WO2000010557A1 - Preparations solides stabilisees - Google Patents

Preparations solides stabilisees Download PDF

Info

Publication number
WO2000010557A1
WO2000010557A1 PCT/JP1999/004536 JP9904536W WO0010557A1 WO 2000010557 A1 WO2000010557 A1 WO 2000010557A1 JP 9904536 W JP9904536 W JP 9904536W WO 0010557 A1 WO0010557 A1 WO 0010557A1
Authority
WO
WIPO (PCT)
Prior art keywords
solid preparation
hydrochloride
amino
stabilized solid
present
Prior art date
Application number
PCT/JP1999/004536
Other languages
English (en)
Japanese (ja)
Inventor
Toshinori Tanaka
Tadaji Nishimura
Koichi Nakamichi
Original Assignee
Nippon Shinyaku 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 Nippon Shinyaku Co.,Ltd. filed Critical Nippon Shinyaku Co.,Ltd.
Publication of WO2000010557A1 publication Critical patent/WO2000010557A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin

Definitions

  • the present invention provides (R) — (1) -3 ′ — (2—amino: I—hydroxyxetil) -14′—fluoromethansulfonanilide hydrochloride having the following structure [I]: (Hereinafter referred to as “the compound of the present application”).
  • the compound of the present invention is an effective therapeutic agent for a disease such as urinary incontinence at a very small dose of 0.2 to 3.Omg per adult, and is currently being developed by the present applicant. It is a known substance.
  • a solid formulation of the compound of the present invention is secured by adding an excipient and the like in order to secure an appropriate size and weight, and to reduce the weight deviation. It is necessary to granulate.
  • the compound of the present invention is very stable in itself, and general excipients and the like used in pharmaceutical preparations are inert.
  • the compound of the present invention is It is supposed to be constant. However, it has been found that there is a problem with respect to the stability of the compound of the present invention even when the compound of the present invention is formed into a solid preparation by an ordinary method.
  • An object of the present invention is to provide a stable solid preparation of the compound of the present invention.
  • the present inventors have conducted intensive studies and as a result, have found that the above-mentioned problems can be solved by using a sugar alcohol and starch as excipients, and have completed the present invention.
  • One aspect of the present invention is a stabilized solid preparation of the compound of the present invention, which comprises a sugar alcohol and starch as excipients (hereinafter, referred to as “the solid preparation of the present invention”).
  • the solid preparation of the present invention further containing an organic acid can be mentioned as one of the present invention, and the stability thereof is usually higher than that of a preparation not containing an organic acid.
  • the solid preparation of the present invention can further contain at least one selected from the group consisting of a disintegrant, a binder, and a lubricant. In the solid preparation of the present invention, those containing a binder and a lubricant are preferred.
  • Examples of the dosage form of the solid preparation of the present invention include tablets, powders, granules, fine granules, and capsules. Tablets are particularly suitable.
  • examples of the “sugar alcohol” as an excipient include mannitol, xylitol, sorbitol, and erythritol. Of these, mannitol is particularly suitable.
  • starch examples include corn starch, wheat starch, rice starch, and potato starch. In this, Corn starch is suitable.
  • organic acid examples include tartaric acid, phthalic acid, lingic acid, citric acid, fumaric acid, and succinic acid. Of these, tartaric acid is suitable.
  • disintegrant examples include low-substituted hydroxypropyl cellulose, starches and carmellose.
  • starch examples include the same starch as the excipient.
  • binder examples include hydroxypropyl cellulose, hydroxypropyl methylcellulose, methylcellulose, carboxymethylcellulose, polyvinyl alcohol, polyvinylpyridone, starches, arabia gum, gelatin, glucose, sucrose, traga And sodium alginate.
  • starch examples include the same starch as the excipient.
  • the “lubricant” examples include stearic acid, magnesium stearate, calcium stearate, and talc.
  • the residual ratio of the compound of the present invention is 90% after 3 months under the condition of 60 ° C, or at 40 and 6 months under the condition of 75% relative humidity. The above can be mentioned, preferably those of 95% or more.
  • the solid preparation of the present invention can be produced by a conventional method according to the selected dosage form after appropriately granulating the compound of the present invention.
  • a so-called wet method Specifically, a prescribed amount of sugar alcohol and starch are charged into a fluidized bed granulator, mixed for a certain period of time, and mixed. Binder with dissolved amount of the compound of the present invention The solution is evenly sprayed on the mixture and granulated. After the granules are sized, a lubricant is added and mixed, and the mixture is compression-molded with a suitable tableting machine to produce the solid preparation (tablet) of the present invention.
  • the solid preparation of the present invention as such a tablet can be subjected to film coating and sugar coating.
  • the total content of sugar alcohols and starches in one preparation can be in the range of 70 to 99.999 w / w%, preferably in the range of 90 to 98 w / w%.
  • the content ratio (weight ratio) of the sugar alcohol to the starch is preferably in the range of 1: 9 to 9: 1, and more preferably in the range of 6: 4 to 4: 6.
  • the concentration of the compound of the present application in one preparation varies depending on the dosage form and is not particularly limited, but is preferably in the range of 0.001 to 5 w / w%, and more preferably in the range of 0.1 to 1 w / w%. .
  • the solid preparation of the present invention can be provided as a therapeutic agent for urinary incontinence and the like.o
  • Mannitol and potato starch were employed as excipients, and a formulation of the present invention (tablet) was prepared in the same manner as in Example 1.
  • mannitol shape preparation
  • 213 g of starch excipient
  • polyvinyl alcohol in which 1.5 g of the compound of the present invention is dissolved.
  • 180 g of a 7% solution (binder) was sprayed and granulated.
  • Magnesium stearate (lubricant) (2.7 g) was added to the granulated product and mixed with a V-type mixer. The mixture was filled into the first capsule, and 260 mg of the solid preparation (capsule) of the present invention per capsule was obtained. It was prepared.
  • Sorbitol (shaping agent) 267.8 g, potato starch (excipient) 191.3 g and low-substituted hydroxypropylcellulose (disintegrant) 23 g were charged into a fluidized bed granulator and mixed for 3 minutes. Thereafter, 180 g of a 7% solution (binder) of hydroxypropyl cellulose in which 3 g of the compound of the present invention was dissolved was sprayed and granulated. This granulated product is sized with a X-mill, then 2.3 g of magnesium stearate (lubricant) is added and mixed with a V-type mixer. Then, the mixed granules were compression-molded with a tableting machine at a compression pressure of a 700 kg heavy punch to prepare 130.5 mg of the solid preparation of the present invention (tablet) per tablet.
  • Lactose (excipient) 290 g and corn starch (excipient) 193 g were charged into a fluidized bed granulator and mixed for 3 minutes. Thereafter, 180 g of a 7% polyvinyl alcohol solution (binder) in which 3 g of the compound of the present invention was dissolved was sprayed and granulated. The granules are sized with a fuser mill, and 1.5 g of magnesium stearate (lubricant) is added and mixed with a V-type mixer. The mixed granules are 700 kg heavy punch with a tableting machine. The tablets were compression-molded at a compression molding pressure of 13.4 mg to prepare a solid preparation (tablet) for comparison test of 130.4 mg per tablet. Comparative Example 2
  • Lactose (excipient) 350 g and microcrystalline cellulose (excipient) 33 g were charged into a fluidized bed granulator and mixed for 3 minutes. Thereafter, 180 g of a 7% solution (binder) of hydroxypropylcellulose in which 3 g of the compound of the present invention was dissolved was sprayed and granulated. After sieving this granulated product with a fuser mill, stir 1.5 g of magnesium phosphate (lubricant) was added and mixed with a V-type mixer. The mixed granules were compression-molded with a tableting machine at a compression molding pressure of 700 kg weight / punch. 4 mg of a comparative solid preparation (tablet) was prepared. Test Example 1 (Formulation change test)
  • the abuse test was performed under severe conditions (at 60), and the residual ratio of the compound of the present invention after 3 days in a solid state was measured.
  • 2 mg of each of the above excipients and 2 mg of the compound of the present invention were dissolved in 2 ml of water, and the compound of the present invention was dissolved in a solution state under severe conditions (60 ° C) for 15 hours.
  • the residual rate of the product was measured. The results are shown in Table 1.
  • Formulation Amount (mg)
  • the preparations of the present invention containing sugar alcohols and starches as excipients all retained the stability of the compound of the present invention sufficiently, but lactose and starch, lactose and crystalline cellulose None of the preparations according to the comparative examples using as an excipient could sufficiently maintain the stability of the compound of the present invention.
  • the preparation of the present invention also contained an organic acid such as tartaric acid.
  • the preparation of the present invention retained the stability of the compound of the present invention higher than the preparation of the present invention containing no such acid.

Abstract

L'invention concerne des préparations solides stabilisées de chlorhydrate de (R)-(-)-3'-(2-amino-1-hydroxyéthyle)-4'-fluorométhanesulfonanilide qui constituent d'excellents médicaments. Ces préparations solides stabilisées du composé susmentionné se caractérisent, par exemple, en ce qu'elles contiennent des alcools de sucre et des amidons comme agents de remplissage.
PCT/JP1999/004536 1998-08-25 1999-08-24 Preparations solides stabilisees WO2000010557A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP10/238058 1998-08-25
JP23805898 1998-08-25

Publications (1)

Publication Number Publication Date
WO2000010557A1 true WO2000010557A1 (fr) 2000-03-02

Family

ID=17024543

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/JP1999/004536 WO2000010557A1 (fr) 1998-08-25 1999-08-24 Preparations solides stabilisees

Country Status (1)

Country Link
WO (1) WO2000010557A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10104369A1 (de) * 2001-02-01 2002-08-08 Boehringer Ingelheim Pharma Verwendung von 2-Amino-(4-hydroxy-2-methansulfonamidophenyl)ethanol zur Behandlung der Harninkontinenz
US6660772B2 (en) 2001-02-01 2003-12-09 Boehringer Ingelheim Pharma Kg Use of 2-amino-1-(4-hydroxy-2-methanesulfonamidophenyl)ethanol for treating urinary incontinence
WO2004075890A1 (fr) * 2003-02-26 2004-09-10 Takeda Pharmaceutical Company Composition medicamenteuse contenant un derive d'imidazole stabilise et procede de stabilisation d'un derive d'imidazole
JP2005249570A (ja) * 2004-03-04 2005-09-15 Eisai Co Ltd 配合適性試験用試料の調製方法及びそれに用いるキット
JP2007119453A (ja) * 2005-09-29 2007-05-17 Daiichi Sankyo Healthcare Co Ltd 塩酸ブロムヘキシン含有量低下の防止方法

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6197256A (ja) * 1984-10-15 1986-05-15 イーライ・リリー・アンド・カンパニー アルキルスルホンアミドフエニルアルキルアミン類
WO1991012236A1 (fr) * 1990-02-07 1991-08-22 Nippon Shinyaku Co., Ltd. Derive de sulfonanilide et medicament

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS6197256A (ja) * 1984-10-15 1986-05-15 イーライ・リリー・アンド・カンパニー アルキルスルホンアミドフエニルアルキルアミン類
WO1991012236A1 (fr) * 1990-02-07 1991-08-22 Nippon Shinyaku Co., Ltd. Derive de sulfonanilide et medicament

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE10104369A1 (de) * 2001-02-01 2002-08-08 Boehringer Ingelheim Pharma Verwendung von 2-Amino-(4-hydroxy-2-methansulfonamidophenyl)ethanol zur Behandlung der Harninkontinenz
US6660772B2 (en) 2001-02-01 2003-12-09 Boehringer Ingelheim Pharma Kg Use of 2-amino-1-(4-hydroxy-2-methanesulfonamidophenyl)ethanol for treating urinary incontinence
WO2004075890A1 (fr) * 2003-02-26 2004-09-10 Takeda Pharmaceutical Company Composition medicamenteuse contenant un derive d'imidazole stabilise et procede de stabilisation d'un derive d'imidazole
JP2005249570A (ja) * 2004-03-04 2005-09-15 Eisai Co Ltd 配合適性試験用試料の調製方法及びそれに用いるキット
JP4526838B2 (ja) * 2004-03-04 2010-08-18 エーザイ・アール・アンド・ディー・マネジメント株式会社 配合適性試験用試料の調製方法及びそれに用いるキット
JP2007119453A (ja) * 2005-09-29 2007-05-17 Daiichi Sankyo Healthcare Co Ltd 塩酸ブロムヘキシン含有量低下の防止方法

Similar Documents

Publication Publication Date Title
EP0281200B1 (fr) Composition pharmaceutique, granulé pharmaceutique et leur procédé de fabrication
JP4084309B2 (ja) 単一の結晶形を含有する固形製剤
AU737738B2 (en) Pharmaceutical preparation comprising clodronate as active ingredient and silicified microcrystalline cellulose as excipient
JP5875231B2 (ja) ピモベンダンを含む医薬組成物
EP1810676B1 (fr) Formulations de Levetiracetam et méthodes pour leur fabrication
US20110206827A1 (en) Film-coated tablet or granules containing as active ingredient a pyridylpyrimidine compound or a pharmaceutically acceptable salt of this compound
EP0605514B1 (fr) Preparations pharmaceutiques a liberation regulee
WO2020249001A1 (fr) Comprimé solide pour voie orale comprenant un inhibiteur de tyrosine kinase de bruton et son procédé de préparation
CN104363896A (zh) 恩替卡韦的药物组合物及制造方法
WO2006123213A1 (fr) Preparations a liberation modifiee de gliclazide
WO2012006154A1 (fr) Compositions pharmaceutiques contenant de la vanoxérine
FI96480B (fi) Menetelmä pitkävaikutteisen moniraetabletin valmistamiseksi
WO2000010557A1 (fr) Preparations solides stabilisees
CN114053421A (zh) 一种血小板生成素受体激动剂的组合物及其制备方法
CN105407876A (zh) 包含异烟肼颗粒和利福喷汀颗粒的呈可分散的片剂形式的抗结核病的稳定的药物组合物及其制备方法
EP3511001B1 (fr) Comprimé contenant de la pirfénidone et formulation de capsule
CN112057427A (zh) 一种含有布鲁顿氏酪氨酸激酶抑制剂的口服固体片剂及其制备方法
CN105407875A (zh) 包含异烟肼颗粒和利福喷汀颗粒的呈包衣片剂形式的抗结核病的稳定的药物组合物及其制备方法
CN115212206B (zh) 一种含吡非尼酮的药物组合物及其制备方法
KR20150096787A (ko) Ｎ-[5-[2-(3,5-디메톡시페닐)에틸]-2ｈ-피라졸-3-일]-4-[(3ｒ,5ｓ)-3,5-디메틸피페라진-1-일]벤즈아미드의 약학 제제
JP2002173428A (ja) クラリスロマイシン錠剤およびその製造法
EP2255791B1 (fr) Composition pharmaceutique à libération prolongée comprenant du succinate de métoprolol
CN116211814A (zh) 含高血压复方药物的制剂
KR20160141045A (ko) 보센탄을 함유한 약학적 조성물
CN113768889A (zh) 一种含西洛他唑的药物组合物及其制备方法

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): CA CN JP KR US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE

DFPE Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101)
121 Ep: the epo has been informed by wipo that ep was designated in this application
122 Ep: pct application non-entry in european phase
NENP Non-entry into the national phase

Ref country code: JP

Ref document number: 2000565878

Format of ref document f/p: F