WO2000025759A1 - Forme therapeutique administrable par voie orale, se desintegrant spontanement au contact d'un liquide, et son procede de fabrication - Google Patents

Forme therapeutique administrable par voie orale, se desintegrant spontanement au contact d'un liquide, et son procede de fabrication Download PDF

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Publication number
WO2000025759A1
WO2000025759A1 PCT/EP1999/007940 EP9907940W WO0025759A1 WO 2000025759 A1 WO2000025759 A1 WO 2000025759A1 EP 9907940 W EP9907940 W EP 9907940W WO 0025759 A1 WO0025759 A1 WO 0025759A1
Authority
WO
WIPO (PCT)
Prior art keywords
dosage form
preparation
capsule
protective cover
spontaneously
Prior art date
Application number
PCT/EP1999/007940
Other languages
German (de)
English (en)
Inventor
Frank Becher
Original Assignee
Lts Lohmann Therapie-Systeme 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 Lts Lohmann Therapie-Systeme Ag filed Critical Lts Lohmann Therapie-Systeme Ag
Priority to AU11528/00A priority Critical patent/AU1152800A/en
Publication of WO2000025759A1 publication Critical patent/WO2000025759A1/fr

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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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
    • 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
    • A61K9/4808—Preparations in capsules, e.g. of gelatin, of chocolate characterised by the form of the capsule or the structure of the filling; Capsules containing small tablets; Capsules with outer layer for immediate drug release

Definitions

  • the invention relates to an orally administrable dosage form, containing a preparation which spontaneously disintegrates upon contact with liquid and releases active substance, and a process for its preparation.
  • Capsules filled with an active substance preparation are known which, after reaching the stomach, dissolve quickly under the influence of the gastric fluid, so that a larger amount of active substance is suddenly released. Combinations of such capsule fillings are also known, which initially release a lot of active substance and then implement slower release kinetics to maintain the active substance plasma level which was initially achieved.
  • Such systems have the disadvantage that the active ingredient or the preparation containing the active ingredient must be provided in a special way with properties by means of which it is released spontaneously, for example by freeze-drying or in another manner known to the person skilled in the art via so-called instant preparations.
  • instant preparations can be filled into capsules only with great difficulty because there is a risk that the preparations will be damaged in the process.
  • Another disadvantage is that after the capsule has been filled, a production or quality control is no longer possible.
  • Other preparations in powder form do not exclude with certainty or with absolute certainty the risk that the accessories formation clumps and the spontaneous effect of a release is not achieved.
  • wafers which disintegrate in the oral cavity.
  • the active ingredient released from it is only slowly and not suddenly - if at all - transferred into the stomach.
  • Systems of this type are therefore unsuitable for the desired goal of releasing the active ingredient as quickly as possible.
  • US 5,658,589 describes a capsule-like medicament comprising an underlayer of a mixture of a water-soluble film-forming polymer, for example hydroxypropyl methyl cellulose and a hydrophobic plasticizer, e.g. Castor oil, which favors a smooth, uniform and substantially bubble-free outer layer, for example gelatin; the capsule-like form of the drug can contain a variety of different active ingredients.
  • a water-soluble film-forming polymer for example hydroxypropyl methyl cellulose and a hydrophobic plasticizer, e.g. Castor oil, which favors a smooth, uniform and substantially bubble-free outer layer, for example gelatin
  • a hydrophobic plasticizer e.g. Castor oil
  • WO 97/24109 A describes a bioadhesive composition containing an active ingredient, 80-98.8% by weight of pregelatinized starch, 1-10% by weight of a polymer forming a hydrophilic matrix and 0.2-5% by weight of alkali C 16 _ 22 alkyl fumarate as a lubricant.
  • the dosage form can be used as an active ingredient-containing tablet or capsule for oral, nasal, rectal or vaginal administration.
  • No. 5,296,233 describes a capsule-like medicament, comprising a dual underlayer of a water-soluble film-forming polymer, for example povidone, with * a second underlayer composed of a mixture of two film-forming polymers, for example povidone and hydroxypropyl methylcellulose, and a hydrophobic plasticizer, for example castor oil, which is used for a smooth, uniform and substantially bubble-free outer layer ensures, for example gelatin for a capsule-like medication.
  • a water-soluble film-forming polymer for example povidone
  • a second underlayer composed of a mixture of two film-forming polymers, for example povidone and hydroxypropyl methylcellulose
  • a hydrophobic plasticizer for example castor oil
  • No. 4,983,401 describes a pharmaceutical preparation for long-term release of active substance using a pH-controllable diffusion membrane, consisting of a pH-sensitive film-forming polymer.
  • a pH-sensitive film-forming polymer may contain phthalic acid as a starting polymer with a carboxyl group attached to the starting polymer through an ester bond, while the second carboxyl group remains as a free acid, so that the modified film-forming polymer is hydrophobic at a low pH and hydrophilic at a higher pH.
  • Hydrophobic stearyl side chains are bound to the starting polymer, which means that the pH-controlled diffusion membrane remains insoluble at high pH.
  • the pH-sensitive film-forming polymer can be a polymer containing hydrophobic free acid groups, so that the modified film-forming polymer is hydrophobic at low pH and hydrophilic at high pH, but insoluble.
  • the preparation for long-term drug release is applied to drug particles for the production of a pH-controlled diffusion membrane for coating the drug with formation of mi Croparticles for mixing with medication or slow-release medication and introduced into gelatin capsules or tableted.
  • the invention has for its object to provide an orally administrable therapeutic dosage form of the type mentioned in the preamble of claim 1, which is suitable for a • drug after oral administration while preventing a premature dissolution on the way from the oral cavity via release the esophagus into the stomach only spontaneously after reaching the stomach, but then in larger amounts of active substance.
  • the invention proposes that an orally administrable dosage form containing a preparation which spontaneously disintegrates and releases active substance upon contact with liquid, in particular gastric liquid, to prevent premature dissolution on the way from the oral cavity via the esophagus into the stomach is surrounded with a protective cover.
  • the protective cover is an extremely thin capsule made of gelatin-like polymer.
  • the protective cover can consist of pH-sensitive material, which is released in the acidic environment of the gastric juice and releases the preparation spontaneously and allows it to disintegrate.
  • the protective cover can consist of a mixture of a water-soluble film-forming polymer, for example of hydroxyporpylmethyl cellulose and a hydrophobic plasticizer, for example castor oil.
  • a water-soluble film-forming polymer for example of hydroxyporpylmethyl cellulose
  • a hydrophobic plasticizer for example castor oil.
  • the protective casing contains corn starch. This has the advantage that when dry it results in a comparatively dimensionally stable shell, which, however, immediately loses this shape upon contact with gastric fluid and releases the contents of the capsule.
  • the dosage form is characterized in that it is a sheet-like, active substance-containing structure made of film-forming polymer and is present in the cover as a roll or folded body.
  • the casing for the spontaneous release of the preparation in the stomach has a tear-open aid in the form of a line of weakness running in the transverse or longitudinal direction thereof.
  • a method for producing the orally administrable, sheet-like dosage form which comprises a preparation which spontaneously disintegrates and releases active substance upon contact with liquid, in particular gastric juice, can advantageously be used, this being introduced as a roll or folded body into a casing to form a capsule, come to use, which is characterized in that after the completion of the dosage form using a laser beam is provided with the tear-open aid in the form of a line of weakness.
  • the weakening line can advantageously be formed from perforation lines or from embrittlement lines.
  • the tear-open aid can also be designed with two intersecting lines of weakness.
  • Section a section line B-B of FIG.lb an orally administrable therapeutic dosage form in the form of an oval capsule 5
  • FIG. 1b the capsule 5 in the section of the sectional plane A-A of FIG.la, containing the preparation in the form of a folding body
  • FIG.lc in section A-A in FIG.la containing the preparation in the form of a roll.
  • the orally administrable dosage form shown in FIG.la containing a preparation 6 which spontaneously disintegrates upon contact with liquid and releases active substance, is characterized in that it is in the form of a to prevent premature release on the way from the oral cavity via the esophagus into the stomach Capsule 5 is surrounded by a protective cover 1.
  • the protective cover 1 can be an extremely thin capsule 5 on gelatin-like polymer.
  • the protective sheath 1 can advantageously also consist of pH-sensitive material, which dissolves faster in the acidic environment of the gastric juice and spontaneously releases the preparation 6 and allows it to disintegrate.
  • the protective cover 1 consists of a mixture of a water-soluble film-forming polymer, for example hydroxypropylmethyl cellulose, and a hydrophobic plasticizer, e.g. Castor oil.
  • the protective cover can also contain 1 corn starch.
  • the preparation 6 contained in the capsule 5 is a leaf-shaped Total, active substance-containing structure made of film-forming polymer and contained in the shell 1 as a roll 3 (FIG.lc) or as a folded body 2 (FIG.lb).
  • FIGS. 1 a and 1 b show an embodiment of the casing 1 with a tear-open aid in the form of a weakening line 4 or 4 ′ running in the transverse or longitudinal direction.
  • These weakening lines 4, 4 ' are designed either as a perforation line or as an embrittlement line and are produced in accordance with the method according to the invention after the protective casing 1 or the thin capsule 5 formed therefrom using a laser beam.
  • the tear-open aid can preferably be designed with two intersecting lines of weakness 4, 4 ′.
  • the production using a laser beam is economical and uncomplicated and can be carried out, for example, with the aid of a pulsating laser beam in the form of tiny perforations lying next to one another in a line, or the envelope 1 for the weakening line 4 or 4 "can be carried out with the aid of the laser beam thermal embrittlement of the material of the shell 1 are produced.
  • 5 gas formers can be added to the capsule according to the method in an amount sufficient to expand and destroy the capsule along the tear aids 4, 4 '.

Landscapes

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

Abstract

L'invention concerne une forme thérapeutique administrable par voie orale, contenant une préparation se désintégrant spontanément au contact d'un liquide et libérant un principe actif. Cette forme thérapeutique est caractérisée en ce qu'elle est enrobée d'un revêtement protecteur sous la forme d'une gélule pour l'empêcher de se désintégrer prématurément sur la voie allant de la cavité buccale à l'estomac en passant par l'oesophage.
PCT/EP1999/007940 1998-10-29 1999-10-19 Forme therapeutique administrable par voie orale, se desintegrant spontanement au contact d'un liquide, et son procede de fabrication WO2000025759A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU11528/00A AU1152800A (en) 1998-10-29 1999-10-19 Orally applicable therapeutic dosage form which spontaneously disintegrates uponcontact with a liquid and method for producing the same

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19849848.9 1998-10-29
DE1998149848 DE19849848A1 (de) 1998-10-29 1998-10-29 Oral applizierbare, mit Flüssigkeit spontan zerfallende therapeutische Darreichungsform und Verfahren zu ihrer Herstellung

Publications (1)

Publication Number Publication Date
WO2000025759A1 true WO2000025759A1 (fr) 2000-05-11

Family

ID=7886029

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1999/007940 WO2000025759A1 (fr) 1998-10-29 1999-10-19 Forme therapeutique administrable par voie orale, se desintegrant spontanement au contact d'un liquide, et son procede de fabrication

Country Status (3)

Country Link
AU (1) AU1152800A (fr)
DE (1) DE19849848A1 (fr)
WO (1) WO2000025759A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109601670A (zh) * 2019-01-22 2019-04-12 海南钟晨生物工程有限责任公司 芦荟泡腾片的制备方法

Families Citing this family (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ITBO20110233A1 (it) * 2011-04-29 2012-10-30 I M A Ind Macchine Automatic He S P A Procedimento e apparecchiatura per realizzare una forma solida di materiale
WO2021198353A1 (fr) * 2020-03-31 2021-10-07 Danmarks Tekniske Universitet Feuille souple pour l'administration de charges thérapeutiques

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3444290A (en) * 1965-02-15 1969-05-13 Biorex Laboratories Ltd Dosage unit forms for the administration of medicaments
FR2170751A5 (fr) * 1972-02-03 1973-09-14 Parke Davis & Co
US3952741A (en) * 1975-01-09 1976-04-27 Bend Research Inc. Controlled release delivery system by an osmotic bursting mechanism
US4128445A (en) * 1975-12-15 1978-12-05 Hoffmann-La Roche Inc. Manufacture of pharmaceutical unit dosage forms
DE4419818A1 (de) * 1994-06-07 1995-12-14 Lohmann Therapie Syst Lts Wirkstoffträger zur kontrollierten Freisetzung von Wirkstoffen im Gastrointestinaltrakt mit verzögerter Pyloruspassage
WO1997031747A1 (fr) * 1996-02-29 1997-09-04 Merck & Co., Inc. Procede de perçage par laser a deflecteur acoustico-optique destine a percer des series de trous dans des doses de produits chimiques
DE19800523A1 (de) * 1997-01-14 1998-07-30 Lohmann Therapie Syst Lts Expandierbares gastroretentives Therapie-System mit kontrollierter Wirkstofffreisetzung im Gastrointestinaltrakt

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4339428A (en) * 1980-08-18 1982-07-13 Bristol-Myers Company Capsule product containing high dosage of aspirin in powder or granulated form and alkaline tablet or pellet comprising magnesium carbonate, calcium carbonate and a magnesium dry component
NZ233403A (en) * 1989-04-28 1992-09-25 Mcneil Ppc Inc Simulated capsule-like medicament
US5198227A (en) * 1990-01-22 1993-03-30 Mcneil-Ppc, Inc. Dual subcoated simulated capsule medicament
DE4219702A1 (de) * 1992-06-16 1993-12-23 Roemmers Sa Pharmazeutische Weichkapseln enthaltend Lysinclonixinat und ein Verfahren zu dessen Herstellung
DE4303844A1 (de) * 1993-02-10 1994-08-11 Merck Patent Gmbh Pharmazeutische Zubereitung
DE19500977C2 (de) * 1995-01-14 1999-01-07 Lohmann Therapie Syst Lts Feste Arzneimittelform mit in polymerem Material verteiltem Wirkstoff
DE19648576C2 (de) * 1996-11-23 1999-08-12 Lohmann Therapie Syst Lts Lutschtablette zur modifizierten Freisetzung von Wirkstoffen im Gastrointestinaltrakt
FR2757173A1 (fr) * 1996-12-17 1998-06-19 Warner Lambert Co Compositions polymeres d'origine non-animale pour la formation de films

Patent Citations (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3444290A (en) * 1965-02-15 1969-05-13 Biorex Laboratories Ltd Dosage unit forms for the administration of medicaments
FR2170751A5 (fr) * 1972-02-03 1973-09-14 Parke Davis & Co
US3952741A (en) * 1975-01-09 1976-04-27 Bend Research Inc. Controlled release delivery system by an osmotic bursting mechanism
US3952741B1 (fr) * 1975-01-09 1983-01-18
US4128445A (en) * 1975-12-15 1978-12-05 Hoffmann-La Roche Inc. Manufacture of pharmaceutical unit dosage forms
DE4419818A1 (de) * 1994-06-07 1995-12-14 Lohmann Therapie Syst Lts Wirkstoffträger zur kontrollierten Freisetzung von Wirkstoffen im Gastrointestinaltrakt mit verzögerter Pyloruspassage
WO1997031747A1 (fr) * 1996-02-29 1997-09-04 Merck & Co., Inc. Procede de perçage par laser a deflecteur acoustico-optique destine a percer des series de trous dans des doses de produits chimiques
DE19800523A1 (de) * 1997-01-14 1998-07-30 Lohmann Therapie Syst Lts Expandierbares gastroretentives Therapie-System mit kontrollierter Wirkstofffreisetzung im Gastrointestinaltrakt

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109601670A (zh) * 2019-01-22 2019-04-12 海南钟晨生物工程有限责任公司 芦荟泡腾片的制备方法
CN109601670B (zh) * 2019-01-22 2021-06-08 海南钟晨生物工程有限责任公司 芦荟泡腾片的制备方法

Also Published As

Publication number Publication date
AU1152800A (en) 2000-05-22
DE19849848A1 (de) 2000-05-04

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