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WO1999034780A1 - Procede et dispositif pour encapsuler des principes actifs - Google Patents

Procede et dispositif pour encapsuler des principes actifs Download PDF

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Publication number
WO1999034780A1
WO1999034780A1 PCT/CH1998/000350 CH9800350W WO9934780A1 WO 1999034780 A1 WO1999034780 A1 WO 1999034780A1 CH 9800350 W CH9800350 W CH 9800350W WO 9934780 A1 WO9934780 A1 WO 9934780A1
Authority
WO
WIPO (PCT)
Prior art keywords
vitamins
pharmaceuticals
extruder
active ingredients
flavorings
Prior art date
Application number
PCT/CH1998/000350
Other languages
German (de)
English (en)
Inventor
Federico Innerebner
Original Assignee
Bühler AG
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 Bühler AG filed Critical Bühler AG
Priority to AU86213/98A priority Critical patent/AU8621398A/en
Publication of WO1999034780A1 publication Critical patent/WO1999034780A1/fr

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
    • A61K9/14—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
    • A61K9/1682—Processes
    • A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
    • 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
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2095—Tabletting processes; Dosage units made by direct compression of powders or specially processed granules, by eliminating solvents, by melt-extrusion, by injection molding, by 3D printing

Definitions

  • the invention relates to a method for encapsulating or blending one or more active ingredients, pharmaceuticals, vitamins, and / or flavorings in a carrier substance.
  • the taste, the application or the delayed action of one or more active ingredients, pharmaceuticals, vitamins, and / or flavorings it is desirable to encapsulate them or to provide them with a coating.
  • This measure is particularly suitable for thermolabile substances.
  • DE 40 02 257 A1 discloses a method for encapsulating or for coating one or more active substances in or with a carrier substance.
  • a mixture of essentially native starch and at least one agent which at least partially swells the starch is used as the encapsulating or coating carrier substance, which is mixed together with the active ingredient and at least one emulsifier for the encapsulation or for the coating.
  • the method proposed above cannot be used for hydrophobic active substances, pharmaceuticals, vitamins and / or flavorings. Furthermore, a targeted setting of parameters such as type of starch, molecular weight, selection and concentration of the emulsifier, type and content of plasticizer etc. (please complete) is not possible or is possible only with great difficulty.
  • the object of the present invention is now to eliminate the disadvantages mentioned above.
  • the method according to the invention is intended to enable encapsulation of thermolabile substances, ie the melting temperatures should be low and the heat load should be short-lived.
  • the object is achieved in that the active ingredients, pharmaceuticals, vitamins and / or flavorings are dispersed and encapsulated in a matrix of thermoplastic starch and an intermediate layer or phase mediator layer by melt extrusion, the substance to be encapsulated or coated at a temperature of 20 ° C to a maximum of 80 ° C, preferably from 30 ° C to 60 ° C is exposed.
  • This process is an encapsulation.
  • the substance to be encapsulated is dispersed in a carrier matrix made of thermoplastic or pregelatinized starch. Between the matrix and the substance to be encapsulated there is an intermediate layer, also called a phase mediator. On the one hand, this intermediate layer takes over the function of the adhesion promoter, so that the material to be encapsulated is integrated as well as possible into the matrix. Furthermore, the encapsulation of pharmaceutical active substances is of therapeutic importance in such a way that the layer thickness and material of this intermediate layer influence the retardation of the pharmaceutical active substance in the human body.
  • the active ingredients, pharmaceuticals, vitamins and / or flavorings are preferably metered into the extruder as an emulsion or natively.
  • Thermoplastic starch for example, is used as the matrix or carrier material.
  • the starch can be in native form, but preferably in a pregelatinized one Condition. Different levels of starch degradation, so-called sugar starches, are also used depending on the requirements.
  • the partial or total metering of the emulsifier or emulsifiers or similar auxiliaries such as.
  • the emulsifiers and / or the auxiliaries can additionally be used as an intermediate layer or phase mediator layer.
  • the emulsifiers and / or the auxiliaries can thus assume a dual role. On the one hand, they serve as a means of lowering the surface tension and thus achieving deep melting temperature control. On the other hand, they can be used simultaneously as an intermediate layer or a phase mediator layer.
  • Water and / or low or high molecular weight polyhydric alcohols are preferably used as plasticizers individually or in combination.
  • glycerin, sorbtol etc. can be used as plasticizers individually or in combination.
  • the active ingredients, pharmaceuticals, vitamins and / or flavorings are metered in as shortly as possible before the extruder outlet. Dosing the substances to be encapsulated as late as possible shortens the duration of the heat load in the extruder.
  • the active ingredients, pharmaceuticals, vitamins, and / or flavorings are exposed to a residence time of 5 seconds to a maximum of one minute, preferably 10 to 30 seconds, in the extruder.
  • the active ingredients, pharmaceuticals, vitamins and / or flavorings are preferably exposed to 4 to 8 LJD process lengths in the extruder.
  • the encapsulation and / or the partial blinding is carried out by means of an extruder with at least two screws and the subsequent granulation is carried out by means of a downstream single-shaft extruder.
  • twin-screw or multi-screw extruders are used in this method according to the invention.
  • a small single-screw extruder can be used to produce very small granules, for example with a granule diameter of less than 1 mm.
  • the advantage of the downstream extruder is, in particular, that the low shearing action and possible low temperature control mean that lower melting temperatures can be achieved.
  • FIG. 2 shows an extruder configuration according to Examples 2 and 4.
  • FIG. 1 shows a preferred extruder configuration of a twin-screw extruder with individual housings 1 to 10.
  • Dosages D1 to D4 are shown schematically in different housings. In Figure 1, the dosages on the housings sen 1, 2, 7, and 9 are provided. Dosages on other housings are also mentioned in the examples.
  • a vacuum device 11 for degassing is arranged in the housing 5. The end of the extruder is formed by a nozzle 12. The nozzle can be arranged centrally or decentrally to the extruder axis.
  • FIG. 2 instead of the nozzle 12, a single-shaft extruder 14 is connected via an intermediate section 13. Otherwise, FIG. 2 corresponds to FIG. 1.
  • 15 kg of pregelatinized starch is metered into housing 1.
  • 8 kg of a mixture of 6 parts of water, 1 part of glycerol and 1 part of lecithin are introduced into housing 2.
  • the active ingredient for example 0.5 kg of acetyl-salicylic acid, is added to the extruder via the housing 9.
  • the temperature is controlled in such a way that the product temperatures in the housings 2 to 7 are around 70 ° C, in the housings 8 to 10 around 60 ° C and at the nozzle around 70 ° C
  • the granulation takes place by means of a head granulation known per se after the extruder exit, the granulate size being approximately 2 to 3 mm.
  • 15 kg of pregelatinized starch is metered into housing 1.
  • 2 parts of glycerol are entered and Le ⁇ 2 kg cithin in housing 7.
  • the active ingredient for example 0.5 kg acetylsalicylic acid is added over the housing 9 of the extruder.
  • the twin-screw extruder is followed by a single-screw extruder with subsequent head granulation with a granulate size of approx. 1 mm.
  • the temperature is controlled in such a way that the product temperatures in the housings 2 to 7 at approx. 70 ° C, in the housings 8 to 10 at approx. 50 ° C and on the single-screw extruder approx. 50 °.
  • the nozzle is around 70 ° C
  • 15 kg of pregelatinized starch is metered into housing 1.
  • 6 kg of a mixture of 4 parts of water and 2 parts of glycerin are introduced into housing 2.
  • Another 3 kg of a mixture of 1 part, lecithin, 1.5 parts water and 0.5 parts of an active ingredient, for example acetyl-salicylic acid, is added to the extruder via the housing 8.
  • Example 2 The composition corresponds to that of Example 3.
  • the temperature control, granulation size and the arrangement of a two-screw extruder in connection with a downstream single-shaft extruder corresponds to Example 2.
  • 18 kg of native starch with approx. 18% water is metered into housing 1.
  • 4 kg of a mixture of 3 parts of water and 1 part of glycerol are introduced into housing 2 and 1.5 kg of a mixture of 1 part of lecithin and 0.5 part of glycerol monostearate into housing 7.
  • the active ingredient for example 0.5 kg of acetylsalicylic acid, is added via the Housing 8 added to the extruder.
  • a vacuum device is connected to the housing 5 for degassing.
  • the twin-screw extruder configuration corresponds to that of Example 1.m.
  • the temperature is controlled in such a way that the product temperatures in the housing 2 at approx. 80 ° C, in the housing 3 at approx. 120 °, in the housings 4 and 5 at approx. 100 °, in the housings 6 and 7 at approx 70 ° and in the housings 8 and 9 at approx. 60 ° C

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  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Epidemiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Biophysics (AREA)
  • Molecular Biology (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention concerne un procédé permettant d'encapsuler ou de mélanger un ou plusieurs principes actifs, des préparations pharmaceutiques, des vitamines, et/ou des aromatisants dans un excipient. Selon ce procédé, les principes actifs, les préparations pharmaceutiques, les vitamines, et/ou les aromatisants sont dispersés par extrusion de matière fondue et encapsulés dans une matrice à base d'amidon thermoplastique et d'une couche intermédiaire ou d'une couche médiatrice de phase. La substance à encapsuler ou à enrober est soumise à l'action d'une température comprise entre 20 et 80 °C au plus, de préférence entre 30 et 60 °C.
PCT/CH1998/000350 1998-01-12 1998-08-19 Procede et dispositif pour encapsuler des principes actifs WO1999034780A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU86213/98A AU8621398A (en) 1998-01-12 1998-08-19 Method and device for capsulating active ingredients

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19800742 1998-01-12
DE19800742.6 1998-01-12

Publications (1)

Publication Number Publication Date
WO1999034780A1 true WO1999034780A1 (fr) 1999-07-15

Family

ID=7854338

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/CH1998/000350 WO1999034780A1 (fr) 1998-01-12 1998-08-19 Procede et dispositif pour encapsuler des principes actifs

Country Status (2)

Country Link
AU (1) AU8621398A (fr)
WO (1) WO1999034780A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR100432282B1 (ko) * 2000-07-14 2004-05-20 주식회사 오리온 α-토코페롤의 미세캡슐화 및 저장 안정성 증진 방법
WO2004091770A1 (fr) * 2003-04-17 2004-10-28 Innogel Ag Systeme d'encapsulation
EP1839651A1 (fr) * 1999-04-22 2007-10-03 Euro-Celtique S.A. Procédé de réalisation d'une matrice à action prolongée amorphe insoluble dans l'eau
US8753705B2 (en) 2005-06-07 2014-06-17 Mgpi Processing, Inc. Mineral-bound starch compositions and methods of making the same
CN110227036A (zh) * 2019-05-21 2019-09-13 南京神奇科技开发有限公司 一种化妆品用原料及其制备方法

Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2179044A1 (fr) * 1972-04-03 1973-11-16 Scherer Corp R P
EP0240906A2 (fr) * 1986-04-11 1987-10-14 BASF Aktiengesellschaft Procédé pour pastiller en continu
DE3830749A1 (de) * 1987-09-11 1989-03-30 Squibb & Sons Inc Arzneimittel in form von kuegelchen mit hohem arzneistoffgehalt und verfahren zu ihrer herstellung
WO1992000140A1 (fr) * 1990-06-25 1992-01-09 The United States Of America, As Represented By The Secretary, U.S. Department Of Commerce Encapsulage amylace d'agents biologiquement actifs au moyen d'un processus continu
EP0474095A1 (fr) * 1990-09-03 1992-03-11 Bühler Ag Composition et procédé pour former des articles d'usage biodégradable
EP0516030A2 (fr) * 1991-05-29 1992-12-02 Ems-Inventa Ag Procédé et appareil pour la préparation de fontes d'amidon et produits obtenus par ce procédé
EP0580860A1 (fr) * 1991-04-16 1994-02-02 Nippon Shinyaku Company, Limited Procede de production d'une dispersion solide
WO1995025546A1 (fr) * 1994-03-24 1995-09-28 Boehringer Ingelheim Agrovet A/S Unite de distribution contenant un produit particulaire et s'utilisant pour administrer des medicaments ou des preparations nutritives a des animaux, et procede de fabrication du produit particulaire
EP0729748A1 (fr) * 1993-11-18 1996-09-04 Nippon Shinyaku Company, Limited Procede pour produire une composition de medicament stable, et preparation pharmaceutique

Patent Citations (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2179044A1 (fr) * 1972-04-03 1973-11-16 Scherer Corp R P
EP0240906A2 (fr) * 1986-04-11 1987-10-14 BASF Aktiengesellschaft Procédé pour pastiller en continu
DE3830749A1 (de) * 1987-09-11 1989-03-30 Squibb & Sons Inc Arzneimittel in form von kuegelchen mit hohem arzneistoffgehalt und verfahren zu ihrer herstellung
WO1992000140A1 (fr) * 1990-06-25 1992-01-09 The United States Of America, As Represented By The Secretary, U.S. Department Of Commerce Encapsulage amylace d'agents biologiquement actifs au moyen d'un processus continu
EP0474095A1 (fr) * 1990-09-03 1992-03-11 Bühler Ag Composition et procédé pour former des articles d'usage biodégradable
EP0580860A1 (fr) * 1991-04-16 1994-02-02 Nippon Shinyaku Company, Limited Procede de production d'une dispersion solide
EP0516030A2 (fr) * 1991-05-29 1992-12-02 Ems-Inventa Ag Procédé et appareil pour la préparation de fontes d'amidon et produits obtenus par ce procédé
EP0729748A1 (fr) * 1993-11-18 1996-09-04 Nippon Shinyaku Company, Limited Procede pour produire une composition de medicament stable, et preparation pharmaceutique
WO1995025546A1 (fr) * 1994-03-24 1995-09-28 Boehringer Ingelheim Agrovet A/S Unite de distribution contenant un produit particulaire et s'utilisant pour administrer des medicaments ou des preparations nutritives a des animaux, et procede de fabrication du produit particulaire

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1839651A1 (fr) * 1999-04-22 2007-10-03 Euro-Celtique S.A. Procédé de réalisation d'une matrice à action prolongée amorphe insoluble dans l'eau
KR100432282B1 (ko) * 2000-07-14 2004-05-20 주식회사 오리온 α-토코페롤의 미세캡슐화 및 저장 안정성 증진 방법
WO2004091770A1 (fr) * 2003-04-17 2004-10-28 Innogel Ag Systeme d'encapsulation
US8753705B2 (en) 2005-06-07 2014-06-17 Mgpi Processing, Inc. Mineral-bound starch compositions and methods of making the same
CN110227036A (zh) * 2019-05-21 2019-09-13 南京神奇科技开发有限公司 一种化妆品用原料及其制备方法

Also Published As

Publication number Publication date
AU8621398A (en) 1999-07-26

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