[go: up one dir, main page]

WO2024144084A1 - Composition pharmaceutique de dutastéride à dose élevée sous forme de comprimé pour administration hebdomadaire et son procédé de préparation - Google Patents

Composition pharmaceutique de dutastéride à dose élevée sous forme de comprimé pour administration hebdomadaire et son procédé de préparation Download PDF

Info

Publication number
WO2024144084A1
WO2024144084A1 PCT/KR2023/021192 KR2023021192W WO2024144084A1 WO 2024144084 A1 WO2024144084 A1 WO 2024144084A1 KR 2023021192 W KR2023021192 W KR 2023021192W WO 2024144084 A1 WO2024144084 A1 WO 2024144084A1
Authority
WO
WIPO (PCT)
Prior art keywords
dutasteride
weight
parts
self
pharmaceutical composition
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/KR2023/021192
Other languages
English (en)
Korean (ko)
Inventor
송충길
조효상
조민관
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.)
YOO YOUNG PHARM Co Ltd
Original Assignee
YOO YOUNG PHARM 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
Priority claimed from KR1020230185507A external-priority patent/KR20240102854A/ko
Application filed by YOO YOUNG PHARM Co Ltd filed Critical YOO YOUNG PHARM Co Ltd
Publication of WO2024144084A1 publication Critical patent/WO2024144084A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Images

Classifications

    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
    • 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
    • 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
    • A61P13/08—Drugs for disorders of the urinary system of the prostate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A61P17/14—Drugs for dermatological disorders for baldness or alopecia

Definitions

  • Patent Document 3 Korean Patent No. 10-0962447
  • the present invention is a high-dose Dutasteride drug that can solubilize high-dose dutasteride, a poorly soluble drug, through self-emulsifying emulsion technology and formulate it in a tablet form that can overcome the disadvantages of the soft capsule formulation.
  • the object is to provide a pharmaceutical composition of lead and a method for producing the same.
  • the present invention must contain a high dose of dutasteride for administration once a week.
  • Dutasteride known as a poorly soluble drug, is administered once a week by solubilizing a high dose of the drug through self-emulsifying emulsion technology. It can contain a high content of dutasteride for.
  • the pharmaceutical composition may include a self-emulsifying composition and one or more pharmaceutical additives selected from the group consisting of an adsorbent to which the self-emulsifying composition is adsorbed, an excipient, a disintegrant, and a lubricant, but is not limited thereto.
  • the adsorbent to which the self-emulsifying composition is adsorbed is an adsorbent carrier for preparing the liquid self-emulsifying composition in the form of powder-type granules, and includes magnesium aluminosilicate, magnesium aluminometasilicate, and low-substituted hydroxypropyl. It may be one or more selected from the group consisting of cellulose, silicon dioxide, colloidal silicon dioxide, calcium silicate, bentonite, and kaolin, but is not limited thereto.
  • the excipient is a substance intended to increase productivity and stability and increase the volume or quantity of tablets, and may be any one or more of lactose, D-mannitol, or silicate microcrystalline cellulose, but is not limited thereto.
  • the disintegrant is used to promote disintegration of the formulation to improve dissolution of the drug, and may specifically be any one or more of crospovidone, croscarmellose sodium, or low-substituted hydroxypropyl cellulose. It is not limited.
  • the pharmaceutical composition may include 0.1 parts by weight to 0.6 parts by weight of dutasteride, based on 100 parts by weight of the pharmaceutical composition. 3.5 parts by weight to 7.5 parts by weight of oil; 12.0 parts by weight to 20.0 parts by weight of surfactant; and a self-emulsifying composition containing 6.0 to 13.0 parts by weight of a co-surfactant, and 20.0 to 55.0 parts by weight of an adsorbent to which the self-emulsifying composition is adsorbed; 15.0 parts by weight to 35.0 parts by weight of excipient; 2.5 parts by weight to 6.0 parts by weight of disintegrant; and 0.5 to 1.5 parts by weight of a lubricant, but is not limited thereto.
  • parts by weight refers to the weight ratio between each component, and is specifically interpreted to mean the relative weight ratio of other components mixed when assuming that the standard component is 100 parts by weight. Therefore, the parts by weight in the above can be viewed as indicating the relative ratio of each ingredient included in the pharmaceutical composition, assuming that the entire pharmaceutical composition as a standard is 100 parts by weight.
  • dutasteride when the pharmaceutical composition in the form of a tablet is eluted in 0.1N HCl containing 2.0% SLS (sodium lauryl sulfate), more than 85% of dutasteride may be of an immediate-release type that is eluted within 15 minutes. and is not limited to this.
  • the pharmaceutical composition in the form of a tablet may be a preparation for the treatment of benign prostatic hyperplasia or androgenetic alopecia, but is not limited thereto.
  • the present invention includes the steps of (S1) preparing a self-emulsifying composition by mixing dutasteride, oil, surfactant and co-surfactant; (S2) dissolving the self-emulsifying composition in an organic solvent; (S3) mixing a solution in which the self-emulsifying composition is dissolved in an organic solvent with an adsorbent to prepare an adsorbent to which the self-emulsifying composition is adsorbed; and (S4) mixing one or more pharmaceutical additives selected from the group consisting of adsorbents to which the self-emulsifying composition is adsorbed, excipients, disintegrants, and lubricants, and then compressing into tablets. .
  • the step (S2) is mixing 1,500 to 2,500 parts by weight of oil, 4,000 to 6,000 parts by weight of surfactant, and 2,000 to 4,000 parts by weight of cosurfactant with respect to 100 parts by weight of dutasteride. It may be a step, and specifically, it is a step of mixing 1600 to 1800 parts by weight of oil, 4500 to 5500 parts by weight of surfactant, and 2500 to 3000 parts by weight of cosurfactant with respect to 100 parts by weight of dutasteride. It can be done and is not limited to this.
  • the step (S3) may be a step of preparing an adsorbent to which the self-emulsifying composition is adsorbed by mixing 50.0 to 250.0 parts by weight of an adsorbent with respect to 100 parts by weight of the self-emulsifying composition.
  • the self-emulsifying composition 100 parts by weight.
  • This may be a step of preparing an adsorbent to which the self-emulsifying composition is adsorbed by mixing 66.0 to 198.0 parts by weight of the adsorbent, but is not limited to this.
  • the step (S4) includes 10.0 parts by weight to 70.0 parts by weight of an excipient, 1.0 parts by weight to 15.0 parts by weight of a disintegrant, and 0.1 parts by weight of a lubricant based on 100 parts by weight of the adsorbent to which the self-emulsifying composition is adsorbed.
  • This may be a step of mixing 2.5 parts by weight and tableting, and specifically, 20.0 parts by weight to 60.0 parts by weight of excipient, 5.0 parts by weight to 10.0 parts by weight of disintegrant, and lubricant for 100 parts by weight of adsorbent to which the self-emulsifying composition is adsorbed.
  • This may be a step of mixing 1.0 to 2.0 parts by weight and tableting, but is not limited to this.
  • the information regarding the pharmaceutical composition in the form of a tablet described above can be applied to all methods for producing the pharmaceutical composition in the form of a tablet, as long as there is no conflict with each other.
  • dutasteride-containing solution 10 g of magnesium aluminometasilicate was added to a 250 mL beaker, the dutasteride-containing solution was added, and the mixture was stirred with a mechanical stirrer at a speed of 800 rpm to obtain a mixture.
  • the obtained mixture was dried in a hot air dryer to prepare a dutasteride-containing adsorbent in which the self-emulsifying composition was adsorbed on an adsorbent.
  • dutasteride-containing solution 15 g of magnesium aluminometasilicate was added to a 250 mL beaker, the dutasteride-containing solution was added, and the mixture was stirred using a mechanical stirrer at a speed of 800 rpm to obtain a mixture.
  • the obtained mixture was dried in a hot air dryer to prepare a dutasteride-containing adsorbent in which the self-emulsifying composition was adsorbed on an adsorbent.
  • the raw drug quantity in Table 1 refers to the content of the dutasteride-containing adsorbent for manufacturing 100 tablets containing dutasteride.
  • composition in Table 5 According to the composition in Table 5 below, 30.15 g of the dutasteride-containing adsorbent onto which the self-emulsifying composition prepared in Example 3 was adsorbed was sieved through a 35 mesh and placed in a polyethylene bag, and Croscarmel sieved through a 35 mesh was added. 2.5 g of lost sodium, 12.4 g of silicate microcrystalline cellulose, and 4.45 g of lactose hydrate were added and mixed 100 times. Here, 0.5 g of magnesium stearate sieved through a 35 mesh was added and mixed 50 times. The mixture was compressed into tablets with a total weight of 500 mg per tablet and a hardness of approximately 6 to 10 kp to prepare tablets containing dutasteride.
  • a comparative dissolution test was conducted on the high-dose dutasteride-containing tablet prepared according to Example 14 of the present invention and the commercially available Avodart soft capsule (Avodart ® ).
  • Preparation of standard solution Place approximately 15 mg of dutasteride standard in a 50 mL volumetric flask, add diluent to completely dissolve, and then adjust to the marking line. Take 5 mL of this solution, place it in a 50 mL volumetric flask, adjust the mark with the diluent, and then filter the solution through a 0.45 ⁇ m PVDF syringe filter and use it as the standard solution.
  • Group 1 was administered Avodart soft capsules (Avodart ® ) 0.5 mg orally as a single dose, 1 capsule at a time, and Group 2 was administered 0.5 mg of Avodart ® soft capsules.
  • the group was administered a single oral dose of 0.5 mg of Avordart soft capsules (Avordart ® ), 6 capsules (total 3.0 mg) once, and the third group was administered a high-dose dutasteride-containing tablet prepared according to Example 14 of the present invention once. Two tablets (total 3.0 mg) were administered orally as a single dose.

Landscapes

  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Dermatology (AREA)
  • Urology & Nephrology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne : une composition pharmaceutique de dutastéride, pouvant être administrée par voie orale une fois par semaine, et augmentant la commodité d'administration par réduction du nombre d'administrations ; et un procédé de préparation de la composition pharmaceutique.
PCT/KR2023/021192 2022-12-26 2023-12-21 Composition pharmaceutique de dutastéride à dose élevée sous forme de comprimé pour administration hebdomadaire et son procédé de préparation Ceased WO2024144084A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
KR20220184626 2022-12-26
KR10-2022-0184626 2022-12-26
KR10-2023-0185507 2023-12-19
KR1020230185507A KR20240102854A (ko) 2022-12-26 2023-12-19 주 1회 투여를 위한 정제 형태의 고함량 두타스테리드 약제학적 조성물 및 이의 제조방법

Publications (1)

Publication Number Publication Date
WO2024144084A1 true WO2024144084A1 (fr) 2024-07-04

Family

ID=91718675

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2023/021192 Ceased WO2024144084A1 (fr) 2022-12-26 2023-12-21 Composition pharmaceutique de dutastéride à dose élevée sous forme de comprimé pour administration hebdomadaire et son procédé de préparation

Country Status (1)

Country Link
WO (1) WO2024144084A1 (fr)

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5565467A (en) * 1993-09-17 1996-10-15 Glaxo Wellcome Inc. Androstenone derivative
KR101055412B1 (ko) * 2010-11-19 2011-08-08 (주)비씨월드제약 두타스테라이드를 포함하는 자가유화 에멀젼 조성물 및 이의 제조방법
KR20170059961A (ko) * 2012-01-25 2017-05-31 한미약품 주식회사 두타스테라이드 함유 자가 유화 약물전달 시스템용 조성물 및 이의 제조 방법
KR101897995B1 (ko) * 2017-11-21 2018-09-12 한국프라임제약주식회사 두타스테리드의 고체분산체, 이의 제조방법, 및 이를 포함하는 약학적 조성물
KR20180132389A (ko) * 2017-06-02 2018-12-12 (주)인벤티지랩 두타스테라이드 함유 고형 경구 제형 및 이의 제조 방법
KR102352888B1 (ko) * 2020-01-15 2022-01-18 한국프라임제약주식회사 두타스테리드를 포함하는 경구용 약제학적 조성물

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5565467A (en) * 1993-09-17 1996-10-15 Glaxo Wellcome Inc. Androstenone derivative
KR101055412B1 (ko) * 2010-11-19 2011-08-08 (주)비씨월드제약 두타스테라이드를 포함하는 자가유화 에멀젼 조성물 및 이의 제조방법
KR20170059961A (ko) * 2012-01-25 2017-05-31 한미약품 주식회사 두타스테라이드 함유 자가 유화 약물전달 시스템용 조성물 및 이의 제조 방법
KR20180132389A (ko) * 2017-06-02 2018-12-12 (주)인벤티지랩 두타스테라이드 함유 고형 경구 제형 및 이의 제조 방법
KR101897995B1 (ko) * 2017-11-21 2018-09-12 한국프라임제약주식회사 두타스테리드의 고체분산체, 이의 제조방법, 및 이를 포함하는 약학적 조성물
KR102352888B1 (ko) * 2020-01-15 2022-01-18 한국프라임제약주식회사 두타스테리드를 포함하는 경구용 약제학적 조성물

Similar Documents

Publication Publication Date Title
WO2021125797A1 (fr) Composition présentant une solubilité et une biodisponibilité améliorées de l'olaparib
WO2018021772A1 (fr) Formulation ayant des caractéristiques améliorées de libération de médicament en fonction du ph, contenant de l'ésoméprazole ou un sel pharmaceutiquement acceptable de celui-ci
WO2017003186A1 (fr) Formule complexe pharmaceutique comprenant de l'amlodipine, du losartan et de la rosuvastatine
WO2019199133A1 (fr) Composition de comprimé enrobé à administration par voie orale à base de lénalidomide
WO2019045501A1 (fr) Préparation solide comprenant du dutastéride et procédé de préparation associé
WO2016126058A2 (fr) Dispersion solide contenant du dutastéride et composition la contenant
WO2017043913A1 (fr) Composition pharmaceutique comprenant du dutastéride et formulation en gélule la comprenant
WO2020017808A1 (fr) Comprimé à désintégration orale contenant de la nalfuron
EP3648745A1 (fr) Composition pharmaceutique comprenant un comprimé sphéroïdal à unités multiples contenant de l'ésoméprazole et un sel de qualité pharmaceutique de celui-ci, et procédé de préparation de la composition pharmaceutique
WO2018124700A1 (fr) Nouvelle préparation contenant un dérivé de benzimidazole
WO2024144084A1 (fr) Composition pharmaceutique de dutastéride à dose élevée sous forme de comprimé pour administration hebdomadaire et son procédé de préparation
WO2023113488A1 (fr) Combinaison pharmaceutique à commodité améliorée à usage interne par réduction de taille pour formulation comprenant de la dapagliflozine et de la sitagliptine et son procédé de préparation
WO2012148181A2 (fr) Composition à libération contrôlée de médicaments
WO2018079984A1 (fr) Comprimé complexe à action rapide contenant du dutastéride et du tadalafil
WO2021167364A1 (fr) Composition pharmaceutique comprenant de l'ésoméprazole et du bicarbonate de sodium présentant d'excellentes propriétés de libération
WO2024144207A1 (fr) Comprimé à libération prolongée comprenant de l'apixaban
WO2019245309A1 (fr) Préparation pharmaceutique à libération prolongée comprenant du tacrolimus
WO2020096210A1 (fr) Composition d'hydrogel de silice comprenant de la goséréline pour injection sous-cutanée à libération prolongée et à libération lente
KR20240102854A (ko) 주 1회 투여를 위한 정제 형태의 고함량 두타스테리드 약제학적 조성물 및 이의 제조방법
WO2013032206A1 (fr) Composition orale à libération prolongée contenant du chlorhydrate d'itopride, et procédé de préparation associé
WO2022146007A1 (fr) Composition orale d'éfinaconazole
WO2016137266A2 (fr) Composition pharmaceutique contenant de l'épérisone et du pélubiprofène
WO2017116031A1 (fr) Composition pharmaceutique contenant du géfitinib, pouvant être administrée à des patients présentant une intolérance au lactose, et présentant une commodité de dosage améliorée
WO2022035003A1 (fr) Composition pharmaceutique comprenant du dutastéride
WO2020213868A1 (fr) Préparation d'une association de produits pharmaceutiques comprenant de l'ézétimibe et du losartan

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 23912759

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE