EP1058539A1 - Procede de preparation d'un principe actif pharmaceutique contenant un medicament non hydrosoluble et composition pharmaceutique pour l'administration orale contenant ledit principe - Google Patents

Procede de preparation d'un principe actif pharmaceutique contenant un medicament non hydrosoluble et composition pharmaceutique pour l'administration orale contenant ledit principe

Info

Publication number
EP1058539A1
EP1058539A1 EP99901236A EP99901236A EP1058539A1 EP 1058539 A1 EP1058539 A1 EP 1058539A1 EP 99901236 A EP99901236 A EP 99901236A EP 99901236 A EP99901236 A EP 99901236A EP 1058539 A1 EP1058539 A1 EP 1058539A1
Authority
EP
European Patent Office
Prior art keywords
water
oil
drug
insoluble drug
active ingredient
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.)
Withdrawn
Application number
EP99901236A
Other languages
German (de)
English (en)
Inventor
Soon-Hong Yuk
Sun-Hang Cho
Hai-Bang Lee
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.)
Korea Research Institute of Chemical Technology KRICT
Original Assignee
Korea Research Institute of Chemical Technology KRICT
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 Korea Research Institute of Chemical Technology KRICT filed Critical Korea Research Institute of Chemical Technology KRICT
Publication of EP1058539A1 publication Critical patent/EP1058539A1/fr
Withdrawn legal-status Critical Current

Links

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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4858—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
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
    • 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
    • A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers

Definitions

  • the present invention relates to method of preparing a pharmaceutical active ingredient comprising water-insoluble drug and a pharmaceutical composition for oral administration comprising the same and, more particularly, to a method of preparing a pharmaceutical active ingredient comprising the water-insoluble improved bioavailability with simple process.
  • Korean Patent Laid-open No. 96-5136 discloses that drug in alcohol such as ethanol or isopopanol or acetone is mixed with excess water under the condition of forming hydrosol and dried by rotary drying or freeze- drying to make preparation.
  • a method of preparing a pharmaceutical active ingredient comprising a water-insoluble drug includes the steps of mixing a water-insoluble drug in an organic solvent with a water-soluble polymer in an aqueous solvent and spray-drying the mixture.
  • the present invention provides the pharmaceutical composition for oral administration including a pharmaceutical active ingredient including water-insoluble drug microparticles combined with a water-soluble polymer.
  • FIG. 1 is a graph showing water-insoluble drug excretion rate after pharmaceutical compositions including pharmaceutical active ingredients of examples 1 to 2 and comparative example 1 is oral administrated;
  • FIG. 2 is a schematic diagram showing sprayer for producing water- insoluble drug microparticles combined with a water-soluble polymer used in the present invention.
  • the present invention provides a pharmaceutical active ingredient including water-insoluble drug.
  • the pharmaceutical active ingredient exhibits good bioavailability.
  • microparticles is formed by using a water-insoluble drug and water-soluble polymer without a surfactant which causes gastrointestinal tract damage.
  • a water-insoluble drug is dissolved in an organic solvent such as acetone to prepare a drug solution.
  • an organic solvent such as acetone
  • ipriflavone biphenyl dimethyl dicarboxylate and cyclosporin may be used.
  • a water-soluble polymer is dissolved in an organic solvent such as ethanol aqueous solution to prepare a polymer solution.
  • cellulose type compound may be used as the water-soluble polymer.
  • the exemplary of cellulose type compound is ethylcellulose, polyethyleneglycol, carboxymethylcellulose, polyethyleneglycol, polyvinylpyrollidone, dextran, poloxamer and a mixture thereof.
  • the drug is mixed with the polymer in the weight ratio of 1 : 0.1 to 10, preferably 1 : 0.1 to 2.
  • the mixed solution is spray-dried, thereby obtaining water-insoluble drug powder, microparticles combined with water-soluble polymer.
  • the preparation is complicate, thereby requiring the specific technology.
  • the preparation is simple and therefor, it is not required the specific technology.
  • the exemplary of a spray dryer used in the spray-drying step in the present invention is shown in Fig. 2.
  • the mixed solution and air are injected into a spray-dryer body, while raising the ambient temperature by the heated air and mixed solution is changed from solution form to microparticle form by heated air.
  • the drug microparticles combined with polymer may be mixed with oil in the weight of 1 : 1 to 10. It is preferred that the drug microparticles mixed with oil because bioavailability increases.
  • oil amount is lower than 1 , it is difficult to mix the drug micropartices with oil. On the contrary, oil amount exceeds 10, it is difficult to charge the mixture to a capsule.
  • oil corn oil, peanut oil, coconut oil, caster oil, sesame oil, perilla oil, sunflower oil, walnut oil and cacao butter may be used.
  • the water-insoluble drug microparticles combined with water-soluble polymer may be used as an active ingredient for a pharmaceutical composition for oral administration.
  • the pharmaceutical composition further includes vehicle or a disintegrant, a lubricant.
  • the pharmaceutical compositon may inlcude other pharmaceutical excipients such as stabilizer, a preservatives, an electrolyte, etc used in the pharmaceutics.
  • Example 1 1 part by weight of ipriflavone was dissolved in 8 parts by weight of acetone to prepare a water-insoluble drug solution. 2 parts by weight of hydroxypropylmethylcellurose was dissolved in an aqueous ethanol solution including 1 part by weight of water and 1 part by weight of ethanol to prepare a water-soluble polymer solution. 4 parts by weight of the polymer solution was added to 9 parts by weight of the drug solution and mixed well by using a
  • the mixed solution was spray-dried at 50 ° C for 20 minutes by
  • Example 2 A pharmaceutical active ingredient was prepared by the same procedure in Example 1 except that corn oil was not used.
  • Comparative example 1 The commercial product of Ipriflavone was used for oral administrating water-insoluble drug.
  • compositions of the present invention were prepared by the conventional pharmaceutical process with these pharmaceutical active ingredients of examples 1 to 2. Furthermore, pharmaceutical compositions of comparative example 1 was prepared by disintegrating 0.27 parts by weight of Ipriflavone of comparative example 1 in water. These pharmaceutical compositions was used as powder or tablets. These tablets or powder were oral administered into white rats in the amount of 50 mg of drug per kg of rat's weight with conventional method. The amounts of ipriflavone in the tablets or powder which did not absorbed in the rat's body and excreted to the out of the body were determined. The result shows in Fig. 1.
  • comparative example 1 show that the most of ingredient ipriflavone did not absorbed in the rat's body and excreted to the out of the body were shown in Fig. 1.
  • Fig. 1 when the pharmaceutical active ingredient including the drug microparticles and water of the Example 2 was oral administered, absorption in the body increased two times more than the Comparative example 1.
  • the pharmaceutical active ingredient including oil of example 1 absorbing in the body is seven times more than the comparative example 1.
  • the drug of the present invention can be oral administered. Furthermore, it is not required for the drug to administered into a patient three or four times a day rather than the conventional water-insoluble drug.

Landscapes

  • Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

Procédé de préparation d'un principe actif pharmaceutique contenant un médicament non hydrosoluble. Selon ledit procédé, un médicament non hydrosoluble se trouvant dans un solvant organique est mélangé avec un polymère hydrosoluble se trouvant dans un solvant aqueux et séché par atomisation. Ensuite, les microparticules de médicament sont mélangées à de l'huile. Ledit procédé permet de préparer facilement un principe actif pharmaceutique contenant un médicament non hydrosoluble, qui possède une excellente biodisponibilité. Par conséquent, la préparation dudit principe ne nécessite pas une technologie spécifique.
EP99901236A 1999-01-06 1999-01-06 Procede de preparation d'un principe actif pharmaceutique contenant un medicament non hydrosoluble et composition pharmaceutique pour l'administration orale contenant ledit principe Withdrawn EP1058539A1 (fr)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/KR1999/000025 WO2000040220A1 (fr) 1999-01-06 1999-01-06 Procede de preparation d'un principe actif pharmaceutique contenant un medicament non hydrosoluble et composition pharmaceutique pour l'administration orale contenant ledit principe

Publications (1)

Publication Number Publication Date
EP1058539A1 true EP1058539A1 (fr) 2000-12-13

Family

ID=19570693

Family Applications (1)

Application Number Title Priority Date Filing Date
EP99901236A Withdrawn EP1058539A1 (fr) 1999-01-06 1999-01-06 Procede de preparation d'un principe actif pharmaceutique contenant un medicament non hydrosoluble et composition pharmaceutique pour l'administration orale contenant ledit principe

Country Status (3)

Country Link
EP (1) EP1058539A1 (fr)
JP (1) JP2002534371A (fr)
WO (1) WO2000040220A1 (fr)

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AU2331801A (en) 1999-12-23 2001-07-09 F.H. Faulding & Co. Limited Improved pharmaceutical compositions for poorly soluble drugs
DE10026698A1 (de) 2000-05-30 2001-12-06 Basf Ag Selbstemulgierende Wirkstoffformulierung und Verwendung dieser Formulierung
US8067032B2 (en) 2000-12-22 2011-11-29 Baxter International Inc. Method for preparing submicron particles of antineoplastic agents
US9700866B2 (en) 2000-12-22 2017-07-11 Baxter International Inc. Surfactant systems for delivery of organic compounds
US20060003012A9 (en) 2001-09-26 2006-01-05 Sean Brynjelsen Preparation of submicron solid particle suspensions by sonication of multiphase systems
JP2005504090A (ja) 2001-09-26 2005-02-10 バクスター・インターナショナル・インコーポレイテッド 分散体および溶媒相または液相の除去によるサブミクロンサイズ−ナノ粒子の調製
KR20040047056A (ko) * 2002-11-29 2004-06-05 한미약품 주식회사 비페닐디메틸디카복실레이트의 경구용 마이크로에멀젼조성물
US8025899B2 (en) 2003-08-28 2011-09-27 Abbott Laboratories Solid pharmaceutical dosage form
US8377952B2 (en) 2003-08-28 2013-02-19 Abbott Laboratories Solid pharmaceutical dosage formulation
WO2007016435A2 (fr) 2005-07-28 2007-02-08 Isp Investments Inc. Procede d'amelioration des caracteristiques de poudres sechees par atomisation et de materiaux granules, et produits obtenus par ce procede
GB0613925D0 (en) * 2006-07-13 2006-08-23 Unilever Plc Improvements relating to nanodispersions
US8613946B2 (en) 2006-12-21 2013-12-24 Isp Investment Inc. Carotenoids of enhanced bioavailability
CN101622302B (zh) 2007-01-26 2013-01-23 Isp投资公司 生产喷雾干燥产品的制剂工艺方法
JP4588791B2 (ja) * 2007-02-16 2010-12-01 あすか製薬株式会社 微粒子油性懸濁液を含む医薬組成物
GB0814953D0 (en) * 2008-08-18 2008-09-24 Unilever Plc Improvements relating to nanodisperse compositions
CN102458373A (zh) * 2009-05-27 2012-05-16 株式会社三养生物制药 生物利用度提高的包含难溶性药物的微球及其制备方法
JP5672880B2 (ja) * 2010-09-14 2015-02-18 大正製薬株式会社 イプリフラボン可溶化組成物
JP2014500782A (ja) * 2010-10-05 2014-01-16 イオタ・ナノソリューションズ・リミテッド 改善された組成物の調製方法
EP2863911A4 (fr) 2012-06-21 2016-07-13 Mayne Pharma Int Pty Ltd Compositions et formes galéniques d'itraconazole et leurs procédés d'utilisation
WO2015071841A1 (fr) 2013-11-12 2015-05-21 Druggability Technologies Holdings Limited Complexes de dabigatran et ses dérivés, procédé de préparation de ceux-ci et compositions pharmaceutiques contenant ceux-ci

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NZ270145A (en) * 1994-03-01 1996-08-27 Lilly Co Eli Non-aqueous pharmaceutical formulation for oral administration comprising water-insoluble active agent, fatty acid solubilising agent, an oil and a surface active agent
RU2119351C1 (ru) * 1994-06-01 1998-09-27 Юхан Корпорейшн Иммуносупрессорная композиция, содержащая циклоспорин, и способ ее получения
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Also Published As

Publication number Publication date
WO2000040220A1 (fr) 2000-07-13
JP2002534371A (ja) 2002-10-15

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