CN114469881A

CN114469881A - Nitroglycerin tablet and preparation method thereof

Info

Publication number: CN114469881A
Application number: CN202210248611.2A
Authority: CN
Inventors: 赵晓雷; 樊根遥; 赵亚翡; 张倩如; 任玉新; 张岩; 常章峰; 杨春光; 李萍
Original assignee: Hebei Kunan Pharmaceutical Co ltd
Current assignee: Hebei Kunan Pharmaceutical Co ltd
Priority date: 2022-03-14
Filing date: 2022-03-14
Publication date: 2022-05-13

Abstract

The invention discloses a nitroglycerin tablet and a preparation method thereof, wherein the nitroglycerin tablet comprises nitroglycerin, a first diluent, a stabilizer, a flow aid, a disintegrating agent and a lubricant; wherein the content of the nitroglycerin is 1.25 wt% -1.85 wt%, the content of the first diluent is 61.5 wt% -75 wt%, the first diluent is granular lactose, and the particle size of the granular lactose is 150-500 μm. According to the nitroglycerin tablet provided by the invention, the first diluent is limited to be the granular lactose with the grain diameter of 150-500 mu m, and the dosage of the nitroglycerin and the first diluent in the tablet is combined, so that the dissolving speed and the stability of the nitroglycerin can be obviously improved, and the nitroglycerin tablet is good in mouth feel when being taken sublingually.

Description

Nitroglycerin tablet and preparation method thereof

Technical Field

The invention belongs to the technical field of medicines, and particularly relates to a nitroglycerin tablet and a preparation method thereof.

Background

Nitroglycerin, also known as glyceryl trinitrate, of the formula: c₃H₅N₃O₉Molecular weight: 227.09, having the formula:

nitroglycerin is a potent vasodilator of peripheral circulation and coronary arteries, and is widely used clinically in the treatment and prevention of coronary heart disease, angina pectoris, and the treatment of lowering blood pressure or congestive heart failure, and its sublingual administration can be rapidly dissolved into blood to achieve the effect of dilating coronary arteries, and can moderately lower blood pressure and reduce heart consumption.

The nitroglycerin is light yellow viscous liquid, is insoluble in water, and is miscible in acetone, diethyl ether, ethanol, nitrobenzene, pyridine, ethyl acetate and the like. Nitroglycerin has high vapor pressure and is unstable under illumination, so the nitroglycerin has strong volatility, is easy to degrade under illumination, and is easily influenced by factors such as temperature, illumination and the like particularly in the production and storage processes of tablets, so key indexes such as content, related substances and the like are changed, and the curative effect is reduced or disappeared.

In order to improve the stability of the nitroglycerin sublingual tablet, stabilizers such as microcrystalline cellulose (MCC) and polyvinylpyrrolidone (PVP) are mostly added into a formula in the prior art to reduce the volatilization of the nitroglycerin, for example, an ethanol solution of the nitroglycerin and the polyvinylpyrrolidone are prepared into a mixed solution, and then the mixed solution is added into auxiliary materials such as microcrystalline cellulose and lactose to be mixed to prepare the tablet. Although the above-described method can prevent volatilization by adsorbing nitroglycerin with polyvinylpyrrolidone, polyvinylpyrrolidone as a binder commonly used causes a delay in disintegration and dissolution of tablets. Moreover, the gritty sensation of microcrystalline cellulose in the oral cavity can make the sublingual tablet have a poor taste.

Disclosure of Invention

In view of this, the invention provides a nitroglycerin tablet and a preparation method thereof, the nitroglycerin tablet can effectively reduce volatilization and light decomposition of nitroglycerin, the stability of the nitroglycerin tablet is obviously improved, when the tablet is taken sublingually, the nitroglycerin can be rapidly released within a few seconds, and the mouth feel of sublingual administration is good.

In order to achieve the purpose of the invention, the embodiment of the invention adopts the following technical scheme:

a nitroglycerin tablet, comprising nitroglycerin, a first diluent, a stabilizer, a glidant, a disintegrant and a lubricant;

wherein the content of the nitroglycerin is 1.25 wt% -1.85 wt%, the content of the first diluent is 61.5 wt% -75 wt%, the first diluent is granular lactose, and the particle size of the granular lactose is 150-500 μm.

The nitroglycerin tablet provided by the invention has the advantages that the first diluent is limited to be the granular lactose with the grain diameter of 150-500 mu m, the dissolving-out speed and the stability of the nitroglycerin can be obviously improved by combining the dosage of the nitroglycerin and the first diluent in the tablet, and after the nitroglycerin tablet is placed for 6 months at the temperature of 40 soil and 2 ℃ and the relative humidity of 75 +/-5%, the nitroglycerin tablet not only has stable content and the total impurity can be controlled within 0.4%, but also has good mouth feel when being taken sublingually.

Optionally, the mass ratio of the nitroglycerin to the first diluent is 1 (40-50).

Optionally, the nitroglycerin tablet further comprises a second diluent, and the second diluent is granular lactose or ground lactose.

Optionally, the content of the second diluent is 2 wt% to 8 wt%.

Optionally, the nitroglycerin tablet further comprises a third diluent, and the third diluent is granular lactose.

Optionally, the content of the third diluent is 5 wt% to 10 wt%.

Optionally, the content of the stabilizer is 1 wt% -2 wt%;

the content of the glidant is 0.1 to 0.5 percent by weight;

the content of the disintegrating agent is 10-15 wt%;

the content of the lubricant is 0.5 wt% to 1.0 wt%.

Optionally, the stabilizer is a glycerolipid. Preferably, the stabilizer is glyceryl mono-bis stearate.

Optionally, the glidant is silicon dioxide and/or talc;

the disintegrating agent is one or more of pregelatinized starch, crospovidone, croscarmellose sodium, sodium carboxymethyl starch, carboxymethylcellulose and carboxymethylcellulose calcium;

the lubricant is one or more of calcium stearate, magnesium stearate and sodium stearyl fumarate.

The invention also provides a preparation method of the nitroglycerin tablet, which comprises the following steps:

mixing 9-11% (mg/mL) nitroglycerin ethanol solution with a first diluent, drying, and grading to obtain a first mixture;

mixing the stabilizing agent and the flow aid, crushing and sieving to obtain a second mixture;

and mixing the first mixture, the second mixture and a disintegrating agent, adding a lubricant, mixing, and tabletting to obtain the nitroglycerin tablets.

The preparation method of the nitroglycerin tablets provided by the invention comprises the steps of mixing an ethanol solution of nitroglycerin with first diluent particle lactose, drying and then granulating. Because the granular lactose has a loose and porous spherical structure, in the mixing process, the ethanol solution of the nitroglycerin can enter the pores of the granular lactose, and after drying, the anhydrous ethanol volatilizes, the nitroglycerin can be uniformly dispersed in the granular lactose and can form a firm combination with the granular lactose after tabletting, so that the nitroglycerin is prevented from being influenced by external conditions such as high temperature, illumination and the like, the quality of the tablet is kept stable for a long time, when the tablet is subjected to dissolution media or sublingual buccal administration, the lactose in the tablet is dissolved in water, the nitroglycerin can be quickly released, and the sublingual buccal administration has good taste. If the above mixing manner is changed, for example, mixing the ethanol solution of nitroglycerin with the first diluent and other auxiliary materials, omitting the drying step, or mixing the first mixture with the stabilizer, glidant and disintegrant, etc., the stability of the nitroglycerin tablet is seriously affected.

The nitroglycerin tablet prepared by the preparation method of the nitroglycerin tablet provided by the invention is obviously superior to the original American preparation in the aspects of dissolution speed and stability, and is more obviously superior to the domestic same preparation in the aspect of sublingual buccal mouthfeel.

Optionally, the preparation method of the nitroglycerin tablet further comprises the step of mixing a second diluent with the stabilizer and the glidant.

Optionally, the preparation method of the nitroglycerin tablet further comprises the step of mixing a third diluent with the first mixture, the second mixture and the disintegrant.

Detailed Description

In order to make the objects, technical solutions and advantages of the present invention more apparent, the present invention is further described in detail with reference to the following embodiments. It should be understood that the specific embodiments described herein are merely illustrative of the invention and are not intended to limit the invention.

The nitroglycerin tablet is used as a first-aid medicine, and the nitroglycerin tablet is required to have the characteristics of high content, quick release and long storage period (good stability), but the nitroglycerin tablet has higher vapor pressure, so the nitroglycerin tablet has stronger volatility and is easy to decompose under the illumination, so the nitroglycerin tablet is extremely easy to be influenced by factors such as temperature, illumination and the like, and is easy to volatilize and decompose in the preparation and placement processes and quite unstable. According to clinical statistics, the nitroglycerin tablets produced by different manufacturers at home and abroad have certain difference in curative effect, different storage periods and long disintegration time, and the safety of clinical medication is greatly reduced.

In order to solve the above problems, the prior art is mostly improved from two aspects of a formula and a process, the formula is basically characterized in that stabilizers such as microcrystalline cellulose (MCC), polyvinylpyrrolidone (PVP) and cyclodextrin (β -CD) are added, the process mostly adopts wet granulation, and then the mixing sequence of auxiliary materials is adjusted, or blank particles containing drug particles and auxiliary materials are mixed and tableted, but the methods have no significant effect on improving the stability of the nitroglycerin tablet, and even cause new problems, such as delay of tablet disintegration and dissolution, easy material delamination in the processes of material transportation and tabletting, and uneven content, and the like. Therefore, the stability problem of nitroglycerin tablets has been a major and difficult point of research in the industry.

Through a large number of experimental researches, the inventor finds that the stability of the nitroglycerin tablets can be obviously improved by adding granular lactose with a specific particle size into a formula and combining the limitation of the content of the granular lactose and the content of the nitroglycerin. The specific technical scheme is as follows:

The related granular lactose can meet the implementation of the technical scheme, and the commercially available granular lactose with the particle size of 150-500 mu m can also be obtained by performing wet granulation on lactose fine powder with the particle size of below 50 mu m. The microstructure of the granular lactose (the grain diameter is 150-500 mu m) is a complex formed by stacking and embedding fine powder lactose, the unique structure determines that the inside of the granular lactose has more cavities, and the nitroglycerin is in the cavities of the granular lactose and can prevent the degradation and volatilization of the nitroglycerin under the influence of external factors such as high temperature, illumination and the like.

If the lactose content of the first diluent particles is too high, this will result in increased costs; if the content is too small, nitroglycerin cannot be completely hidden in the hollow of the granular lactose, resulting in a significant decrease in the stability of the tablet.

If the particle size of the granular lactose is lower than the lower limit of 150 mu m, the granular lactose cannot be completely stacked and embedded, and a hollow structure cannot be formed; if the particle size of the lactose particles is higher than the upper limit of 500 μm, the particle size difference between the lactose particles and other excipients is too large, which affects the mixing uniformity. In addition, if the particle size of the lactose is too large or too small (not in the range defined by 150-500 μm), the fluidity of the whole material and the stability of the tablet quality are also affected.

Specifically, the mass ratio of the nitroglycerin to the first diluent is 1 (40-50). By further reducing the proportion of nitroglycerin to the first diluent, the stability of the tablet can be further improved, and the total impurities accelerated for 6 months can be controlled within 3.8%.

Specifically, the nitroglycerin tablet can further comprise a second diluent, wherein the second diluent is granular lactose or ground lactose;

the content of the second diluent is 2-8 wt%.

By adding the second diluent into the tablet and combining the limitation of the type and the dosage of the second diluent, auxiliary materials such as a dispersion stabilizer, a flow aid and the like can be diluted and dispersed, and the stability of the nitroglycerin tablet is further improved. The effect of using ground lactose as the second diluent is equivalent to using granular lactose, and when the second diluent is granular lactose, the grain size is not limited, and the granular lactose in any grain size range can meet the implementation of the scheme. When the second diluent is the ground lactose, the cost can be reduced, the market competitiveness can be improved, and the ground lactose sold in the market can meet the implementation of the technical scheme of the invention.

Specifically, the nitroglycerin tablet can further comprise a third diluent, wherein the third diluent is granular lactose; the content of the third diluent is 5 wt% -10 wt%.

By adding the third diluent into the nitroglycerin tablets, the type and the dosage of the third diluent are limited, and the overall fluidity of the material can be improved. If the third diluent is replaced by the ground lactose from the granular lactose, the content uniformity and the partial weight difference of the nitroglycerin tablets are unqualified due to poor fluidity of the ground lactose. The particle size of the third diluent lactose is not limited, and the technical scheme of the invention can be realized by the existing lactose particles with different particle size ranges.

Specifically, the stabilizer may be selected from conventional stabilizers such as glycerols; preferably, the stabilizer is glyceryl mono-bis stearate; the content of the stabilizer can be selected from 1 wt% to 2 wt%, such as 1 wt%, 1.2 wt%, 1.5 wt%, 1.8 wt%, 2 wt%, etc.;

the glidant is selected from silicon dioxide, talcum powder and the like, and the content of the glidant can be selected from 0.1 wt% -0.5 wt%, such as 0.1 wt%, 0.2 wt%, 0.5 wt%, 0.3 wt% and the like;

the disintegrating agent is selected from one or more of pregelatinized starch, crospovidone, croscarmellose sodium, sodium carboxymethyl starch, carboxymethylcellulose and carboxymethylcellulose calcium; the content of the disintegrant is 10 wt% -15 wt%, such as 10 wt%, 15 wt%, 11 wt%, 12 wt%, 13 wt%, 14 wt%, etc.;

the lubricant is one or more of calcium stearate, magnesium stearate, sodium stearyl fumarate and the like. The content of the lubricant is 0.5 wt% to 1.0 wt%, such as 0.5 wt%, 1.0 wt%, 0.6 wt%, 0.8 wt%, 0.7 wt%, 0.9 wt%, etc.

The dosage of the stabilizer, the glidant, the disintegrant, the lubricant and other auxiliary materials can be adjusted according to actual needs, and even if the dosage is not in the respective limited range, the stability of the product in the period of validity is not influenced, and only in the limited range, the stability of the final tablet is more excellent. The auxiliary materials such as the stabilizer, the glidant, the disintegrant, the lubricant and the like can be selected from conventional materials in the field, and the effect of the nitroglycerin tablet is not influenced.

The preparation method of the nitroglycerin tablets provided by the invention comprises the following steps:

and mixing the first mixture, the second mixture and a disintegrating agent, adding a lubricant, mixing, and tabletting to obtain the nitroglycerin tablet.

The preparation method comprises the following key steps that when the ethanol solution of the nitroglycerin is mixed with the granular lactose, the microstructure of the granular lactose (the granular lactose is a complex formed by stacking and embedding of fine powder lactose, and has more cavities inside) is utilized, liquid can enter the cavities along gaps at the joint of the fine powder lactose, when the nitroglycerin and the ethanol completely infiltrate the lactose firstly until the nitroglycerin and the ethanol enter the lactose, the ethanol is evaporated in time by utilizing the difference of saturated vapor pressure of the nitroglycerin and the ethanol during drying, the nitroglycerin can be remained in the gaps and the cavities inside the granular lactose while being solidified, and the granular lactose is deformed by the pressure of a punch in the subsequent tabletting process, the gap between the materials is sharply reduced, and the nitroglycerin is sealed in the gap and the hollow. When the tablet is influenced by external factors such as high temperature, illumination and the like, the volatilization and degradation tendency of the nitroglycerin in the closed space can be remarkably delayed, and the stability of the nitroglycerin tablet is further remarkably improved.

In the existing preparation method of nitroglycerin tablets, the nitroglycerin tablets are prepared by respectively preparing medicine-containing granules and blank granules, then sieving the medicine-containing granules and the blank granules by a 16-mesh sieve and tabletting. However, because the particle size of the particles is large, the materials are easy to be layered in the material transferring and tabletting processes. According to the preparation method of the nitroglycerin tablets, the first diluent particle lactose is only mixed in the ethanol solution of nitroglycerin with the concentration of 10% (mg/ml) for wet mixing, no granulation process is carried out, the particles are not bonded, and the particle size of the mixed material is below 500 microns; the process of mixing the stabilizer and the glidant, crushing and sieving to prepare the second mixture is combined, and the steps are matched with each other, so that the situation of mixing and layering cannot occur.

Specifically, the drying temperature is 10-40 deg.C, and the drying time is 0.5-3 h. The drying may be carried out by a conventional drying method in the art such as boiling drying or forced air drying. By further limiting the drying time and temperature, the two cooperate with each other, and the stability of the nitroglycerin tablet can be obviously improved. If the temperature and time for drying are not within the defined ranges, the content of the nitroglycerin tablets and related substances are affected.

Specifically, the sieving can be selected from 40-60 mesh sieve. If the particle size is too large after pulverization during the preparation of the second mixture, the subsequent mixing is not uniform.

Specifically, the preparation method of the nitroglycerin tablet further comprises the step of mixing a second diluent with the stabilizer and the flow aid.

By mixing the second diluent with the stabilizer and the glidant, the subsequent crushing and sieving are facilitated in the process of diluting the stabilizer and the glidant, the uniform mixing is promoted, and the content uniformity and stability of the tablet are improved.

Specifically, the preparation method of the nitroglycerin tablet further comprises a step of mixing a third diluent with the first mixture, the second mixture and the disintegrant.

The third diluent is mixed with the first mixture, the second mixture and the disintegrating agent and then mixed with the lubricant, so that the flowability of the material can be remarkably increased, and the uniform mixing is promoted.

The examples do not show the specific experimental steps or conditions, and can be performed according to the conventional experimental steps described in the literature in the field. The reagents or instruments used are not indicated by manufacturers, and are all conventional reagent products which can be obtained commercially.

For convenience of comparison, the first diluent used in the following examples is 150-500 μm particle lactose, the second diluent used is ground lactose, and the third diluent used is 150-500 μm particle lactose.

Example 1

The present embodiment provides a nitroglycerin tablet, which has the following formula:

the preparation method comprises the following steps:

mixing 9% (9mg/100mL) nitroglycerin ethanol solution (the mass of nitroglycerin is 0.5g after the dosage is converted) with a first diluent, boiling and drying at 10-20 ℃ for 0.5h, and granulating to obtain a first mixture;

mixing the second diluent, glyceryl monostearate and silicon dioxide, crushing, and sieving with a 60-mesh sieve to obtain a second mixture;

and uniformly mixing the first mixture, the second mixture, the third diluent and the pregelatinized starch, adding calcium stearate, mixing, and tabletting to obtain the nitroglycerin tablets.

Example 2

the preparation method comprises the following steps:

mixing 10% (10mg/100mL) nitroglycerin ethanol solution (the mass of nitroglycerin is 0.5g after the dosage is converted) with a first diluent, carrying out forced air drying at 20-30 ℃ for 2h, and finishing granules to obtain a first mixture;

mixing the second diluent, glyceryl monostearate and silicon dioxide, crushing, and sieving with a 40-mesh sieve to obtain a second mixture;

Example 3

the preparation method comprises the following steps:

mixing 11% (11mg/100mL) nitroglycerin ethanol solution (the mass of nitroglycerin is 0.5g after the dosage is converted) with a first diluent, carrying out forced air drying at 30-40 ℃ for 1h, and finishing granules to obtain a first mixture;

mixing the second diluent, glyceryl monostearate and silicon dioxide, crushing, and sieving with a 50-mesh sieve to obtain a second mixture;

Example 4

the preparation method comprises the following steps:

mixing 10% (10mg/100mL) nitroglycerin ethanol solution (the mass of nitroglycerin is 0.5g after the dosage is converted) with a first diluent, boiling and drying at 25-35 ℃ for 0.5h, and granulating to obtain a first mixture;

Example 5

the preparation method comprises the following steps:

mixing 10% (10mg/100mL) nitroglycerin ethanol solution (the mass of nitroglycerin is 0.5g after the dosage is converted) with a first diluent, carrying out forced air drying at 20-30 ℃ for 1.5h, and finishing granules to obtain a first mixture;

Example 6

the preparation method comprises the following steps:

mixing 10% (10mg/100mL) nitroglycerin ethanol solution (the mass of nitroglycerin is 0.75g after the dosage is converted) with a first diluent, carrying out forced air drying at 20-30 ℃ for 3h, and carrying out granulation to obtain a first mixture;

Example 7

the preparation method comprises the following steps:

mixing 10% (10mg/100mL) nitroglycerin ethanol solution (the mass of nitroglycerin is 0.34g after the dosage is converted) with a first diluent, carrying out forced air drying at 20-30 ℃ for 1h, and finishing granules to obtain a first mixture;

Comparative example 1

The comparative example provides a nitroglycerin tablet, which has the same formula as that of example 2, and is different only in that the drying step is omitted in the preparation process, and the specific preparation method is as follows:

mixing a 10% (10mg/100mL) nitroglycerin ethanol solution (the mass of nitroglycerin is 0.5g after the dosage is converted) with a first diluent, and finishing granules to obtain a first mixture;

and mixing the first mixture, the second mixture, the third diluent and the pregelatinized starch, then adding calcium stearate, mixing and tabletting to obtain the nitroglycerin tablet.

Comparative example 2

This comparative example provides a nitroglycerin tablet, which was prepared in the same manner as in example 2, except that the formulation was different (the first diluent was replaced with granulated lactose for ground lactose in this comparative example), and the specific formulation in this comparative example was as follows:

experimental example 1 examination of dissolution Curve of nitroglycerin tablet

Examples 1-7, comparative example 1, and the American stock of drug research (manufacturer: Pfizer Pharmaceuticals LLC, lot number: N30296) were tested for dissolution profiles in phosphate buffer at pH 6.5, according to the nitroglycerin sublingual tablet dissolution method published in the FDA dissolution database, and the results are shown in the following table.

TABLE 1 dissolution data

Time

Example 1

Example 2

Example 3

Example 4

Example 5

Example 6

Example 7

Comparative example 1

American original preparation

1min

62.5％

60.9％

63.2％

58.8％

61.9％

56.2％

63.5％

37.1％

40.7％

3min

98.7％

99.6％

98.9％

96.8％

98.5％

95.2％

99.1％

89.9％

94.6％

The nitroglycerin tablets are first-aid medicines, and the specification specifically indicates that: at the time of acute angina pectoris, one tablet should be taken sublingually immediately, and if the symptom is not relieved within 5 minutes, the administration can be repeated at intervals of 5 minutes, and the maximum is 3 tablets. If the nitroglycerin tablet is to complete the process from release to absorption within 5 minutes, even to take effect, the nitroglycerin should be dissolved out as fast as possible. As can be seen from the data in the above table, the dissolution rates of examples 1-7 are significantly faster than those of comparative example 1 and the original formulation, which is particularly important in emergency treatment of critically ill patients.

Experimental example 2 stability examination of nitroglycerin tablets

The nitroglycerin tablets prepared in example 2, comparative example 1 and comparative example 2 and the original American research reagent (manufacturer: Pfizer Pharmaceuticals LLC, batch number: N30296) are respectively placed for 6 months under the condition of accelerated test (temperature 40 ℃ soil 2 ℃, relative humidity 75% + -5%), and are respectively sampled at the end of 0 month, 1 month, 2 months, 3 months and 6 months, and the properties, the content, the dissolution rate and related substances are examined, wherein the dissolution rate is measured in phosphate buffer solution with pH 6.5, and the specific method refers to the nitroglycerin sublingual tablet dissolution method published by FDA dissolution database; the characters, contents and related substances are tested according to a corresponding detection method under the item of the second nitroglycerin tablets in the 'Chinese pharmacopoeia' 2020 edition, and specific results are shown in the following tables 2 to 5, wherein the dissolution rates in the following tables 2 to 5 are all the results of sampling detection at 8 min.

Wherein the structural formulas of the impurity A and the impurity B are as follows:

table 2 accelerated test results of nitroglycerin tablets obtained in example 2

TABLE 3 accelerated test results for the American original formulation

As can be seen from the data in table 2 and table 3 above, the quality attributes of the nitroglycerin tablets prepared by the preparation method of nitroglycerin tablets provided by the present invention have no significant change under the accelerated test conditions, and although the related substances are slightly increased, the increase is significantly lower than that of the original preparation in the united states, which indicates that the nitroglycerin tablets provided by the present invention have more excellent stability.

Similarly, in order to verify the stability of the nitroglycerin tablets obtained in other examples, the above tests were carried out on the nitroglycerin tablets obtained in example 1 and examples 3 to 7, respectively, in the same manner as described above; through tests, the test results of the test items of the nitroglycerin tablets prepared in the example 1 and the examples 3-7 are consistent with the overall trend of the test result of the example 2, and the increase of related substances is obviously lower than that of the original American developer, so that the nitroglycerin tablets provided by the invention are high in stability.

Table 4 accelerated test results of comparative example 1

TABLE 5 accelerated test results of comparative example 2

As can be seen from the data in table 2, table 4 and table 5 above, the quality attributes of the tablets prepared by the preparation method of the nitroglycerin tablets provided by the present invention are significantly better than those of comparative example 1 and comparative example 2 under the accelerated test conditions, which indicates that the method of combining the first diluent with the production process adopted by the present invention has a significant stabilizing effect on the quality of the nitroglycerin tablets.

The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents or improvements made within the spirit and principle of the present invention should be included in the scope of the present invention.

Claims

1. The nitroglycerin tablet is characterized by comprising nitroglycerin, a first diluent, a stabilizer, a glidant, a disintegrant and a lubricant;

2. The nitroglycerin tablet of claim 1, wherein a mass ratio of the nitroglycerin to the first diluent is 1:40 to 50.

3. The nitroglycerin tablet of claim 1, further comprising a second diluent, wherein the second diluent is granular lactose or ground lactose.

4. The nitroglycerin tablet of claim 3, wherein the content of the second diluent is 2 wt% to 8 wt%.

5. The nitroglycerin tablet of claim 1, further comprising a third diluent, wherein the third diluent is particulate lactose.

6. The nitroglycerin tablet of claim 5, wherein the content of the third diluent is 5 wt% to 10 wt%.

7. The nitroglycerin tablet according to any one of claims 1 to 6, wherein the content of the stabilizer is 1% by weight to 2% by weight; and/or

The content of the glidant is 0.1 to 0.5 percent by weight; and/or

The content of the disintegrating agent is 10-15 wt%; and/or

The content of the lubricant is 0.5 wt% to 1.0 wt%.

8. A method for preparing nitroglycerin tablets according to any one of claims 1 to 7, comprising the steps of:

mixing an ethanol solution of 9% -11% nitroglycerin with a first diluent, drying, and finishing granules to obtain a first mixture;

mixing the stabilizer and the glidant, crushing and sieving to obtain a second mixture;

9. The method of making nitroglycerin tablets of claim 8, further comprising the step of mixing a second diluent with the stabilizer and the glidant.

10. The method of preparing nitroglycerin tablets according to claim 8 or 9, further comprising a step of mixing a third diluent with the first mixture, the second mixture, and a disintegrant.