TW201922242A - Formulation having improved hygroscopic property and dissolution rate comprising telmisartan or its pharmaceutically acceptable salt - Google Patents

Abstract

The present invention relates to a pharmaceutical formulation having improved hygroscopic property and dissolution rate, comprising telmisartan or its pharmaceutically acceptable salt. Specifically, the present invention relates to a tablet comprising telmisartan or its pharmaceutically acceptable salt as an active ingredient, characterized in comprising a high dose of the active ingredient and having a property close to a circular shape. Further, the present invention relates to a pharmaceutical combination comprising a first layer comprising telmisartan or its pharmaceutically acceptable salt; and a second layer comprising (S)-amlodipine or its pharmaceutically acceptable salt, characterized in that the combination has 1:1 to 1:1.6 of a ratio of the short axis to the long axis.

Description

Formulation with improved hygroscopicity and dissolution rate containing telmisartan or a pharmaceutically acceptable salt thereof

The present invention relates to a stable formulation comprising telmisartan or a pharmaceutically acceptable salt thereof. Specifically, the present invention relates to a lozenge containing telmisartan or a pharmaceutically acceptable salt thereof as an active ingredient, the lozenge is characterized by containing a high dose of the active ingredient and having properties close to a circular shape, The tablet has improved hygroscopic properties and dissolution rate.

Hypertension is a condition in which blood pressure is consistently observed above the normal range. High blood pressure can cause various complications and ultimately death. Hypertension is divided into primary hypertension or secondary hypertension according to the cause of elevated blood pressure. Primary hypertension is normal hypertension, and the cause of the elevated blood pressure is unknown, while secondary hypertension refers to high blood pressure caused by a specific disease or condition. Secondary hypertension can be treated by identifying the cause of the elevated blood pressure. However, essential hypertension accounts for about 95% of total hypertension cases and the cause is unknown, so drug therapy is currently used to treat patients with essential hypertension based on several hypotensive mechanisms.

The drug-based mechanisms commonly used to treat hypertensive drugs mainly include vasodilators, diuretics, and sympatholytic agents. The currently used vasodilators are divided into angiotensin converting enzyme (ACE) inhibitors, angiotensin receptor blocker (hereinafter referred to as "ARB") and calcium ions according to their mechanism of action. Channel blocker (hereinafter referred to as "CCB").

In hypertension, it is important to keep blood pressure within the normal range to prevent cardiovascular complications (for example, stroke, renal failure, and coronary artery disease, including heart failure and myocardial infarction, etc.) rather than treating blood pressure itself . Because of this, stability of blood pressure and patient control are important. Since antihypertensive drugs need to be taken for a long period of time, care should be taken to select a therapeutic drug. Therefore, in order to achieve the purpose of continuous treatment, it is necessary to use several drugs with different mechanisms in combination instead of choosing only one drug in order to exert better preventive and therapeutic effects. In addition, combination therapy should be used to allow a reduction in the amount of each drug to reduce any side effects caused by long-term use of the drug.

In particular, the combination therapy of ARB and CCB (their respective mechanisms of action in the human body are different) is the first choice for combination therapy if monotherapy fails to control blood pressure. This is because the two drugs have different pharmacological effects for lowering blood pressure. Therefore, the combination therapy of the two drugs can not only effectively lower blood pressure, but also reduce the dosage of the drug, so that the side effects of each component can be greatly reduced.

Telmisartan is one of the ARBs. It is currently sold in the market under the trade name "Micardis" in 20 mg, 40 mg, and 80 mg doses. Telmisartan is a prescription drug used to treat essential hypertension. In this condition, the angiotensin type II receptor acts as a strong vasoconstrictor in the renin-angiotensin-aldosterone system. Tan will selectively act on the angiotensin type II receptor, especially the AT1 receptor, which is involved in major physiological functions, including vasoconstriction.

Despite the excellent effect of telmisartan, the disadvantage of conventional agents containing telmisartan is that when exposed to moisture in the air, it is extremely hygroscopic and causes the product to deteriorate. Therefore, aluminum blister packaging is needed to prevent deterioration during distribution and storage. However, bulky aluminum blister packs are not convenient to carry. Furthermore, if the packaging is damaged during storage and transportation, the medical drug may deteriorate.

technical problem

The literature reports that Telmisartan has very poor solubility in water at physiological pH ranging from 1 to 7. Therefore, in the formulation design, telmisartan is preferably used in combination with an alkaline agent to improve solubility and assist solubilization. In this case, telmisartan becomes hygroscopic if exposed to water or taken, and the lozenges often become sticky or melt.

Increasing the amount of adjuvant (including calcium silicate) to solve the problem will cause the volume of the lozenge to increase and increase the ratio of the long axis to the short axis of the lozenge, thus making the lozenge easy to break.

Therefore, the inventors of the present invention have completed the present invention to provide a high-dose tablet with improved hygroscopicity and dissolution rate and not easily broken when formulating a tablet containing telmisartan or its pharmaceutically acceptable salt as an active agent Agent. Problem solution

In order to achieve the above object, the present invention provides a lozenge containing telmisartan or a pharmaceutically acceptable salt thereof as an active ingredient. The lozenge contains a high dose of the active ingredient based on the total weight of the lozenge In addition, the ratio of the long axis to the short axis is reduced to have a property close to a circular shape.

Among the currently sold Micardis containing telmisartan as an active ingredient, the content of the active ingredient accounts for about 17% of the total weight of the lozenge.

The present invention provides a high-dose lozenge containing at least 20% by weight of telmisartan, preferably in the range of 25% to 30% by weight, based on the total weight of the lozenge.

Furthermore, the present invention provides a lozenge having a property close to a circular shape by confirming that the ratio of the major axis to the minor axis of the lozenge is small and the degree of fragmentation of the lozenge is low. Therefore, the present invention provides a lozenge, wherein the ratio of the short axis to the long axis ranges from 1: 1 to 1: 1.6.

The lozenges of the present invention contain calcium silicate to improve the hygroscopic properties of telmisartan. As the amount of calcium silicate increases, the volume of the lozenge increases. In addition, it is difficult to maintain the properties of the tablets in a circular shape. Therefore, in the lozenge of the present invention, the weight ratio between telmisartan or a pharmaceutically acceptable salt thereof and calcium silicate is 10: 0.5 to 10: 5.

In addition, the present invention further includes a dispersant to enhance the dissolution rate of the lozenge. The disintegrating agent may include, but is not limited to, at least one selected from the group consisting of low substituted hydroxypropyl cellulose, croscarmellose sodium, crosslinked polymer Crospovidone and sodium starch glycolate. It may be preferable to include low-substituted hydroxypropyl cellulose as the dispersant of the present invention.

Furthermore, based on the total weight of the tablet, the present invention may include 3% to 15% by weight of low-substituted hydroxypropyl cellulose, so that the tablet exhibits improved effects in terms of disintegration and dissolution of the active ingredient. .

In addition, the present invention may be a pharmaceutical composition comprising: a first layer containing telmisartan or a pharmaceutically acceptable salt thereof; and a second layer containing another pharmacologically active ingredient.

The invention provides a pharmaceutical composition comprising a first layer comprising telmisartan or a pharmaceutically acceptable salt thereof; and a second layer comprising another pharmacologically active ingredient, characterized in that the first layer Based on the total weight of telmisartan or a pharmaceutically acceptable salt thereof, it contains at least 20% by weight, and the composition has a short-axis to long-axis ratio of 1: 1 to 1: 1.6.

The pharmacologically active ingredient can be formulated with telmisartan or a pharmaceutically acceptable salt thereof. The pharmacologically active ingredient includes, but is not limited to, such as a hypertension treatment agent, atenolol, metoprolol ), Nadolol and pindolol as beta receptor blockers; amlodipine, nifedipine, nicardipine And verapamil as CCB; enalapril, captopril, and ramipril as ACE inhibitors; losartan and candesartan (candesartan) as ARB; and the like.

Preferably, the first layer containing telmisartan or a pharmaceutically acceptable salt thereof may further include calcium silicate.

More preferably, the first layer containing telmisartan or a pharmaceutically acceptable salt thereof may further include low-substituted hydroxypropyl cellulose.

In addition, the present invention may be a double-layered lozenge consisting of: a first layer containing telmisartan or a pharmaceutically acceptable salt thereof; and (S) -amiclodipine Or a second layer of a pharmaceutically acceptable salt thereof.

The double-layered or multi-layered lozenge of the present invention has the property of being nearly circular, so that the possibility of layer separation and cracking of the lozenge is low. Invention effect

The preparation of the present invention includes a high dose of the active ingredient and has properties close to a circular shape, so that the preparation not only has improved hygroscopicity, stability and dissolution rate, but also has a good pharmacy with low possibility of rupture of the lozenge. nature.

In addition, the double-layered or multi-layered lozenge of the present invention has a low possibility of separation and cracking of the lozenge layer, thereby facilitating the preparation and storage.

According to the present invention, "Telmisartan" means a chemical name of (2- (4-{[4-methyl-6- (1-methyl-1hydro-1,3-benzodi Azol-2-yl) -2-propyl-1hydro-1,3-benzodiazol-1-yl] methyl} phenyl) benzoic acid) (2- (4-{[4-methyl-6 -(1-methyl-1H-1,3-benzodiazol-2-yl) -2-propyl-1H-1,3-benzodiazol-1-yl] methyl} phenyl) benzoic acid), ie, the following formula 1 Compound: [Formula 1]

Telmisartan used in the present invention may be commercially available or synthesized by a method known in the art, and is not limited thereto.

Telmisartan according to the present invention can be used in various forms, including the free acid of telmisartan or its pharmaceutically acceptable salts, isomers, racemates, hydrates, and solvates, as long as it is maintained, etc. Effective pharmacological activity is sufficient.

The pharmaceutically acceptable salts include salts derived from a pharmaceutically acceptable acid or base. "Pharmaceutically acceptable salt" according to the present invention means that it exerts a relatively non-toxic and harmless effective effect in a patient's body at a concentration and wherein the side effects caused by the salt do not reduce the pharmacologically active ingredient Any and all organic or inorganic addition salts of beneficial effects.

Preferably, the pharmaceutically acceptable salts of telmisartan according to the present invention may be, but are not limited to, sodium, potassium, magnesium, and calcium salts.

More preferably, the pharmaceutical preparation of the present invention comprises free acid of telmisartan.

Telmisartan is mainly used as an agent for treating essential hypertension. In this condition, the angiotensin type II receptor acts as a strong vasoconstrictor in the renin-angiotensin-aldosterone system. Tan will selectively act on the angiotensin type II receptor, especially the AT1 receptor, which is involved in major physiological functions such as vasoconstriction. Because telmisartan continues to show antihypertensive effects for up to 24 hours, the blood pressure control effect of the drug taken the previous day can even continue to the next morning when the blood pressure sharply rises. In addition, because renal excretion is less than 2%, no dose adjustment is necessary for patients with mild or even severe renal failure.

"(S) -Amlodipine ((S) -amlodipine)" according to the present invention means a chemical name of "3-ethyl-5-methyl-2- (2-aminoethoxymethyl)- 4- (2-chlorophenyl) -1,4-dihydro-6-methyl-3,5-pyridine dicarboxylic acid ester (3-ethyl-5-methyl-2- (2-aminoethoxymethyl) -4- (2-chlorophenyl) -1,4-dihydro-6-methyl-3,5-pyridinedicarboxylate) ", that is, a compound of the following formula 2: [Formula 2]

(S) -Amlodipine used in the present invention may be commercially available or synthesized by a method known in the technical field, and is not limited thereto.

The (S) -amiclodipine according to the present invention can be used in various forms including the free base of (S) -amiclodipine or a pharmaceutically acceptable salt, isomer, racemate, hydrate and The solvate is only required to maintain equivalent pharmacological activity.

The pharmaceutically acceptable salts include salts derived from a pharmaceutically acceptable acid or base. "Pharmaceutically acceptable salt" according to the present invention means any one that exerts a relatively non-toxic and harmless effective effect in a patient's body at a concentration and wherein the side effects caused by the salt do not reduce the beneficial effects of the pharmacologically active ingredient And all organic or inorganic addition salts.

Preferably, the pharmaceutically acceptable salts of (S) -amiclodipine according to the present invention may include, but are not limited to, (S) -amlodipine besylate, ( S) -Amlodipine maleate ((S) -amlodipine maleate), (S) -Amlodipine orotate, (S) -Amlodipine camphor sulfonate ((S) -amlodipine camsylate), (S) -amlodipine adipic acid salt ((S) -amlodipine adipate) or (S) -amlodipine mesylate ((S) -amlodipine mesylate).

More preferably, the pharmaceutical composition of the present invention comprises (S) -amlodipine besylate.

Amlodipine as a CCB can have a half-life of 30 hours to 50 hours, and is a very useful calcium ion channel blocker that can exhibit consistent activity over a long period of time. Amlodipine blocks calcium from flowing into vascular smooth muscle and causes peripheral arteries to dilate, thereby lowering blood pressure and effectively treating vasospasm angina.

Amlodipine is a chiral compound with a palm center. Amlodipine (S) -mirror isomers, which are known as strong calcium ion channel blockers, exhibit higher activity than their mixtures (racemates), see Arrowsmith et al., J. Med. Chem., 29, 1696 (1986). (R) -enantiomer is 1000 times less active than (S) -enantiomer, and a kinin-mediated nitrogen oxide mechanism (kinin) that is speculated to be related to side effects was observed -mediated nitrogen oxide mechanism), see Hintze et al., J. Cardiovasc. Pharmacol., 39 (2): 208-14 (2002).

Therefore, when the pure image isomer of (S) -amiclodipine isolated is administered, its selectivity for the receptor binding is higher than that of amlodipine racemate, and the dose can be reduced. half. Therefore, there is an advantage that the possibility of drug interaction and side effects can be reduced.

The lozenges of the present invention may further include at least one pharmaceutically acceptable excipient. Unless the adjuvant interacts with telmisartan or a pharmaceutically acceptable salt thereof and interferes with medicinal effects, the adjuvant may be a conventional adjuvant known in the art.

For example, the pharmaceutically acceptable adjuvant may be, but is not limited to, at least one selected from the group consisting of a diluent, an adhesive, a dispersant, a slip agent, and a coating agent.

The "diluent" according to the present invention means an inactive substance used as a filler to provide a desired volume, fluidity, and compressibility when preparing a solid dosage form. For example, the diluent may be, but is not limited to, lactose hydrate, anhydrous lactose, sucrose, corn starch, anhydrous dibasic calcium phosphate, or dibasic calcium phosphate hydrate.

"Binder" according to the present invention means a substance that can provide elasticity and adhesiveness to increase the strength of the formed preparation, especially the lozenge. For example, the binder may be, but is not limited to, sodium carboxymethyl cellulose (CMC-Na), starch paste, polyvinyl pyrrolidone (PVP), gum arabic, or hydroxypropyl cellulose ( HPC).

"Disintegrating agent" according to the present invention means a substance used to accelerate the disintegration of a solid dosage form so that the dosage form releases an active ingredient exhibiting a medicinal effect in a short time. For example, as a disintegrant, carboxymethyl cellulose calcium (CMC-Ca), cross-linked polyvinyl pyrrolidone, sodium carboxymethyl starch, sodium carboxymethyl cellulose, or low-substituted hydroxypropyl may be used. Cellulose.

"Glidant" according to the present invention means a substance that can improve the fluidity of a formulation. For example, when used as a slip agent, colloidal silica, magnesium stearate, stearic acid, talc, or sodium stearyl fumarate can be used.

In one embodiment according to the present invention, the pharmaceutical composition of the present invention may be a solid preparation for oral use. Preferably, the pharmaceutical composition of the present invention is a bilayer tablet.

In another embodiment according to the present invention, a method for preparing a single agent comprising telmisartan or a composition comprising telmisartan and (S) -amiclodipine is provided. The pharmaceutical single agents and compositions of the present invention can be prepared using techniques such as wet granulation, direct compression, dry granulation, and the like known to those skilled in the art. Lozenges and other dosage forms.

In the following, the present invention can be better understood through the following examples and examples, but these examples should not be considered as a limitation of the present invention. The following examples are provided for detailed explanation only for those skilled in the art. [ Example 1]

According to the ratio of the minor axis to the major axis of the tablet, the rupture test of the telmisartan tablet was performed.

The tablets of Examples 1 to 6 containing telmisartan as an active ingredient were prepared, wherein the composition was as described in [Table 1], and the ratio of the short axis to the long axis was as described in [Table 2].

[ Examples 1 to 6] Preparation of telmisartan-containing lozenges

Telmisartan, dry sodium carbonate, povidone, and yellow iron oxide are added to the water, and the first adhesive solution is prepared by heating, stirring, and dissolving. Separately, calcium silicate was added to water and stirred uniformly to prepare a second adhesive solution. Microcrystalline cellulose is injected into a fluidized bed granulator to be fluidized, and then the first adhesive solution and the second adhesive solution are sequentially sprayed to prepare granules. After the granules are dried, the co-milling granulator is used. (co-mill sizing machine) The dried materials are sized. The granulated material was sieved through a 30 mesh screen, and then sodium fumarate sodium stearate was added and the material was mixed to prepare a granulated mixture of telmisartan. These tablets were prepared using a tablet press (Examples 1 to 6), where the ratio of the short axis to the long axis of each tablet was 1: 1, 1: 1.3, 1: 1.5, 1: 1.6, 1: 1.7 or 1: 1.8.

[Table 1]

The tablets of Examples 1 to 6 prepared above were subjected to a free fall drop test according to the following method.

90 tablets are packaged in high-density polyethylene (HDPE) bottles, each containing 30 tablets. The drop test was performed 10 times at a position 1 meter above a flat solid floor. After the drop test, the bottle was opened to detect whether the tablets were broken. The test conditions were maintained at room temperature (1 ° C to 30 ° C) and a relative humidity of up to 75%. The rupture rate of the tablet was measured. The measurement results are shown in [Table 2].

[Table 2]

As shown in the above [Table 2], the lozenges of Examples 1 to 4 did not crack and the durability was improved. In addition, the rupture rate (%) of the tablet increased as the ratio of the major axis to the minor axis increased.

Therefore, it was confirmed that as the ratio of the short axis to the long axis approaches 1: 1, the probability of the tablet breaking is reduced. [ Example 2]

Fracture test of telmisartan and amlodipine composition tablets according to the ratio of the short axis to the long axis of the tablets

The tablets of Examples 7 to 12 containing telmisartan and amlodipine as active ingredients were prepared, wherein the composition was as described in [Table 3], and the ratio of the short axis to the long axis was as [Table 4] As described in.

[ Examples 7 to 12] Preparation of tablets containing telmisartan and amlodipine

Telmisartan, dry sodium carbonate, polyvinylpyrrolidone, and yellow iron oxide are added to water, and the first adhesive solution is prepared by heating, stirring, and dissolving. Separately, calcium silicate was added to water and stirred uniformly to prepare a second adhesive solution. Microcrystalline cellulose is injected into a fluidized bed granulator to be fluidized, and then the first adhesive solution and the second adhesive solution are sequentially sprayed to prepare granules. After the granules are dried, the co-milling granulator is used. The dried material is granulated. The granulated material was sieved through a 30-mesh sieve, and sodium fumarate was then added and the material was mixed to prepare a granulated mixture of telmisartan. An anhydrous dibasic calcium phosphate was added to the (S) -amiclodipine benzene sulfonate, followed by adding microcrystalline cellulose, sodium carboxymethyl starch, and sodium fumarate stearate and mixing the material. The mixture was extruded and sieved using a roller compactor equipped with a 16-mesh screen to prepare granules, and the co-mill granulators were used to granulate the granules. Microcrystalline cellulose was added to the blue No. 2 pigment and powdered to crush the pigment. Microcrystalline cellulose, sodium carboxymethyl starch, and anhydrous dibasic calcium phosphate were added to the granulated granules and the pulverized mixture of the pigments, and mixed, followed by the addition of antibutane through a 30 mesh screen. Sodium stearate and the mixture were mixed to prepare the (S) -amiclodipine granulated mixture. The granulation mixture of the telmisartan and the granulation mixture of (S) -amiclodipine was processed using a tablet press to prepare the tablets (Examples 7 to 12), in which the short The ratio of the shaft to the long axis is 1: 1, 1: 1.3, 1: 1.5, 1: 1.6, 1: 1.7, or 1: 1.8.

[table 3]

The tablets of Examples 7 to 12 prepared above were subjected to a free drop test to measure the cracking rate of the tablets and the separation rate of the layers. The measurement results are shown in [Table 4].

[Table 4]

As shown in [Table 4] above, the lozenges of Examples 7 to 10 did not break and there was no separation between the layers. Therefore, the results show that the durability is improved. In addition, the rupture rate (%) of the tablet increased as the ratio of the major axis to the minor axis increased.

Therefore, it was confirmed that as the ratio of the short axis to the long axis approaches 1: 1, the probability of the tablet breaking is reduced. [ Example 3]

Experiment on hygroscopic properties of telmisartan tablets based on the amount of calcium silicate

The telmisartan tablets of Examples 13 to 17 were prepared according to the preparation method described in Example 1, provided that the composition was as described in [Table 5].

[table 5]

The tablets of Examples 13 to 17 prepared above were evaluated for hygroscopic properties. The specific method used to evaluate the hygroscopic properties is to expose each medicine without any packaging to accelerated conditions (relative humidity: 75 ± 5%, temperature: 40 ± 2 ° C). After one day, observe the changes in gloss and color on the surface of the lozenge.

The following [Table 6] shows changes in gloss and color as a result of evaluating the hygroscopic property. This property change is shown in [Fig. 1].

[TABLE 6]

As shown in [Table 6] above, little gloss and color change were observed in the tablets of Examples 13 to 15. In addition, as shown in [Fig. 1], little gloss and color change were also observed in the tablets of Examples 13 to 15.

Therefore, the lozenges of Examples 13 to 15 showed little change in gloss, color, and properties. Therefore, it was proved that the hygroscopic property was improved. [ Example 4]

Dissolution rate experiment of telmisartan tablets according to the type of disintegrating agent

The telmisartan tablets of Examples 18 to 21 were prepared according to the preparation method described in Example 1, provided that the composition was as described in [Table 7].

[TABLE 7]

The disintegration time of the tablets of Examples 18 to 21 prepared above was measured. The disintegration time was measured according to the disintegration test method contained in the Korean Pharmacopoeia, in which pure water was used as a disintegration medium and the water temperature was maintained at 37 ± 2 ° C. The disintegration time is determined as the time it takes for the tablets to completely disappear from the bottom of the pulverizer. The measurement results of the disintegration time are shown in [Table 8] below.

[TABLE 8]

As shown in [Table 8] above, the lozenge of Example 18 showed the shortest disintegration time. Therefore, it was confirmed that low-substituted hydroxypropyl cellulose is the most suitable dispersant. [ Example 5]

Dissolution rate (%) experiment of telmisartan tablets according to the amount of disintegrating agent

The telmisartan tablets of Examples 22 to 24 were prepared according to the preparation method described in Example 1, provided that the composition was as described in [Table 9].

[TABLE 9]

The dissolution rate per unit time of the tablets of Examples 18 and 22 to 24 was measured.

The dissolution rate was measured according to the method II (paddle method) contained in the Korean Pharmacopoeia, and 900 ml (ml) of a phosphate buffer solution (pH 7.5) was used as the dissolution medium, and the dissolution temperature was 37 ± 0.5 ° C, and the speed is 75 rpm. The dissolution medium was removed at 5 minutes, 10 minutes, 15 minutes, and 30 minutes after the start of dissolution. The filtered solution was then used as a test solution, and the test solution was analyzed using a liquid chromatograph and a standard solution.

The dissolution rate per hour is shown in [Figure 2], and the dissolution rate within 30 minutes is shown in [Table 10].

[TABLE 10]

As shown in [Table 10] above, when the amount of low-substituted hydroxypropyl cellulose is increased, the dissolution rate is increased accordingly. Example 24, which contains 9% by weight of a disintegrating agent, showed the most excellent dissolution rate.

no

Figure 1 shows the relationship between the hygroscopic properties of the telmisartan tablet and the content of calcium silicate.

Figure 2 shows the dissolution rate of the telmisartan, which varies according to the amount of low-substituted hydroxypropyl cellulose.

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Claims (14)

A lozenge containing telmisartan or a pharmaceutically acceptable salt thereof as an active ingredient, characterized in that the active ingredient contains at least 20% by weight based on a total weight of the lozenge, and the lozenge The ratio of the short axis to the long axis is 1: 1 to 1: 1.6. The lozenge according to claim 1, characterized in that the active ingredient is contained in an amount of 25% to 30% by weight based on the total weight of the lozenge. The lozenge according to claim 1, further comprising calcium silicate. The lozenge according to claim 3, wherein a weight ratio of telmisartan or a pharmaceutically acceptable salt thereof to calcium silicate is 10: 0.5 to 10: 5. The tablet according to claim 1, further comprising a disintegrant. The tablet according to claim 5, characterized in that the dispersant is at least one selected from the group consisting of low-substituted hydroxypropyl cellulose, croscarmellose sodium, cross-linked polyvinyl pyrrolidone, and Sodium carboxymethyl starch. The lozenge according to claim 5, characterized in that the dispersant is low-substituted hydroxypropyl cellulose. The lozenge according to claim 7, characterized in that it comprises 3 to 15% by weight of low-substituted hydroxypropyl cellulose based on the total weight of the lozenge. A pharmaceutical composition comprising a first layer comprising telmisartan or one of its pharmaceutically acceptable salts; and a second layer comprising a pharmacologically active ingredient one, characterized by the total weight of the first layer In total, telmisartan or a pharmaceutically acceptable salt thereof is at least 20% by weight, and the ratio of the short axis to the long axis of the composition is 1: 1 to 1: 1.6. The pharmaceutical composition according to claim 9, characterized in that the pharmacologically active ingredient is selected from the group consisting of atenolol, metoprolol, nadolol, indole Pindolol, amlodipine, nifedipine, nicardipine, verapamil, enalapril, captopril ), Ramipril, losartan, and candesartan, and pharmaceutically acceptable salts thereof. The pharmaceutical composition according to claim 9, wherein the pharmacologically active ingredient is (S) -amiclodipine or a pharmaceutically acceptable salt thereof. The pharmaceutical composition according to claim 9, wherein the first layer comprising telmisartan or a pharmaceutically acceptable salt thereof further comprises calcium silicate. The pharmaceutical composition according to claim 9, wherein the first layer comprising telmisartan or a pharmaceutically acceptable salt thereof further comprises low-substituted hydroxypropyl cellulose. The composition according to claim 9, characterized in that the composition is a bilayer tablet.