CN107028904B

CN107028904B - Preparation method of trazodone hydrochloride tablets

Info

Publication number: CN107028904B
Application number: CN201710338977.8A
Authority: CN
Inventors: 王鹏; 刘冠; 薛昊
Original assignee: Shenyang Pharmtech Pharmaceutical R & D Ltd
Current assignee: Shenyang Pharmtech Pharmaceutical R & D Ltd
Priority date: 2017-05-15
Filing date: 2017-05-15
Publication date: 2021-05-11
Anticipated expiration: 2037-05-15
Also published as: CN107028904A

Abstract

The invention relates to a preparation method of trazodone hydrochloride tablets, which mainly comprises the following steps: (1) uniformly mixing trazodone hydrochloride with a part of filling agent in the prescription, and granulating to obtain medicine-containing granules; (2) granulating the rest filling agent in the prescription to obtain empty and white granules; (3) and (3) respectively sieving the granules prepared in the step (1) and the step (2), alternately granulating, uniformly mixing and tabletting to obtain the tablet. The preparation method provided by the invention can effectively prevent the problem of color change in the production and placement processes, so that the product is more stable, and the effectiveness and safety of the product are ensured.

Description

Preparation method of trazodone hydrochloride tablets

Technical Field

The invention relates to the technical field of medicines, and particularly relates to a preparation method of trazodone hydrochloride tablets.

Background

Trazodone hydrochloride is mainly used as an antidepressant drug and is also commonly applied to the diseases of antianxiety, insomnia, erectile dysfunction and the like clinically. It is a medicine with wide treatment range, good curative effect and high safety. However, the trazodone hydrochloride tablet, which is the most common dosage form on the market, is very easy to discolor during the drying process and the placing process during the production, and the color is changed from white to off-white to pink, and gradually deepens along with the prolonging of the placing time of the tablet. At present, most manufacturers of trazodone hydrochloride tablets improve the properties of the tablets by preparing coated tablets or adding pigments to prepare colored tablets so as to make the products more beautiful in appearance, such as Watson Laboratories, Qualitest Pharmaceuticals and Sun Pharmaceutical Industries, etc., make trazodone hydrochloride tablets into coated tablets, Meisuyu produced by chemical pharmacy in Taiwan, and make the tablets into pink by adding colorants. However, these methods only cover the color-variable nature of the product, and do not fundamentally solve the problem of color change. The discoloration usually indicates the change of the quality and the property of the product, and the change not only can possibly influence the curative effect of the product, but also can possibly cause some adverse reactions and influence the safety of the product. Therefore, the development of a new preparation process of trazodone hydrochloride tablets is urgently needed, the problem of color change in the production process is fundamentally solved, the product is more stable, and the effectiveness and the safety of the product are ensured.

Disclosure of Invention

The invention aims to provide a preparation method of trazodone hydrochloride tablets, which solves the problem of color change in the production and placement processes. In order to solve the technical problem, the invention is realized by the following technical scheme.

The preparation method of trazodone hydrochloride tablets is characterized by mainly comprising the following steps:

(1) uniformly mixing trazodone hydrochloride with a part of filling agent in the prescription, and granulating to obtain medicine-containing granules;

(2) granulating the rest filling agent in the prescription to obtain empty and white granules;

(3) and (3) respectively sieving the granules prepared in the step (1) and the step (2), alternately granulating, uniformly mixing and tabletting to obtain the tablet.

The granulation described in steps (1) and (2) may be dry granulation or wet granulation.

The filler in the steps (1) and (2) can be one or more of microcrystalline cellulose, pregelatinized starch, corn starch, lactose and dextrin. Preferably, a portion of the bulking agent described in step (1) comprises pregelatinized starch.

And (3) adding a proper amount of adhesive in the steps (1) and (2). The adhesive can be one of polyvinylpyrrolidone, hydroxypropyl methylcellulose and starch, and the solvent is water.

One or more of a disintegrating agent and a lubricating agent can also be added in each step. The disintegrating agent can be one or more of sodium carboxymethyl starch, cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethyl starch, cross-linked sodium carboxymethyl cellulose and low-substituted hydroxypropyl cellulose; the lubricant can be one or more of magnesium stearate, talcum powder, silicon dioxide and polyethylene glycol.

In order to solve the problem of discoloration of trazodone hydrochloride tablets, the present inventors have conducted a number of experimental studies. In the research process, the prepared product still quickly shows a color change phenomenon no matter different pharmaceutical auxiliary materials such as a filling agent, a disintegrating agent, a lubricating agent, a binding agent and the like are selected, dry granulation or wet granulation is selected, or drying conditions are adjusted when the traditional process is adopted for one-step granulation, the color is basically changed from white to light pink in the drying process during production, and the color is deepened along with the prolonging of the standing time after the tablet is prepared. In continuous exploration, the inventor tries to prepare trazodone hydrochloride tablets by adopting a separate granulation method, namely preparing trazodone hydrochloride raw materials and part of filling agents in a prescription into medicine-containing granules, preparing the rest filling agents in the prescription into blank granules, sieving the blank granules respectively, alternately finishing granules, mixing the granules uniformly and tabletting. In the whole preparation process, other pharmaceutic adjuvants such as a binder beneficial to tablet forming, a disintegrant beneficial to rapid dissolution and absorption of the tablet in a body, a lubricant for preventing sticking and the like are added in each step according to needs. The inventor selects different pharmaceutic adjuvants and different drying conditions (drying temperature: 40-80 ℃, drying time 3-6 h) to carry out tests, and the results show that the trazodone hydrochloride tablets prepared by adopting a separate granulation method (namely, a part of filling agent and trazodone hydrochloride in a prescription are prepared into medicine-containing granules, and the rest filling agent is prepared into blank granules) are lighter in color change in the drying process and the placing process during production than the tablets prepared by adopting a traditional one-step granulation method under the same conditions no matter how the adding sequence and the types of other pharmaceutic adjuvants (such as an adhesive, a disintegrating agent, a lubricant and the like) are selected and the drying conditions are changed. More surprisingly, when the filler in the preparation of the drug-containing particles contains pregelatinized starch, the prepared trazodone hydrochloride tablet has no color change phenomenon in the drying process or the placing process, thereby thoroughly solving the problem of color change. The test result shows that compared with the traditional preparation method, the preparation method provided by the invention can obviously reduce or even eliminate the color change phenomenon of the product, is more beneficial to the stability of the product, and ensures the quality of the product, thereby ensuring the effectiveness and safety of the product.

Detailed Description

The present invention will be described below with reference to some examples, but the present invention is not limited to these examples.

Example 1 preparation of trazodone hydrochloride tablets.

The prescription is shown in table 1, and the dosage is 1000 tablets.

The preparation method comprises the following steps:

1. and (4) preparing raw and auxiliary materials.

Preparing an adhesive in advance according to a prescription for later use; the trazodone hydrochloride is crushed and sieved by a 100-mesh sieve for standby; other pharmaceutic adjuvants needing to be sieved in the prescription are directly sieved by a 100-mesh sieve for later use.

2. And (3) preparing medicine-containing particles.

Taking trazodone hydrochloride in the prescription amount and a part of fillers in the prescription (the part of fillers in the prescription respectively refer to the prescription 1-40 g of corn starch, the prescription 2-40 g of microcrystalline cellulose + 20g of dextrin, the prescription 3-50 g of microcrystalline cellulose, the prescription 4-70 g of pregelatinized starch, the prescription 5-30 g of pregelatinized starch + 20g of dextrin and the prescription 6-50 g of microcrystalline cellulose), fully mixing, adding the adhesive listed in the prescription to prepare a soft material, granulating by using a 16-mesh sieve, and drying for 4 hours at 80 ℃.

3. And (3) preparing blank particles.

Taking the rest fillers in the prescription (the rest fillers in the prescription respectively refer to prescription 1-microcrystalline cellulose 80g, prescription 2-lactose 60g, prescription 3-corn starch 25g + dextrin 50g, prescription 4-microcrystalline cellulose 50g, prescription 5-microcrystalline cellulose 70g and prescription 6-microcrystalline cellulose 70 g), adding the adhesive listed in the prescription to prepare a soft material, granulating by using a 16-mesh sieve, and drying at 80 ℃ for 4 hours.

4. And (3) alternately finishing the granules prepared in the step (1) and the step (2) by using a 16-mesh sieve for later use.

5. Adding other auxiliary materials in the prescription, and fully and uniformly mixing.

6. Tabletting to obtain trazodone hydrochloride tablets.

Example 2 color change observation of trazodone hydrochloride tablets prepared by different preparation processes.

Trazodone hydrochloride tablets were prepared by a conventional one-step granulation method (without separately preparing drug-containing granules and blank granules, and drying wet granules at 80 ℃ for 4 hours) according to the formulation ratio in example 1, the prepared tablets were compared with the tablets prepared by the separate granulation method in example 1, and the color change of each tablet during the drying process and the leaving process was observed, and the results are shown in table 2 below.

From the results, the tablets prepared by the one-step granulation method of the traditional process all have the phenomenon of color change in the drying process, the color changes from white to off-white to pink, and the color change is more and more obvious along with the prolonging of the standing time. Under the same condition, the color change phenomenon of the tablets prepared by adopting the separate granulation methods provided by the invention is not obvious, and when the medicine-containing granules contain pregelatinized starch, the tablets do not change color in the drying process or the placing process. Compared with the tablet prepared by the separate granulation method, the tablet prepared by the separate granulation method can obviously better reduce or even eliminate the color change phenomenon of the trazodone hydrochloride tablet.

Claims

1. The preparation method of trazodone hydrochloride tablets is characterized by comprising the following steps:

2. The method of claim 1, wherein the granulation in steps (1) and (2) is dry granulation or wet granulation.

3. The preparation method according to claim 1 or 2, wherein the filler in steps (1) and (2) can be one or more of microcrystalline cellulose, pregelatinized starch, corn starch, lactose and dextrin.

4. The method of claim 3, wherein the filler in step (1) comprises pregelatinized starch.

5. The method of claim 1, wherein the steps (1) and (2) are carried out by adding a proper amount of binder.

6. The method according to claim 5, wherein the binder is one of polyvinylpyrrolidone, hypromellose and starch, and the solvent is water.

7. The preparation method according to claim 1 or 2, wherein one or more of a disintegrant and a lubricant can be added in each step.

8. The preparation method according to claim 7, wherein the disintegrant is one or more selected from sodium carboxymethyl starch, crospolyvinylpyrrolidone, sodium croscarmellose, and low substituted hydroxypropyl cellulose.

9. The preparation method according to claim 7, wherein the lubricant is one or more of magnesium stearate, talc, silicon dioxide and polyethylene glycol.