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WO2013035423A1 - Composition pharmaceutique contenant du candésartan cilexétil - Google Patents

Composition pharmaceutique contenant du candésartan cilexétil Download PDF

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Publication number
WO2013035423A1
WO2013035423A1 PCT/JP2012/067428 JP2012067428W WO2013035423A1 WO 2013035423 A1 WO2013035423 A1 WO 2013035423A1 JP 2012067428 W JP2012067428 W JP 2012067428W WO 2013035423 A1 WO2013035423 A1 WO 2013035423A1
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WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
capsule
preparation
candesartan cilexetil
formulation
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/JP2012/067428
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English (en)
Japanese (ja)
Inventor
高橋　雅人
後藤　正浩
遠藤　隆浩
愛 吉野
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Toyo Capsule Co Ltd
Original Assignee
Toyo Capsule Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Toyo Capsule Co Ltd filed Critical Toyo Capsule Co Ltd
Priority to JP2013532485A priority Critical patent/JP5991978B2/ja
Publication of WO2013035423A1 publication Critical patent/WO2013035423A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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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
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1658—Proteins, e.g. albumin, gelatin
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4858—Organic compounds
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/06—Antihyperlipidemics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/12—Antihypertensives

Definitions

  • the present invention relates to a pharmaceutical composition
  • a pharmaceutical composition comprising candesartan cilexetil as an active ingredient, and the elution rate and stability of the active ingredient are enhanced.
  • Candesartan cilexetil is an antihypertensive agent that exhibits angiotensin II (AII) receptor antagonism.
  • AII angiotensin II
  • Commercially available formulations are tablets for oral administration, but candesartan cilexetil is very poorly soluble in water. (Solubility ⁇ 0.05 ⁇ g / ml)
  • this compound is polyvinyl pyrrolidone (PVP), or this compound, PVP and nonionic surfactant are dissolved in ethanol, and then the formed component is granulated using this solution as a binder, and then compressed into tablets. Made up of.
  • PVP polyvinyl pyrrolidone
  • Patent Document 2 proposes the use of polyethylene glycol 6000 as a stabilizer that suppresses the degradation of the active ingredient over time in solid preparations such as tablets containing candesartan cilexetil (Compound V). ing.
  • This technique is not sufficiently considered for improving the dissolution rate.
  • the aforementioned solid preparation for oral administration containing candesartan cilexetil in a substantially amorphous form and a solubilizer requires a complicated process including the use of an organic solvent such as ethanol, and is resistant to heat.
  • This compound which is unstable and unstable, has not been fully considered for its formulation process and storage stability.
  • the dissolution rate is not sufficiently considered.
  • the object of the present invention is therefore to provide a new formulation for oral administration of candesartan cilexetil which is improved in these drawbacks, in particular a formulation which is even higher than was possible by the prior art in terms of both dissolution rate and stability. It is to be.
  • the pharmaceutical composition of the present invention is provided by uniformly dispersing candesartan cilexetil in a crystalline state in a carrier containing a gelling agent.
  • the carrier containing the gelling agent can contain an adjuvant (adjuvant) that can combine functions such as drug elution rate and / or viscosity adjustment of the preparation and / or drug stabilization.
  • the pharmaceutical composition of the present invention is a pharmaceutical composition in which candesartan cilexetil in a crystalline state is supported on a hydrogel of a gelling agent used in the pharmaceutical field.
  • the pharmaceutical composition of the present invention can be made into solid preparations such as tablets, capsules, granules, powders, oral jelly preparations and the like by conventional formulation techniques.
  • a particulate preparation, a capsule preparation, and a multilayer capsule preparation are desirable.
  • the particulate preparation is a solid preparation produced by dropping a pharmaceutical composition onto a cooling medium that is not compatible with the pharmaceutical composition and solidifying.
  • the capsule preparation is a solid preparation produced by filling a pharmaceutical composition into a capsule or encapsulating with a capsule film, or using the pharmaceutical composition as a capsule film.
  • Multi-layer capsule formulation is a solid product produced by dripping and solidifying a pharmaceutical composition at least triple or more concentrically increasing multiple concentric nozzles in a cooling medium incompatible with the solution dripped from the outermost layer. It is a formulation.
  • the pharmaceutical composition of the present invention uniformly disperses candesartan cilexetil, it is possible to provide a preparation with high content uniformity.
  • the solid preparation prepared using the pharmaceutical composition of the present invention comprises only a step of uniformly dispersing candesartan cilexetil and a preparation step, and can provide a preparation with a very simple manufacturing process.
  • the pharmaceutical composition of the present invention can be blended with ingredients classified as antihypertensive agents or hyperlipidemia agents.
  • the compounding component can be contained in a pharmaceutical composition containing candesartan cilexetil.
  • candesartan cilexetil When it is difficult to mix together, such as when stability is reduced when blended with candesartan cilexetil, or when the blended component is a liquid / semi-solid component, the capsule formulation or multilayer capsule formulation should be used.
  • candesartan cilexetil and the blending component can be blended separately in the same preparation. This makes it possible to provide a compounding agent having excellent stability.
  • a higher elution rate than that of candesartan cilexetil drug substance can be obtained. This is because the wettability of candesartan cilexetil was greatly improved by uniformly dispersing candesartan cilexetil in a carrier containing a gelling agent. In addition, by uniformly dispersing candesartan cilexetil, variation in elution is reduced and a stable elution rate is obtained.
  • Candesartan cilexetil is known to be destabilized by crystal distortion caused by heat, pressure, friction, etc., but candesartan cilexetil is uniformly dispersed in a crystalline state in a carrier containing a gelling agent. Thus, stability in the preparation is ensured, and storage stability is also ensured.
  • the example of the particulate formulation manufactured by dripping a pharmaceutical composition on the cooling medium incompatible with a pharmaceutical composition, and solidifying The example of the capsule formulation which used the pharmaceutical composition as the capsule content. The example of the capsule formulation which used the pharmaceutical composition as the capsule membrane
  • 10 is a graph obtained by measuring the elution rate of the compositions of Sample 7 to Sample 12 tested in Test Example 2.
  • 10 is a graph obtained by measuring the elution rate of the compositions of Sample 13 to Sample 18 tested in Test Example 2. The graph which compared the elution rate of the composition of the prescription 1 thru
  • 10 is a graph comparing the dissolution rate of the compositions of Formulations 7 to 11 tested in Test Example 3 with the dissolution rate of the control (candesartan cilexetil drug substance).
  • the pharmaceutical composition of the present invention it is convenient to start from the step of preparing a hydrous sol of the gelling agent to be used in advance and supporting candesartan cilexetil in the crystalline state.
  • various additives including a plasticizer such as glycerin are also dissolved in water together with the gelling agent to prepare a hydrous sol containing the additive, and candesartan cilexetil is uniformly dispersed therein.
  • the hydrous sol loaded with candesartan cilexetil can then be processed into oral dosage formulations such as particulate formulations, capsule formulations, multilayer capsule formulations, capsule coatings and the like.
  • Gelling agent is a chemical substance that gels and solidifies liquid. Those used in the pharmaceutical field are selected. Specifically, agar, carrageenan, alginate, pectin, cellulose, gelatin, mannan, glucomannan, gum arabic, tragacanth gum, tamarind gum, modified starch polymer, dextrin, soybean Examples include protein, collagen, ovalbumin, casein, fibrin, elastin, keratin, chitosan, curdlan, gellan gum, xanthan gum, and hyaluronic acid. Gelatin is preferable.
  • the carrier containing the gelling agent can use the gelling agent alone or a mixture thereof.
  • a plasticizer, a preservative, etc. can be used for the support
  • the gelling agent is 0.01 to 10000 parts by weight, preferably 0.1 to 1000 parts by weight, more preferably 1 to 100 parts by weight with respect to 1 part by weight of candesartan cilexetil.
  • Candesartan cilexetil is uniformly dispersed in a carrier containing a gelling agent in a crystalline state. At this time, in order to uniformly disperse candesartan cilexetil, it is preferable that the gelling agent is heated, dissolved, and mixed together with a plasticizer, an antiseptic, and the like in advance.
  • candesartan cilexetil is dispersed in a carrier, it can be dispersed at an arbitrary ratio with respect to the carrier.
  • auxiliary additives other than plasticity and preservatives can be used.
  • the auxiliary additive can have functions such as control of drug dissolution rate, viscosity adjustment, and drug stabilization.
  • auxiliary additives that can be used include:
  • sucrose fatty acid ester polyvinylpyrrolidone, crospovidone, crystalline cellulose, polyethylene glycol, titanium oxide, light anhydrous silicic acid, magnesium stearate, hypromellose, methylcellulose and the like.
  • sucrose fatty acid esters include DK esters (SS, F-160, F-140, F-110, F-90, F-70, F-50, F-20W, F-10) (Daiichi Kogyo Seiyaku) Manufactured).
  • polyvinylpyrrolidone include Kollidon K25, Kollidon K30, Kollidon K90 (manufactured by BASF Japan) and the like.
  • Examples of crospovidone include Kollidon CL-M (manufactured by BASF Japan).
  • Examples of the crystalline cellulose include Theolas (manufactured by San-Eigen F.F.I.).
  • As polyethylene glycol macrogol 200, macrogol 300, macrogol 400, macrogol 600, macrogol 1000, macrogol 1500, macrogol 1540, macrogol 4000, macrogol 6000, macrogol 20000, macrogol 35000 (Sanyo) Chemical Industries).
  • Examples of titanium oxide include titanium oxide (manufactured by Sakai Chemical Industry), titanium oxide A-HR (manufactured by Freund Industries), and the like.
  • Examples of the light silicic acid anhydride include ADSOLIDER-101 (manufactured by Freund Sangyo).
  • magnesium stearate examples include magnesium stearate (manufactured by Saneigen F.F.I, manufactured by NOF Corporation).
  • hydroxypropylcellulose examples include TC-5 (manufactured by San-Eigen F.F.I.).
  • methyl cellulose examples include METALOSE SM (Shin-Etsu Chemical Co., Ltd.).
  • the auxiliary additive can be added in an amount of 0.1 to 100 parts by weight, preferably 20 parts by weight, based on 1 part by weight of candesartan cilexetil.
  • the pharmaceutical composition of the present invention in which candesartan cilexetil in a crystalline state is supported on a water-containing gel is prepared by a conventional formulation technique using tablets, capsules, It can be a solid preparation such as a granule, powder, or oral jelly.
  • the capsule composition can also be made into a capsule preparation by making the pharmaceutical composition of the present invention into a capsule content or a capsule film.
  • the capsule preparation can be produced by a conventional method for producing soft capsules or hard capsules.
  • the soft capsule can be produced by any one of a seamless method, a flat plate method, and a rotary die method.
  • a hard capsule can be manufactured by the method of filling the content of a capsule of a granule, a liquid, and a paste. Specific examples of the preparation are shown in FIGS.
  • the pharmaceutical composition of the present invention is dropped into a cooling medium that is incompatible with the solution dripped from the outermost layer using at least three or more concentrically increasing concentric multiple nozzles, and solidified to form a multilayer capsule formulation Is also possible.
  • the multilayer capsule preparation is composed of layers formed by dropping from each nozzle of a multiple nozzle, and is expressed as a first layer, a second layer, a third layer, and the like (hereinafter the same) from the center.
  • the multilayer capsule preparation containing the pharmaceutical composition of the present invention is formed by dropping the pharmaceutical composition from any one of the multiple nozzles. Moreover, it can also be set as a compounding formulation by dripping a compounding component from either nozzle at this time. A specific example of the formulation is shown in FIG.
  • the gelling agent when the gelling agent is gelatin, it dissolves well in hot water and gels at 35 ° C or lower. Therefore, in order to uniformly disperse the drug, it is necessary to add it before gelation of the gelatin solution.
  • a hot gelatin solution in which the drug is dispersed is dropped as a droplet into a cold hydrophobic liquid such as vegetable oil or medium-chain fatty acid triglyceride to cause gelation.
  • a hot gelatin solution in which the drug is dispersed is dropped as a droplet into a cold hydrophobic liquid such as vegetable oil or medium-chain fatty acid triglyceride to cause gelation.
  • the amount of hot water for dissolving gelatin is desirably the minimum necessary, but generally, the total amount of glycerin added as a plasticizer is the same amount to 5 times the weight of gelatin.
  • a particle preparation made of a gel carrying a drug needs to be dried to reduce the moisture of the gel in order to prevent sticking and microbial growth.
  • the drying method is arbitrary, it is better to avoid a high temperature of 40 ° C. or higher.
  • a plasticizer is included, it does not become brittle even if it is dried to the same extent as the moisture content of 9 to 12% of the dry gelatin.
  • As a simple method for measuring the degree of drying of the gel there is a method for measuring the water activity of the gel.
  • Water activity can be considered as 1/100 of the equilibrium relative humidity in the sealed container containing the sample, and is used as a numerical value indicating the amount of free water in the food that microorganisms can use for growth. These measuring instruments are commercially available. In the case of the present invention, the degree of drying of the granular preparation or capsule film is sufficient if the water activity is below 0.8.
  • the pharmaceutical composition of this invention can also mix
  • Antihypertensive agents include, for example, amlodipine besilate, azelnidipine, alanidipine, efonidipine hydrochloride, cilnidipine, nicardipine hydrochloride, nisoldipine, nitrendipine, nifedipine, nilvadipine, varnidipine hydrochloride, felodipine, benidipine hydrochloride, manidipine hydrochloride, azelnidipine, Compounds with calcium antagonism such as diltiazem hydrochloride and benidipine hydrochloride, hydrochlorothiazide, trichlormethiazide, benchylhydrochlorothiazide, meticlan, ind
  • drugs for hyperlipidemia examples include pravastatin sodium, simvastatin, fluvastatin sodium, atorvastatin calcium hydrate, statins such as pitavastatin calcium and rosuvastatin calcium, anion exchange resins such as colestimilan and colestimide, clofibrate Fibrates such as clinofibrate, bezafibrate and fenofibrate, nicotinic acid derivatives such as tocopherol nicotinate, nicomol and niceritrol, cholesterol absorption inhibitors ezetimibe, probucol and ethyl icosapentate.
  • statins such as pitavastatin calcium and rosuvastatin calcium
  • anion exchange resins such as colestimilan and colestimide
  • clofibrate Fibrates such as clinofibrate, bezafibrate and fenofibrate
  • nicotinic acid derivatives such as tocopherol nico
  • the compounding component can be compounded in a pharmaceutical composition containing candesartan cilexetil.
  • the stability decreases, or the compounding component is a liquid / semi-solid component.
  • candesartan cilexetil and the blending component can be blended separately as a capsule preparation or a multilayer capsule preparation. A specific example of the formulation is shown in FIG.
  • the packaging form is not particularly limited, but a packaging form considering ease of taking is desirable, and a stick shape or the like is preferred.
  • Test example 1 First, in order to examine the storage stability of candesartan cilexetil (hereinafter simply referred to as “drug”) in various auxiliary additives, the following severe stability test was conducted. 30 mg of the drug and 0.9 g of various additive components were weighed in a transparent glass container and heated at about 80 ° C. for 30 minutes, and it was visually observed whether or not the drug was dissolved in these components. Next, the liquid was transferred to a glass bottle, sealed, and stored for 2 weeks in an environment of temperature 50 ° C. and humidity 75% RH, and the drug content after storage was quantified by HPLC to calculate the residual rate. The results are shown in Table 1.
  • Test example 2 Next, in order to confirm the dissolution property of the drug by the auxiliary additive, a dissolution test using a powdered powder was performed. Samples 1 to 18 were prepared by uniformly mixing 0.95 g of various auxiliary additives shown in Table 2 with 50 mg of the drug. An amount of each sample corresponding to 2 mg of drug was taken, filled into a hard capsule, and a dissolution test was performed. The dissolution test was conducted by the Japanese Pharmacopoeia, General Test, and dissolution test paddle method. The test solution was 20% 1.0% polysorbate solution, 900 mL, and the rotation speed was 50 rpm. A sinker was used. 20 mL was sampled at the specified time and the drug content was measured by HPLC. The results are shown in FIG. 6, FIG. 7, and FIG.
  • Test example 3 In order to observe the effect on the drug dissolution of the specimens whose dissolution was improved in Test Example 2, the effect on the drug dissolution by preparing a particulate formulation for formulations 1 to 11 shown in Table 3 was observed.
  • An appropriate amount of water was added to the ingredients excluding the drug and mixed, and the mixture was heated at about 70 ° C. to dissolve the gelatin.
  • the drug was added and dispersed uniformly to obtain a pharmaceutical composition.
  • the pharmaceutical composition is dropped into an incompatible cooling medium, which is a medium-chain fatty acid triglyceride, and the particles obtained by solidification are dried to a water activity of 0.3 to obtain a particulate preparation in the form of a hydrogel. Prepared.
  • the dissolution test was conducted by the Japanese Pharmacopoeia, General Test, and dissolution test paddle method.
  • the test solution was 20% 1.0% polysorbate solution, 900 mL, and the rotation speed was 50 rpm.
  • the test was carried out by taking an amount corresponding to 2 mg of drug for each particulate preparation.
  • the test was conducted at 10 mg for convenience of collection. 20 mL was sampled at the specified time and the drug content was measured by HPLC. About each result, it converted into the elution rate with respect to the amount of active ingredients, and the elution property was compared.
  • Test example 4 In order to examine the storage stability of the particulate preparation prepared in Test Example 3, the following severe stability test was conducted. The particulate preparation was put in a glass bottle and sealed, and stored in an environment of a temperature of 50 ° C. and a humidity of 75% RH, taken out after 2 weeks and 4 weeks, the drug content was quantified by HPLC, and the residual rate was calculated. The results are shown in Table 4.
  • Prescription Example 1 The following ingredients except the particulate drug were mixed and heated at about 70 ° C. to dissolve the gelatin. After dissolution, the drug was added and dispersed uniformly to obtain a pharmaceutical composition. The pharmaceutical composition was added dropwise to an incompatible cooling medium (for example, medium-chain fatty acid triglyceride) and dried to have a water activity of 0.3 to produce a particulate preparation. At this time, it was manufactured so that the drug content per grain was, for example, 0.125 to 1 mg.
  • an incompatible cooling medium for example, medium-chain fatty acid triglyceride
  • Particulate preparation (compound) The following components excluding the drug and blended components were mixed and heated at about 70 ° C. to dissolve the gelatin. After dissolution, the drug and compounding ingredients were added and dispersed uniformly to obtain a pharmaceutical composition. The pharmaceutical composition was added dropwise to an incompatible cooling medium (for example, medium-chain fatty acid triglyceride) and dried to have a water activity of 0.3 to produce a particulate preparation. At this time, it was manufactured so that the drug content per grain was, for example, 0.125 to 1 mg.
  • an incompatible cooling medium for example, medium-chain fatty acid triglyceride
  • Capsule formulation The capsule contents except the drug were mixed and dissolved by heating at about 70C. After dissolution, the drug was added and dispersed uniformly to produce a pharmaceutical composition.
  • the pharmaceutical composition was filled into a capsule film by a conventional method for producing soft capsules to produce a capsule preparation. At this time, it was filled in such an amount that the drug content per capsule was 2 mg, for example.
  • the capsule preparation was dried to have a water activity of 0.5.
  • Capsule formulation (compound)
  • the capsule content components excluding the drug and the compounding components were mixed and heated at about 70 ° C. to dissolve. After dissolution, the drug and compounding ingredients were added to produce a pharmaceutical composition.
  • the pharmaceutical composition was filled into a capsule film by a conventional method for producing soft capsules to produce a capsule preparation. At this time, it was filled in such an amount that the drug content per capsule was 2 mg, for example.
  • the capsule preparation was dried to have a water activity of 0.5.
  • [Prescription Example 17] Capsule formulation The capsule contents except the drug were mixed and dissolved by heating at about 70C. After dissolution, the drug was added and dispersed uniformly to produce a pharmaceutical composition. The pharmaceutical composition was filled into hard capsules in an amount such that the drug content per capsule was 2 mg, for example, by a conventional method for producing hard capsules to obtain a capsule preparation.
  • [Prescription Example 19] Capsule formulation The capsule contents except the drug were mixed and dissolved by heating at about 70C. After dissolution, the drug was added, and the uniformly dispersed product was granulated and dried to a water activity of 0.3 to produce a pharmaceutical composition. The pharmaceutical composition was filled into hard capsules in an amount such that the drug content per capsule was 2 mg, for example, by a conventional method for producing hard capsules.
  • [Prescription Example 20] Capsule formulation The capsule film components except the drug were mixed and dissolved by heating at about 70C. After dissolution, the drug was added and dispersed uniformly to produce a pharmaceutical composition. The capsule contents were filled into the capsule film (pharmaceutical composition) by a conventional method for producing soft capsules to produce a capsule preparation. At this time, the drug content per capsule was, for example, 2 mg. The capsule preparation was dried to have a water activity of 0.5.
  • Capsule formulation Capsule film components excluding the drug were mixed and heated at about 70C to dissolve gelatin. After dissolution, the drug was added and dispersed uniformly to produce a pharmaceutical composition. The capsule contents were simultaneously dropped from the central nozzle and the pharmaceutical composition was simultaneously dropped from the outer nozzle, and a capsule preparation was produced according to a conventional seamless capsule production method. At this time, the capsule preparation was dried to have a water activity of 0.5.
  • Multi-layer capsule formulation The ingredients of the third layer excluding the drug were mixed and heated at about 70C to dissolve the gelatin. After dissolution, the drug was added and dispersed uniformly to produce a pharmaceutical composition. A first layer, a second layer, and a third layer (pharmaceutical composition) were simultaneously dropped from the center, and a multilayer capsule preparation was produced according to a conventional method for producing seamless capsules. At this time, the multilayer capsule preparation was dried so that the water activity was 0.3.
  • compositions of Formulation Examples 1 to 9 and Formulation Examples 26 to 30 prepared to contain 0.125 mg to 1 mg of active ingredient per preparation are counted in the number corresponding to the single dose shown in Table 5 and packaged and packaged.
  • the packaging form is, for example, packaged in a stick-shaped package.

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Abstract

L'invention concerne une composition pharmaceutique contenant du candésartan cilexétil, dans laquelle la stabilité et le taux d'élution du médicament sont augmentés par rapport à ceux obtenus dans des compositions pharmaceutiques classiques. L'invention concerne une composition pharmaceutique comprenant : un hydrogel d'un agent gélifiant et du candésartan cilexétil qui est sous forme cristalline et est supporté sur l'hydrogel.
PCT/JP2012/067428 2011-09-09 2012-07-09 Composition pharmaceutique contenant du candésartan cilexétil Ceased WO2013035423A1 (fr)

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JP2013532485A JP5991978B2 (ja) 2011-09-09 2012-07-09 カンデサルタンシレキセチル含有医薬組成物

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Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2017210415A (ja) * 2016-05-24 2017-11-30 三生医薬株式会社 経口医薬組成物及び該組成物からなる粒子状製剤の製造方法
CN111000821A (zh) * 2019-12-30 2020-04-14 河南新孚望新材料科技有限公司 一种羟丙基淀粉空心胶囊及其制备方法
CN111743869A (zh) * 2019-03-29 2020-10-09 南京济群医药科技股份有限公司 一种匹伐他汀钙片剂及其制备方法

Citations (4)

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