa, adjust the speed of the peristaltic pump, and spray purified water into the above premixed material through the spray gun at a flow rate of 40g/min for wet granulation. The stirring speed of the granulation process is 500 rpm , the rotation speed of the granulation knife is 600 rpm, continue to granulate for 3 minutes after adding the purified water, discharge the material, then pass through a 20-mesh sieve for granulation, and then transfer to the boiling dryer for drying, the air inlet temperature is 55°C, Get particles;

Step 4, add the magnesium stearate of recipe quantity to above-mentioned granule, mix evenly, mixing rotating speed is 12 revolutions/min, and mixing time is 8min, and the intermediate content of mixed material is detected, determines sheet weight according to intermediate content, Put the intermediate material into the hopper of the tablet press, press the tablet, and control the tablet core hardness to 90-120N;

Step 5: Coating with Opadry coating solution with a mass concentration of 10%, the weight gain of the coating is 3% of the total mass of the tablet core, to obtain pentoxifylline sustained-release tablets.

Example 3

Step 2, each component is weighed respectively according to the prescription amount, and the weighed pentoxifylline, carrageenan, xanthan gum and povidone K25 are added into the granulator for stirring and premixing, and the stirring paddle in the granulator is The rotating speed is 110 rev/min, the rotating speed of the granulating knife is 280 rev/min, and the premixing time is 10min to obtain the premix;

Step 3. Adjust the pressure of the spray gun to 0.35MPa, adjust the speed of the peristaltic pump, and spray purified water into the above premixed material through the spray gun at a flow rate of 50g/min for wet granulation. The stirring speed of the granulation process is 380 rpm , the rotation speed of the granulation knife is 700 rpm, continue to granulate for 1 minute after adding purified water, discharge the material, then pass through a 24-mesh sieve for granulation, and then transfer to a boiling dryer for drying, the inlet air temperature is 60°C, Get particles;

Step 4, add the magnesium stearate of formula quantity to above-mentioned granule, mix evenly, mixing rotating speed is 12 revolutions/min, and mixing time is 7min, and the intermediate content of mixed material is detected, determines sheet weight according to intermediate content, Put the intermediate material into the hopper of the tablet press, press the tablet, and control the tablet core hardness to 80-100N;

Step 5: Coating with Opadry coating solution with a mass concentration of 12%, the weight gain of the coating is 2% of the total mass of the tablet core, to obtain pentoxifylline sustained-release tablets.

Example 4

Step 2, each component is weighed respectively according to the prescription amount, and the weighed pentoxifylline, carrageenan, xanthan gum and povidone K25 are added into the granulator for stirring and premixing, and the stirring paddle in the granulator is The rotating speed is 106 rev/min, the rotating speed of the granulating knife is 300 rev/min, and the premixing time is 10min to obtain the premix;

Step 3. Adjust the pressure of the spray gun to 0.35MPa, adjust the speed of the peristaltic pump, and spray purified water into the above premix through the spray gun at a flow rate of 40g/min for wet granulation. The stirring speed of the granulation process is 350 rpm , the rotation speed of the granulation knife is 600 rpm, continue to granulate for 1 minute after adding the purified water, discharge the material, then pass through a 20-mesh sieve for granulation, and then transfer to the boiling dryer for drying, the air inlet temperature is 60°C, Get particles;

Step 4, add the magnesium stearate of recipe quantity to above-mentioned granule, mix evenly, mixing rotating speed is 15 revolutions/min, and mixing time is 5min, and the intermediate content of the mixed material is detected, and the sheet weight is determined according to the intermediate content, Put the intermediate material into the hopper of the tablet press, press the tablet, and control the tablet core hardness to 70-120N;

Example 5

Step 2, each component is weighed respectively according to the prescription amount, and the weighed pentoxifylline, carrageenan, xanthan gum and povidone K25 are added into the granulator for stirring and premixing, and the stirring paddle in the granulator is The rotating speed is 120 rev/min, the rotating speed of the granulating knife is 300 rev/min, and the premixing time is 6min to obtain the premix;

Step 3. Adjust the pressure of the spray gun to 0.35MPa, adjust the speed of the peristaltic pump, and spray purified water into the above premixed material through the spray gun at a flow rate of 50g/min for wet granulation. The stirring speed of the granulation process is 300 rpm , the rotation speed of the granulation knife is 500 rpm, continue to granulate for 2 minutes after adding the purified water, discharge the material, then pass through a 20-mesh sieve for granulation, and then transfer to the boiling dryer for drying, the air inlet temperature is 55°C, Get particles;

Step 4, add the magnesium stearate of formula quantity to above-mentioned granule, mix evenly, mixing rotating speed is 12 revolutions/min, and mixing time is 7min, and the intermediate content of mixed material is detected, determines sheet weight according to intermediate content, Put the intermediate material into the hopper of the tablet press, press the tablet, and control the tablet core hardness to 90-120N;

Example 6

Step 2, each component is weighed respectively according to the prescription amount, and the weighed pentoxifylline, carrageenan, xanthan gum and povidone K25 are added into the granulator for stirring and premixing, and the stirring paddle in the granulator is The rotating speed is 150 rev/min, the rotating speed of the granulating knife is 200 rev/min, and the premixing time is 7min to obtain the premix;

Step 3. Adjust the pressure of the spray gun to 0.35MPa, adjust the speed of the peristaltic pump, and spray purified water into the above premixed material through the spray gun at a flow rate of 25g/min for wet granulation. The stirring speed of the granulation process is 400 rpm , the rotation speed of the granulation knife is 550 rpm, continue to granulate for 1 minute after adding the purified water, discharge the material, then pass through a 20-mesh sieve for granulation, and then transfer to the boiling dryer for drying, the air inlet temperature is 58°C, Get particles;

Step 5: Coating with Opadry coating solution with a mass concentration of 10%, the weight gain of the coating is 2% of the total mass of the tablet core, to obtain pentoxifylline sustained-release tablets.

Comparative example 1

This comparative example provides a pentoxifylline sustained-release tablet, the prescription amount and preparation method of which are exactly the same as those in Example 1, except that the xanthan gum in Example 1 is replaced with an equivalent amount of carrageenan.

Comparative example 2

This comparative example provides a pentoxifylline sustained-release tablet, the prescription amount and preparation method of which are exactly the same as those in Example 1, except that the carrageenan in Example 1 is replaced by an equivalent amount of xanthan gum.

Comparative example 3

This comparative example provides a pentoxifylline sustained-release tablet, the prescription amount and preparation method of which are exactly the same as those in Example 1, except that the carrageenan in Example 1 is replaced by an equivalent amount of chitosan.

Comparative example 4

This comparative example provides a pentoxifylline sustained-release tablet, the prescription amount and preparation method of which are exactly the same as those in Example 1, except that the xanthan gum in Example 1 is replaced by an equivalent amount of gum arabic.

quality research

In order to investigate the in vitro dissolution effect of the pentoxifylline sustained-release tablets prepared in Examples 1-6 and Comparative Examples 1-4 of the present application, an in vitro dissolution test was carried out in hydrochloric acid medium.

According to the second method of the four general rules of the "Chinese Pharmacopoeia" 2020 edition, use 900mL of hydrochloric acid solution with pH = 1.0 as the dissolution medium, and the rotation speed is 50 rpm, and operate according to the second method of the four general rules of the "Chinese Pharmacopoeia" 2020 edition. After 2h, 6h, 12h and 16h, take 5mL of dissolution solution, and replenish the same temperature and volume of dissolution medium in time. Accurately measure 1mL of the dissolution solution of 2h, 6h, 12h and 16h respectively, place them in 10mL, 25mL, 25mL, and 25mL volumetric flasks, add dissolution medium to dilute to the mark, and shake well to obtain the test solution.

According to the ultraviolet-visible spectrophotometry ("Chinese Pharmacopoeia" 2020 edition four general rules 0401), the absorbance was measured at a wavelength of 274nm, and the dissolution amount of each pentoxifylline sustained-release tablet at different times was calculated. The results are shown in Table 1.

The dissolution rate result of table 1 embodiment 1-6 and comparative example 1-4

Note: The original preparation is Pentoxifylline Sustained-release Tablets produced by Sanofi, batch number: C112.

As can be seen from the above table, the sustained-release effect of the pentoxifylline sustained-release tablets prepared in Examples 1-6 of the present application is stable, and the dissolution curve consistency with the original preparation is good, and it can reach the standard for the in vitro dissolution of this variety in domestic and foreign pharmacopoeias. Require. The dissolution rate of pentoxifylline sustained-release tablets prepared by using xanthan gum or carrageenan alone or compounding (mixing) carrageenan with other sustained-release materials except xanthan gum or konjac gum may be faster Or slow, unable to reach the same level as the original preparation. This proves that the slow-release material compounded by carrageenan and xanthan gum or carrageenan and konjac gum in this application can make the slow-release effect of pentoxifylline stable, consistent with the dissolution of the original preparation, and has wide application in the development of generic drugs prospect.

Three batches of pentoxifylline sustained-release tablets were prepared according to the prescription amount and preparation method of Example 1, and then the in vitro dissolution curve test was carried out according to the above dissolution method, and the results are shown in Table 2. At the same time, three batches of original preparations (batch numbers: C112, 0U002, and 0U005) were tested for in vitro dissolution curves according to the above dissolution method, and the results are shown in Table 3.

Table 2 The dissolution results of three batches of Example 1 samples

Table 3 Dissolution results of three batches of original preparations

Among them, RSD (%) means relative standard deviation.

It can be seen from the above table that the process of the pentoxifylline sustained-release tablets prepared by the present application is stable, the difference between batches is small, and the quality of the original preparations of different batches can be consistent.

Influencing factor test

In order to investigate the stability of the pentoxifylline sustained-release tablets prepared in the examples of the present application, according to the requirements of the "Chinese Pharmacopoeia" 2020 Edition Four General Rules "Guidelines for the Stability Test of Raw Materials and Pharmaceutical Preparations" and ICH Q1A Q1B, to the requirements of the examples 1. The Pentoxifylline Sustained-release Tablets prepared in Example 4 and the original preparation (Trental, batch number C112) were tested on the influencing factors at a high temperature of 60°C, and samples were taken at 0 days, 5 days, 10 days and 30 days respectively. Dissolution test, the test investigates the change of the dissolution rate, the test method is the same as above, and the test results are shown in Table 4-Table 6.

Table 4 Results of Dissolution at 60°C of Influencing Factors in Example 1

Table 5 Example 4 Influencing Factors Dissolution Results at 60°C

Table 6 Dissolution results at 60°C of influencing factors of the original preparation

It can be seen from the above table that the dissolution rate of the original preparation increases with the storage time under the condition of high temperature storage, and the dissolution rate is obviously accelerated after 6 hours, showing that it is unstable to high temperature. Compared with the original preparation, the pentoxifylline sustained-release tablets prepared in Examples 1 and 4 of the present application have no obvious change in dissolution rate and more stable dissolution properties after being placed at a high temperature of 60°C for 30 days. This proves that the pentoxifylline sustained-release tablets prepared in the examples of the present application have a more stable sustained-release effect under high-temperature storage conditions, and the product quality stability is obviously better than that of the original preparation.

In summary, the sustained-release effect of the pentoxifylline sustained-release tablets prepared in the examples of the present application is stable, and can be highly consistent with the dissolution curve of the original research product, and the high temperature stability is obviously better than that of the original research preparation, which can realize the improvement of the original research product. The replacement of the preparation; the production process of the preparation is simple, and it is easy to realize industrialized large-scale production.

The above description is only a preferred embodiment of the application, and is not intended to limit the application. Any modification, equivalent replacement or improvement made within the spirit and principles of the application shall be included in the protection of the application. within range.

Claims

A pentoxifylline sustained-release tablet, characterized in that it comprises the following raw material components in parts by weight: 370-420 parts of pentoxifylline, 120-160 parts of sustained-release material, 10-16 parts of adhesive, lubricating 5-10 parts of agent and 150-300 parts of wetting agent;

Wherein, the slow-release material is a mixture of carrageenan and xanthan gum, or a mixture of carrageenan and konjac gum; the wetting agent is purified water.
The pentoxifylline sustained-release tablet according to claim 1, wherein the sustained-release material is a mixture of carrageenan and xanthan gum with a mass ratio of 0.75-1.0:1.
The pentoxifylline sustained-release tablet according to claim 1, wherein the sustained-release material is a mixture of carrageenan and konjac gum in a mass ratio of 1.6-3.0:1.
The pentoxifylline sustained-release tablet according to claim 1, wherein the binder is povidone K25.
The pentoxifylline sustained-release tablet according to claim 1, wherein the lubricant is magnesium stearate.
The pentoxifylline sustained-release tablet according to any one of claims 1-5, wherein the pentoxifylline sustained-release tablet comprises the following raw material components in parts by weight: 400 parts of pentoxifylline , 70 parts of carrageenan, 70 parts of xanthan gum, 10 parts of binder, 10 parts of lubricant and 220 parts of wetting agent.
The pentoxifylline sustained-release tablet according to any one of claims 1-5, wherein the pentoxifylline sustained-release tablet comprises the following raw material components in parts by weight: 400 parts of pentoxifylline , 105 parts of carrageenan, 35 parts of konjac gum, 10 parts of adhesive, 8 parts of lubricant and 260 parts of wetting agent.
A preparation method of the pentoxifylline sustained-release tablet described in any one of claims 1-7, is characterized in that, comprises the steps:

Step a, weighing each component according to the designed proportion, adding pentoxifylline, binder and slow-release material into a granulator for premixing to obtain a premix;

Step b, atomizing and spraying a wetting agent into the premix to granulate, granulate, and dry to obtain granules;

In step c, the granules and the lubricant are uniformly mixed, compressed into tablets, and coated to obtain pentoxifylline sustained-release tablets.
The preparation method of pentoxifylline sustained-release tablets as claimed in claim 8, characterized in that, in step a, in the premixing process, the stirring speed is 100-150 rpm, and the granulating knife rotational speed is 200-300 rpm /min, the premixing time is 5-10min; and/or

In step b, in the granulation process, the stirring speed is 300-500 rpm, and the granulation knife speed is 500-700 rpm; and/or

In step b, the injection flow rate of the wetting agent is 25-50 g/min.
The preparation method of pentoxifylline sustained-release tablets according to claim 8, wherein in step b, the granulation is passing the primary granules obtained by granulation through a 20-24 mesh sieve; and/or

In step c, the core hardness of the compressed tablet is 60-120N.