WO1996000389A1 - Procede de determination de la quantite de principe actif liberee de preparations solides ou semi-liquides utilisees chez l'homme et chez l'animal - Google Patents

Procede de determination de la quantite de principe actif liberee de preparations solides ou semi-liquides utilisees chez l'homme et chez l'animal Download PDF

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Publication number
WO1996000389A1
WO1996000389A1 PCT/EP1995/002269 EP9502269W WO9600389A1 WO 1996000389 A1 WO1996000389 A1 WO 1996000389A1 EP 9502269 W EP9502269 W EP 9502269W WO 9600389 A1 WO9600389 A1 WO 9600389A1
Authority
WO
WIPO (PCT)
Prior art keywords
test solution
dosage form
solid
membrane bag
active substance
Prior art date
Application number
PCT/EP1995/002269
Other languages
German (de)
English (en)
Inventor
Joel Sinnreich
Original Assignee
Ciba-Geigy 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 Ciba-Geigy Ag filed Critical Ciba-Geigy Ag
Priority to AU27912/95A priority Critical patent/AU2791295A/en
Publication of WO1996000389A1 publication Critical patent/WO1996000389A1/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
    • A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
    • A61K9/009—Sachets, pouches characterised by the material or function of the envelope
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/15—Medicinal preparations ; Physical properties thereof, e.g. dissolubility

Definitions

  • the invention relates to a method for determining the release of active substance from solid or semi-solid dosage forms for use in humans and animals according to the preamble of claim 1.
  • Dosage forms that are to be used on the human or animal organism must be adapted to the physiological conditions prevailing on or in the living organism, for example on the skin or in the gastrointestinal tract, in order, for example, with regard to their dissolution rate and the release behavior of a pharmacological active ingredient to be optimal on the living Organism and the therapeutic requirements to be coordinated.
  • analysis regulations e.g. "United States Pharmacopoeia XXII, 1990" have been recommended by the authorities, which are based on the real physiological conditions of the living organism and should allow a comparison of the dosage forms.
  • the determination of the dissolution rate and the release of active substance is used, for example, to test different production batches of one dosage form for their similarity.
  • Such analyzes are also used regularly for stability tests of dosage forms depending on the storage period and climatic load
  • the dosage forms intended for use in humans or animals generally do not only consist of the pure active ingredient, but rather they mostly comprise a relatively large amount of fillers and carriers, auxiliaries or binders etc.
  • a method for determining the release of active substance from solid or semi-solid dosage forms for use in humans and animals is to be improved so that the test solution can be analyzed optically reliably and without additional effort. Additional separation stages, filtration or centrifugation steps or other possible cleaning steps should be dispensed with.
  • the solid or semi-solid dosage form to be examined is introduced into a test solution which corresponds to the physiological conditions when the dosage form is administered to the human or animal organism;
  • the dosage form is dissolved in the test solution under controlled conditions, the active ingredient contained in the dosage form being converted into solution;
  • the solid or semi-solid dosage form to be tested is completely covered with a membrane bag that is permeable to the test solution, but which, on the other hand, is water-insoluble components of the dosage form and, if necessary, still essentially retains undissolved active ingredient
  • the membrane bag completely envelops the dosage form to be tested and retains impurities in the membrane bag, but allows a largely unhindered inflow and the outflow of the test liquid or test solution.
  • the active ingredient contained in the dosage form can be converted into solution without hindrance, while the fillers and carriers, auxiliaries or binders are essentially retained in the membrane bag.
  • the membrane bag can be easily removed from the test solution and disposed of. Because the fillers and carriers, auxiliaries or binders contained in the solid or semi-solid dosage form are retained within the membrane bag, this residue can also be checked very easily if necessary.
  • the solid or semi-solid dosage form to be tested is made from a hydrophilic material (for water-soluble drugs) or from a membrane bag lipophilic membrane (for lipophilic active substances) coated This allows the most diverse types of solid or semi-solid dosage forms to be investigated by carefully selecting the covering membrane.
  • Single or multilayer laminates that are porous or teabag-like are used as materials for the membrane bag, for example.
  • the preferred material for the membrane bag is polymeric films, especially films made of cellulose ethers such as methyl or ethyl cellulose, hydroxypropyl cellulose, methyl or ethyl hydroxyethyl cellulose, methyl or ethyl hydroxypropyl cellulose, carboxymethyl cellulose, polyvinyl acetate, polyvinyl pyrrolidone, or copolymer made from polyacrylonitrile, made from copolymeric, polyacrylonitrile several of the polymers mentioned, for example, from copolymers of acrylic and methacrylic acid esters with a low content of quaternary ammonium groups (such as EUDRAGIT® RL 12.5 or RS 12.5 from Röhm Pharma GmbH, Germany), from mixtures of polyvinylpyrrolidone with polyvinyl alcohol, resins based on phthalic anhydride-polyhydroxy alcohol , Urethanes, polyamides or from polyvinyl alcohol.
  • cellulose ethers such as
  • plasticizers can be added to the film materials. This is particularly advantageous if a test apparatus is used which simulates the peristaltic kneading movements of the gastrointestinal tract.
  • the plasticizer ensures that the membrane bag material has sufficient elasticity that the membrane bag does not burst during the simulated kneading movements.
  • Glycerol polyethylene glycol fatty acid esters such as polyethylene glycol 400 stearate or polyethylene glycol 2000 stearate, triethyl citrate, diethyl phthalate or diethyl sebacate are preferably added as plasticizers.
  • FIG. 2 shows the time course of the release of the active ingredient of the dosage form from FIG. 1 with a membrane bag covering
  • the solid or semi-solid dosage forms are tested in a test solution made of synthetic gastric juice.
  • the test apparatus and test method used for this corresponds, for example, to the "paddle apparatus” or "United States Pharmacopoeia XX ⁇ , 1990", pages 1577-1583 "Paddle method”.
  • a sample identical to the solid dosage form according to Example 1 is first completely encased and sealed with a membrane bag made of polyvinyl alcohol (Moviol 28/99 from Hoechst, Germany) and then the membrane bag with the solid dosage form is added to the test solution and directly via optical Absorption measurement determines the active substance concentration in the test solution, that is, extractions or filtrations are omitted before the actual measurement process, since the test solution remains clear.
  • the results of the measurement are shown in FIG. 2.
  • Curve C therein shows the active substance release in percent.
  • the bar chart display shows the actually measured concentration.
  • a squeeze containing 25 mg of active ingredient and 120 mg of polyethylene glycol stearate is placed in a test solution made of synthetic gastric juice. A cloudy mixture with excessive UV extinction is formed. An optical absorption measurement to determine the active substance concentration in the test solution is not possible.
  • a squeeze according to Example 3 is first enveloped and sealed with a membrane bag made of polyvinyl alcohol.
  • the membrane bag with the dosage form contained therein is used in synthetic gastric juice.
  • the test solution remains clear and is subjected directly to an optical absorption measurement in order to determine the active ingredient concentration in the test solution over time ( one measurement every two hours).
  • the material release curves of three such samples are designated D, E and F.
  • the curve shape corresponds qualitatively to the curve shapes from FIGS. 1 and 2.
  • the membrane bag completely envelops the dosage form to be tested and retains impurities in the membrane bag, but allows a largely unimpeded inflow and the outflow of the test liquid or the test solution.
  • the active ingredient contained in the dosage form can be converted into solution without hindrance, while the fillers and carriers, auxiliaries or binders are essentially retained in the membrane bag.
  • the concentration of the released active ingredient in the test solution can be determined directly, lengthy filtration, extractions and chromatographic preparation of the test solution are unnecessary.
  • the test equipment remains free and free from grease or other water-insoluble substances.
  • the membrane bag can be easily removed from the test solution and disposed of. Because the fillers and carriers, auxiliaries or binders contained in the solid or semi-solid dosage form are retained within the membrane bag, this residue can also be checked very easily if necessary.

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

Abstract

L'invention concerne un procédé qui permet de déterminer la quantité de principe actif libérée de préparations utilisées chez l'homme et chez l'animal, selon lequel: - la forme galénique à analyser est introduite dans une solution de contrôle qui reproduit les conditions physiologiques qui régnent au moment où la préparation est libérée dans l'organisme humain ou animal, - la préparation est dissoute dans la solution de contrôle dans des conditions contrôlées, et le principe actif contenu dans la préparation est alors converti en solution, - la solution de contrôle qui contient le principe actif dissous est analysée à intervalles déterminés, l'analyse se présentant de préférence sous forme de mesure optique d'absorption, afin de déterminer à des moments précis la concentration en principe actif d'un volume donné de solution de contrôle; - la préparation à vérifier est entièrement enrobée d'un sachet membranaire perméable à la solution de contrôle, mais qui retient par contre essentiellement les constituants insolubles dans l'eau de la préparation et éventuellement du principe actif qui n'est pas encore dissous.
PCT/EP1995/002269 1994-06-24 1995-06-12 Procede de determination de la quantite de principe actif liberee de preparations solides ou semi-liquides utilisees chez l'homme et chez l'animal WO1996000389A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU27912/95A AU2791295A (en) 1994-06-24 1995-06-12 Method of determining the amount of active substance released from solid or semi-solid preparations administered to humans or animals

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
CH2030/94-0 1994-06-24
CH203094 1994-06-24

Publications (1)

Publication Number Publication Date
WO1996000389A1 true WO1996000389A1 (fr) 1996-01-04

Family

ID=4224287

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1995/002269 WO1996000389A1 (fr) 1994-06-24 1995-06-12 Procede de determination de la quantite de principe actif liberee de preparations solides ou semi-liquides utilisees chez l'homme et chez l'animal

Country Status (2)

Country Link
AU (1) AU2791295A (fr)
WO (1) WO1996000389A1 (fr)

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2304327A1 (fr) * 1975-03-19 1976-10-15 Procter & Gamble Article a liberation controlee
FR2391721A1 (fr) * 1977-05-23 1978-12-22 Alza Corp Systemes en copolyesters segmentes pour apporter des substances a un milieu environnant
US4207890A (en) * 1977-01-04 1980-06-17 Mcneilab, Inc. Drug-dispensing device and method
EP0071170A2 (fr) * 1981-07-28 1983-02-09 Hoechst Aktiengesellschaft Articles sélectivement perméable aux gaz et aux fluides, conformés à partir de copolymères fluorés, et ayant également des propriétés oléophiles et oléophobes
EP0164569A2 (fr) * 1984-05-11 1985-12-18 Koken Co. Ltd. Composition pour la libération d'un médicament
EP0262893A2 (fr) * 1986-10-02 1988-04-06 Sohrab Darougar Dispositif d'insertion oculaire
EP0307904A1 (fr) * 1987-09-18 1989-03-22 Ciba-Geigy Ag Formes à liberation prolongée enrobées

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2304327A1 (fr) * 1975-03-19 1976-10-15 Procter & Gamble Article a liberation controlee
US4207890A (en) * 1977-01-04 1980-06-17 Mcneilab, Inc. Drug-dispensing device and method
FR2391721A1 (fr) * 1977-05-23 1978-12-22 Alza Corp Systemes en copolyesters segmentes pour apporter des substances a un milieu environnant
EP0071170A2 (fr) * 1981-07-28 1983-02-09 Hoechst Aktiengesellschaft Articles sélectivement perméable aux gaz et aux fluides, conformés à partir de copolymères fluorés, et ayant également des propriétés oléophiles et oléophobes
EP0164569A2 (fr) * 1984-05-11 1985-12-18 Koken Co. Ltd. Composition pour la libération d'un médicament
EP0262893A2 (fr) * 1986-10-02 1988-04-06 Sohrab Darougar Dispositif d'insertion oculaire
EP0307904A1 (fr) * 1987-09-18 1989-03-22 Ciba-Geigy Ag Formes à liberation prolongée enrobées

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
RUDOLF VOIGT; MANFRED BORNSCHEIN: "Lehrbuch der pharmazeutischen Technologie", VERLAG CHEMIE, WEINHEIM, DE; DEERFIELD BEACH, FL, US; BASEL, CH *

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Publication number Publication date
AU2791295A (en) 1996-01-19

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