WO2021182467A1 - 顆粒及びそれを用いた製剤 - Google Patents

顆粒及びそれを用いた製剤 Download PDF

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Publication number
WO2021182467A1
WO2021182467A1 PCT/JP2021/009284 JP2021009284W WO2021182467A1 WO 2021182467 A1 WO2021182467 A1 WO 2021182467A1 JP 2021009284 W JP2021009284 W JP 2021009284W WO 2021182467 A1 WO2021182467 A1 WO 2021182467A1
Authority
WO
WIPO (PCT)
Prior art keywords
polymer
drug substance
component
granules
molten component
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/JP2021/009284
Other languages
English (en)
French (fr)
Japanese (ja)
Inventor
尚輝 吉原
翔太 橋本
崚太 木全
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.)
Sawai Pharmaceutical Co Ltd
Original Assignee
Sawai Pharmaceutical 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 Sawai Pharmaceutical Co Ltd filed Critical Sawai Pharmaceutical Co Ltd
Priority to KR1020227026916A priority Critical patent/KR20220123689A/ko
Priority to CN202180017989.5A priority patent/CN115209876A/zh
Priority to EP21766854.0A priority patent/EP4119129A4/en
Priority to JP2022507218A priority patent/JP7487290B2/ja
Publication of WO2021182467A1 publication Critical patent/WO2021182467A1/ja
Anticipated expiration legal-status Critical
Priority to US17/942,333 priority patent/US20230014578A1/en
Priority to JP2024029031A priority patent/JP2024063111A/ja
Ceased legal-status Critical Current

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Classifications

    • 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
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/145—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with 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
    • A61K9/14—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
    • A61K9/1617—Organic compounds, e.g. phospholipids, fats
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/4985—Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems
    • 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
    • A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
    • A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular 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
    • A61K9/14—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
    • A61K9/1635—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
    • 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
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin

Definitions

  • the present invention relates to granules having a high content, a drug substance, and a uniform particle size, and a preparation using the same.
  • the drug substance is granulated with various additives.
  • the granulation method is divided into wet granulation and dry granulation depending on the presence or absence of a solvent.
  • a dry granulation method that does not use a solvent is selected.
  • the melt granulation method in which the additive is melted by heat and used as a binder is used.
  • Patent Document 1 describes drug-containing particles produced by the melt granulation method.
  • the particles described in Patent Document 1 have not been studied at all for the control of granulated particles.
  • one object of the present invention is to provide a molten granulated product having a high drug content.
  • Another object of the present invention is to provide a pharmaceutical composition using the molten granulated product.
  • a granule containing a drug substance, a molten component, and a polymer, to which the drug substance, the molten component, and the polymer are bound.
  • the polymer may be solid at room temperature and have a glass transition point of 100 ° C. or lower.
  • the polymer may be selected from the group consisting of aminoalkyl methacrylate copolymers, ammonioalkyl methacrylate copolymers, methacrylic acid copolymers, hypromellose acetate succinates, or polyvinylpyrrolidone. good.
  • the drug substance, the molten component, and the polymer may have a structure in which they are melted and mixed with each other.
  • It may have a structure in which a part of the drug substance, the molten component, and the polymer is melted and bonded to each other.
  • 50% by mass or more of the drug substance may be contained with respect to the total mass of the drug substance, the molten component and the polymer.
  • a pharmaceutical product containing any of the above granules and one or more pharmaceutically acceptable additives is provided.
  • the additive may be a disintegrant.
  • granules having a high content of API and a uniform particle size are provided.
  • a preparation containing granules having a high content of a drug substance and a uniform particle size is provided.
  • FIG. 1 is a schematic view (cross-sectional view) showing the granules 10 according to the embodiment of the present invention.
  • Granule 10 contains drug substance 11, melt component 13, and polymer 15.
  • the granule 10 is a particle formed by binding the drug substance 11, the molten component 13, and the polymer 15 by melt granulation.
  • the API 11 is not particularly limited.
  • a solvent, particularly water is not used, so that a water-unstable API can be preferably used.
  • the melt component 13 constituting the granule 10 is selected from oil-based additives applicable to melt granulation. Further, the molten component 13 is preferably selected from additives in which the API 11 is not denatured or a significant increase in related substances is observed due to contact with the API 11. Since the granules 10 are formed by the melt granulation method, the melt component 13 is selected from additives that are solid at room temperature. Considering the temperature range generally used in the melt granulation method, the melt component 13 is preferably selected from the additives having a melting point of 100 ° C. or lower, and the drug substance 11 is denatured and a remarkable increase in related substances is observed. It is preferable to select from additives having a melting point in a temperature range that does not cause damage. Further, the molten component 13 is selected in consideration of the combination with the polymer 15.
  • the polymer 15 is compatible with the molten component and is selected from additives applicable to melt granulation.
  • the polymer is "compatible" with respect to the molten component, it means that the molten component and the polymer are not separated from each other. Alternatively, it indicates a state in which the polymer is dispersed in the molten component, or a state in which the molten component is dispersed in the polymer. In one embodiment, the state in which the molten component and the polymer are not separated is confirmed by an increase in the viscosity of the mixture (liquid or semi-solid having fluidity) when the molten component and the polymer are mixed and the molten component is melted. can do.
  • the polymer 15 is preferably selected from additives in which the API 11 is not denatured by contact with the API 11 or a significant increase in related substances is observed.
  • the polymer 15 is selected from additives that are solid at room temperature. Considering the temperature range generally used in the melt granulation method, the polymer 15 is preferably selected from additives having a glass transition point of 100 ° C. or lower, and the drug substance 11 is modified or a significant increase in related substances is observed. It is preferable to select from additives having a glass transition point in a temperature range that is not recognized. Further, the polymer 15 is selected in consideration of the combination with the molten component 13.
  • the polymer 15 is an aminoalkyl methacrylate copolymer, an ammonioalkyl methacrylate copolymer, a methacrylic acid copolymer, or hypromellose.
  • Acetate ester succinate or polyvinylpyrrolidone can be combined.
  • stearic acid can be combined as the melt component 13
  • aminoalkyl methacrylate copolymer, ammonioalkyl methacrylate copolymer, or polyvinylpyrrolidone can be combined as the polymer 15.
  • lauromacrogol as the molten component 13 and aminoalkyl methacrylate copolymer, ammonioalkyl methacrylate copolymer, methacrylic acid copolymer, or hypromellose acetate succinate ester can be combined as the polymer 15.
  • the drug substance 11, the melt component 13, and the polymer 15 need only form granules, and the drug substance 11, the melt component 13, and the polymer 15 are melted and mixed with each other. It may have a structure in which a part of the drug substance 11, the molten component 13, and the polymer 15 are melted and bonded to each other.
  • FIG. 2 is a flow chart illustrating a method for producing granules according to an embodiment of the present invention.
  • the drug substance 11, the melt component 13 and the polymer 15 are mixed, and the drug substance 11, the melt component 13 and the polymer 15 are melted and granulated by a melt granulation method to form granules 10 (S101).
  • the temperature of these additives is heated to a temperature equal to or higher than the melting point of the molten component 13 and equal to or higher than the glass transition point of the polymer 15.
  • the heating temperature is 100 ° C. or lower. It is preferable to perform melt granulation in a temperature range in which the API 11 is not denatured or a significant increase in related substances is observed.
  • the drug substance 11, the molten component 13, and the polymer 15 can be bound to each other to produce the granules 10.
  • the granules 10 can be easily produced by the melt granulation method.
  • a preparation using the granule 10 can be produced.
  • granules 10 and a pharmaceutically acceptable known additive may be mixed to prepare a pharmaceutical composition.
  • the pharmaceutical composition may be tableted into tablets.
  • the pharmaceutical composition to which the disintegrant is added may be tableted to obtain an orally disintegrating tablet.
  • the pharmaceutical composition may be encapsulated in a capsule to form a capsule tablet.
  • aminoalkyl methacrylate copolymer E (Evonik, Eudragit (registered trademark) EPO), ammonioalkyl methacrylate copolymer RL (Evonik, Eudragit (registered trademark) RLPO), methacrylate copolymer L (Evonik, Eudragit (registered trademark)) L100-55), hypromellose acetate succinate (Shin-Etsu Chemical Co., Ltd., Shin-Etsu AQOAT® HPMC AS LF), or polyvinylpyrrolidone (BASF, K30) was used.
  • Example 1 310.2 g of sitagliptin phosphate as a drug substance, 37.5 g of stearic acid (Nichiyu Co., Ltd.) as a melting component, and 37.5 g of aminoalkyl methacrylate copolymer E (Ebonic, Eudragit® EPO) as a polymer. It was put into a dynamic granulator (Paurec Co., Ltd., MP-01), and the rotor rotation speed was 400 rpm, the supply air volume was 0.24 L / min to 0.37 L / min, and the supply air temperature was 82.9 ° C to 89.6 ° C. Granulation was performed for 100 minutes. At this time, the temperature of the additive was 55.4 ° C to 68.1 ° C.
  • SEM scanning electron microscope

Landscapes

  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Public Health (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Medicinal Preparation (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Glanulating (AREA)
PCT/JP2021/009284 2020-03-11 2021-03-09 顆粒及びそれを用いた製剤 Ceased WO2021182467A1 (ja)

Priority Applications (6)

Application Number Priority Date Filing Date Title
KR1020227026916A KR20220123689A (ko) 2020-03-11 2021-03-09 과립 및 그것을 이용한 제제
CN202180017989.5A CN115209876A (zh) 2020-03-11 2021-03-09 颗粒和使用该颗粒的制剂
EP21766854.0A EP4119129A4 (en) 2020-03-11 2021-03-09 GRANULES AND THEIR USE
JP2022507218A JP7487290B2 (ja) 2020-03-11 2021-03-09 顆粒及びそれを用いた製剤
US17/942,333 US20230014578A1 (en) 2020-03-11 2022-09-12 Granules and preparation using same
JP2024029031A JP2024063111A (ja) 2020-03-11 2024-02-28 顆粒及びそれを用いた製剤

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US202062988083P 2020-03-11 2020-03-11
US62/988,083 2020-03-11

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US17/942,333 Continuation US20230014578A1 (en) 2020-03-11 2022-09-12 Granules and preparation using same

Publications (1)

Publication Number Publication Date
WO2021182467A1 true WO2021182467A1 (ja) 2021-09-16

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ID=77670617

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Application Number Title Priority Date Filing Date
PCT/JP2021/009284 Ceased WO2021182467A1 (ja) 2020-03-11 2021-03-09 顆粒及びそれを用いた製剤

Country Status (7)

Country Link
US (1) US20230014578A1 (https=)
EP (1) EP4119129A4 (https=)
JP (2) JP7487290B2 (https=)
KR (1) KR20220123689A (https=)
CN (1) CN115209876A (https=)
TW (1) TWI850539B (https=)
WO (1) WO2021182467A1 (https=)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2024115533A (ja) * 2023-02-14 2024-08-26 沢井製薬株式会社 コーティング顆粒、コーティング顆粒を含む製剤及びそれらの製造方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH05194193A (ja) * 1991-11-14 1993-08-03 Dai Ichi Seiyaku Co Ltd マスクされた粒状物
JPH06116138A (ja) * 1992-03-12 1994-04-26 Taisho Pharmaceut Co Ltd 経口製剤用組成物
JP2016511223A (ja) 2012-12-21 2016-04-14 サノフイ フェキソフェナジン高含有固形単位およびその製造法

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US5965161A (en) * 1994-11-04 1999-10-12 Euro-Celtique, S.A. Extruded multi-particulates
UA80393C2 (uk) * 2000-12-07 2007-09-25 Алтана Фарма Аг Фармацевтична композиція, яка містить інгібітор фде 4, диспергований в матриці
JP4310605B2 (ja) * 2001-05-25 2009-08-12 大塚製薬株式会社 医薬用組成物
KR100913281B1 (ko) * 2002-02-21 2009-08-21 오츠카 세이야쿠 가부시키가이샤 서방 제제 및 그의 제조 방법
JP4779970B2 (ja) * 2004-06-03 2011-09-28 大正製薬株式会社 経口製剤およびその製造方法
JP5905872B2 (ja) * 2010-04-07 2016-04-20 ルピン・リミテッド タペンタドールの制御放出医薬組成物
JP2015054822A (ja) * 2013-09-10 2015-03-23 ニプロ株式会社 クロピドグレル含有錠剤およびその製造方法
WO2017196712A1 (en) * 2016-05-09 2017-11-16 Dispersol Technologies, Llc Improved drug formulations
JP2018083809A (ja) * 2016-11-16 2018-05-31 沢井製薬株式会社 シロドシン含有粒子の製造方法及びシロドシン含有口腔内崩壊錠の製造方法
JP6895779B2 (ja) * 2017-03-17 2021-06-30 東和薬品株式会社 アジルサルタン含有固形医薬組成物

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH05194193A (ja) * 1991-11-14 1993-08-03 Dai Ichi Seiyaku Co Ltd マスクされた粒状物
JPH06116138A (ja) * 1992-03-12 1994-04-26 Taisho Pharmaceut Co Ltd 経口製剤用組成物
JP2016511223A (ja) 2012-12-21 2016-04-14 サノフイ フェキソフェナジン高含有固形単位およびその製造法

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
PAWAR, A. H. ET AL.: "Development and evaluation of taste masked granular formulation of satranidazole by melt granulation technique", JOURNAL OF PHARMACEUTICS, vol. 2014, 789676, 12 February 2014 (2014-02-12), pages 1 - 7, XP055856729 *
See also references of EP4119129A4

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2024115533A (ja) * 2023-02-14 2024-08-26 沢井製薬株式会社 コーティング顆粒、コーティング顆粒を含む製剤及びそれらの製造方法
JP7817300B2 (ja) 2023-02-14 2026-02-18 沢井製薬株式会社 コーティング顆粒、コーティング顆粒を含む製剤及びそれらの製造方法

Also Published As

Publication number Publication date
EP4119129A1 (en) 2023-01-18
EP4119129A4 (en) 2024-01-24
TWI850539B (zh) 2024-08-01
KR20220123689A (ko) 2022-09-08
JP2024063111A (ja) 2024-05-10
CN115209876A (zh) 2022-10-18
JP7487290B2 (ja) 2024-05-20
JPWO2021182467A1 (https=) 2021-09-16
TW202200118A (zh) 2022-01-01
US20230014578A1 (en) 2023-01-19

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