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WO2009125483A1 - Capsule dure - Google Patents

Capsule dure Download PDF

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Publication number
WO2009125483A1
WO2009125483A1 PCT/JP2008/057084 JP2008057084W WO2009125483A1 WO 2009125483 A1 WO2009125483 A1 WO 2009125483A1 JP 2008057084 W JP2008057084 W JP 2008057084W WO 2009125483 A1 WO2009125483 A1 WO 2009125483A1
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WO
WIPO (PCT)
Prior art keywords
capsule
film
hard capsule
polyvinyl alcohol
pva
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/JP2008/057084
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English (en)
Japanese (ja)
Inventor
信治 栃尾
光一 吉中
忠省 峯田
邦夫 西
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.)
Qualicaps Co Ltd
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Qualicaps 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 Qualicaps Co Ltd filed Critical Qualicaps Co Ltd
Priority to PCT/JP2008/057084 priority Critical patent/WO2009125483A1/fr
Priority to JP2010507091A priority patent/JP5289429B2/ja
Publication of WO2009125483A1 publication Critical patent/WO2009125483A1/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
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4816—Wall or shell material
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61J—CONTAINERS SPECIALLY ADAPTED FOR MEDICAL OR PHARMACEUTICAL PURPOSES; DEVICES OR METHODS SPECIALLY ADAPTED FOR BRINGING PHARMACEUTICAL PRODUCTS INTO PARTICULAR PHYSICAL OR ADMINISTERING FORMS; DEVICES FOR ADMINISTERING FOOD OR MEDICINES ORALLY; BABY COMFORTERS; DEVICES FOR RECEIVING SPITTLE
    • A61J3/00—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms
    • A61J3/07—Devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms into the form of capsules or similar small containers for oral use

Definitions

  • This invention relates to the improvement of the hard capsule which uses a polyvinyl alcohol copolymer as a capsule film component. More specifically, the present invention relates to a hard capsule having improved crack resistance and impact resistance by improving the elongation at break of the capsule film (film) of the hard capsule, and a method for preparing the same. Furthermore, the present invention relates to a hard capsule obtained by filling the hard capsule with contents such as pharmaceuticals and foods, and a method for preparing the same.
  • a hard capsule as one of solid preparations such as pharmaceuticals and foods. This is usually filled with a powder, granule, or liquid (oil) pharmaceutical ingredient or food ingredient in a cap-like container, which is usually formed of a gelatin film, and open at one end. And completed.
  • a hard gelatin capsules are widely used because they are easy to formulate and easy to take due to the taste-masking and / or taste-masking action of pharmaceutical ingredients and food ingredients.
  • the gelatin film (coating) used in the hard gelatin capsule has a drawback that its mechanical strength is extremely lowered when the moisture contained therein is reduced.
  • hard gelatin capsules usually contain about 13 to 15% of moisture in the film, but if this is less than 10%, the film becomes less flexible and extremely brittle. For this reason, when filled with contents that require a low moisture environment as storage conditions, such as water-absorbing or water-reactive drugs and foods, the capsule film (film) will be cracked, cracked or chipped. May cause damage.
  • a capsule (Patent Document 1) using a water-soluble cellulose derivative, particularly hydroxypropylmethylcellulose (hereinafter referred to as “HPMC”) as a base material has been proposed.
  • the crack elongation and the impact resistance are enhanced by improving the elongation at break while maintaining a predetermined maximum stress of the capsule film (film). It is an object to provide a hard capsule.
  • the inventors of the present invention have been diligently studying day and night to achieve the above object, and as a film component of the capsule, polyvinyl alcohol copolymer (hereinafter referred to as “PVA copolymer”) and polyvinyl alcohol (hereinafter referred to as “ PVA ”) and a combination of an organic acid such as acetic acid and tartaric acid or a salt thereof, while maintaining the predetermined maximum stress required for hard capsules, the capsule film breaks. It was found that the elongation was improved, and as a result, it was confirmed that it was possible to prepare a hard capsule that was more resistant to breakage and resistant to impact.
  • PVA copolymer polyvinyl alcohol copolymer
  • PVA polyvinyl alcohol
  • the present invention has been completed based on such knowledge and includes the following aspects.
  • Capsule molding pin is dipped in a capsule preparation liquid containing PVA copolymer and PVA, and the capsule preparation liquid attached to the molding pin is gelled and dried, and then molded.
  • Hard capsule (II) A hard capsule comprising the hard capsule described in any one of (I-1) to (I-10) filled with polyethylene glycol or a composition containing polyethylene glycol .
  • Capsule film break elongation improvement method (III) Capsule film break elongation improvement method (III-1) Capsule film break elongation improvement method containing a PVA copolymer, characterized in that a PVA copolymer and PVA are used in combination as film components. how to.
  • the weight ratio of the PVA copolymer to PVA blended in the capsule film is 100: 1 to 1: 100, preferably 99: 1 to 1:99, (III-1) A method for improving the breaking elongation of a capsule film to be described.
  • the weight ratio of the PVA copolymer to PVA blended in the capsule film is 90:10 to 1: 100, preferably 90:10 to 1:99. A method for improving the breaking elongation of a capsule film to be described.
  • the weight ratio of the PVA copolymer to PVA blended in the capsule film is 50:50 to 1: 100, preferably 50:50 to 1:99. A method for improving the breaking elongation of a capsule film to be described.
  • the film component further includes at least one selected from the group consisting of an organic acid and a salt thereof, and is described in any one of (III-1) to (III-4) Method for improving elongation at break of capsule film.
  • the hard capsule of the present invention has almost the same maximum as a capsule film (coating) prepared by using a PVA copolymer without using PVA by using a PVA copolymer and PVA together as a film component. Although it is provided with stress, the elongation at break is improved, and as a result, it is a hard capsule in which cracks and cracks are less likely to occur even under low moisture (improved crack resistance). Improved cracking resistance improves (1) the production of defective products such as cracks and chips during capsule production, and improves production efficiency. (2) Physical properties such as shock and vibration during transport of capsules. There are advantages in that capsule breakage due to mechanical load is reduced, and (3) capsule breakage due to physical load caused by formulation machines such as filling machines and visual inspection machines is reduced.
  • capsules filled with the contents also reduce (i) capsule breakage due to physical loads such as impact and vibration during transportation. (Ii) Extrude PTP-packed capsules with fingers. There is an advantage that the breakage of the capsule due to the physical load at the time of taking out is reduced.
  • the hard capsule of the present invention is a low-molecular-weight PEG, a glycerin fatty acid ester, a medium-chain fatty acid triglyceride, and the like, similar to a hard capsule prepared using a conventional PVA or PVA copolymer (see Patent Documents 2 to 4). Oils and fats can be filled without any inconvenience, and there is no permeation of water vapor or oxygen, and the water-reactive substance can be suitably applied to the filling of the oxidizable substance.
  • the hard capsule of the present invention is characterized in that polyvinyl alcohol (PVA) and polyvinyl alcohol copolymer (PVA copolymer) are used in combination as components for forming a hard capsule film (capsule film). To do.
  • PVA polyvinyl alcohol
  • PVA copolymer polyvinyl alcohol copolymer
  • PVA is a polymer obtained by saponifying polyvinyl acetate.
  • the saponification degree is 97 mol% or more and a complete saponification product represented by the following formula (1), the saponification degree is 78 to 96 mol%, and the following formula:
  • any of the above-mentioned completely saponified product and partially saponified product can be used, and is not particularly limited.
  • a partially saponified product having a saponification degree of 78 to 96 mol%, particularly about 86 to 90 mol% is preferably used. It is done.
  • the degree of polymerization (n) of PVA is not particularly limited as long as it is within a range where film forming ability can be exhibited, but it is usually preferably about 400 to 3300, particularly about 400 to 2000.
  • the weight average molecular weight of the PVA is calculated from the degree of polymerization and the degree of saponification to be about 18000 to about 175000, but is not particularly limited thereto.
  • Examples of the PVA copolymer include a PVA copolymer obtained by copolymerizing a polymerizable vinyl monomer with the aforementioned PVA or a derivative thereof.
  • examples of PVA derivatives include known PVA derivatives such as amine-modified PVA, ethylene-modified PVA, and PVA having a thiol group at the terminal (terminal thiol-modified PVA). Terminal thiol-modified PVA is preferred.
  • Examples of the polymerizable vinyl monomer include (1) acrylic acid, methacrylic acid, fumaric acid, maleic acid, itaconic acid; (2) sodium salt, potassium salt, ammonium salt or alkylamine salt of the compound described in (1) above. (3) methyl methacrylate, methyl acrylate, ethyl methacrylate, ethyl acrylate, butyl methacrylate, butyl acrylate, isobutyl methacrylate, isobutyl acrylate, cyclohexyl methacrylate, cyclohexyl acrylate, 2-ethylhexyl methacrylate, 2-ethylhexyl acrylate, acrylonitrile, acrylamide, Dimethylacrylamide, styrene, vinyl acetate, hydroxyethyl methacrylate, hydroxyethyl acrylate, polyethylene glycol and methacrylic acid Ester, esters of polyethylene glycol and acrylic acid, esters of poly
  • the polymerizable vinyl monomer is preferably a combination of at least one compound selected from the group consisting of (1) and (2) and at least one compound selected from the group consisting of (3). used. Particularly preferred is a combination use of acrylic acid or methacrylic acid and methyl methacrylate.
  • the PVA copolymer is preferably a polymer copolymer obtained by copolymerizing acrylic acid and methyl methacrylate with the above-described partially saponified PVA as a skeleton.
  • Specific examples of such polymer copolymers include POVACOAT (POVACOAT (registered trademark) Type F, Type R, and Type L (manufactured by Daido Kasei Co., Ltd.)) used in the experimental examples and examples described below. it can.
  • the ratio is preferably 99: 1 to 1:99, more preferably 90:10 to 1:99, and still more preferably 80:20 to 1:99.
  • the ratio of the PVA copolymer to PVA is 50:50 to 1: 100, preferably 50:50 to 1:99, the viscosity of the capsule preparation liquid (52 ° C.
  • the ratio of PVA copolymer to PVA is 40:60 to 1: 100, preferably 40:60 to 1:99
  • the viscosity of the capsule preparation liquid (52 ° C.) Is reduced to about 1350 Pa ⁇ s or less, and accordingly, the production yield (%) of the hard capsule is also improved to 90% or more.
  • the ratio of the PVA copolymer and PVA (total amount) contained in the hard capsule (capsule film) used in the present invention is not particularly limited, but when the weight of the capsule film excluding moisture is 100% by weight, The ratio can be 70 to 99.9% by weight, preferably 80 to 99.7% by weight, and more preferably 90 to 99.5% by weight.
  • the hard capsule (capsule film) of the present invention in addition to the PVA copolymer and PVA, at least one selected from the group consisting of organic acids and salts thereof may be blended.
  • organic acid salt include, but are not limited to, edible organic acids such as acetic acid, tartaric acid, lactic acid, malic acid, succinic acid and succinic acid, or alkali metal salts thereof, particularly sodium salt and potassium salt. .
  • Acetic acid and tartaric acid or sodium and potassium salts thereof are preferred, and sodium acetate and sodium tartrate are more preferred. These may be used alone or in any combination of two or more.
  • organic acids and / or salts thereof are not limited, but usually, the organic acid and / or PVA copolymer and PVA contained in the hard capsule and the organic acid and / or salt thereof in a total amount of 100% by weight.
  • the salt (total amount) is used in such a proportion that it is contained in an amount of 0.1 to 19% by weight, preferably 0.15 to 8% by weight in terms of the proportion of the organic acid.
  • the proportion is more preferably 0.2 to 3% by weight, particularly preferably 0.5 to 1% by weight.
  • a gelling agent can also be blended in the hard capsule (capsule film) used in the present invention.
  • the gelling agent used here include carrageenan, tamarind seed polysaccharide, pectin, xanthan gum, locust bean gum, curdlan, gelatin, fur celerane, agar, and gellan gum. These may be used alone or in any combination of two or more.
  • carrageenan is an optimal gelling agent because of its high gel strength and excellent gelling properties when used in a small amount in the presence of specific ions.
  • three types of carrageenan are known: kappa-carrageenan, iota-carrageenan, and lambda-carrageenan.
  • kappa and iota-carrageenan having gelling ability can be preferably used.
  • Pectin can be classified into LM pectin and HM pectin depending on the degree of esterification, and gellan gum can be classified into acylated gellan gum (native gellan gum) and deacylated gellan gum according to the presence or absence of acylation. Can also be used without distinction.
  • a gelling aid can be used depending on the type of gelling agent used.
  • kappa-carrageenan can give one or more of potassium ion, ammonium ion and calcium ion in water.
  • compounds such as potassium chloride, potassium phosphate, ammonium chloride, ammonium acetate, calcium chloride.
  • calcium ion can be given in water, for example, calcium chloride.
  • a gelling adjuvant that can be used in combination when gellan gum is used as a gelling agent
  • carrageenan As the gelling agent used in combination, carrageenan, tamarind seed polysaccharide, xanthan gum, locust bean gum, and gellan gum are preferable, and carrageenan is particularly preferable.
  • potassium chloride can be illustrated suitably as a gelatinization adjuvant which uses this together.
  • the content is 0.05 to 10% by weight when the weight of the capsule film excluding moisture is 100% by weight.
  • 0.1 to 5% by weight more preferably 0.2 to 2.5% by weight, and still more preferably 0.3 to 2% by weight.
  • a gelling aid such as potassium chloride
  • the content thereof is in the range of 2.2% by weight or less, preferably 0.1 to 1.5% by weight, more preferably 0.2 to 1% by weight, Preferably, 0.3 to 0.8% by weight can be mentioned.
  • the hard capsule (capsule film) needs Depending on the case, a plasticizer, a metal sequestering agent, an opacifying agent, a coloring agent or a fragrance can be blended.
  • the plasticizer is not particularly limited as long as it can be used for pharmaceuticals or foods.
  • the content in the hard capsule (capsule film) used in the present invention is usually 15% by weight or less when the weight of the capsule film excluding moisture is 100% by weight. Can do. Preferably it is 13 weight% or less, More preferably, it is 11 weight% or less, More preferably, it is the range of 8 weight% or less.
  • ethylenediaminetetraacetic acid ethylenediaminetetraacetic acid, acetic acid, boric acid, citric acid, gluconic acid, lactic acid, phosphoric acid, tartaric acid, or salts thereof, metaphosphate, dihydroxyethylglycine, lecithin, ⁇ -cyclodextrin, or these Combinations can be mentioned.
  • the opacifying agent and the fragrance are not particularly limited as long as they can be used for pharmaceuticals or foods.
  • the hard capsule used in the present invention can be produced by using a conventional dipping method. Specifically, an aqueous solution containing the above-described components (hereinafter referred to as “capsule preparation solution”) is used as the dipping solution.
  • the capsule molding pin can be immersed in this, and then pulled up to cool and gel the film made of the capsule preparation liquid formed on the outer surface of the capsule molding pin, and then dried.
  • the concentration of each component contained in the capsule preparation liquid can be appropriately adjusted according to the ratio of each component in the capsule film described above.
  • the total amount of the PVA copolymer and PVA can be 5 to 30% by weight, preferably 10 to 28% by weight, more preferably 16 to 24% by weight.
  • the organic acid and / or salt thereof is 0.02 to 3.8% by weight, preferably 0.04 to 1.6% by weight, more preferably 0.04 to 0% in terms of the ratio of the organic acid. 2% by weight can be mentioned.
  • the concentration in the capsule preparation liquid is 0.01 to 2% by weight, preferably 0.02 to 1% by weight, more preferably 0.03 to 0.5% by weight. it can.
  • the concentration in the capsule preparation liquid is 0.01 to 0.5% by weight, preferably 0.02 to 0.3% by weight, more preferably 0.03 to 0.3%. 2% by weight can be mentioned.
  • the amount of the solvent (water) contained in the capsule preparation liquid is not limited, but is a temperature (immersion liquid temperature) condition (30 to 80 ° C., preferably 40 to 60 ° C.) employed when the capsule molding pin is immersed. ),
  • the ratio of the viscosity of the capsule preparation liquid is 100 to 20000 mPa ⁇ s, preferably 300 to 10000 mPa ⁇ s.
  • the viscosity of the capsule preparation liquid at a temperature condition of 52 ° C. is 300 to 3600 mPa ⁇ s, more preferably 500 to 3100 mPa ⁇ s, still more preferably 500 to 2600 mPa ⁇ s, and still more preferably 500 to 2000 mPa ⁇ s.
  • the ratio is particularly preferably 500 to 1500 mPa ⁇ s.
  • the viscosity specified in the present invention is a B-type rotational viscometer.
  • the rotor number is 2, and when the viscosity is 500 mPa ⁇ s or more and less than 2000 mPa ⁇ s, the rotor number is 3 and the viscosity is 2000 mPa ⁇ s or more.
  • the viscosity is measured when the rotor number 4 is used and measured at a predetermined temperature under the conditions of a rotation speed of 60 rpm and a measurement time of 1 minute (hereinafter the same).
  • the solvent content is 60 to 90% by weight, preferably 70 to 85% by weight.
  • the dissolution order of the above-mentioned components is not limited, and the gelling agent and the gelling auxiliary agent may be prepared by dissolving the essential components (PVA and PVA copolymer) first. Or may be dissolved simultaneously.
  • the melting temperature is usually 60 ° C. or higher, it is not particularly limited.
  • the capsule preparation liquid is preferably subjected to capsule molding by the dipping method in a state where fine bubbles are removed by vacuum degassing, ultrasonic defoaming or standing, and the temperature is kept at 50 to 60 ° C.
  • the hard capsule of the present invention was soaked in the capsule preparation liquid (immersion liquid) thus prepared, and then pulled up to gel the solution adhering to the capsule molding pin, and then gelled.
  • the film is produced by drying at a temperature of about 20 to 80 ° C.
  • the hard capsule used in the present invention can be produced through the following steps.
  • Capsule molding pin in a capsule preparation liquid (immersion liquid) containing a PVA copolymer and PVA (or an organic acid and / or a salt thereof, or a gelling agent or a gelling aid, if necessary) The step of immersing (immersion step), (2) A step of pulling up the capsule molding pin from the capsule preparation solution (immersion solution) to gel the capsule preparation solution adhering to the outer surface of the pin (gelation step), (3) A step of drying the gelled capsule film (gelated film) formed on the outer surface of the capsule molding pin (drying step), (4) A step of detaching the dried capsule film (film) from the capsule molding pin (detachment step).
  • said (2) gelatinization process can be performed by heating or cooling according to the characteristic of the gelatinizer to be used.
  • a solution containing carrageenan as a gelling agent is used as a capsule preparation liquid (immersion liquid)
  • the temperature around the capsule manufacturing machine is adjusted by utilizing that the solution gels at a temperature of 50 ° C. or less.
  • the gelation step (2) is carried out by allowing the capsule preparation solution adhering to the outer surface of the capsule molding pin to stand to cool at 35 ° C. or lower, preferably 30 ° C. or lower, preferably at room temperature. Yes (cold gel method).
  • the capsule molding pin is pulled up from the capsule preparation solution (immersion liquid)
  • the capsule preparation solution attached to the outer surface of the pin is gelled.
  • the drying step (3) can be performed at a temperature of about 20 to 80 ° C. Preferably, it is performed by blowing air at 60 ° C.
  • the detachment step (4) is performed by extracting the dry capsule film formed on the surface of the capsule molding pin from the capsule molding pin.
  • the capsule film thus prepared can be provided as a hard capsule in a state where the body part and the cap part are fitted together or not fitted after being cut and adjusted to a predetermined length.
  • edible oil or the like as a release agent to the molding pin in advance, the release properties of the obtained capsule (body part and cap part) are improved, and the obtained hard capsule can be easily peeled and collected. can do.
  • the hard capsule of the present invention is characterized by having a large elongation at break as compared with a hard capsule prepared without using PVA and a PVA copolymer in combination.
  • a breaking elongation in the range of 5 to 20 mm is usually required, and the breaking elongation is preferably as large as possible with a maximum stress in the range of 70 to 130 N.
  • the thickness is preferably 8 to 20 mm, more preferably 8.5 to 20 mm, still more preferably 9 to 20 mm, and still more preferably 9.5 to 20 mm.
  • the maximum stress is not particularly limited as long as it is within the above range, but is preferably 75 to 130N, more preferably 80 to 130N.
  • the maximum stress (N) and elongation at break (mm) were measured using an autograph AGS-J (manufactured by Shimadzu Corporation), a tensile speed of 150 mm / min, a distance between chucks of 20 mm, a tensile distance of 20 mm, 23 ° C. It can be determined by a tensile test performed in an environment with a relative humidity of 40%.
  • the maximum stress means the maximum value of the stress measured by such a method
  • the elongation at break means the tensile stroke at 1/3 of the maximum stress (see FIG. 1).
  • the target capsule (capsule film) was dried at 60 ° C. for 2 hours and then stored at 23 ° C. in an environment of 40% relative humidity for 1 week. Later, a tensile test was performed using the above conditions (Autograph AGS-J (manufactured by Shimadzu Corporation) under the environment of a tensile speed of 150 mm / min, a distance between chucks of 20 mm, a tensile distance of 20 mm, 23 ° C., and a relative humidity of 40%). Is the value obtained.
  • Hard capsule and its preparation method The body part and the cap part of the hard capsule thus prepared are filled with the above-mentioned contents, and then the body part is covered with the cap part to fit them together. Can be provided as a hard capsule.
  • the hard capsule of the present invention includes those obtained by attaching a band seal to the fitting part of the body part and the cap part of the hard capsule prepared above.
  • a hard capsule after fitting and joining the body part and the cap part, around the end edge part of the cap part, on the surface of the body part and the surface of the cap part with a constant width so as to straddle it, It can be prepared by applying the band seal preparation solution once to a plurality of times, preferably once or twice in the circumferential direction and sealing the fitting portion.
  • the fitting width where the outer circumference of the body part and the inner circumference of the cap part overlap is the distance in the axial direction of the capsule.
  • About 4 to 6 mm is generally preferred for 4.5-6.5 mm, No. 4 capsules.
  • the sealing width is generally about 1.5 to 3 mm for the No. 3 capsule and about 1.5 to 2.8 mm for the No. 4 capsule.
  • the band seal formation of the hard capsule of the present invention is not limited as long as it has at least band sealability, but preferably PVA copolymer, PVA, or PVA copolymer having the same composition as the hard capsule described above.
  • a band seal preparation solution containing a polymer and PVA also used in combination with an organic acid and / or a salt thereof, or a gelling agent or a gelling aid as required is used.
  • sorbitol can also be blended in the band seal preparation liquid as a plasticizer.
  • a plasticizer sorbitol
  • the blending ratio of sorbitol in the band seal is not particularly limited as long as it does not impair the band sealability of the PVA or / PVA copolymer, but in terms of the above effects, the band seal (in terms of dry weight: 100% by weight) ) In the range of 0.01 to 70% by weight, preferably 0.01 to 35% by weight, more preferably 0.01 to 30% by weight, and particularly preferably 1 to 30% by weight.
  • band sealability means that a film for sealing (sealing) the body part and the cap part of a hard capsule can be formed (film forming ability), and the body is sealed by sealing with this film. It means the property of the band seal that can prevent the contents from leaking out from the fitting portion between the cap portion and the cap portion (leakage prevention capability).
  • the presence or absence of the “band sealability” is determined by sealing the cap part of the capsule filled with polyethylene glycol (PEG400) with an average molecular weight of 400 (PEG400) and the fitting part of the body part using the target band seal preparation solution (band seal) When this is left on a white copy paper for 12 hours in an environment of 25 ° C. and a relative humidity of 40%, it can be evaluated by whether or not the contents leak from the band seal portion.
  • PEG400 polyethylene glycol
  • band seal target band seal preparation solution
  • the presence or absence of leakage of the contents can be determined from the following criteria as shown in Experimental Example 5: (a) Whether the contents (PEG400) are attached to the surface of the white copy paper that has been in contact with the sealed hard capsule after standing for 12 hours. (b) Whether the contents (PEG400) adhere to the white copy paper surface when the sealed hard capsule is rolled on the white copy paper after being left for 12 hours.
  • the hard capsule which uses the PVA copolymer as a base material described in Experimental Example 5 mentioned later, or the hard capsule which uses PVA as a base material can be mentioned.
  • the amount of PEG 400 filled therein may be 600 ⁇ L when the hard capsule is a size 0 capsule defined by the Japanese Pharmacopoeia, and 470 ⁇ L when the hard capsule is a size 1 capsule.
  • the band seal is optionally colored (for example, titanium oxide, bengara, tar colorant, etc.), opaque, as long as the effect of the present invention, ie, the band sealability is not hindered.
  • Additives usually used in the preparation of hard capsules such as agents or fragrances can also be blended.
  • the blending ratio of these additives to the band seal can be appropriately selected from the range of usually 0.1 to 7% by weight in consideration of the band sealing property.
  • a band seal preparation solution is usually used.
  • the band seal preparation solution is prepared by dissolving the above band seal component in water, a hydrophilic solvent, or a mixture of water and a hydrophilic solvent at room temperature or under heating (about 30 to 60 ° C.). can do.
  • a mixed solution of water and a hydrophilic solvent is used.
  • the hydrophilic solvent include organic solvents compatible with water, and specific examples include lower alcohols such as ethanol and isopropanol. Ethanol is preferable.
  • the ratio of the hydrophilic solvent in 100% by weight of the mixed liquid is 5 to 80% by weight, preferably 8 to 65% by weight, more preferably May be 10 to 50% by weight.
  • the band seal preparation liquid is adjusted so that the final viscosity of the preparation liquid is usually in the range of 100 to 5000 mPa ⁇ s under the condition of 23 ° C.
  • the viscosity is a B-type rotational viscometer.
  • the rotor number is 2
  • the viscosity is 500 mPa ⁇ s or more and less than 2000 mPa ⁇ s
  • the rotor number is 3
  • the viscosity is 2000 mPa ⁇ s or more
  • the rotor is The number 4 is used to mean the viscosity when measured under the conditions of 23 ° C., rotation speed 60 rpm, and measurement time 1 minute.
  • the band seal preparation liquid in the range where the viscosity is applied, a strong band seal with a large sealing force (sealing force) can be formed in the fitting part of the hard capsule body and cap part, and at the time of manufacture There is no stringing and the handling in production is easy. If the viscosity of the band seal preparation liquid is significantly lower than the above range (100 to 5000 mPa ⁇ s, 23 ° C.), the band seal preparation liquid may be applied without dripping onto the fitting surface of the hard capsule. It may be difficult to form a band seal excellent in sealing power.
  • the viscosity of the band seal preparation liquid when the viscosity of the band seal preparation liquid is significantly higher than the above range (100 to 5000 mPa ⁇ s, 23 ° C.), the viscosity may be too high to form a band seal with a machine.
  • the preferred viscosity of the band seal preparation liquid is 125 to 4700 mPa ⁇ s, more preferably 150 to 4500 mPa ⁇ s, at 23 ° C.
  • the viscosity of the band seal preparation liquid can be easily adjusted by adjusting the concentration of the PVA copolymer, PVA or a mixture thereof mixed in the band seal preparation liquid, or the mixing ratio of both. Specifically, the viscosity tends to decrease as the proportion of PVA used in combination with the PVA copolymer is increased.
  • the concentration of PVA in the band seal preparation liquid is usually 4 to 31% by weight, preferably 5 to 30% by weight, more preferably 6%, although it depends on the type of PVA copolymer and PVA to be blended and the degree of polymerization.
  • the concentration of PVA copolymer is usually from 5 to 27% by weight, preferably from 6 to 26% by weight, more preferably from 7 to 25% by weight.
  • the viscosity can be adjusted in consideration of the viscosity (100 to 5000 mPa ⁇ s, 23 ° C.) on the basis of the ratio of each component.
  • the concentration in the band seal preparation liquid can be determined according to the blending ratio of sorbitol in the band seal described above. Specifically, the sorbitol concentration in the band seal (100 wt%) is 0.01 to 70 wt%, preferably while considering that the viscosity of the band seal preparation solution is in the range of 100 to 5000 mPa ⁇ s. It is preferable to adjust the band seal preparation solution so as to be 0.01 to 35% by weight, more preferably 0.01 to 30% by weight, and particularly preferably 1 to 30% by weight.
  • Such a band seal is suitable as a band seal of a hard capsule in which the hard capsule of the present invention is filled with polyethylene glycol (PEG) or a composition containing the same.
  • PEG polyethylene glycol
  • the PEG is not particularly limited, and the PEG having an average molecular weight of about 20000 or less, specifically, the average molecular weight is 200, 300, 400, 600, 800, 1000, 1500, 2000, 3000, 4000, Mention may be made of 6000, 8000 or 20000 PEG.
  • PEG having each of these average molecular weights can be obtained from each manufacturer according to Japanese Pharmacopoeia and pharmaceutical additive standards (see “Japanese Pharmacopoeia” and “Pharmaceutical Additives Standards”).
  • XX indicates the approximate average molecular weight of the above-mentioned PEG).
  • Such PEG can be used individually by 1 type or in combination of 2 or more types.
  • low molecular weight PEG such as PEG having an average molecular weight of 200 to 600 (also referred to as “PEG 200 to 600”) is a PEG that is suitably used as a filling component of a hard capsule in the use of the band seal of the present invention. That is, according to the band seal of the present invention, there is no problem of bleeding even when PEG 200 to 600 is filled, and the effect of the present invention can be enjoyed more effectively.
  • the average molecular weight of PEG can be measured according to the following test according to the standards defined in “Japanese Pharmacopoeia” and “Pharmaceutical Additives Standard”.
  • PEG 200 has an average molecular weight in the range of about 190-210
  • PEG 300 has an average molecular weight in the range of about 285-315
  • PEG 400 has an average molecular weight in the range of about 380-420
  • PEG 600 has an average molecular weight of about It can be determined as being in the range of 570 to 630.
  • the content of the hard capsule may be PEG or a composition containing at least PEG as described above, and as such a composition, human or animal pharmaceuticals, quasi drugs, cosmetics, and foods containing PEG are included. Can be mentioned without limitation.
  • the proportion of PEG contained in such a composition is not particularly limited, but is usually 0.1 to 99.9% by weight, preferably 1 to 99.9% by weight, more preferably 10 to 99.9% by weight, still more preferably. 50 to 99.9% by weight can be mentioned.
  • the shape of the contents is not particularly limited.
  • it may be a liquid, gel, powder, granule, tablet, pellet, or a mixed form (hybrid) thereof.
  • tonics for example, nourishing tonics, antipyretic analgesics, antipsychotics, anxiolytics, antidepressants, hypnotic sedatives, antispasmodics, central nervous system drugs, brain Metabolic improver, cerebral circulation modifier, antiepileptic agent, sympathomimetic agent, gastrointestinal agent, antacid, antiulcer agent, antitussive expectorant, antiemetic agent, respiratory accelerator, bronchodilator, allergic agent, dental oral cavity Drugs, antihistamines, cardiotonic drugs, arrhythmia drugs, diuretics.
  • docosahexaenoic acid for example, docosahexaenoic acid, eicosapentaenoic acid, ⁇ -lipoic acid, royal jelly, isoflavone, agaricus, acerola, aloe, aloe vera, turmeric, ercarnitine, oligosaccharide, cacao, catechin, capsaicin, chamomile, agar, Tocopherol, linolenic acid, xylitol, chitosan, GABA, citric acid, chlorella, glucosamine, ginseng, coenzyme Q10, brown sugar, collagen, chondroitin, sorghum, squalene, stevia, ceramide, taurine, saponin, lecithin, dextrin, dodomi, niacin, Natto, bittern, lactic acid bacteria, saw palmetto, honey, hatomugi, plum extract, pantothenic acid,
  • Filling of the contents into the hard capsule may be performed by a capsule filling machine known per se, for example, a fully automatic capsule filling machine (model name: LIQFILsuper 80/150, manufactured by Qualicaps), a capsule filling / sealing machine (model name: LIQFILsuperFS, Qualicaps Co., Ltd.) can be used.
  • sealing of hard capsules can be carried out using a capsule filling and sealing machine known per se, such as the capsule filling and sealing machine or capsule sealing machine (model name: HICAPSEALSE40 / 100, manufactured by Qualicaps Co., Ltd.). .
  • the band seal preparation liquid can be generally used at room temperature or under heating. From the viewpoint of preventing liquid leakage of the hard capsule, it is desirable to use a seal preparation liquid preferably within a temperature range of about 23 to 45 ° C, more preferably about 23 to 35 ° C, and most preferably about 25 to 35 ° C.
  • the temperature adjustment of the seal preparation liquid can be carried out by a method known per se such as a panel heater and a hot water heater. For example, a circulating hot water heater or a seal pan unit of the integrated capsule filling and sealing machine is circulated. It is preferable to adjust with a hot water heater type modified because the temperature range can be finely adjusted.
  • alcohol for example, ethanol in the seal preparation liquid may volatilize depending on temperature conditions, it is preferable to appropriately replenish the component composition of the seal preparation liquid.
  • the thus obtained hard capsule of the present invention is excellent in operability without leaching even when PEG, particularly low molecular weight PEG having an average molecular weight of 200 to 600 is filled therein.
  • PEG particularly low molecular weight PEG having an average molecular weight of 200 to 600 is filled therein.
  • the film does not become brittle even when glycerin fatty acid ester or medium chain fatty acid triglyceride of low molecular weight PEG is filled, these low molecular weight PEG, its glycerin fatty acid ester and medium chain fatty acid triglyceride are used as excipients. It can be applied well to drugs that contain it. In addition, good strength can be maintained even when the water content in the film is reduced, and there is no inconvenience such as cracking. Therefore, it is also suitable for use in drugs that have water absorption or recommended to be stored under low moisture. Furthermore, since water vapor and oxygen hardly permeate, it is preferably used for water-reactive substances and oxidizable
  • the present invention provides a method for improving the elongation at break for a capsule film (film) containing a PVA copolymer.
  • a PVA copolymer and PVA are used in combination, and at least one selected from PVA copolymer, PVA, and an organic acid and a salt thereof. It can carry out by using together.
  • the types of organic acids and / or their salts used in combination therewith can be the same as those described in I.
  • the ratio of the organic acid and / or salt thereof used in combination with PVA and the PVA copolymer is not particularly limited.
  • the ratio of the organic acid and / or salt (total amount) contained in 100% by weight of the total amount of the PVA and PVA copolymer and organic acid and / or salt thereof is 0 in terms of the amount of organic acid.
  • the ratio can be raised to 0.1 to 19% by weight, preferably 0.15 to 8% by weight, more preferably 0.2 to 3% by weight, and particularly preferably 0.5 to 1% by weight.
  • the capsule film contains a gelling agent as described in I. It is also possible to add a gelling aid as necessary. Those types and blending ratios can also be the same as those described in I above.
  • the above components may be included in the capsule film as long as the effects of the present invention are not impaired.
  • a gelling aid if necessary, a plasticizer, a metal sequestering agent, an opacifying agent, a coloring agent or a fragrance can be blended.
  • Hard capsules obtained by applying the method for improving elongation at break of the present invention are hard capsules prepared without using PVA (hard capsules prepared by the same formulation and manufacturing method except that PVA is not used, hereinafter referred to as “control capsule”. Since the elongation at break is larger than that of the other), cracks and cracks are less likely to occur even under low moisture, and it is excellent in crack resistance and impact resistance. As described above, the hard capsule is usually required to have a breaking elongation in the range of 5 mm to 20 mm. The breaking elongation is preferably as large as possible with the maximum stress in the range of 70 to 130 N.
  • the breaking elongation is preferably 8 to 20 mm, more preferably 8.5 to 20 mm, still more preferably 9 to 20 mm, and still more preferably 9.5 to 20 mm.
  • “under low moisture” means that the moisture content (%) of the capsule film is usually 5% or less, preferably 3 to 5%, more preferably 3 to 4%.
  • the moisture content (%) of the capsule film can be measured according to the method described in Experimental Example 2 (2).
  • PVA polyvinyl alcohol
  • a capsule preparation solution containing 144% and potassium chloride (gelling aid) 0.072% was prepared, and this was applied to a glass plate using a film making applicator so that the dry thickness was 0.1 mm. Casting. This was dried at 60 ° C. for 2 hours and stored for one week in an environment of 23 ° C. and relative humidity of 40%, and then cut into a film having a length of 70 mm and a width of 10 mm to obtain a test film.
  • the tensile test was performed using an autograph AGS-J (manufactured by Shimadzu Corporation) in an environment where the tensile speed was 150 mm / min, the distance between chucks was 20 mm, the tensile distance was 20 mm, 23 ° C., and the relative humidity was 40%.
  • the maximum stress (N) and elongation at break (mm) were measured.
  • FIG. 1 shows a stress-strain curve obtained in this tensile test.
  • the maximum value of the stress (N) thus obtained corresponds to the “maximum stress” in the present invention, and the tensile stroke (tensile distance) at 1/3 of the maximum stress corresponds to the “breaking elongation” in the present invention. Equivalent to.
  • the stress at a tensile distance of 20 mm was 1/3 or more of the maximum stress
  • the elongation at break was 20 mm.
  • the viscosity (mPa ⁇ s) at 52 ° C. of the capsule preparation liquid, the water content (%), the maximum stress (N), and the elongation at break (mm) of the prepared capsule film were measured according to the following methods.
  • Viscosity (mPa ⁇ s) of capsule preparation liquid 52 ° C
  • the viscosity was measured using a B-type rotational viscometer (rotor number 3) under the conditions of 52 ° C., a rotation speed of 12 rpm, and a measurement time of 1 minute.
  • each measurement result is shown in Table 2 together with the ratio of PVA, PVA copolymer and organic acid salt of each capsule film (converted with the total amount of these components as 100% by weight).
  • the converted organic acid% means the amount of the added organic acid salt is converted into the amount of the organic acid and made a percentage with respect to the total amount.
  • FIGS. 3 to 13 show the comparison results of the measurement results of the stress (N) and the tensile stroke (mm) of the sample 1 not containing PVA and the measurement results of the samples 2 to 12 containing PVA, respectively.
  • the PVA copolymer can be combined with PVA or PVA and an organic acid salt to reduce the moisture content to 5% or less. It is considered that a hard capsule that is resistant to impact and hard to crack even under moisture conditions can be prepared.
  • Capsule production yield (%) is determined by a visual inspection machine that sorts out defective products such as bubbles in capsule film and deformation of capsules for hard capsules that have been created. The number of capsules per unit time (number of non-defective products after visual inspection) and the number of theoretical capsules manufactured per unit time (the number of theoretical capsules manufactured) were calculated according to the following formula.
  • the production yield exceeds 50% by setting the viscosity (52 ° C) of the capsule preparation liquid to about 3100 mPa ⁇ s or less, and further to about 2000 mPa ⁇ s or less.
  • the production yield exceeds 80%, and in particular, the production yield exceeds 90% by setting it to about 1500 mPa ⁇ s or less, particularly 1350 ⁇ mPa ⁇ s or less (see FIG. 14 and Table 3).
  • the capsule preparation liquid when the blending ratio of the PVA copolymer and PVA is particularly 50:50 to 1: 100, the capsule preparation liquid has a viscosity of about 1500 mPa ⁇ s or less and 40:60 to 1: 100.
  • the viscosity of the preparation liquid can be adjusted to about 1350 mPa ⁇ s or less, and as a result, the production yield of capsules can be increased to 90% or more.
  • aqueous solution thus prepared (capsule preparation solution) as an immersion liquid
  • capsule preparation solution aqueous solution
  • the size 1 hard capsule was maintained according to a conventional method while maintaining the temperature of the immersion liquid at 50 to 55 ° C. (Cap, body) was prepared.
  • the hard capsule water content (%) was determined for each of the hard capsules prepared above and stored for 1 week in an environment of 23 ° C., 12%, 22%, 33%, 43% and 53% relative humidity. Specifically, first, the weight (wet weight) of the hard capsules after the storage was measured, and then dried by heating at 105 ° C. for 2 hours, and the weight (dry weight) of each hard capsule was measured again. Next, the ratio of the amount of water that decreases by heating and drying at 105 ° C. for 2 hours according to the following formula from the difference between the weight before drying (wet weight) and the weight after drying (dry weight) (hard capsule moisture amount%) was calculated.
  • Hard capsule crack rate (%) Each hard capsule prepared above was stored for 1 week in an environment of 23 ° C., 12%, 22%, 33%, 43% and 53% relative humidity, and the cracking rate (%) of the hard capsule was determined. Specifically, a 50 g weight was naturally dropped from a height of 10 cm to each hard capsule after the storage, and the number of broken hard capsules was counted. The cracking rate (%) of the hard capsules was calculated from the number of broken hard capsules according to the following formula.
  • the obtained band seal preparation liquid was filled with 470 ⁇ L of PEG400 into a hard capsule prepared according to the method of Example 1 using a fully automatic capsule filling and sealing machine (manufactured by Qualicaps Co., Ltd.), and the above band seal preparation was performed.
  • the body part of the hard capsule and the fitting part of the cap part were sealed with a liquid to prepare a hard capsule.
  • the appearance of the sealed hard capsule was visually observed to observe the presence or absence of leakage or sorbitol precipitation, and in accordance with the following method, the temperature was 25 ° C. and the relative humidity was 40%.
  • the band sealability was evaluated from the presence or absence of leakage of the contents after standing for a period of time.
  • Viscosity of the band seal preparation liquid is measured using a B-type rotational viscometer (rotor number 2 when the viscosity is less than 500 mPa ⁇ s, rotor number 3 when the viscosity is 500 mPa ⁇ s to less than 2000 mPa ⁇ s, and viscosity is 2000 mPa In the case of s or more, the measurement was performed using a rotor number 4) under the conditions of 23 ° C., rotation speed 60 rpm, and measurement time 1 minute.
  • each sealed hard capsule was left on a white copy paper for 12 hours in an environment of a temperature of 25 ° C. and a relative humidity of 40%. After 12 hours, the presence or absence of leakage of the contents (PEG400) from the band seal part was confirmed by the following method and criteria.
  • band sealability: ⁇ when there is no adhesion of the contents to the white copy paper, that is, no leakage of the contents is recognized, “band sealability: ⁇ ”, (a) and (b) In any of the cases, the case where leakage of the contents is recognized is determined as “no band sealability: x”.
  • the PVA and PVA copolymer can be suitably used as a band seal raw material alone or as a mixture thereof, and even when sorbitol is blended in a proportion of 70% by weight or less, It turned out that it can be used conveniently.
  • the blending ratio of sorbitol is not particularly problematic if it is 70% by weight or less from the viewpoint of band sealability, but less than 40% by weight, preferably 35% by weight or less, more preferably from the point of precipitation of sorbitol. It is preferable that it is 30 weight% or less.
  • Example 1 Preparation of hard capsule (1) Preparation of hard capsule 48 kg of PVA (partially saponified PVA, polymerization degree 1000, saponification degree 86-90 mol%, manufactured by Wako Pure Chemical Industries, Ltd.) in 170 L of purified water at 40 ° C. In addition, the mixture was dispersed and heated to 82 ° C. to dissolve the PVA. This was cooled to 60 ° C. to prepare an aqueous PVA solution.
  • PVA partially saponified PVA, polymerization degree 1000, saponification degree 86-90 mol%, manufactured by Wako Pure Chemical Industries, Ltd.

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Abstract

Cette invention concerne une capsule dure fabriquée à partir d'un copolymère d'alcool polyvinylique à titre de composant de film, qui est améliorée du point de vue de l'allongement à la rupture du film de capsule, la contrainte maximale du film étant maintenue à un niveau prédéterminé et est, par conséquent, améliorée du point de vue de la résistance à la rupture et de la résistance au choc. La capsule dure selon l'invention est caractérisée en ce qu'elle est constituée d'un film de capsule préparé à partir d'une combinaison d'un copolymère d'alcool polyvinylique avec l'alcool polyvinylique.
PCT/JP2008/057084 2008-04-10 2008-04-10 Capsule dure Ceased WO2009125483A1 (fr)

Priority Applications (2)

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PCT/JP2008/057084 WO2009125483A1 (fr) 2008-04-10 2008-04-10 Capsule dure
JP2010507091A JP5289429B2 (ja) 2008-04-10 2008-04-10 硬質カプセル剤

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Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011105534A1 (fr) 2010-02-26 2011-09-01 日新化成株式会社 Capsule dure et sa méthode de production
JP2015017245A (ja) * 2013-06-13 2015-01-29 花王株式会社 洗浄剤組成物
WO2018008660A1 (fr) 2016-07-06 2018-01-11 クオリカプス株式会社 Capsule dure à dureté améliorée et son procédé de fabrication
WO2020071393A1 (fr) 2018-10-02 2020-04-09 クオリカプス株式会社 Gélule dure à résistance améliorée et son procédé de production
WO2020071395A1 (fr) 2018-10-02 2020-04-09 クオリカプス株式会社 Gélule dure à résistance améliorée et son procédé de production
KR102157584B1 (ko) * 2020-04-15 2020-09-18 (주)한국원자력 엔지니어링 알약의 제조방법
WO2021024930A1 (fr) 2019-08-02 2021-02-11 クオリカプス株式会社 Formulation de capsule dure scellée avec un bande de scellement comprenant une étiquette

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH09216818A (ja) * 1995-12-04 1997-08-19 Kyowa Hakko Kogyo Co Ltd 硬カプセル剤
JP2001170137A (ja) * 1999-12-16 2001-06-26 Shionogi Qualicaps Kk 硬質カプセル及びその製造方法
US20010043999A1 (en) * 1998-03-11 2001-11-22 Scott Robert A. Polyvinyl alcohol compositions
WO2002017848A1 (fr) * 2000-08-29 2002-03-07 Nisshin Kasei Co., Ltd. Capsule en dur

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH09216818A (ja) * 1995-12-04 1997-08-19 Kyowa Hakko Kogyo Co Ltd 硬カプセル剤
US20010043999A1 (en) * 1998-03-11 2001-11-22 Scott Robert A. Polyvinyl alcohol compositions
JP2001170137A (ja) * 1999-12-16 2001-06-26 Shionogi Qualicaps Kk 硬質カプセル及びその製造方法
WO2002017848A1 (fr) * 2000-08-29 2002-03-07 Nisshin Kasei Co., Ltd. Capsule en dur

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2011105534A1 (fr) 2010-02-26 2011-09-01 日新化成株式会社 Capsule dure et sa méthode de production
JPWO2011105534A1 (ja) * 2010-02-26 2013-06-20 日新化成株式会社 硬カプセルおよびその製造方法
US8900628B2 (en) 2010-02-26 2014-12-02 Nisshin Kasei Co., Ltd. Hard capsule and method for producing same
JP2015017245A (ja) * 2013-06-13 2015-01-29 花王株式会社 洗浄剤組成物
WO2018008660A1 (fr) 2016-07-06 2018-01-11 クオリカプス株式会社 Capsule dure à dureté améliorée et son procédé de fabrication
US11318101B2 (en) 2016-07-06 2022-05-03 Qualicaps Co., Ltd. Hard capsule having improved hardness, and method for manufacturing same
WO2020071393A1 (fr) 2018-10-02 2020-04-09 クオリカプス株式会社 Gélule dure à résistance améliorée et son procédé de production
WO2020071395A1 (fr) 2018-10-02 2020-04-09 クオリカプス株式会社 Gélule dure à résistance améliorée et son procédé de production
WO2021024930A1 (fr) 2019-08-02 2021-02-11 クオリカプス株式会社 Formulation de capsule dure scellée avec un bande de scellement comprenant une étiquette
KR102157584B1 (ko) * 2020-04-15 2020-09-18 (주)한국원자력 엔지니어링 알약의 제조방법

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