A torasemide tablet and a preparation method thereof

Abstract

The application relates to the technical field of medicine production, and particularly discloses a torasemide tablet and a preparation method thereof. The torasemide tablet comprises the following components in parts by weight: 4.2-4.6 parts of torasemide microcapsules, 0.42-0.46 parts of lactase, 12.4-12.8 parts of lactose, 3-5 parts of hydroxypropyl methyl cellulose, 2.2-2.4 parts of ethyl cellulose, 0.4-0.6 parts of sodium dodecyl sulfate, 1.4-1.8 parts of magnesium stearate, 2.6-3.4 parts of talc, the torasemide microcapsules comprise a capsule wall and a capsule core, the components of the capsule wall comprise calcium alginate, and the components of the capsule core comprise torasemide. The lactase is used for promoting the hydrolysis of lactose in the intestinal tract, the possibility of gastrointestinal function disorder of a lactose-intolerant medicine taker after taking medicine is reduced, and the medicine taker is favorable for torasemide absorption.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of medicine production, and more particularly to a torasemide tablet and a preparation method thereof. BACKGROUND

[0002] Torasemide is a kind of antihypertensive drug, which has certain curative effect on hypertension, heart and kidney failure, liver ascites, diabetes insipidus and the like. At present, torasemide is mainly produced and sold in the form of tablets. According to the treatment principle of WHO, antihypertensive drugs should be able to be taken for a long time and need to have a stable antihypertensive effect, which requires that the torasemide tablet needs to have a certain sustained-release effect.

[0003] In the related art, there is a sustained-release tablet containing torasemide active ingredient, which includes the following components by weight: torasemide 1 g, lactose 15 g, hydroxypropyl methylcellulose 2 g, ethyl cellulose 1 g, sodium dodecyl sulfate 0.5 g, and also includes appropriate amounts of water, magnesium stearate and talc.

[0004] In view of the above-mentioned related art, the inventors believe that although the related art provides a sustained-release tablet containing torasemide active ingredient, the tablet contains a large amount of lactose. For patients with lactose intolerance, the lactose in the sustained-release tablet can induce gastrointestinal dysfunction after taking the sustained-release tablet, thereby affecting the absorption of torasemide in the intestinal tract. If lactase is added to the sustained-release tablet, the disintegration of the sustained-release tablet may be accelerated, which can cause a large amount of torasemide to be released, thereby easily causing adverse reactions. SUMMARY

[0005] For patients with lactose intolerance, taking the torasemide tablet in the related art can easily cause gastrointestinal dysfunction, thereby affecting the absorption of torasemide in the intestinal tract. If lactase is added to the sustained-release tablet, the disintegration of the sustained-release tablet may be accelerated, which can cause a large amount of torasemide to be released, thereby easily causing adverse reactions. In order to improve this defect, the present application provides a torasemide tablet and a preparation method thereof.

[0006] In a first aspect, the present application provides a torasemide tablet, which adopts the following technical solution:

[0007] A torasemide tablet, which includes the following components by weight: torasemide microcapsules 4.2-4.6 parts, lactase 0.42-0.46 parts, lactose 12.4-12.8 parts, hydroxypropyl methylcellulose 3-5 parts, ethyl cellulose 2.2-2.4 parts, sodium dodecyl sulfate 0.4-0.6 parts, magnesium stearate 1.4-1.8 parts, and talc 2.6-3.4 parts. The torasemide microcapsules include a capsule wall and a capsule core. The components of the capsule wall include calcium alginate, and the components of the capsule core include torasemide.

[0008] By adopting the technical scheme, the lactase is added in the torasemide tablet together with the lactose, the lactase can promote the hydrolysis of lactose, which helps to reduce the possibility of lactose inducing gastrointestinal dysfunction, and is beneficial to the absorption of torasemide by the intestinal tract of the drug taker. While adding the lactase, the torasemide is stored in the microcapsule structure, and the microcapsule structure is used to realize the slow release of torasemide.

[0009] After the drug taker takes the torasemide tablet, the lactose does not hydrolyze in the stomach, and thus the lactose can block the gastric acid, reducing the possibility of inactivation of lactase in the gastric juice. In the intestinal tract of the drug taker, the lactose is hydrolyzed under the action of lactase, and the hydrolysis product of lactose is easily decomposed by intestinal flora into various organic acids including lactic acid, which can temporarily reduce the pH in the surrounding of the torasemide tablet, thereby increasing the solubility of calcium alginate in the capsule wall of the torasemide microcapsule, and promoting the dissolution of calcium ions. With the dissolution of calcium alginate in the capsule wall, the core is gradually released, thereby realizing the slow release of torasemide. In addition, in the acidic environment produced by the organic acids, the solubility of torasemide also increases, which is beneficial to the absorption of torasemide by the intestinal tract.

[0010] Preferably, the torasemide tablet comprises the following components by weight: 4.3-4.5 parts of torasemide microcapsule, 0.43-0.45 parts of lactase, 12.5-12.7 parts of lactose, 3.5-4.5 parts of hydroxypropyl methyl cellulose, 2.2-2.4 parts of ethyl cellulose, 0.4-0.6 parts of sodium dodecyl sulfate, 1.4-1.8 parts of magnesium stearate, and 2.6-3.4 parts of talc.

[0011] By adopting the technical scheme, the raw material ratio of the torasemide tablet is optimized, the slow release effect is realized, and the stimulation of lactose to the gastrointestinal tract is reduced, which is beneficial to the absorption of torasemide by the drug taker with lactose intolerance.

[0012] Preferably, the torasemide microcapsule is prepared by the following method:

[0013] (1) Sodium alginate is added to the base solution to obtain solution A; water-soluble calcium salt is added to the base solution to obtain solution B; in this step, the components of the base solution include water;

[0014] (2) The torasemide powder is mixed with solution A, and a torasemide suspension is obtained after adjusting the pH with an acidifying agent;

[0015] (3) The torasemide suspension is sprayed into the calcium salt aqueous solution through the nozzle of a spray dryer, and after standing for 1-2 h, filtration is performed, the filtrate is removed, and after drying, torasemide microcapsules are obtained.

[0016] By adopting the technical scheme, the solution A containing sodium alginate and the solution B containing calcium ions are prepared respectively, then the torasemide powder is mixed with the solution A, and the torasemide powder is coated with the calcium alginate gel by the reaction between sodium alginate and calcium ions, and the torasemide-containing capsule core and the calcium alginate-containing capsule wall are obtained after the calcium alginate gel is solidified and dried, and the torasemide microcapsule is prepared.

[0017] Preferably, in the step (2) of preparing the torasemide microcapsule, the pH value of the obtained torasemide suspension is 2.8-3.2.

[0018] By adopting the technical scheme, when the pH value of the torasemide suspension is 2.8-3.2, the viscosity of sodium alginate is relatively large, the suspension effect of the torasemide powder is good, and the torasemide powder is not easy to settle and aggregate, which is beneficial to the molding of the torasemide microcapsule. Meanwhile, under this condition, the torasemide is more easily dissolved than in a neutral environment, the dissolved torasemide is captured by the calcium alginate gel, and the calcium alginate and the torasemide jointly form the capsule wall. The torasemide in the capsule wall can enter the intestinal tract of the drug taker before the capsule core is completely released, and the effective time of the torasemide is accelerated.

[0019] Preferably, in the step (2) of preparing the torasemide microcapsule, the release aid is also mixed with the torasemide powder and the solution A, and the release aid is a polyhydroxy compound.

[0020] By adopting the technical scheme, when the release aid is mixed with the torasemide powder and the solution A, the release aid can be adsorbed to the polar groups of the torasemide powder through the hydroxyl groups, and the release aid and the torasemide powder are combined to form the capsule core. The adsorption of the release aid makes the torasemide in the capsule core more stable when dissolved, and the release effect of the torasemide is improved.

[0021] Preferably, the release aid is at least one of carboxymethyl starch and chitosan.

[0022] By adopting the technical scheme, the carboxymethyl starch and the chitosan both contain a large number of hydroxyl groups, and therefore can be used as the release aid. The carboxyl groups in the carboxymethyl starch can also be combined with calcium ions, so that the combination degree between the capsule wall and the capsule core is strengthened, and the duration of the torasemide efficacy is further prolonged. The chitosan can inhibit the activity of lactic acid bacteria in the intestinal tract, so that the lactic acid bacteria cannot timely consume the hydrolysis product of lactose to generate lactic acid and other organic acids, and the dissolution rate of the capsule wall of the torasemide microcapsule is slowed down, which also helps to further prolong the duration of the torasemide efficacy.

[0023] When the carboxymethyl starch and the chitosan are used together, a part of the protonated amino groups in the chitosan also electrostatically adsorb the carboxymethyl starch, so that the adsorption force between the carboxymethyl starch and the torasemide is weakened, and the torasemide is easier to release, which helps to improve the blood drug concentration of the torasemide.

[0024] As a preference, the acidifying agent is citric acid.

[0025] By adopting the technical scheme, when the release aid is chitosan, the citrate ions ionized from the citric acid can electrostatically adsorb the protonated amino groups in the chitosan and the protonated amine groups in the torasemide molecules, so that the adsorption of the chitosan to the torasemide is strengthened, and the duration of the torasemide efficacy is prolonged.

[0026] As a preference, in the step (1) of preparing the torasemide microcapsule, the base solution is a saturated solution of torasemide.

[0027] By adopting the technical scheme, when the saturated solution of torasemide is used as the base solution, in the prepared solution A and solution B, the torasemide is in a saturated state, and when the solution A and the solution B are mixed, the calcium alginate gel generated adsorbs the torasemide originally dissolved in the base solution and the torasemide newly dissolved due to acidification, so that the content of the torasemide in the capsule wall is increased, which helps to increase the content of the effective ingredient of the torasemide tablet. In addition, using the saturated solution of torasemide as the base solution can limit the dissolution amount of the torasemide powder, and reduce the possibility of excessive dissolution of the torasemide powder in the suspended state.

[0028] As a preference, the torasemide powder is obtained by grinding torasemide crystal form I.

[0029] By adopting the technical scheme, when the torasemide in the capsule wall recrystallizes during the drying process, the torasemide powder in the capsule core can induce the crystallization process of the torasemide from the inside of the capsule wall, and the generation of torasemide crystal form II is reduced. Torasemide crystal form I and crystal form II have different dissolution rates, and the already generated torasemide crystal form I will not spontaneously convert into crystal form II, so the induction of the torasemide crystal form I reduces the difference in the dissolution rate of the torasemide between different tablets of the same batch, which helps to improve the stability of the torasemide tablet administration rate.

[0030] In a second aspect, the application provides a preparation method of a torasemide tablet, which adopts the following technical scheme.

[0031] A preparation method of a torasemide tablet, comprising the following steps:

[0032] (1) The torasemide microcapsule, lactase, lactose, hydroxypropyl methyl cellulose, ethyl cellulose, and sodium dodecyl sulfate are mixed and sieved to obtain a mixed dry material;

[0033] (2) The mixed dry material is mixed with ethanol, sieved, granulated, and then dried to obtain precursor granules;

[0034] (3) The precursor granules, magnesium stearate, and talc powder are mixed and tableted to obtain torasemide tablets.

[0035] By using the above technical solution, the torasemide microcapsule, lactase, lactose, hydroxypropyl methyl cellulose, ethyl cellulose, and sodium dodecyl sulfate are first prepared into precursor granules, and then the precursor granules, magnesium stearate, and talc powder are mixed and tableted to obtain torasemide tablets with a slow-release function and suitable for lactose-intolerant people.

[0036] In summary, the present application has the following advantages:

[0037] 1. The present application uses lactase to promote the hydrolysis of lactose in the intestinal tract, reducing the possibility of gastrointestinal dysfunction in lactose-intolerant drug users, and facilitating the absorption of torasemide by the drug users. At the same time, the hydrolysis products of lactose produce various organic acids under the action of intestinal flora, causing the pH around the torasemide tablets to temporarily decrease, and the acidic environment causes the calcium alginate in the capsule wall to gradually dissolve, achieving the slow release of torasemide.

[0038] 2. In the present application, the torasemide powder is obtained by grinding torasemide crystal form I. When the torasemide in the capsule wall recrystallizes during the drying process, the torasemide powder in the capsule core can induce the crystallization process of torasemide from the inside of the capsule wall, reducing the generation of torasemide crystal form II. The already generated torasemide crystal form I will not spontaneously convert to crystal form II, thereby reducing the difference in torasemide dissolution rate between different tablets of the same batch, and helping to improve the stability of the torasemide tablet administration rate.

[0039] 3. The method of the present application first prepares torasemide microcapsules, lactase, lactose, hydroxypropyl methyl cellulose, ethyl cellulose, and sodium dodecyl sulfate into precursor granules, and then mixes the precursor granules, magnesium stearate, and talc powder, and tablets to obtain torasemide tablets with a slow-release function and suitable for lactose-intolerant people. DETAILED DESCRIPTION

[0040] The present application is further described in detail below in conjunction with examples, preparation examples, and comparative examples. The raw materials involved in the present application can be obtained through commercial channels.

[0041] Preparation example of torasemide microcapsule

[0042] The following is illustrated by way of example of Preparation Example 1.

[0043] Preparation Example 1

[0044] In this preparation example, the torasemide microcapsules are prepared according to the following method:

[0045] (1) Sodium alginate is added to the base solution to obtain solution A with a sodium alginate concentration of 2 wt%; water-soluble calcium salt is added to the base solution to obtain solution B with a calcium ion concentration of 1 mol / L; in this step, the base solution is deionized water, and the water-soluble calcium salt is calcium chloride;

[0046] (2) Torasemide powder is mixed with solution A at a weight ratio of 1:8, and a torasemide suspension is obtained after adjusting the pH to 3.4 using an acidifying agent; in this step, the torasemide powder is obtained by grinding torasemide Form II, and the acidifying agent is acetic acid;

[0047] (3) At an air speed of 500 L / h, the feed speed of the spray dryer is set to 2 mL / min, and the torasemide suspension is sprayed into the calcium salt aqueous solution through the nozzle of the spray dryer, and after standing for 1.5 h, filtration is performed, the filtrate is removed, and torasemide microcapsules are obtained after drying at 50°C.

[0048] As shown in Table 1, the differences between Preparation Examples 1-5 are that in step (2) of preparing the torasemide microcapsules, the pH value of the obtained torasemide suspension is different.

[0049] Table 1

[0050] Sample Preparation Example 1 Preparation Example 2 Preparation Example 3 Preparation Example 4 Preparation Example 5 pH of torasemide suspension 3.4 3.2 3.0 2.8 2.6

[0051] Preparation Example 6

[0052] The difference between this preparation example and Preparation Example 3 is that in step (2) of preparing the torasemide microcapsules, a release aid is also mixed with the torasemide powder and solution A, and the release aid is carboxymethyl starch.

[0053] Preparation Example 7

[0054] The difference between this preparation example and Preparation Example 6 is that the release aid is chitosan.

[0055] Preparation Example 8

[0056] The difference between this preparation example and Preparation Example 7 is that the release aid is a mixture of chitosan and carboxymethyl starch at a weight ratio of 1:1.

[0057] Preparation Example 9

[0058] The difference between this preparation example and Preparation Example 7 is that the acidifying agent is citric acid.

[0059] Preparation Example 10

[0060] The difference between this preparation example and Preparation Example 1 is that the base solution is a saturated aqueous solution of torasemide.

[0061] Preparation Example 11

[0062] The difference between this preparation example and Preparation Example 1 is that the torasemide powder is obtained by grinding torasemide Form I.

[0063] Example

[0064] Examples 1-5

[0065] The following is described by taking Example 1 as an example.

[0066] Example 1

[0067] In this example, each torasemide tablet comprises the following components by weight: torasemide microcapsules 4.2 g, lactase 0.42 g, lactose 12.4 g, hydroxypropyl methylcellulose 3 g, ethyl cellulose 2.2 g, sodium dodecyl sulfate 0.4 g, magnesium stearate 1.4 g, talc 2.6 g. Among them, the torasemide microcapsules are prepared according to the method of Preparation Example 1.

[0068] In this example, the torasemide tablet is prepared according to the following steps:

[0069] (1) The torasemide microcapsules, lactase, lactose, hydroxypropyl methylcellulose, ethyl cellulose, and sodium dodecyl sulfate are mixed and then passed through a 100-mesh sieve for use, to obtain a mixed dry material;

[0070] (2) The mixed dry material is mixed with ethanol according to a weight ratio of 10:1, and then granulated through a 20-mesh sieve, followed by drying, and then the granules are passed through a 20-mesh sieve to obtain precursor granules;

[0071] (3) The precursor granules, magnesium stearate, and talc are mixed and then subjected to tabletting processing to obtain torasemide tablets.

[0072] As shown in Table 2, the main difference between Examples 1-5 is the different proportions of raw materials of the torasemide tablets.

[0073] Table 2

[0074]

[0075] Examples 6-15

[0076] As shown in Table 3, the difference between Example 3 and Examples 6-15 is that the preparation examples of the torasemide microcapsules are different.

[0077] Table 3

[0078]

[0079]

[0080] Comparative Example

[0081] Comparative Example 1

[0082] The present comparative example provides a sustained-release tablet containing a torasemide active ingredient, which comprises the following components by weight: torasemide 1 g, lactose 15 g, hydroxypropyl methylcellulose 2 g, ethyl cellulose 1 g, sodium dodecyl sulfate 0.5 g, magnesium stearate 1.6 g, talc 3 g.

[0083] The present comparative example also provides a method for preparing a sustained-release tablet containing a torasemide active ingredient, which comprises the following steps:

[0084] (1) Mix torasemide, lactose, hydroxypropyl methylcellulose, ethyl cellulose, and sodium dodecyl sulfate, and pass through a 100-mesh sieve to obtain a mixture of dry materials;

[0085] (2) Mix the mixture of dry materials with ethanol at a weight ratio of 10:1, then granulate by passing through a 20-mesh sieve, dry, and pass through a 20-mesh sieve to obtain precursor granules;

[0086] (3) Mix the precursor granules, magnesium stearate, and talc, and then perform tabletting to obtain torasemide tablets.

[0087] Comparative Example 2

[0088] The present comparative example differs from Example 3 in that the torasemide microcapsules are replaced with torasemide (crystal form I).

[0089] Performance detection test method

[0090] Beagle dogs with lactose intolerance symptoms and close body weights (within ±3 g of the body weight difference between different individuals) were taken, and the beagle dogs were divided into groups and orally administered tablets of Examples 1-15 and Comparative Examples 1-2 in equal amounts. Then, the blood of the beagle dogs was drawn every 60 min, and 0.5 mL of serum was separated by centrifugation after each blood draw. The concentration of torasemide in the serum was detected until the concentration of torasemide was 0 for three consecutive times. During the test, it was recorded whether the beagle dogs in the corresponding group had diarrhea.

[0091] The data measured were statistically analyzed, and the time t1 at which the concentration of torasemide in the serum of the beagle dogs began to rise, the average time t2 at which the peak value appeared, and the time t3 at which the concentration returned to 0 for the first time after the peak value was detected were recorded. For beagle dogs taking the same type of tablets, the average value of t1 was taken to obtain T1, the average value of t2 was taken to obtain T2, and the average value of t3 was taken to obtain T3. The values of T1, T2, and T3 are shown in Table 4.

[0092] The maximum value in the peak data of the concentration of torasemide is denoted as D0, then the ratio of the peak value of the concentration of torasemide in the serum of each beagle dog to D0 is calculated, and then the average value M of the ratio of the same group of samples is calculated, and the result is expressed in percentage, as shown in Table 4.

[0093] Table 4

[0094] Sample T1 / min T2 / min T3 / min M / ％ Diarrhea or not Example 1 17 314 2340 46.8 No Example 2 18 316 2336 47.1 No Example 3 18 317 2348 47.0 No Example 4 17 315 2345 46.9 No Example 5 17 316 2344 47.0 No Example 6 15 315 2345 46.7 No Example 7 12 313 2344 46.6 No Example 8 12 314 2346 46.6 No Example 9 11 316 2341 46.7 No Example 10 24 331 2408 42.6 No Example 11 35 389 2642 34.5 No Example 12 22 319 2386 43.5 No Example 13 38 352 2675 32.6 No Example 14 13 297 2572 51.2 No Example 15 15 305 2316 49.3 No Comparative Example 1 18 245 546 22.6 Yes Comparative Example 2 8 152 1632 100.0 No

[0095] It can be seen from Examples 1-5 and Comparative Example 1 in combination with Table 4 that T1 measured in Examples 1-5 is close to that of Comparative Example 1, T2 and T3 are both greater than that of Comparative Example 1, and M measured in Examples 1-5 is much greater than that of Comparative Example 1, indicating that the beagle dogs in Examples 1-5 absorb more torasemide after taking the medicine, while the lactose in the tablets of Comparative Example 1 causes gastrointestinal dysfunction in beagle dogs and leads to diarrhea, shortening the residence time of the tablets in the beagle dogs' intestines and affecting the absorption of torasemide by beagle dogs.

[0096] It can be seen from Example 3 and Comparative Example 2 in combination with Table 4 that T1, T2 and T3 measured in Example 3 are all greater than those of Comparative Example 2, and the M value is less than that of Comparative Example 2, indicating that after the addition of lactase in Comparative Example 2, the hydrolysis of lactose by lactase speeds up the disintegration of the tablets, leading to the release of torasemide too quickly and a shortened duration of drug effect, making it difficult to achieve a good sustained-release effect.

[0097] It can be seen from Example 3 and Examples 6-9 in combination with Table 4 that as the pH value of the torasemide suspension in the preparation decreases, the value of T1 decreases, indicating that the solubility of torasemide is increasing. In the finally formed capsule wall, the recrystallized torasemide after dissolution increases, causing the time of torasemide release to be advanced. Considering that the viscosity of the torasemide suspension is too large when the pH value is 2.6, increasing the difficulty of preparing microcapsules, therefore, the preferred pH value is 2.8-3.2.

[0098] It can be seen from Example 7, Example 10 in combination with Table 4 that T1, T2 and T3 measured in Example 10 are all greater than those of Example 7, and the M value is less than that of Example 7, indicating that carboxymethyl starch can be adsorbed by the polar groups of torasemide powder through the hydroxyl groups, and the carboxyl groups in carboxymethyl starch can also be combined with calcium ions, thereby strengthening the bonding degree between the capsule wall and the capsule core, slowing down the release speed of torasemide and prolonging the duration of the drug effect of torasemide.

[0099] It can be seen from the combination of Example 10, Example 11 and Table 4 that the T1, T2 and T3 measured in Example 11 are all greater than those in Example 10, and the M value is less than that in Example 10, indicating that the chitosan inhibits the activity of the lactic acid bacteria in the intestines of the beagle dogs, reduces the efficiency of the lactic acid bacteria in consuming the hydrolysis product of lactose to generate lactic acid and other organic acids, and slows down the dissolution rate of the capsule wall of the torasemide microcapsule, thereby prolonging the duration of the efficacy of torasemide.

[0100] It can be seen from the combination of Example 10-12 and Table 4 that the T1, T2 and T3 measured in Example 12 are less than those in Example 10-11, and the M value is greater than that in Example 10-11, indicating that the carboxymethyl starch and citric acid are both electrostatically adsorbed with the protonated amino groups in the chitosan, which weakens the binding effect between the chitosan and the cell membrane of the lactic acid bacteria, thereby reducing the inhibitory effect of the chitosan on the metabolism of the lactic acid bacteria, which is conducive to the further decomposition of the hydrolysis product of lactose into lactic acid by the lactic acid bacteria in the intestines of the drug taker, and also weakens the adsorption force between the carboxymethyl starch and torasemide, thereby improving the peak blood drug concentration of torasemide.

[0101] It can be seen from the combination of Example 11, Example 13 and Table 4 that the T1, T2 and T3 measured in Example 13 are all greater than those in Example 10, and the M value is less than that in Example 10, indicating that the anion generated by acetic acid cannot be adsorbed by both the chitosan and torasemide, while the citrate ion ionized from citric acid can be electrostatically adsorbed with both the protonated amino groups in the chitosan and the protonated amine groups in the torasemide molecule, thereby strengthening the adsorption of the chitosan on the torasemide and prolonging the duration of the efficacy of torasemide.

[0102] It can be seen from the combination of Example 3, Example 14 and Table 4 that the T1 and T2 measured in Example 14 are less than those in Example 3, while the T3 is greater than that in Example 3, and the M value is also greater than that in Example 3, indicating that the content of torasemide in the capsule wall is higher in the torasemide microcapsule in Example 14, thereby increasing the content of the effective ingredient of the torasemide tablet.

[0103] It can be seen from the combination of Example 3, Example 15 and Table 4 that the T1, T2 and T3 measured in Example 14 are all less than those in Example 3, while the M value is greater than that in Example 3, indicating that under the induction of torasemide crystal form I, the content of torasemide crystal form I in the torasemide microcapsule increases, and the dissolution rate of torasemide crystal form I is fast, thereby accelerating the onset speed of torasemide and improving the peak blood drug concentration of torasemide.

[0104] The embodiments are only illustrative of the present application, and are not intended to limit the present application, and those skilled in the art can make modifications to the embodiments without creative contribution after reading the specification, but as long as the modifications are within the scope of the claims of the present application, they are protected by the patent law.

Claims

1. A torasemide tablet, characterized by, The torasemide tablet comprises the following components in parts by weight: torasemide microcapsules 4.2-4.6 parts, lactase 0.42-0.46 parts, lactose 12.4-12.8 parts, hydroxypropyl methyl cellulose 3-5 parts, ethyl cellulose 2.2-2.4 parts, sodium dodecyl sulfate 0.4-0.6 parts, magnesium stearate 1.4-1.8 parts, talc 2.6-3.4 parts, the torasemide microcapsules comprising a capsule wall and a capsule core, the components of the capsule wall comprising calcium alginate, the components of the capsule core comprising torasemide; The torasemide microcapsules are prepared by the following method: (1) adding sodium alginate into a base solution to obtain solution A; adding a water-soluble calcium salt into the base solution to obtain solution B; in this step, the components of the base solution comprise water; (2) mixing torasemide powder with solution A, and using an acidifying agent to adjust the pH to obtain a torasemide suspension; in this step, the pH of the obtained torasemide suspension is 2.8-3.2; (3) spraying the torasemide suspension into the calcium salt aqueous solution through the nozzle of a spray dryer, standing for 1-2 h, then filtering, removing the filtrate, and drying to obtain torasemide microcapsules.

2. The torasemide tablet according to claim 1, characterized by, The torasemide tablet comprises the following components in parts by weight: torasemide microcapsules 4.3-4.5 parts, lactase 0.43-0.45 parts, lactose 12.5-12.7 parts, hydroxypropyl methyl cellulose 3.5-4.5 parts, ethyl cellulose 2.2-2.4 parts, sodium dodecyl sulfate 0.4-0.6 parts, magnesium stearate 1.4-1.8 parts, talc 2.6-3.4 parts.

3. The torasemide tablet according to claim 1, characterized by, In step (2) of preparing the torasemide microcapsules, a sustained-release aid is also mixed with the torasemide powder and solution A, and the sustained-release aid is a polyhydroxy compound.

4. The torasemide tablet according to claim 3, characterized by, The sustained-release aid is at least one of carboxymethyl starch and chitosan.

5. The torasemide tablet according to claim 4, characterized in that, The acidifying agent is citric acid.

6. The torsemide tablet according to claim 1, wherein In step (1) of preparing the torasemide microcapsules, the base solution is a saturated solution of torasemide.

7. The torasemide tablet according to claim 6, characterized in that, The torasemide powder is obtained by grinding torasemide crystal form I.

8. Process for the preparation of torasemide tablets according to any one of claims 1 to 7, characterized in that, The method comprises the following steps: (1) mixing torasemide microcapsules, lactase, lactose, hydroxypropyl methyl cellulose, ethyl cellulose, and sodium dodecyl sulfate, and sieving to obtain mixed dry materials; (2) mixing the mixed dry materials with ethanol, sieving, granulating, and then drying to obtain precursor granules; (3) mixing the precursor granules, magnesium stearate, and talc, and then performing tabletting processing to obtain torasemide tablets.

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