KR20170012703A - A pharmaceutical composition comprising telmisartan and a preparation method thereof - Google Patents
A pharmaceutical composition comprising telmisartan and a preparation method thereof Download PDFInfo
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
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- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
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- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
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Abstract
Description
The present invention relates to a telmisartan-containing pharmaceutical composition having improved stability and solubility, and a process for producing the same.
Telmisartan is an angiotensin II receptor antagonist developed to treat hypertension and the like (European Patent Publication No. EP 0502314). The name of telmisartan is 4'- [2-n-propyl-4-methyl-6- (1-methylbenzimidazol-2-yl) -benzimidazol- 1 -ylmethyl] Carboxylic acid, the molecular formula is C 33 H 30 N 4 O 2 , and the molecular weight is 514.62 g / mol. The structural formula of telmisartan is as follows:
[Chemical Formula 1]
Telmisartan is a poorly soluble material with a very low water solubility in the pH range of 3 to 9 (Pratikkumar A. Patel et al., International Journal of Pharmacology and Research (IJPSR) Vol. 1 (8), 2010, 282- 292). In addition, telmisartan exists as two polymorphs having different melting points (International Patent Publication WO 00/43370), polymorph B having a low melting point is irreversibly converted to polymorph A having a high melting point by heat and moisture do.
Telmisartan with these physical characteristics exhibits different dissolution rates due to crystalline polymorphism and pH-dependent solubility, leading to differences in the absorption of individual drugs.
Telmisartan has a t max value of about 0.3-1.0 hours, which is characterized by the rapid release of drug from the stomach.
Various solutions have been proposed to increase the solubility of telmisartan, a poorly soluble material with low solubility at pH 9 or lower.
International Patent Publication No. WO 03/059327 discloses a method in which telmisartan is dissolved in water together with a basic agent to prepare an aqueous solution, followed by spray drying to obtain amorphous telmisartan. However, such a spray drying method has a low yield in the production process and it is difficult to obtain amorphous telmisartan of a certain size.
Korean Patent No. 1302883 attempts to solve the problem of lowering the stability of telmisartan by using alkali metal phosphate as a new solubilizing agent, but there is a problem that the production cost is increased due to the use of expensive excipients.
Korean Patent No. 1446603 increases the stability of telmisartan by adsorbing telmisartan dissolved in an alkalizing agent to an aluminum silicate compound and mixing it with a calcium channel blocker to improve the stability of telmisartan, The release and about 10% of the lubricant may cause problems in the stability of the manufacturing process and the purification.
Korean Patent No. 0960953 discloses that telmisartan is made into a wet granule by dissolving a basic agent and using a solidifying agent having a high wetting ratio. When a solidifying agent having a high wetting rate is used, There is a possibility that stability may be lowered, and it takes a lot of time to remove moisture in the manufacturing process, which may lead to an increase in the process cost.
As such, telmisartan has the problem of reduced stability in tablets made by methods known in the art, such as spray drying or wet methods.
Amlodipine is a dihydropyridine-based calcium channel blocker and is a representative drug used in the treatment of hypertension or angina. When the drug is absorbed, it relaxes the smooth muscle of the arterial wall, thereby lowering blood pressure and increasing blood flow to the myocardium. Amlodipine is commercially available in the form of various salts such as bevylic acid, maleic acid, and camphanic acid, and amlodipine besylate is the most widely used. The structure of amlodipine is represented by the following formula 2:
(2)
Amlodipine preparations are generally made by combining amlodipine, a drug-efficacious ingredient, with salts that aid in the activation and formulation of medicinal products. The salt is a part to help stabilize amlodipine as an active ingredient. Although amlodipine is in the form of free base, it is preferably administered in salt form with pharmaceutically acceptable acid because of its low solubility in water. A combination of amlodipine with another drug that can be used in combination with a salt for synergy is widely used.
Amlodipine is an unstable free base and has a disadvantage that it is greatly affected by light, heat and moisture and its therapeutic effect is inferior. To overcome this problem, amlodipine is marketed in combination with various acid addition salts described above, And the stability is maintained. However, the achievement of securing pharmaceutical stability is still insignificant.
The present invention is to provide a novel pharmaceutical formulation capable of improving the stability and solubility of telmisartan, which is a poorly soluble drug of BCS (class II) (i.e., high permeability but low solubility).
The present invention provides a medicinal composition comprising telmisartan or a pharmaceutically acceptable salt thereof, a water-insoluble carrier, and a basic agent, wherein isomalt or sorbitol having a specific surface area is used as the water-insoluble carrier, Stability and solubility.
The telmisartan-containing pharmaceutical composition according to the present invention can improve the stability, solubility, and saturation of telmisartan formulations by using isomalt or a specific surface area of sorbitol as a water-insoluble carrier. In addition, the stability and titability of telmisartan and amlodipine are improved in the preparation of the combination of telmisartan and amlodipine.
The present invention relates to a medicinal composition comprising telmisartan or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable water-insoluble carrier, and a basic agent.
The present invention also relates to a pharmaceutical composition comprising: (a) preparing a dispersion by dispersing telmisartan or a pharmaceutically acceptable salt thereof in a solvent (for example, water, ethanol, methanol or a mixed solvent thereof) together with a basic agent; And (b) spray coating the dispersion prepared in step (a) on the surface of the carrier. The present invention also relates to a method for producing telmisartan-containing granules.
Alternatively, the medicinal composition containing telmisartan according to the present invention may be prepared by mixing a mixture comprising telmisartan or a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable water-insoluble carrier, and a basic agent, for example, by wet granulation Method or the like.
In the present invention, the carrier may be a water-insoluble carrier such as an oligosaccharide (for example, sucrose, lactose, etc.), a sugar alcohol (for example, mannitol, sorbitol, xylitol, isomalt, etc.) Cellulose, powdered cellulose, corn starch, etc.), and the like.
In the present invention, isomalt or sorbitol having a specific surface area of 0.7 m 2 / g or less is preferably used as the carrier. More preferably, isomalt or sorbitol having a specific surface area of 0.3 to 0.7 m 2 / g is used as a carrier. As used herein, "specific surface area" is the value measured under nitrogen at 77 ° K using a BET device (Micromeritics ASAP 2400 or equivalent) that is suitable under the consideration of USP monograph <846>, Method 2. The sample weight is 3-5 g. The sample is degassed at 40 < 0 > C under vacuum for 2 hours. The 6-point measurement is made at p / p0 = 0.07-0.22.
In the present invention, the basicizing agent includes basic amino acids (e.g., arginine, lysine, etc.), alkali metal hydroxides (e.g., sodium hydroxide, potassium hydroxide, etc.), alkaline earth metal oxides (e.g., magnesium oxide) , Meglumine, sodium carbonate, sodium bicarbonate, and the like.
Using the telmisartan-containing granular composition according to the present invention, conventional solid preparations such as tablets or capsules can be prepared. (For example, a two-layer tablet or a core-shell tablet form) comprising a first solid part comprising a telmisartan-containing granule composition according to the present invention and a second solid part comprising a calcium channel blocker such as amlodipine and a therapeutic agent for hypertension, Can be produced.
The telmisartan softening test for the medicinal composition according to the present invention confirmed that the composition according to the present invention improved the stability of the formulation.
Amlodipine is an unstable free base, which is greatly influenced by light, heat and moisture, and has a disadvantage in that its therapeutic effect is inferior. To overcome this, amlodipine is marketed in combination with various acid addition salts, and its stability is maintained . However, the achievement of securing pharmaceutical stability is still insignificant. In particular, when telmisartan and amlodipine are physically mixed, the ester linkage of amlodipine is hydrolyzed by the basic agent used for release of telmisartan, thereby lowering the content of amlodipine and increasing the amount of the flexible substance, There is a problem of deterioration.
In order to solve the stability problem of amlodipine as described above, the present invention has developed a compounding agent such as dibasil which can minimize the physical bonding between telmisartan and amlodipine, and improved the content of amlodipine in manufacturing by double- And the stability can be improved.
Hereinafter, the present invention will be described in detail based on the following examples. However, the following examples are for illustrative purposes only and are not intended to limit the scope of the invention.
[Comparative Example 1]
80 g of telmisartan, 6.72 g of sodium hydroxide as a basic agent, 24 g of meglumine and 24 g of povidone as a binder were dissolved in purified water to prepare a spray solution. Then 300 g of sorbitol (specific surface area 1.3 m 2 / g) was injected into the fluidized bed granulator to fluidize it. Then, the sprayed fluid prepared above was sprayed into the fluidized bed granulator, whereby telmisartan was coated on the surface of the carrier, . Thus, granules were prepared by mixing 37.28 g of sorbitol (specific surface area 1.3 m 2 / g) and 8.0 g of magnesium stearate on the granules attached to the carrier surface with telmisartan.
6.935 g of amlodipine, corn starch, microcrystalline cellulose, pregelatinized starch, colloidal silica, and magnesium stearate as excipients were mixed and lubricated to prepare amlodipine-containing granules.
Finally, the two granules were tableted in two layers.
Fluidized bed granulator inlet air temperature (inlet temp.) And the 60 ~ 70 ℃, discharge air temperature (exhaust temp.) And the 25 ~ 35 ℃, the inlet air velocity was carried out at 25 ~ 30 m 3 / h condition.
[Example 1]
80 g of telmisartan, 0.5 g of magnesium oxide as a basic agent, and 24 g of povidone as a binder were dispersed in purified water to prepare a spray solution. Then, 300 g of isomalt was injected as a water-insoluble carrier in the fluidized bed granulator to fluidize it. Then, the sprayed solution prepared above was sprayed into the fluidized bed granule, whereby telmisartan was coated on the surface of the carrier to prepare attached granules. In this way, granules were prepared by mixing 63.78 g of isomalt, 6.7 g of magnesium oxide and 5.02 g of magnesium stearate in the granules attached to the carrier surface with telmisartan.
6.935 g of amlodipine, corn starch, microcrystalline cellulose, pregelatinized starch, colloidal silica and magnesium stearate as excipients were mixed and lubricated to prepare amlodipine-containing granules.
Afterwards, the two granules were tableted in two layers.
Fluidized bed granulator inlet air temperature (inlet temp.) And the 60 ~ 70 ℃, discharge air temperature (exhaust temp.) And the 25 ~ 35 ℃, the inlet air velocity was carried out at 25 ~ 30 m 3 / h condition.
[Example 2]
80 g of telmisartan, 1.0 g of magnesium oxide as a basic agent, and 24 g of povidone as a binder were dispersed in purified water to prepare a spray solution. Then, 300 g of isomalt was injected as a water-insoluble carrier in the fluidized bed granulator to fluidize it. Then, the sprayed solution prepared above was sprayed into the fluidized bed granule, whereby telmisartan was coated on the surface of the carrier to prepare attached granules. In this way, granules were prepared by mixing 57.98 g of isomalt, 12.0 g of magnesium oxide, and 5.02 g of magnesium stearate in the granules attached to the carrier surface with telmisartan.
6.935 g of amlodipine and corn starch, microcrystalline cellulose, pregelatinized starch, colloidal silica and magnesium stearate as excipients were mixed and lubricated to prepare amlodipine-containing granules, and the two granules were tableted in a two-layer tablet.
Fluidized bed granulator inlet air temperature (inlet temp.) And the 60 ~ 70 ℃, discharge air temperature (exhaust temp.) And the 25 ~ 35 ℃, the inlet air velocity was carried out at 25 ~ 30 m 3 / h condition.
[Example 3]
80 g of telmisartan, 6.7 g of sodium hydroxide as a basic agent, 24 g of meglumine and 24 g of povidone as a binder were dispersed in 90% ethanol to prepare a spray solution. Then, 300 g of isomalt was injected as a water-insoluble carrier in the fluidized bed granulator to fluidize it. Then, the sprayed solution prepared above was sprayed into the fluidized bed granule, whereby telmisartan was coated on the surface of the carrier to prepare attached granules. Thus, granules were prepared by mixing 42.28 g of isomalt and 5.02 g of magnesium stearate in the granules attached to the carrier surface with telmisartan.
6.935 g of amlodipine, corn starch, microcrystalline cellulose, pregelatinized starch, colloidal silica and magnesium stearate as excipients were mixed and lubricated to prepare amlodipine-containing granules.
Afterwards, the two granules were tableted in two layers.
Fluidized bed granulator inlet air temperature (inlet temp.) And the 60 ~ 70 ℃, discharge air temperature (exhaust temp.) And the 25 ~ 35 ℃, the inlet air velocity was carried out at 25 ~ 30 m 3 / h condition.
[Example 4]
80 g of telmisartan, 30 g of sodium bicarbonate as a basic agent, and 24 g of povidone as a binder were dispersed in purified water to prepare a spray solution. Then, 300 g of isomalt was injected as a water-insoluble carrier in the fluidized bed granulator to fluidize it. Then, the sprayed solution prepared above was sprayed into the fluidized bed granule, whereby telmisartan was coated on the surface of the carrier to prepare attached granules. In this way, granules were prepared by mixing 40.98 g of isomalt and 5.02 g of magnesium stearate on the granules attached to the carrier surface with telmisartan.
6.935 g of amlodipine, corn starch, microcrystalline cellulose, pregelatinized starch, colloidal silica and magnesium stearate as excipients were mixed and lubricated to prepare amlodipine-containing granules.
Afterwards, the two granules were tableted in two layers.
Fluidized bed granulator inlet air temperature (inlet temp.) And the 60 ~ 70 ℃, discharge air temperature (exhaust temp.) And the 25 ~ 35 ℃, the inlet air velocity was carried out at 25 ~ 30 m 3 / h condition.
[Example 5]
80 g of telmisartan, 30 g of sodium bicarbonate as a basic agent, and 24 g of povidone as a binder were dispersed in purified water to prepare a spray solution. Then, 300 g of isomalt was injected as a water-insoluble carrier in the fluidized bed granulator to fluidize it. Then, the sprayed solution prepared above was sprayed into the fluidized bed granule, whereby telmisartan was coated on the surface of the carrier to prepare attached granules. In this way, granules were prepared by mixing 40.98 g of isomalt and 5.02 g of magnesium stearate on the granules attached to the carrier surface with telmisartan.
6.935 g of amlodipine, corn starch, microcrystalline cellulose, pregelatinized starch, colloidal silica and magnesium stearate as excipients were mixed and lubricated to prepare amlodipine-containing granules.
Afterwards, the two granules were tableted in two layers.
Fluidized bed granulator inlet air temperature (inlet temp.) And the 60 ~ 70 ℃, discharge air temperature (exhaust temp.) And the 25 ~ 35 ℃, the inlet air velocity was carried out at 25 ~ 30 m 3 / h condition.
[Example 6]
80 g of telmisartan, 6.7 g of sodium hydroxide as a basic agent, 24 g of meglumine and 24 g of povidone as a binder were dispersed in 90% ethanol to prepare a spray solution. Then, 300 g of sorbitol (specific surface area: 0.7 m 2 / g) as a water-insoluble carrier was injected into the fluidized bed granulator and fluidized. Then, the above-prepared sprayed liquid was sprayed into the fluidized bed granulator, whereby telmisartan was coated on the surface of the carrier To prepare an attached granule. Thus, granules were prepared by mixing 40.28 g of sorbitol (specific surface area 0.7 m 2 / g) and 5.02 g of magnesium stearate on the granules attached to the carrier surface with telmisartan.
6.935 g of amlodipine, corn starch, microcrystalline cellulose, pregelatinized starch, colloidal silica and magnesium stearate as excipients were mixed and lubricated to prepare amlodipine-containing granules.
Afterwards, the two granules were tableted in two layers.
Fluidized bed granulator inlet air temperature (inlet temp.) And the 60 ~ 70 ℃, discharge air temperature (exhaust temp.) And the 25 ~ 35 ℃, the inlet air velocity was carried out at 25 ~ 30 m 3 / h condition.
[Example 7]
80 g of telmisartan, 0.5 g of magnesium oxide as a basic agent, and 24 g of povidone as a binder were dispersed in purified water to prepare a spray solution. Then, 300 g of sorbitol (specific surface area: 0.5 m 2 / g) as a water-insoluble carrier in a fluidized bed granulator was injected into the fluidized bed granulator and fluidized. Then, the above-prepared sprayed liquid was sprayed into the fluidized bed granulator so that telmisartan was coated on the surface of the carrier To prepare an attached granule. Thus, granules were prepared by mixing 63.78 g of sorbitol (specific surface area: 0.7 m 2 / g), 6.7 g of magnesium oxide and 5.02 g of magnesium stearate in the granules attached to the carrier surface of telmisartan.
6.935 g of amlodipine, corn starch, microcrystalline cellulose, pregelatinized starch, colloidal silica and magnesium stearate as excipients were mixed and lubricated to prepare amlodipine-containing granules.
Afterwards, the two granules were tableted in two layers.
Fluidized bed granulator inlet air temperature (inlet temp.) And the 60 ~ 70 ℃, discharge air temperature (exhaust temp.) And the 25 ~ 35 ℃, the inlet air velocity was carried out at 25 ~ 30 m 3 / h condition.
[Example 8]
80 g of telmisartan, 30 g of sodium bicarbonate as a basic agent, and 24 g of povidone as a binder were dispersed in purified water to prepare a spray solution. Then, 300 g of sorbitol (specific surface area: 0.4 m 2 / g) as a water-insoluble carrier in a fluidized bed granulator was injected and fluidized, and then the spray liquid prepared above was sprayed into the fluidized bed granulator, whereby telmisartan was coated on the surface of the carrier To prepare an attached granule. In this way, granules were prepared by mixing 40.98 g of sorbitol (specific surface area 0.4 m 2 / g) and 5.02 g of magnesium stearate on the granules attached to the carrier surface with telmisartan.
6.935 g of amlodipine, corn starch, microcrystalline cellulose, pregelatinized starch, colloidal silica and magnesium stearate as excipients were mixed and lubricated to prepare amlodipine-containing granules.
Afterwards, the two granules were tableted in two layers.
Fluidized bed granulator inlet air temperature (inlet temp.) And the 60 ~ 70 ℃, discharge air temperature (exhaust temp.) And the 25 ~ 35 ℃, the inlet air velocity was carried out at 25 ~ 30 m 3 / h condition.
[Example 9]
80 g of telmisartan, 30 g of sodium carbonate as a basic agent and 24 g of povidone as a binder were dispersed in purified water to prepare a spray solution. Then, 300 g of sorbitol (specific surface area: 0.7 m 2 / g) as a water-insoluble carrier was injected into the fluidized bed granulator and fluidized. Then, the above-prepared sprayed liquid was sprayed into the fluidized bed granulator, whereby telmisartan was coated on the surface of the carrier To prepare an attached granule. Thus, granules were prepared by mixing 40.98 g of sorbitol (specific surface area 0.7 m 2 / g) and 5.02 g of magnesium stearate on the granules attached to the carrier surface with telmisartan.
6.935 g of amlodipine, corn starch, microcrystalline cellulose, pregelatinized starch, colloidal silica and magnesium stearate as excipients were mixed and lubricated to prepare amlodipine-containing granules.
Afterwards, the two granules were tableted in two layers.
Fluidized bed granulator inlet air temperature (inlet temp.) And the 60 ~ 70 ℃, discharge air temperature (exhaust temp.) And the 25 ~ 35 ℃, the inlet air velocity was carried out at 25 ~ 30 m 3 / h condition.
[Example 10]
80 g of telmisartan, 6.7 g of sodium hydroxide as a basic agent, 24 g of meglumine and 24 g of povidone as a binder were dispersed in 90% ethanol to prepare a spray solution. Then, 300 g of sorbitol (specific surface area: 0.7 m 2 / g) as a water-insoluble carrier was injected into the fluidized bed granulator and fluidized. Then, the above-prepared sprayed liquid was sprayed into the fluidized bed granulator, whereby telmisartan was coated on the surface of the carrier To prepare an attached granule. Thus, granules were prepared by mixing 40.28 g of sorbitol (specific surface area 0.7 m 2 / g) and 5.02 g of magnesium stearate on the granules attached to the carrier surface with telmisartan. The granules were tableted with one tablet.
Fluidized bed granulator inlet air temperature (inlet temp.) And the 60 ~ 70 ℃, discharge air temperature (exhaust temp.) And the 25 ~ 35 ℃, the inlet air velocity was carried out at 25 ~ 30 m 3 / h condition.
[Example 11]
80 g of telmisartan, 6.7 g of sodium hydroxide as a basic agent, 24 g of meglumine and 24 g of povidone as a binder were dispersed in 90% ethanol to prepare a spray solution. Then, 300 g of isomalt was injected as a water-insoluble carrier in the fluidized bed granulator to fluidize it. Then, the sprayed solution prepared above was sprayed into the fluidized bed granule, whereby telmisartan was coated on the surface of the carrier to prepare attached granules. Thus, granules were prepared by mixing 42.28 g of isomalt and 5.02 g of magnesium stearate in the granules attached to the carrier surface with telmisartan. The granules were tableted with one tablet.
Fluidized bed granulator inlet air temperature (inlet temp.) And the 60 ~ 70 ℃, discharge air temperature (exhaust temp.) And the 25 ~ 35 ℃, the inlet air velocity was carried out at 25 ~ 30 m 3 / h condition.
[Experimental Example 1] Content test
Telmisartan, and amlodipine (see Telmisartan Amlodipine Assay in the US Pharmacopeia USP-NF). The contents of telmisartan and amlodipine were measured for 3 months and 6 months under accelerated conditions (40 ° C., 75% relative humidity (RH)) after PTP (alu-alu) packaging. The results are shown in Table 1.
In Comparative Example 1, the content was reduced by about 5%, but the examples according to the present invention showed a decrease of less than 4%, and the change of content was less than Comparative Example 1.
[Experimental Example 2]
Telmisartan and amlodipine-related suppositories were tested (see USPP-NF telmisartan and amlodipine impurity). The stability test for amlodipine suppository was carried out under accelerated conditions (40 ° C., 75% RH) under PTP (alu-alu) packing for 6 months. The results are shown in Table 2.
The amounts of amlodipine in the Examples according to the present invention were smaller than those in Comparative Example 1. Therefore, the examples according to the present invention are superior to the comparative example 1 in terms of stability. It seems that the adsorption of moisture was small due to the specific surface area.
[Experimental Example 3]
Telmisartan was eluted at a rate of 50 rpm in 900 mL of the elution test solution according to Method 2 of the General Test Methods dissolution test described in the Pharmacopoeia General Test Methods, and the dissolution rate of telmisartan was measured. The results are shown in Tables 3 and 4 .
The dissolution rate of telmisartan was measured after dissolving in 900 mL of pH 7.5 dissolution test solution at 75 rpm according to Method 2 of the general test method dissolution test method for telmisartan, and the dissolution rate of telmisartan was measured.
Compared with Comparative Example 1, the embodiments according to the present invention were faster in initial elution at pH 1.2, pH 4.0, pH 7.5 and the like. Therefore, the composition according to the present invention is expected to have excellent biological behavior of telmisartan absorbed from above.
[Experimental Example 4]
Table 6 shows the results of evaluating the titratability of the bilayer of telmisartan and amlodipine.
1) laminating cleavage of the tablets occurred in the bilayer tablet.
In Comparative Example 1, laminating, that is, tablet cleavage occurred in the two-layer tableting. However, it can be confirmed that the examples according to the present invention are excellent in precision such as scratches and hardness.
According to the present invention, solubility and stability of telmisartan-containing medicines are increased.
Claims (11)
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Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0502314A1 (en) | 1991-02-06 | 1992-09-09 | Dr. Karl Thomae GmbH | Benzimidazol, medicaments containing them and process for their preparation |
| WO2000043370A1 (en) | 1999-01-19 | 2000-07-27 | Boehringer Ingelheim Pharma Kg | Telmisartan polymorphs, methods for producing same and their use in the preparation of a medicament |
| WO2003059327A1 (en) | 2002-01-16 | 2003-07-24 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bilayer pharmaceutical tablet comprising telmisartan and a diuretic and preparation thereof |
| KR100960953B1 (en) | 2009-09-01 | 2010-06-03 | 충남대학교산학협력단 | Preparation method of tablet containing telmisartan using wet granulation |
| KR101302883B1 (en) | 2012-07-23 | 2013-09-05 | 삼일제약주식회사 | Pharmaceutical composition comprising telmisartan with improved stability and preparation method thereof |
| KR101446603B1 (en) | 2011-11-22 | 2014-10-07 | 주식회사 인트로팜텍 | Single-layer tablet formulation for combinations comprising telmisartan |
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Patent Citations (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0502314A1 (en) | 1991-02-06 | 1992-09-09 | Dr. Karl Thomae GmbH | Benzimidazol, medicaments containing them and process for their preparation |
| WO2000043370A1 (en) | 1999-01-19 | 2000-07-27 | Boehringer Ingelheim Pharma Kg | Telmisartan polymorphs, methods for producing same and their use in the preparation of a medicament |
| WO2003059327A1 (en) | 2002-01-16 | 2003-07-24 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Bilayer pharmaceutical tablet comprising telmisartan and a diuretic and preparation thereof |
| KR100960953B1 (en) | 2009-09-01 | 2010-06-03 | 충남대학교산학협력단 | Preparation method of tablet containing telmisartan using wet granulation |
| KR101446603B1 (en) | 2011-11-22 | 2014-10-07 | 주식회사 인트로팜텍 | Single-layer tablet formulation for combinations comprising telmisartan |
| KR101302883B1 (en) | 2012-07-23 | 2013-09-05 | 삼일제약주식회사 | Pharmaceutical composition comprising telmisartan with improved stability and preparation method thereof |
Non-Patent Citations (1)
| Title |
|---|
| Pratikkumar A. Patel et al., International Journal of Pharma Sciences and Research (IJPSR) Vol. 1(8), 2010, 282-292. |
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