CN115778912A

CN115778912A - Torasemide-containing tablet and preparation method thereof

Info

Publication number: CN115778912A
Application number: CN202111055458.3A
Authority: CN
Inventors: 唐海涛; 葛滨; 邱丹; 王蓓; 徐杰; 葛海涛
Original assignee: Suzhong Pharmaceutical Group Co ltd
Current assignee: Suzhong Pharmaceutical Group Co ltd
Priority date: 2021-09-09
Filing date: 2021-09-09
Publication date: 2023-03-14

Abstract

The invention relates to a tablet containing torasemide and a preparation method thereof, belonging to the field of pharmaceutical preparations. The torasemide-containing tablet provided by the invention comprises an active component torasemide, a filling agent, a disintegrating agent, a binding agent and a lubricating agent, wherein the active component torasemide, the filling agent, the disintegrating agent, the binding agent and the lubricating agent are respectively as follows by weight: 10 parts of torasemide, 133-148 parts of filler, 1-8.5 parts of disintegrant, 0.5-6.5 parts of adhesive and 0.5-2 parts of lubricant, wherein in the preparation process, the active component, part of filler, disintegrant and adhesive are mixed for granulation, and then the mixture is mixed with the rest of filler and lubricant for tabletting, and the tablets are scored tablets and can be taken by breaking into tablets according to clinical requirements. The formula of the invention has simple process and strong operability, and the prepared tablet has complete dissolution, stable quality and better chemical stability than the original product.

Description

Torasemide-containing tablet and preparation method thereof

Technical Field

The invention belongs to the field of pharmaceutical preparations, and particularly relates to a torasemide-containing tablet and a preparation method thereof.

Background

Diuretics are widely used clinically for treating various diseases such as heart, brain, liver, kidney, etc., and among them, diuretics are classified into three types of high, medium and low efficacy, and promote the excretion of electrolytes and water by acting on different parts of kidney, thus eliminating edema. Torasemide (torasemide) is a long-acting pyridine sulfonylurea type strong loop diuretic with the chemical name of N- [ [ (1-methylethyl) amino ] carbonyl ] -4- [ (3-methylphenyl) amino ] -3-pyridine sulfonylamide, the molecular weight is 348.43, the protein binding rate is up to 99%, the bioavailability is high, the effect is durable, and the adverse reaction is few.

Torasemide with diuretic and Na-excreting effects ⁺ And row of Cl ^- Without significantly altering glomerular filtration rate, renal plasma flux and acid-base balance. It acts on the thick ascending branch segment of the loop to interfere Na of the luminal cell membrane ⁺ -K ⁺ -2Cl ^- Co-rotating system, cl suppression ^- And Na ⁺ The reabsorption of the medicine can increase the concentration of NaCl in the tube fluid, increase the osmotic pressure, reduce NaCl in the renal medullary interstitial fluid and lower the osmotic pressure gradient, thus interfering the concentration process of urine and leading the urine to have Na ⁺ 、Cl ^- And increased excretion of water, exerting diuretic effect; while inhibiting prostaglandin degrading enzyme activity. Increase prostaglandin E (PGE 2) and prostacyclin (PGI 2) concentrations in plasma, compete for antagonism of the vasoconstricting effects of thromboxane A2 (TXA 2) and TXB 2. In addition, torasemide can also inhibit aldosterone secretion, inhibit aldosterone binding with receptor in renal tubular cell cytoplasm, and reduce aldosterone activity, and has sodium-retaining and sodium-expelling effectsThe effect of potassium.

Torasemide is a new drug for the diuretic of the pyridine sulfonylurea loop developed in 1973 by a.christiae societe anonyme (belgium), which was first approved for the market in belgium (first global market) in 1987.04.14, approval specification 2.5mg, trade name: torrem; authorized company, MEDA PHARMS, for the treatment of hypertension, 1991.12.13 supplement specification 10mg, for the treatment of cardiac, hepatic, renal edema. Both of these specifications are currently used for the treatment of hypertension and edema. Subsequently, the original preparation is marketed in several countries, approved specifications are 2.5mg, 5mg, 10mg, 50mg, 200mg, and mainly used for the treatment of hypertension and edema diseases, including nephrotic syndrome, renal insufficiency.

In addition, patent CN100548297C discloses a sustained release pellet containing torasemide active ingredient, which is composed of a drug-containing pellet and a controlled release layer, wherein the drug-containing pellet comprises: 0.5-10% of torasemide, 20-90% of filling agent, 1-25% of adhesive and 1-10% of lubricant, wherein the slow release layer comprises: 0.5-15% of retarder, 0.1-5% of pore-forming agent, 0.1-5% of plasticizer and 0.2-10% of antisticking agent. Patent CN101632665B discloses a torasemide oral pharmaceutical composition, wherein the torasemide taste masking composition is 50%, microcrystalline cellulose 35%, croscarmellose sodium 7%, mannitol 6.75%, orange essence 0.25%, magnesium stearate 1%, the weight ratio of torasemide to mannitol, gelatin, aspartame in the torasemide taste masking composition is 1. Patent CN107157994A discloses a sublingual oral preparation of torasemide, which comprises the following raw materials in parts by weight: 15-35 parts of torasemide, 30-80 parts of penetration enhancer, 35-55 parts of disintegrating agent and 150-200 parts of filler. However, the stability and dissolution of the pharmaceutical preparation of torasemide are found to be poor.

At present, the approved specifications of the domestic torasemide tablets are 5mg, 10mg and 20mg specifications, and are mainly used for treating: (1) essential hypertension; (2) Cardiac edema, hepatic edema, pulmonary edema, renal edema, nephrotic syndrome, and renal insufficiency. The initial dose for treating the primary hypertension is 5mg, while most of the torasemide tablets sold in the market are in the specification of 10mg, and the requirement of the initial dose of 5mg for treating the primary hypertension in clinic cannot be met. In addition, the medicine is often required to be divided into two parts for taking by special people such as the old, the liver and kidney dysfunction and the like, but the defect of inaccurate taking dosage is caused by uneven division because of no special dividing instrument.

Therefore, there is a need to develop a scored tablet that has good dissolution and stability and can accurately divide the dose.

Disclosure of Invention

In order to solve the above problems in the prior art, the present application provides a torasemide pharmaceutical composition and a preparation method thereof. The torasemide pharmaceutical composition comprises the active component torasemide, a filling agent, a disintegrating agent, an adhesive and a lubricating agent, has better stability and dissolution, and can be prepared into scored tablets, so that the dosage can be accurately divided no matter a mechanical dividing mode or direct manual breaking is adopted, and the clinical medication requirement can be met.

In order to achieve the above object, the present invention provides the following technical solutions:

on one hand, the invention provides a torasemide pharmaceutical composition which comprises the following components in parts by weight: 2 to 18 parts, in some embodiments 5 to 15 parts, in some embodiments 8 to 12 parts, in some embodiments 10 parts, of torasemide; fillers 125-155 parts, in some embodiments 130-150 parts, in some embodiments 131.5-149.5 parts, in some embodiments 133-148 parts; 0-10 parts, in some embodiments 0-9.5 parts, in some embodiments 0.5-9 parts, in some embodiments 1-8.5 parts of a disintegrant; 0-10 parts, in some embodiments 0.2-0.8 parts, in some embodiments 0.4-7 parts, in some embodiments 0.5-6.5 parts of binder; alternatively, the lubricant may be present in an amount of 0.1 to 5 parts, in some embodiments 0.2 to 4 parts, in some embodiments 0.3 to 3 parts, and in some embodiments 0.5 to 2 parts.

In some embodiments, the filler is one or more of lactose monohydrate, mannitol, pregelatinized starch, microcrystalline cellulose, corn starch.

In some embodiments, the filler is lactose monohydrate and microcrystalline cellulose in a weight ratio of 0.2-10, in some embodiments 0.4-5, in some embodiments 1-2.

In some embodiments, the disintegrant is one or more of sodium carboxymethyl starch, croscarmellose sodium, and crospovidone, and in some embodiments is crospovidone.

In some embodiments, the binder is one or more of hydroxypropyl cellulose or hypromellose, and in some embodiments, is hydroxypropyl cellulose.

In some embodiments, the lubricant is one or more of magnesium stearate, sodium stearyl fumarate, talc, and in some embodiments magnesium stearate.

In some embodiments, the pharmaceutical composition further comprises pharmaceutically acceptable excipients including, but not limited to, one or more of carriers, excipients, binders, fillers, glidants, flavoring agents, sweeteners, disintegrants, dispersants, surfactants, lubricants, colorants, diluents, solubilizers, wetting agents, plasticizers, stabilizers, permeation enhancers, wetting agents, antifoaming agents, antioxidants, preservatives.

In another aspect, the invention provides a torasemide tablet, which comprises the following components in parts by weight: 2 to 18 parts, in some embodiments 5 to 15 parts, in some embodiments 8 to 12 parts, in some embodiments 10 parts, of torsemide; fillers 125-155 parts, in some embodiments 130-150 parts, in some embodiments 131.5-149.5 parts, in some embodiments 133-148 parts; 0-10 parts, in some embodiments 0-9.5 parts, in some embodiments 0.5-9 parts, in some embodiments 1-8.5 parts of a disintegrant; 0-10 parts, in some embodiments 0.2-8 parts, in some embodiments 0.4-7 parts, in some embodiments 0.5-6.5 parts of binder; alternatively, the lubricant may be present in an amount of 0.1 to 5 parts, in some embodiments 0.2 to 4 parts, in some embodiments 0.3 to 3 parts, and in some embodiments 0.5 to 2 parts.

In some embodiments, the tablet is a scored tablet; the scored tablet is single-sided scored or double-sided scored.

In some embodiments, the filler is lactose monohydrate and microcrystalline cellulose in a weight ratio of 0.2 to 10, in some embodiments 0.4 to 5, in some embodiments 1 to 2.

In some embodiments, the tablet further comprises pharmaceutically acceptable excipients including, but not limited to, one or more of carriers, excipients, binders, fillers, glidants, flavoring agents, sweeteners, disintegrants, dispersants, surfactants, lubricants, colorants, diluents, solubilizers, wetting agents, plasticizers, stabilizers, permeation enhancers, wetting agents, anti-foaming agents, antioxidants, preservatives.

In another aspect, the invention provides the use of the pharmaceutical composition or tablet in preparing a diuretic.

In some embodiments, the diuretic is for the treatment of hypertension and edematous diseases.

In some embodiments, the diuretic is for the treatment of nephrotic syndrome or renal insufficiency.

In another aspect, the present invention provides a method for preparing the above torasemide pharmaceutical composition or tablet, comprising the steps of:

(1) Pre-mixing: mixing torasemide with 0-100% of filler, adhesive and disintegrant;

(2) And (3) wet granulation: adding purified water to prepare a soft material, sieving and granulating to prepare wet granules;

(3) Drying, granulating and mixing: drying the wet granules, sieving, grading, optionally adding the rest filler and lubricant, and mixing;

(4) Adjusting hardness and tabletting.

In some embodiments, the filler is one or more of lactose monohydrate, mannitol, pregelatinized starch, microcrystalline cellulose, corn starch, and in some embodiments, lactose monohydrate and microcrystalline cellulose; the disintegrant is one or more of sodium carboxymethyl starch, croscarmellose sodium, and crospovidone, and in some embodiments is crospovidone; the adhesive is one or two of hydroxypropyl cellulose or hydroxypropyl methylcellulose, and in some embodiments, is hydroxypropyl cellulose; the lubricant is one or more of magnesium stearate, sodium stearyl fumarate, and talc, and in some embodiments, magnesium stearate.

In some embodiments, the filler in step (1) is lactose monohydrate and 50-75% microcrystalline cellulose and the filler in step (3) is 25-50% microcrystalline cellulose. .

In some embodiments, the wet granulation described in step (2) may be performed using a wet granulator or a fluid bed, and in some embodiments, fluid bed granulation may be used.

In some embodiments, the drying described in step (3) may be performed using forced air drying or a fluidized bed, in some embodiments fluidized bed drying; the moisture of the dried granules is controlled to within 5%, and in some embodiments within 3%.

In some embodiments, the pressed scored sheet described in step (4) has a single-sided score or a double-sided score; the hardness is controlled to be 50-90N, in some embodiments 60-80N.

In another aspect, the invention provides a pharmaceutical composition or tablet of torasemide, which is prepared according to the preparation method.

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

(1) The torasemide pharmaceutical composition provided by the invention has the advantages of good stability and dissolution rate, simple preparation process, low energy consumption and easiness in realization of continuous production.

(2) The torasemide tablet prepared by the preparation method can accurately divide the dose no matter a mechanical division mode is adopted or the torasemide tablet is directly broken by hands, and meets the requirement of clinically treating the initial 5mg dose of primary hypertension and the medication requirements of special people such as the old, the liver and kidney dysfunction and the like.

Detailed Description

The present invention will be further illustrated in detail with reference to the following specific examples, which are not intended to limit the present invention but are merely illustrative thereof. The experimental methods used in the following examples, unless otherwise specified, and experimental methods not specified in specific conditions in the examples, are generally commercially available according to conventional conditions, and materials, reagents, and the like used in the following examples, unless otherwise specified.

Example 1 Torasemide tablet and method for preparing the same

1. The composition of the single dose formulation is shown in table 1 below.

TABLE 1

Composition (I)	Single dose (mg)
		Torasemide	10
Lactose monohydrate	80
		Microcrystalline cellulose	Adding 40.0 part of the mixture and 20.5 parts of the mixture
Cross-linked polyvidone	5
		Hydroxypropyl cellulose	3.5
Magnesium stearate	1
		Total up to	160

2. The preparation method comprises the following steps:

adding formula amounts of torasemide, lactose monohydrate, crospovidone, hydroxypropyl cellulose and internally added microcrystalline cellulose into a wet granulator, uniformly mixing, preparing a soft material by taking purified water as a wetting agent, sieving with a 30-mesh sieve for granulation, drying at 55 ℃, and controlling the water content of granules to be 3-4%. Adding microcrystalline cellulose and magnesium stearate in a prescription amount into the granules after 20 meshes of granulation, measuring the content of the intermediate granules after total mixing, and pressing the scored tablet according to the content of the intermediate.

Example 2 Torasemide tablets and preparation method thereof

1. The single dose formulation composition is shown in table 2 below.

TABLE 2

Composition (A)	Single dose (mg)
		Torasemide	10
Lactose monohydrate	80
		Microcrystalline cellulose	Add 35.0 internally and 25.5 externally
Cross-linked polyvidone	5
		Hydroxypropyl cellulose	3.5
Magnesium stearate	1
		Is totaled	160

2. The preparation method comprises the following steps:

adding formula amounts of torasemide, lactose monohydrate, crospovidone, hydroxypropyl cellulose and internally added microcrystalline cellulose into a wet granulator, uniformly mixing, preparing a soft material by taking purified water as a wetting agent, sieving with a 30-mesh sieve for granulation, drying at 55 ℃, and controlling the moisture of granules to be 3-4%. Adding microcrystalline cellulose and magnesium stearate in a prescription amount into granules after 20 meshes of granulation, measuring the content of intermediate granules after total mixing, and pressing scored tablets according to the content of the intermediate.

Example 3 Torasemide tablets and preparation method thereof

1. The single dose formulation composition is shown in table 3 below.

TABLE 3

Composition (A)	Single dose (mg)
		Torasemide	10
Lactose monohydrate	80
		Microcrystalline cellulose	Adding 45.0 part of the total weight of the mixture and 15.5 parts of the total weight of the mixture
Cross-linked polyvidone	5
		Hydroxypropyl cellulose	3.5
Magnesium stearate	1
		Total up to	160

2. The preparation method comprises the following steps:

Example 4 Torasemide tablet and preparation method thereof

1. The single dose formulation composition is shown in table 4 below.

TABLE 4

Composition (I)	Single dose (mg)
		Torasemide	10
Lactose monohydrate	70
		Microcrystalline cellulose	Adding 45.0 part of the total weight of the mixture and 25.5 parts of the total weight of the mixture
Cross-linked polyvidone	5
		Hydroxypropyl cellulose	3.5
Magnesium stearate	1
		Total up to	160

2. The preparation method comprises the following steps:

adding formula amounts of torasemide, lactose monohydrate, crospovidone, hydroxypropyl cellulose and internally added microcrystalline cellulose into a wet granulator, uniformly mixing, preparing a soft material by taking purified water as a wetting agent, sieving with a 30-mesh sieve for granulation, drying at 55 ℃, and controlling the water content of granules to be 3-4%. Adding microcrystalline cellulose and magnesium stearate in a prescription amount into granules after 20 meshes of granulation, measuring the content of intermediate granules after total mixing, and pressing scored tablets according to the content of the intermediate.

Example 5 Torasemide tablets and preparation method thereof

1. The single dose formulation composition is shown in table 5 below.

TABLE 5

Composition (I)	Single dose (mg)
		Torasemide	10
Lactose monohydrate	90
		Microcrystalline cellulose	Adding 35.0 part of the total weight of the mixture and 15.5 parts of the total weight of the mixture
Cross-linked polyvidone	5
		Hydroxypropyl cellulose	3.5
Magnesium stearate	1
		Is totaled	160

2. The preparation method comprises the following steps:

Example 6 Torasemide tablet and preparation method thereof

1. The single dose formulation composition is shown in table 6 below.

TABLE 6

Composition (A)	Single dose (mg)
		Torasemide	10
Lactose monohydrate	87.5
		Microcrystalline cellulose	40.0 portions are added internally and 20.5 portions are added externally
Cross-linked polyvidone	1
		Hydroxypropyl cellulose	0.5
Magnesium stearate	0.5
		Is totaled	160

2. The preparation method comprises the following steps:

adding formula amounts of torasemide, lactose monohydrate, crospovidone, hydroxypropyl cellulose and internally added microcrystalline cellulose into a wet granulator, uniformly mixing, preparing a soft material by taking purified water as a wetting agent, sieving with a 30-mesh sieve for granulation, drying at 55 ℃, and controlling the moisture of granules to be 3-4%. Adding microcrystalline cellulose and magnesium stearate in a prescription amount into the granules after 20 meshes of granulation, measuring the content of the intermediate granules after total mixing, and pressing the scored tablet according to the content of the intermediate.

Example 7 Torasemide tablet and preparation method thereof

1. The single dose formulation composition is shown in table 7 below.

TABLE 7

Composition (I)	Single dose (mg)
		Torasemide	10
Lactose monohydrate	72.5
		Microcrystalline cellulose	40.0 portions are added internally and 20.5 portions are added externally
Cross-linked polyvidone	8.5
		Hydroxypropyl cellulose	6.5
Magnesium stearate	2
		Total up to	160

2. The preparation method comprises the following steps:

Comparative example 1 Torasemide tablet and method for preparing the same

1. The single dose formulation composition is shown in table 8 below.

TABLE 8

Composition (A)	Single dose (mg)
		Hold in palm and drawSaimi rice	10
Lactose monohydrate	80
		Corn starch	Adding 40.0 part of the mixture and 20.5 parts of the mixture
Cross-linked polyvidone	5
		Hydroxypropyl cellulose	3.5
Magnesium stearate	1
		Total up to	160

2. The preparation method comprises the following steps:

adding formula amounts of torasemide, lactose monohydrate, crospovidone, hydroxypropyl cellulose and internally added corn starch into a wet granulator, uniformly mixing, preparing a soft material by taking purified water as a wetting agent, sieving with a 30-mesh sieve for granulation, drying at 55 ℃, and controlling the moisture of granules to be 3-4%. Adding corn starch and magnesium stearate in a prescription amount into granules after 20 meshes of granulation, measuring the content of intermediate granules after total mixing, and pressing scored tablets according to the content of the intermediate.

Comparative example 2 torasemide tablets and preparation method thereof

1. The single dose formulation composition is shown in table 9 below.

TABLE 9

Composition (A)	Single dose (mg)
		Torasemide	10
Lactose monohydrate	Adding 80.0 percent of the total weight of the mixture and 60.5 percent of the total weight of the mixture
		Cross-linked polyvidone	5
Hydroxypropyl cellulose	3.5
		Magnesium stearate	1
Is totaled	160

2. The preparation method comprises the following steps:

adding formula amount of torasemide, lactose monohydrate, crospovidone and hydroxypropyl cellulose into a wet granulator, uniformly mixing, preparing a soft material by taking purified water as a wetting agent, granulating by a 30-mesh sieve, drying at 55 ℃, and controlling the water content of the granules to be 3-4%. Adding lactose monohydrate and magnesium stearate according to the prescription amount into granules after 20 meshes of granulation, measuring the content of intermediate granules after total mixing, and pressing scored tablets according to the content of the intermediate.

Comparative example 3 torasemide tablets and preparation method thereof

1. The single dose formulation composition is shown in table 10 below.

Watch 10

Composition (I)	Single dose (mg)
		Torasemide	10
Lactose monohydrate	80
		Corn starch	69.9
Magnesium stearate	0.1
		Total up to	160

2. The preparation method comprises the following steps:

adding formula amounts of torasemide, lactose monohydrate and corn starch into a wet granulator, uniformly mixing, preparing a soft material by using purified water as a wetting agent, sieving with a 30-mesh sieve for granulation, drying at 55 ℃, and controlling the moisture of the granules to be 3-4%. After 20 meshes of granules are finished, the prescription amount of magnesium stearate is added, the intermediate granule content is measured after the total mixing, and the tablets are pressed and scored according to the intermediate content.

Comparative example 4 torasemide tablets and preparation method thereof

1. The composition of the single dose formulation is shown in table 11 below.

TABLE 11

Composition (I)	Single dose (mg)
		Torasemide	10
Lactose monohydrate	60
		Corn starch	Adding 40.0 part internally and 30.0 parts externally
Cross-linked polyvidone	9.5
		Hydroxypropyl cellulose	8.0
Magnesium stearate	2.5
		Total up to	160

2. The preparation method comprises the following steps:

Comparative example 5

Torasemide tablets: purchased from MEDA Pharma GmbH & co.kg, lot B1901596, specification 10mg.

Experimental example 1

1. The torasemide tablets of examples 1 to 7 and comparative examples 1 to 4 were examined according to the relevant test items "design of functional score and guidelines for research technology of chemical pharmaceutical-mimetic oral tablets", and the results are shown in table 12 below.

TABLE 12

The content uniformity, weight loss, friability and dissolution index of each example were all acceptable.

The qualification standards of the items are as follows:

1) Difference in weight

Randomly taking 30 whole slices, breaking off the slices respectively, weighing the divided part of each slice, and calculating the average weight when the other parts are not used. The weight of the divided parts exceeds 85-115% of the average weight and cannot exceed more than one, if more than one divided parts exceed 85-115% of the average weight or one divided part exceeds 75-125% of the average weight, the divided parts are judged to be unqualified;

2) Content uniformity

The requirement of the content uniformity inspection method in the Chinese pharmacopoeia;

3) Weight loss in cutting:

taking 15 whole tablets, respectively detecting the upper limit and the lower limit of the hardness range planned for the whole tablets, and controlling the weight loss to be within 3.0 percent of the total weight of the 15 whole tablets after the total weight of the whole tablets is divided compared with the total weight of the 15 whole tablets, wherein the tablet fragments in the tablet breaking process do not participate in calculating the weight loss;

4) Friability:

the requirement of the tablet friability inspection method in the Chinese pharmacopoeia;

5) Dissolution rate

900L of 0.1mol/L hydrochloric acid solution is used as a dissolution medium, sampling is carried out for 15 minutes, and the dissolution limit is 80 percent of the marked amount.

The above results show that: the scored sheet prepared by the prescription process meets the related technical requirements of functional scored sheets, and the dosage can be accurately divided no matter a mechanical dividing mode is adopted or the scored sheet is directly broken by hands, so that the clinical requirements are met.

2. The pharmaceutical formulations of torasemide according to examples 1 to 7 and comparative examples 1 to 5 were subjected to the influence factor test: the growth of the impurities was examined at 60 ℃ and at 40. + -. 2 ℃ and 75. + -. 5% relative humidity by accelerated stability tests, the results of which are shown in Table 14 below.

Wherein, the specific information of impurities is detailed in the following table 13.

Watch 13

The specific detection method comprises the following steps: the related substance detection method under the item of European pharmacopoeia EP9.0 torasemide.

TABLE 14

The results of examples 2, 3, 4, 6 and comparative examples 1, 3, 4 are not shown in the table.

Examples 1-7 influence factor tests the results of the increase of impurities i and ii under the respective conditions were superior to those of comparative examples 1-4 and the tablets of the same formulation.

The above results show that: the Torasemide scored tablet has the advantages that the impurity growth speed is obviously lower than that of the original ground tablet at the high temperature of 60 ℃ and in an accelerated stability test, the chemical stability is superior to that of the original grinding agent, and the dissolution rate is also better.

The above are merely embodiments of the present invention, which are described in detail and with particularity, and therefore should not be construed as limiting the scope of the invention. It should be noted that, for those skilled in the art, various changes and modifications can be made without departing from the spirit of the present invention, and these changes and modifications are within the scope of the present invention.

Claims

1. The pharmaceutical composition of torasemide is characterized by comprising the following components in parts by weight: 2-18 parts of torasemide, 125-155 parts of filler, 0-10 parts of disintegrant and 0-10 parts of adhesive; or 0.1-5 parts of lubricant.

2. The pharmaceutical composition according to claim 1, wherein the pharmaceutical composition comprises the following components in parts by weight: 5-15 parts of torasemide, preferably 8-12 parts of torasemide, and more preferably 10 parts of torasemide; 130-150 parts of a filler, preferably 131.5-149.5 parts, and more preferably 133-148 parts; 0-9.5 parts of disintegrating agent, preferably 0.5-9 parts, and more preferably 1-8.5 parts; 0.2-8 parts of adhesive, preferably 0.4-7 parts, and more preferably 0.5-6.5 parts; 0.2 to 4 parts of a lubricant, preferably 0.3 to 3 parts, and more preferably 0.5 to 2 parts.

3. The pharmaceutical composition according to any one of claims 1 or 2, wherein the filler is one or more of lactose monohydrate, mannitol, pregelatinized starch, microcrystalline cellulose, corn starch, preferably lactose monohydrate and microcrystalline cellulose; the disintegrating agent is one or more of sodium carboxymethyl starch, croscarmellose sodium and crospovidone, preferably crospovidone; the adhesive is one or two of hydroxypropyl cellulose or hydroxypropyl methylcellulose, preferably hydroxypropyl cellulose; the lubricant is one or more of magnesium stearate, sodium stearyl fumarate and talcum powder, and is preferably magnesium stearate; the weight ratio of the lactose monohydrate to the microcrystalline cellulose is 0.2-10, preferably 0.4-5, and more preferably 1-2.

4. The torasemide-containing tablet is characterized by comprising the following components in parts by weight: 2-18 parts of torasemide, preferably 5-15 parts, preferably 8-12 parts, and further preferably 10 parts; 125-155 parts of filling agent, preferably 130-150 parts, preferably 131.5-149.5 parts, and more preferably 133-148 parts; 0-10 parts of disintegrating agent, 0-9.5 parts, preferably 0.5-9 parts, and more preferably 1-8.5 parts; 0-10 parts of adhesive, preferably 0.2-8 parts, preferably 0.4-7 parts, and more preferably 0.5-6.5 parts; or, the lubricant is contained in an amount of 0.1 to 5 parts, preferably 0.2 to 4 parts, preferably 0.3 to 3 parts, and more preferably 0.5 to 2 parts.

5. The tablet of claim 4, wherein the tablet is a scored tablet; the scored tablet is single-sided scored or double-sided scored.

6. A tablet according to any of claims 4 or 5, wherein the filler is one or more of lactose monohydrate, mannitol, pregelatinized starch, microcrystalline cellulose, corn starch, preferably lactose monohydrate and microcrystalline cellulose; the disintegrating agent is one or more of sodium carboxymethyl starch, croscarmellose sodium and crospovidone, preferably crospovidone; the adhesive is one or two of hydroxypropyl cellulose or hydroxypropyl methylcellulose, and is preferably hydroxypropyl cellulose; the lubricant is one or more of magnesium stearate, sodium stearyl fumarate and talcum powder, and is preferably magnesium stearate; preferably, the weight ratio of the lactose monohydrate to the microcrystalline cellulose is 0.2-10, preferably 0.4-5, and more preferably 1-2.

7. Use of the pharmaceutical composition of torasemide according to any one of claims 1 to 3 or the tablet according to any one of claims 4 to 6 for the preparation of a diuretic.

8. A process for the preparation of the pharmaceutical composition of torasemide according to any one of claims 1 to 3 or the tablet according to any one of claims 4 to 6, characterized in that it comprises the following steps:

(1) Premixing: mixing torasemide with 0-100% of filler, adhesive and disintegrant;

(2) And (3) wet granulation: adding purified water to prepare soft material, sieving and granulating to obtain wet granules;

(3) Drying, finishing and total mixing: drying the wet granules, sieving, grading, and optionally adding the rest filler and lubricant;

(4) Adjusting hardness and tabletting.

9. The preparation method according to claim 8, wherein the filler is one or more of lactose monohydrate, mannitol, pregelatinized starch, microcrystalline cellulose and corn starch, preferably lactose monohydrate and microcrystalline cellulose; the disintegrating agent is one or more of sodium carboxymethyl starch, croscarmellose sodium and crospovidone, preferably crospovidone; the adhesive is one or two of hydroxypropyl cellulose or hydroxypropyl methylcellulose, and is preferably hydroxypropyl cellulose; the lubricant is one or more of magnesium stearate, sodium stearyl fumarate and talcum powder, and is preferably magnesium stearate; preferably, the filler in step (1) is lactose monohydrate and 50-75% of microcrystalline cellulose, and the filler in step (3) is 25-50% of microcrystalline cellulose.

10. A pharmaceutical composition of torasemide according to any one of claims 1 to 3 or a tablet according to any one of claims 4 to 6, prepared according to the process of any one of claims 8 to 9.