WO2019111960A1 - Emballage de médicament de solifénacine amorphe - Google Patents

Emballage de médicament de solifénacine amorphe Download PDF

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Publication number
WO2019111960A1
WO2019111960A1 PCT/JP2018/044764 JP2018044764W WO2019111960A1 WO 2019111960 A1 WO2019111960 A1 WO 2019111960A1 JP 2018044764 W JP2018044764 W JP 2018044764W WO 2019111960 A1 WO2019111960 A1 WO 2019111960A1
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Prior art keywords
package
solifenacin
weight
preparation
desiccant
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PCT/JP2018/044764
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English (en)
Japanese (ja)
Inventor
浩人 寺田
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大原薬品工業株式会社
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Priority to JP2019558256A priority Critical patent/JPWO2019111960A1/ja
Publication of WO2019111960A1 publication Critical patent/WO2019111960A1/fr

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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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/47—Quinolines; Isoquinolines
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P13/00—Drugs for disorders of the urinary system
    • A61P13/10—Drugs for disorders of the urinary system of the bladder
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00

Definitions

  • the present invention relates to the field of pharmaceutical formulations.
  • Solifenacin (R) -quinuclidin-3-yl (S) -1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate) is a class of anticholinergic drugs that causes contraction of bladder smooth muscle It is a drug to suppress. Solifenacin is a drug with excellent selective antagonism to the muscarinic M3 receptor, and in particular succinate succinate has been used as a treatment for urinary urgency, frequent urination and urge incontinence in overactive bladder There is.
  • Solifenacin or a salt of persimmon has the property of being easily amorphized in a formulation process such as granulation. Because amorphized solifenacin or a salt of salmon is extremely poor in chemical stability, stabilization of the salmon is an important issue in providing a preparation containing solifenacin.
  • the pharmaceutical preparation of amorphous solifenacin or salmon can be pharmaceutically acceptable by including a preparation containing the amorphous form of solifenacin or a pharmaceutically acceptable salt of salmon in a package having a specific configuration. Means are provided to stabilize various salts. Also provided in the present disclosure is a package comprising a formulation comprising amorphous solifenacin or a pharmaceutically acceptable salt of sputum.
  • the pharmaceutically acceptable salt of solifenacin or lupus is solifenacin succinate.
  • the desiccant has a moisture absorption rate (temperature 25 ° C. ⁇ 2.5 ° C., relative humidity 90%, 48 hours) of 10% or more, or 15% or more, preferably 20.0% or more. More preferably, it is 30.0% or more.
  • the desiccant is selected from the group consisting of silica gel, calcium chloride, calcium oxide, zeolite and the like.
  • the desiccant comprises silica gel or calcium chloride.
  • the formulation is a tablet.
  • the package corresponds to a sealed container, an airtight container, or a sealed container in the Japanese Pharmacopoeia.
  • the package is SP packaging, PTP packaging, pillow packaging, stick packaging, glass bottle packaging, plastic bottle packaging or packaging.
  • the preparation contains at least 1.0% by weight, preferably at least 3.0% by weight, of the amorphous form of solifenacin or a pharmaceutically acceptable salt of sputum based on the total weight of the preparation.
  • the amount of the desiccant is at least 100 parts by weight with respect to 100 parts by weight of the amorphous solifenacin or a pharmaceutically acceptable salt of a lozenge.
  • a package containing a preparation comprising amorphous solifenacin or a pharmaceutically acceptable salt of mochi and a desiccant (Item 2) The package described in the above item, wherein the solifenacin or the pharmaceutically acceptable salt of zeta is solifenacin succinate. (Item 3) The packaging body in any one of the said items whose moisture absorption rate of the said desiccant is 20.0% or more in 90% of relative humidity. (Item 4) The packaging body in any one of the said items whose moisture absorption rate of the said desiccant is 30.0% or more in 90% of relative humidity.
  • (Item 5) Package according to any of the preceding items, wherein the desiccant is selected from the group consisting of silica gel, calcium chloride, calcium oxide and zeolite.
  • (Item 6-1) Packaged material according to any of the preceding items, wherein the desiccant comprises silica gel.
  • (Item 6-2) Package according to any of the preceding items, wherein the desiccant comprises calcium chloride.
  • (Item 7) Package according to any of the preceding items, wherein the formulation is a tablet.
  • (Item 8) The package according to any of the preceding items, wherein the package is a closed container, an airtight container or a sealed container.
  • the preparation comprises 1.0% by weight or more of the amorphous form of solifenacin or a pharmaceutically acceptable salt of sputum based on the total weight of the preparation.
  • the preparation comprises 3.0% or more by weight of the amorphous solifenacin or a pharmaceutically acceptable salt of a lozenge based on the total weight of the preparation.
  • (Item 12) The package according to any one of the above items, wherein the desiccant is 100 parts by weight or more relative to 100 parts by weight of the amorphous solifenacin or a pharmaceutically acceptable salt of salmon.
  • (Item 13) A method of treatment of urinary urgency, frequent urination and urge incontinence in overactive bladder comprising providing a package according to any of the preceding items.
  • (Item 14) Use of the package according to any of the above items in the manufacture of a medicament for the treatment of urinary urgency, frequent urination and urge incontinence in overactive bladder.
  • a preparation containing an amorphous solifenacin or an amber salt in the package of the present invention, it is possible to use an amorphous solifenacin or an amber salt (especially an amorphous form), which has poor chemical stability. Even formulations containing solifenacin succinate) can be stored chemically and very stably in the long term. Thereby, it is possible to use the amorphous form of solifenacin or a salt of salmon as a medicine.
  • “pharmaceutically acceptable” refers to a government regulatory agency approved for use in animals, and more particularly humans, or a pharmacopoeia or other generally accepted pharmacopeia It means that it is listed in.
  • amorphous or “amorphous” refers to a solid substance in which atoms or molecules in the solid of the crucible do not form a regular space lattice. Determining whether the material is amorphous is determined using techniques known in the art, such as powder X-ray diffraction (PXRD), DSC, NMR or near infrared spectroscopy. Can.
  • package refers to any material capable of containing a substance (e.g., a pharmaceutical) within the interior of a bottle.
  • hermetic container refers to those defined in the Japanese Pharmacopoeia. More specifically, the term “closed container” refers to a container capable of preventing solid foreign matter from being mixed in under normal handling, transport or storage conditions, and preventing loss of contents. “Airtight container” refers to a container which can prevent loss of solid or liquid foreign matter and prevent loss, dissolution, deliquescence or evaporation of the content drug in a normal handling, transport or storage state. A sealed container refers to a container in which gas does not enter under normal handling, transport or storage conditions.
  • the "hygroscopicity” refers to the ability of the desiccant to absorb moisture at a relative humidity, which is calculated according to the method defined in the JIS standard.
  • the moisture absorption rate is calculated by the following method.
  • the sample is crushed in advance and sieved using a nominal size of 840 or less according to JIS Z 8801 (standard sieve), mixed well and heated at 170 to 190 ° C for about 2 hours, then type A (moisture at low humidity 0.3 to 0.5 g for a desiccant with strong adsorption power, or 0.2 to 0.4 g for a B-type desiccant (a desiccant that absorbs a large amount of moisture at high humidity and has a large adsorption capacity) Quickly spread the entire thickness of the bottom of the flat scale balance bottle (having an outer diameter of 40 mm, a height of 20 mm, and a ground glass stopper according to JIS R 3503 (glassware for chemical analysis) as much as possible.
  • JIS Z 8801 standard sieve
  • the package of the present invention contains a preparation comprising amorphous solifenacin or a pharmaceutically acceptable salt of a lozenge as an active ingredient.
  • Solifenacin (R) -quinuclidin-3-yl (S) -1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate
  • R -quinuclidin-3-yl
  • S -1-phenyl-1,2,3,4-tetrahydroisoquinoline-2-carboxylate
  • Solifenacin is currently marketed as solifenacin succinate (Vesicare®), but in the process of formulation of solifenacin succinate by wet granulation, an amorphous form of solifenacin succinate is formed.
  • solifenacin or salmon's salt is amorphous, its chemical stability is very poor compared to when it is crystalline.
  • the amorphous form of solifenacin or a salt of salmon is easily oxidized, and an oxidized solifenacin is produced as a main decomposition product.
  • the unstable amorphous solifenacin or the salt of an anther is stabilized to provide a preparation containing the active ingredient or a package containing the preparation.
  • salts of solifenacin include succinate, hydrochloride, sulfate, nitrate, acetate, citrate, hydrobromide, maleate, fumarate, pamoate, tartaric acid
  • the salts include, but are not limited to, salts, oxalates and phosphates.
  • the salt of solifenacin is succinate.
  • the package defines an inner space, and the inner space can contain the medicine.
  • the package contains the desiccant together with the medicine in the internal space.
  • the shape and material of the package those known in the art can be used.
  • the package includes a sealed container, an airtight container or a sealed container.
  • the package can be SP packaging, PTP packaging, pillow packaging, stick packaging, glass bottle packaging, plastic bottle packaging or sachets.
  • SP packaging is an abbreviation for Strip Package packaging and includes heat seal type packaging made of aluminum foil or cellophane laminated film laminated thermoplastic polymer film such as low density polyethylene. It is often used for powder and granule sachets.
  • PTP (Press Through Pack) packaging includes sheet-like packaging in which a solid preparation such as a tablet or a capsule is sandwiched between plastic and aluminum. The aluminum part is broken by pushing the plastic part strongly, and the inside of the preparation is taken out one by one.
  • the pillow package is a kind of bag-like package, and includes, for example, a package in which a longitudinal central portion of the packaging material is laminated and the upper and lower ends are sealed.
  • a package in which a longitudinal central portion of the packaging material is laminated and the upper and lower ends are sealed In the case where it is difficult to ensure the quality only by the primary packaging, in many cases, one using a composite film laminated with aluminum foil or the like for protection from moisture and light is used as a secondary packaging.
  • the shape and material of the package it is possible to adopt other shapes and materials of straw.
  • the size of the fold can be adjusted by the way of containing the preparation.
  • the size of the internal space is about 0.2 cm 3 to about 2.0 cm 3 , about 0. It may be about 5 cm 3 to about 1.5 cm 3 , or about 0.8 cm 3 to about 1.2 cm 3 .
  • the size of the internal space is about 1 cm 3 to about 500 cm 3 It may be about 5 cm 3 to about 150 cm 3 , about 10 cm 3 to about 100 cm 3 , about 15 cm 3 to about 60 cm 3 , about 20 cm 3 to about 50 cm 3 , preferably about 30 cm 3 .
  • the package may contain about 1 to about 100 mg, about 5 to about 80 mg, or about 10 to about 50 mg of desiccant per cm 3 of internal space size in the interior space of the tub. Preferably, the package contains about 33 mg of desiccant per cm 3 of internal space size.
  • the package of the present invention preferably contains a desiccant.
  • desiccant those known in the art can be used without limitation, and examples thereof include quick lime, calcium chloride, diphosphorus pentaoxide, concentrated sulfuric acid, sodium hydroxide or potassium hydroxide as a chemical desiccant.
  • Metallic sodium, anhydrous sodium sulfate, anhydrous copper sulfate, magnesium perchlorate are mentioned, and as a physical desiccant (a water surface is adsorbed by the porous surface), silica gel, aluminum oxide, molecular sieve, allophane, zeolite Can be mentioned.
  • the moisture absorption of the desiccant may be greater than or equal to 20.0% at 90% relative humidity, and preferably, the moisture absorption of the desiccant may be greater than or equal to 30.0% at 90% relative humidity.
  • the desiccant is preferably silica gel, calcium chloride or zeolite. It is demonstrated in the examples herein that these desiccants could be used to improve the scientific stability of the amorphous form of solifenacin salt.
  • the desiccant is more preferably silica gel or calcium chloride.
  • Silica gel (silica gel) is a substance obtained by dehydrating and drying silica gel obtained by hydrolysis of an acid component produced by leaving an aqueous solution of sodium metasilicate (Na 2 SiO 3 ).
  • the composition formula is SiO 2 .nH 2 O, and the CAS registration number is 7631-86-9.
  • Silica gel can be used as a desiccant because it has a porous structure (pore structure) and a large surface area. Silica gel as a desiccant can be reused by evaporating water inside the pores by heating with a microwave oven or a frying pan.
  • the amount of desiccant contained in the package can be adjusted according to the shape of the package, for example, containing about 1 mg to about 100 g, about 50 mg to about 50 g, or about 100 mg to about 10 g of desiccant. can do. In one embodiment, the package contains about 1 g of desiccant.
  • the amount of desiccant in the package may be relatively constant relative to the total amount of solifenacin or a pharmaceutically acceptable salt of sputum in the formulation contained in the package.
  • the desiccant in the package is about 50 parts by weight or more, about 60 parts by weight or more, about 70 parts by weight, based on 100 parts by weight of solifenacin or a pharmaceutically acceptable salt of sputum in the formulation contained in the package.
  • the preparation used in the present invention contains amorphous solifenacin or a salt of salmon as a drug substance, and particularly preferably contains amorphous solifenacin succinate.
  • solifenacin or a salt of beard is suspended or dissolved in an aqueous solution together with a binder in order to maintain an amorphous form.
  • the amorphous solifenacin or chewing salt is preferably in the range of 1.0 to 10.0% by weight based on the total weight of the preparation (if the dosage form of the preparation is a tablet, the total weight of the uncoated tablet) And more preferably in the range of 1.5 to 5.0% by weight (if the dosage form of the preparation is a tablet, in an uncoated tablet).
  • the preparation used in the present invention contains croscarmellose sodium for the purpose of improving the chemical stability of amorphous solifenacin or a salt of salmon.
  • Croscarmellose sodium is preferably in the range of 1.0 to 500.0 parts by weight, preferably in the range of 10.0 to 400.0 parts by weight, based on 100.0 parts by weight of solifenacin in an amorphous form or a salt of salmon. And more preferably in the range of 20.0 to 300.0 parts by weight (in the case where the dosage form of the preparation is a tablet, in an uncoated tablet).
  • the preparation used in the present invention desirably contains carmellose or a cocoon salt (preferably a salt of carmellose) for the purpose of improving the dissolution of amorphous solifenacin or cocoon salt.
  • carmellose or persimmon salts include carmellose, carmellose calcium, carmellose sodium and the like, preferably carmellose calcium or carmellose sodium, and more preferably carmellose calcium.
  • the carmellose or cocoon salt is preferably in the range of 20.0 to 400.0 parts by weight, more preferably 40.0 to 300.0 to 100.0 parts by weight of the amorphous solifenacin or cocoon salt. It is contained in the range of 0 parts by weight in the preparation (in the case where the dosage form of the preparation is a tablet, in an uncoated tablet).
  • the method of adding croscarmellose sodium in the manufacturing process of the preparation used in the present invention is a method of simply mixing croscarmellose sodium with granules containing solifenacin in amorphous form or salt of salmon, in amorphous form
  • a method of spraying and coating a granulation liquid containing loin sodium, and the like is preferable, and preferably a method of simply mixing croscarmellose sodium with granules containing amorphous solifenacin or a salt of salmon. It is preferred that carmellose or salmon's salt is added together with croscarmellose sodium in the process of manufacturing the preparation of the present invention.
  • the formulation used in the present invention may contain a stabilizer.
  • the stabilizer is selected from, for example, tocopherol, butylhydroxyanisole, and tocopherol acetate, preferably selected from tocopherol and tocopherol acetate, and most preferably tocopherol.
  • the stabilizer is used in an amount of 1.0 to 100.0 parts by weight, preferably 5.0 to 50.0 parts by weight, based on 100.0 parts by weight of the amorphous solifenacin or anther salt. It is contained in the preparation (in the case of a tablet of the preparation, in an uncoated tablet).
  • compositions used in the preparation of the preparation used in the present invention include commonly used excipients, disintegrants, binders, plasticizers, lubricants, flavoring agents, surface active agents Agents, colorants, coatings and the like can be used.
  • Excipients used in the preparation used in the present invention include, for example, D-mannitol, lactose hydrate, anhydrous lactose, isomalt, trehalose, crystalline cellulose, corn starch and the like, preferably D-mannitol, It is selected from lactose hydrate, anhydrous lactose, isomalt and trehalose, more preferably D-mannitol or trehalose.
  • the excipient is preferably 10.0 to 97.0% by weight, more preferably 70.0 to 92.% by weight based on the total weight of the preparation (the total weight of the uncoated tablet when the dosage form of the preparation is a tablet). It is contained in the range of 0% by weight (in the case where the dosage form of the preparation is a tablet, in an uncoated tablet).
  • the disintegrant used in the preparation used in the present invention is, for example, low substituted hydroxypropyl cellulose, carmellose, carmellose calcium, carmellose sodium, carboxymethyl starch sodium, croscarmellose sodium, crospovidone, crystalline cellulose, starch
  • examples thereof include sodium glycolate and light anhydrous silicic acid and the like, preferably selected from carmellose, carmellose calcium, carmellose sodium and croscarmellose sodium.
  • the disintegrant is preferably 1.0 to 20.0% by weight, more preferably 2.0 to 12.0% by weight of the total weight of the preparation (when the dosage form of the preparation is a tablet, the total weight of uncoated tablets) It is contained in the formulation in the range of% by weight (in the case of a dosage form of the formulation being a tablet, in an uncoated tablet).
  • binder used in the preparation used in the present invention examples include hydroxypropyl cellulose, hypromellose, methyl cellulose, povidone, ethyl cellulose, polyvinyl alcohol, polyvinyl alcohol / acrylic acid / methyl methacrylate copolymer, polyethylene glycol etc.
  • methylcellulose or hypromellose more preferably hypromellose.
  • the binder is used in an amount of 0.01 to 10.0% by weight, preferably 0.05 to 6.0% by weight, based on the total weight of the preparation (when the dosage form of the preparation is a tablet, the total weight of uncoated tablets) In the formulation (if the dosage form of the formulation is a tablet, in an uncoated tablet).
  • the binder is used in an amount of 1.0 to 200.0 parts by weight, preferably 10.0 to 100.0 parts by weight, per 100.0 parts by weight of amorphous solifenacin or a salmon salt. It is contained in the granules containing the crystalline form of solifenacin or a salt of persimmon.
  • the lubricant used in the preparation used in the present invention includes, for example, magnesium stearate, calcium stearate, sodium stearyl fumarate and the like, and preferably magnesium stearate.
  • the lubricant is contained in the preparation in the range of 0.1 to 3.0% by weight based on the total weight of the preparation (if the dosage form of the preparation is a tablet, the total weight of the uncoated tablet) When it is, it is preferable to be contained in uncoated tablets.
  • the coating agent used for the preparation used in the present invention is selected from hypromellose, ethyl cellulose, ethyl cellulose dispersion, ethyl acrylate / methyl methacrylate copolymer dispersion, dimethylamino methacrylate / methyl methacrylate copolymer and the like.
  • the coating agent is preferably contained in the tablet in the range of 0.05 to 10.0% by weight based on the total weight of the uncoated tablet.
  • the preparation used in the present invention is a tablet
  • a general production method preferably, wet granulation compression method via wet granulation such as fluidized bed granulation and agitation granulation, most preferably fluidized bed granulation
  • manufacture by the wet granule compression method via the method for example, it is possible to manufacture by the following manufacturing methods.
  • an aqueous solution (granulated liquid) in which the drug substance and the binder are dissolved is sprayed and dried on the powder of the pharmaceutical additive to be core particles charged into the fluidized bed granulator, and the “coated granules” (core The periphery of the particle is covered with a coating layer (the same applies hereinafter).
  • the obtained coated granules (or granules containing the same) are mixed with a lubricant, croscarmellose sodium (preferably together with carmellose or a salt of salmon) and the like and compressed by a tableting machine into tablets.
  • the obtained uncoated tablet can be provided with a film coating layer.
  • the batting pressure at the time of tableting and manufacturing the tablet used in the present invention is selected from any value within the range of, for example, 300 kgf or more, more preferably 600 to 1300 kgf.
  • the preparation used in the present invention is a granule (a granulated product, preferably a coated granule) containing an amorphous solifenacin or a salt of a sophor, for obtaining an amorphous solifenacin or a salt of the salmon etc.
  • a granulated product preferably a coated granule
  • the coating layer produced through the step of spraying and coating the core particles with a granulated liquid containing, for example, amorphous solifenacin or a salt of salmon It is more preferable to include coated granules containing sophoracin in an amorphous form or a salt of salmon.
  • the above-mentioned granulation liquid contains a binder
  • the above-mentioned granules can be manufactured using a fluid bed granulator, a stirring granulator or the like.
  • a fluidized bed granulator it is manufactured by spraying an aqueous solution (granulation liquid) in which a binder and solifenacin in amorphous form or a salt of salmon are dissolved in flowing core particles. It is possible.
  • an aqueous solution (granulated liquid) in which a binder and solifenacin in amorphous form or a salt of an agar are dissolved is added to core particles in a stirring state, and drying is carried out after an agar It is possible to produce by the method of drying the wet particles on a machine.
  • the core particles are selected from, for example, pharmaceutical additives such as hydrous silicon dioxide, calcium silicate, light anhydrous silicic acid, etc., and are preferably hydrous silicon dioxide.
  • the core particles are contained in an amount of 20.0 to 500.0 parts by weight, preferably 50.0 to 300.0 parts by weight, per 100.0 parts by weight of amorphous solifenacin or anther salt. included.
  • the granules are 5.0 to 95.0% by weight, more preferably 7.0 to 60.0% by weight, based on the total weight of the preparation (the total weight of the uncoated tablet when the dosage form of the preparation is a tablet) It is preferable that the composition is contained in the preparation (in the case where the dosage form of the preparation is a tablet, in an uncoated tablet).
  • the package of the present invention can contain any amount of preparation in its inner space.
  • the unit dose preparation may be contained one in one internal space, and may be contained more than one in one internal space.
  • the unit dose formulation may be contained in the interior space of the package of about 2 to about 200, about 10 to about 150, about 20 to about 100, for example, about 80 formulations.
  • the unit dose solid dosage form may contain any amount of active ingredient, each as described herein, and the total weight per one dosage form is about 50 mg to about 500 mg, about 100 mg. ⁇ 200 mg, or about 120 mg to about 180 mg and so on, for example about 158 mg per formulation.
  • the preparation or package according to the present invention can be used for the treatment of urinary urgency, frequent urination and urge incontinence in overactive bladder, as well as solifenacin or other preparations containing a salt of lupus.
  • a package containing the preparation and the desiccant is provided.
  • a preparation an amorphous solifenacin or a pharmaceutically acceptable salt of anther, particularly one containing solifenacin succinate, is used, and as a desiccant, silica gel, calcium chloride, calcium oxide, and zeolite are used.
  • a desiccant selected from the group consisting of silica gel or calcium chloride is used, and the form of the package itself may be a sealed container, an airtight container or a sealed container, or an SP package, a PTP package, a pillow It may be packaging, stick packaging, glass bottle packaging, plastic bottle packaging or sachets.
  • the moisture absorption rate of the desiccant is about 5.0% or more, about 10.0% or more, about 15.0% or more, about 20.0% or more, about 25.0% or more, or about 30 at a relative humidity of 90%. .0% or more, about 35.0% or more, or about 40.0% or more, preferably about 20.0 or more, more preferably about 30.0% or more.
  • the content of amorphous solifenacin or pharmaceutically acceptable salt in the preparation is about 0.5% by weight, about 1.0% by weight, about 1.5% by weight based on the total weight of the preparation.
  • the desiccant in the package may be about 50 parts by weight or more, about 60 parts by weight or more, about 70 parts by weight or more, about 80 parts by weight, based on 100 parts by weight of the solifenacin or a pharmaceutically acceptable salt of a sputum. More than about 90 parts by weight, about 100 parts by weight, about 110 parts by weight, about 120 parts by weight, about 130 parts by weight, about 140 parts by weight, about 150 parts by weight or more.
  • the content (mg) of each component of the tablet ⁇ was added so as to be the content shown in Table 1 below.
  • Tablet ⁇ A coated tablet (tablet ⁇ ) was obtained in the same manner as the tablet ⁇ , except that “granule A and D-mannitol” in step (B) was replaced with “granule A, D-mannitol and trehalose”.
  • Example 1 Insert 80 tablets into a plastic (polyethylene) bottle (made by No. 2 square bottle / Shinto Chemical Co., Ltd.) (volume approx. 30 mL) and close the cap equipped with silica gel (approximately 1 g) on the back side. Thus, a package in which the tablet and the desiccant were enclosed was produced.
  • a plastic (polyethylene) bottle made by No. 2 square bottle / Shinto Chemical Co., Ltd.
  • silica gel approximately 1 g
  • Example 2 A package was obtained in the same manner as in Example 1 except that tablet ⁇ was replaced with tablet ⁇ .
  • Comparative Example 1 In the same manner as in Example 1 except that silica gel was not used, a package in which only the tablet was enclosed was produced.
  • Comparative Example 2 In the same manner as in Example 2 except that silica gel was not used, a package in which only the tablet was enclosed was produced.
  • Test Example 1 Long-term Storage Test
  • the amount of produced total analogues was measured immediately after production and after storing each preparation package of Examples 1 and 2 and Comparative Examples 1 and 2 for 6 months under conditions of a temperature of 25 ° C. and a relative humidity of 60%.
  • the measurement of sputum was performed by high performance liquid chromatography (quantification method used area percentage method). The results of the above measurement results are shown in Table 2 below.
  • the above-mentioned tablets are zeolite or silica gel (approximately 1 g each) as the desiccant
  • zeolite or silica gel approximately 1 g each
  • the package was further packaged with an aluminum pillow together with a moisture absorption rate at 105C and a relative humidity of 90% at 25 ° C. to produce a package in which the tablet and the desiccant were enclosed.
  • the amount of produced total analogues was measured immediately after production and after storing for 3 months immediately after production and under conditions of temperature 25 ° C. and relative humidity 60%.
  • the measurement of sputum was performed by high performance liquid chromatography (quantification method used area percentage method). The results of the above measurement results are shown in Table 4 below.
  • the present invention can be used to provide a medicament comprising a solifenacin of an amorphous form or a salt of an amber by stabilizing the amorphous form of solifenacin or an amber salt.

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Abstract

La présente invention stabilise soit la solifénacine amorphe, soit un sel de celle-ci. Un mode de réalisation de la présente invention concerne un emballage contenant à la fois un médicament comprenant de la solifénacine amorphe ou un sel pharmaceutiquement acceptable de celle-ci et un déshydratant. Dans un mode de réalisation, la solifénacine ou le sel pharmaceutiquement acceptable est du succinate de solifénacine. Dans un mode de réalisation, le déshydratant est choisi dans le groupe constitué par le gel de silice, le chlorure de calcium, l'oxyde de calcium et les zéolites et est de préférence un gel de silice ou du chlorure de calcium.
PCT/JP2018/044764 2017-12-06 2018-12-05 Emballage de médicament de solifénacine amorphe WO2019111960A1 (fr)

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JP2019558256A JPWO2019111960A1 (ja) 2017-12-06 2018-12-05 非晶質体ソリフェナシン製剤包装体

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Citations (5)

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Publication number Priority date Publication date Assignee Title
JP2007185490A (ja) * 2005-12-16 2007-07-26 Ono Pharmaceut Co Ltd 薬物包装体
US20100137358A1 (en) * 1996-11-05 2010-06-03 Dr. Reddy's Laboratories Ltd. Solifenacin compositions
JP2012006922A (ja) * 2010-05-28 2012-01-12 Kowa Co ロキソプロフェン含有医薬製剤
WO2012029899A1 (fr) * 2010-09-01 2012-03-08 アステラス製薬株式会社 Emballage
JP2018100271A (ja) * 2016-12-21 2018-06-28 ニプロ株式会社 固形製剤及び非晶質体の安定性を向上させる方法

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20100137358A1 (en) * 1996-11-05 2010-06-03 Dr. Reddy's Laboratories Ltd. Solifenacin compositions
JP2007185490A (ja) * 2005-12-16 2007-07-26 Ono Pharmaceut Co Ltd 薬物包装体
JP2012006922A (ja) * 2010-05-28 2012-01-12 Kowa Co ロキソプロフェン含有医薬製剤
WO2012029899A1 (fr) * 2010-09-01 2012-03-08 アステラス製薬株式会社 Emballage
JP2018100271A (ja) * 2016-12-21 2018-06-28 ニプロ株式会社 固形製剤及び非晶質体の安定性を向上させる方法

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
KAWASAKI, NAOYA: "Elucidation of chemical degradation mechanism and formulation design for bilayer tablet of mirabegron /solifenacin succinate", DOCTOR THESIS AT THE GRADUATE SCHOOL OF PHARMACEUTICAL SCIENCES, March 2017 (2017-03-01), pages 1 - 51 *
NAIYO, RYO: "Creation of overactive bladder therapeutic agent solifenacin (Vesicare", PHARM TECH JAPAN, vol. 28, no. 11, pages 93 - 97 *

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