WO1999037308A1 - Method for producing a medicament which quickly dissolves in the mouth and which contains acarbose as an active agent - Google Patents

Method for producing a medicament which quickly dissolves in the mouth and which contains acarbose as an active agent Download PDF

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Publication number
WO1999037308A1
WO1999037308A1 PCT/EP1999/000131 EP9900131W WO9937308A1 WO 1999037308 A1 WO1999037308 A1 WO 1999037308A1 EP 9900131 W EP9900131 W EP 9900131W WO 9937308 A1 WO9937308 A1 WO 9937308A1
Authority
WO
WIPO (PCT)
Prior art keywords
acarbose
mouth
producing
medicament
active agent
Prior art date
Application number
PCT/EP1999/000131
Other languages
German (de)
French (fr)
Inventor
Johanna Berberich
Carola PÖRTNER
Original Assignee
Bayer Aktiengesellschaft
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 Bayer Aktiengesellschaft filed Critical Bayer Aktiengesellschaft
Priority to AU25171/99A priority Critical patent/AU2517199A/en
Publication of WO1999037308A1 publication Critical patent/WO1999037308A1/en

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7008—Compounds having an amino group directly attached to a carbon atom of the saccharide radical, e.g. D-galactosamine, ranimustine
    • 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
    • A61K9/0002—Galenical forms characterised by the drug release technique; Application systems commanded by energy
    • A61K9/0007—Effervescent
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/0056—Mouth soluble or dispersible forms; Suckable, eatable, chewable coherent forms; Forms rapidly disintegrating in the mouth; Lozenges; Lollipops; Bite capsules; Baked products; Baits or other oral forms for animals
    • 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

Definitions

  • Acarbose is the first representative of the class of alpha-glucosidase inhibitors, which, by inhibiting the alpha-glucosidase enzymes, delays the cleavage of sucrose, dextrin and starches in the intestine and thus smoothes the blood sugar level
  • the method according to the invention describes the composition and production of rapidly disintegrating tablets which dissolve in the mouth by contact with the saliva
  • the active ingredient is granulated alone or with parts of the filler with the aid of dry compaction and sieving and compressed to flat wafers on a conventional tablet press
  • Particularly suitable fillers are water-insoluble auxiliaries, for example calcium phosphate or microcrystalline cellulose
  • the proportion of the active ingredient in the formulation is preferably 40-90%, the proportion of fillers and auxiliaries 10-60%.
  • Acarbose, milk sugar and microcrystalline cellulose are mixed in a suitable container.
  • the cross-linked polyvinylpyrollidone and the magnesium stearate are added and mixed again.
  • the ready-to-press mixture is pressed on a conventional tablet press into tablets which have a diameter of 12 mm.
  • the height of the tablets is less than 2 mm.
  • the tablet disintegrates in less than 2 minutes.
  • Acarbose, calcium hydrogen phosphate and sodium bicarbonate are mixed in a suitable container. After dry compaction and subsequent sieving, the citric acid is added.
  • the ready-to-press mixture is compressed in a conventional tablet press to tablets which have a diameter of 12 mm.
  • the height of the tablets is less than 2 mm.
  • the tablet disintegrates in less than 2 minutes.

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

Abstract

The invention relates to a method for producing a tablet which quickly dissolves in the mouth. The invention is characterized in that an auxiliary agent which accelerates dissolving is combined with an unconventional tablet shape having an especially large surface.

Description

Verfahren zur Herstellung einer im Mund schnell zerfallenden Arzneiform, die als Wirkstoff Acarbose enthältProcess for producing a pharmaceutical form that disintegrates rapidly in the mouth and contains acarbose as the active ingredient
Die Erfindung betrifft ein Verfahren zur Herstellung von im Mund schnell zerfallenden Tabletten (=Fast Dissolving Tablets), die Acarbose als Wirkstoff enthaltenThe invention relates to a method for producing tablets (= Fast Dissolving Tablets) that rapidly disintegrate in the mouth and contain acarbose as the active ingredient
Acarbose ist der erste Vertreter der Substanzklasse der alpha-Glucosidase Inhibitoren, die über eine Hemmung der alpha-Glucosidase Enzyme die Spaltung von Saccharose, Dextrin und Starken im Darm verzögert und so den Blutzuckerspiegel glättetAcarbose is the first representative of the class of alpha-glucosidase inhibitors, which, by inhibiting the alpha-glucosidase enzymes, delays the cleavage of sucrose, dextrin and starches in the intestine and thus smoothes the blood sugar level
Da Acarbose mit den ersten Bissen jeder Mahlzeit eingenommen werden muß, bringt eine Arzneiform, die ohne Flüssigkeit eingenommen werden kann, große Vorteile für den PatientenSince acarbose must be taken with the first bite of every meal, a dosage form that can be taken without liquid brings great benefits to the patient
Das erfmdungsgemaße Verfahren beschreibt die Zusammensetzung und Herstellung von schnell zerfallenden Tabletten, die sich in der Mundhohle im Kontakt mit der Speichelflussigkeit von selbst auflosenThe method according to the invention describes the composition and production of rapidly disintegrating tablets which dissolve in the mouth by contact with the saliva
Der Wirkstoff wird allein oder mit Teilen des Füllstoffes mit Hilfe einer Trockenkom- paktierung und Siebung granuliert und auf einer konventionellen Tablettenpresse zu flachen Obladen verpreßtThe active ingredient is granulated alone or with parts of the filler with the aid of dry compaction and sieving and compressed to flat wafers on a conventional tablet press
Als Füllstoffe eignen sich besonders wasserunlösliche Hilfsstoffe, z B Calciumphos- phate oder mikrokristalline CelluloseParticularly suitable fillers are water-insoluble auxiliaries, for example calcium phosphate or microcrystalline cellulose
Als weitere Hilfsstoffe können größere Anteile von Intensivsprengmitteln und/oder Mischungen aus sauren und basischen Hilfsstoffen (zur Erzeugung einer Brausemischung) eingesetzt werden Diesen Hilfsstoffen kommt besondere Bedeutung zu, da so die gewünschte kurze Zerfallszeit von unter 5 Minuten erreicht wird Als Intensivsprengmittel eignen sich z B quervernetztes Polyvinylpyrolhdon oder i atπumcar- boxymethylcellulose, die sauren und basischen Anteile sind z B durch eine Mischung aus Zitronensaure und Natπumhydrogencarbonat gegeben Weiterhin werden z. B. Schmiermittel (z. B. Magnesiumstearat), z. B. Aromen oder z. B. Farbpigmente eingesetzt.Larger proportions of intensive explosives and / or mixtures of acidic and basic auxiliary substances (to produce an effervescent mixture) can be used as further auxiliaries. These auxiliary substances are of particular importance since the desired short disintegration time of less than 5 minutes is achieved cross-linked polyvinylpyrolhdon or i atπumcarboxymethylcellulose, the acidic and basic fractions are, for example, given by a mixture of citric acid and sodium bicarbonate Furthermore, for. B. lubricants (e.g. magnesium stearate), e.g. B. flavors or z. B. color pigments used.
Der Anteil des Wirkstoffes in der Formulierung ist bevorzugt 40 - 90 %, der Anteil an Füll- und Hilfsstoffen 10 - 60 %. The proportion of the active ingredient in the formulation is preferably 40-90%, the proportion of fillers and auxiliaries 10-60%.
BeispieleExamples
Beispiel 1example 1
In einem geeigneten Behälter werden Acarbose, Milchzucker und mikrokristalline Cellulose gemischt. Im zweiten Schritt wird das quervernetzte Polyvinylpyrollidon und das Magnesiumstearat zugegeben und erneut gemischt.Acarbose, milk sugar and microcrystalline cellulose are mixed in a suitable container. In the second step, the cross-linked polyvinylpyrollidone and the magnesium stearate are added and mixed again.
Acarbose 100,0 mg querv. Polyvinylpyrollidon 8,0 mgAcarbose 100.0 mg transverse Polyvinyl pyrollidone 8.0 mg
Mikrokristalline Cellulose 95,5 mgMicrocrystalline cellulose 95.5 mg
Milchzucker 46,0 mgMilk sugar 46.0 mg
Magnesiumstearat 0,5 mgMagnesium stearate 0.5 mg
250,0 mg250.0 mg
Die preßfertige Mischung wird auf einer konventionellen Tablettenpresse zu Tabletten veφreßt, die einen Durchmesser von 12 mm aufweisen. Die Höhe der Tabletten beträgt weniger als 2 mm. Die Zerfallszeit der Tabletten beträgt unter 2 Minuten.The ready-to-press mixture is pressed on a conventional tablet press into tablets which have a diameter of 12 mm. The height of the tablets is less than 2 mm. The tablet disintegrates in less than 2 minutes.
Beispiel 2Example 2
In einem geeigneten Behälter werden Acarbose, Calciumhydrogenphosphat und Natriumhydrogencarbonat gemischt. Nach einer Trockenkompaktierung und anschließenden Siebung wird die Zitronensäure zugegeben.Acarbose, calcium hydrogen phosphate and sodium bicarbonate are mixed in a suitable container. After dry compaction and subsequent sieving, the citric acid is added.
Diese Reihenfolge der Herstellung garantiert beste Stabilitätsergebnisse, da das Natri- umhydrogenphosphat in granulierter Form vorliegt und die Brausereaktion erst durch den Kontakt mit Wasser eingeleitet wird.This order of manufacture guarantees the best stability results, since the sodium hydrogen phosphate is in granular form and the shower reaction is only initiated by contact with water.
Nach der Zugabe von Magnesiumstearat als Schmiermittel ist die Mischung preßfer- tig- Acarbose 100,0 mgAfter adding magnesium stearate as a lubricant, the mixture is ready to be pressed. Acarbose 100.0 mg
Calciumhydrogenphosphat 62,5 mgCalcium hydrogen phosphate 62.5 mg
Natriumhydrogencarbonat 42,5 mgSodium bicarbonate 42.5 mg
Zitronensäure 40,0 mgCitric acid 40.0 mg
Magnesiumstearat 0,5 mgMagnesium stearate 0.5 mg
245,5 mg Die preßfertige Mischung wird auf einer konventionellen Tablettenpresse zu Tabletten veφreßt, die einen Durchmesser von 12 mm aufweisen. Die Höhe der Tabletten beträgt weniger als 2 mm. Die Zerfallszeit der Tabletten beträgt unter 2 Minuten. 245.5 mg The ready-to-press mixture is compressed in a conventional tablet press to tablets which have a diameter of 12 mm. The height of the tablets is less than 2 mm. The tablet disintegrates in less than 2 minutes.

Claims

Patentansprücheclaims
1 Verfahren zur Herstellung von Tabletten, dadurch gekennzeichnet, daß ein Zerfallsbeschleuniger (Intensivsprengmittel oder Brausemischung) mit einer besonders großflächigen und flachen Form der Tablette kombiniert wird1 Process for the production of tablets, characterized in that a disintegrant (intensive disintegrant or effervescent mixture) is combined with a particularly large and flat shape of the tablet
2 Verfahren nach Anspruch 1, dadurch gekennzeichnet, daß der Wirkstoff in dieser Arzneiform Acarbose ist2 The method according to claim 1, characterized in that the active ingredient in this pharmaceutical form is acarbose
3 Verfahren nach Anspruch 1 und 2, dadurch gekennzeichnet, daß als Füllmittel ein wasserunlöslicher Hilfsstoff z B Calciumcarbonate oder mikrokristalline Cellulose eingesetzt wird3 The method according to claim 1 and 2, characterized in that a water-insoluble auxiliary such as calcium carbonate or microcrystalline cellulose is used as filler
4 Verfahren nach Anspruch 1 bis 3, dadurch gekennzeichnet, daß der Anteil an Acarbose 40 - 90 % betragt 4 The method according to claim 1 to 3, characterized in that the proportion of acarbose is 40-90%
PCT/EP1999/000131 1998-01-24 1999-01-12 Method for producing a medicament which quickly dissolves in the mouth and which contains acarbose as an active agent WO1999037308A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU25171/99A AU2517199A (en) 1998-01-24 1999-01-12 Method for producing a medicament which quickly dissolves in the mouth and whichcontains acarbose as an active agent

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE1998102700 DE19802700A1 (en) 1998-01-24 1998-01-24 Preparation of fast-dissolving tablets for controlling blood sugar levels
DE19802700.1 1998-01-24

Publications (1)

Publication Number Publication Date
WO1999037308A1 true WO1999037308A1 (en) 1999-07-29

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AU (1) AU2517199A (en)
DE (1) DE19802700A1 (en)
WO (1) WO1999037308A1 (en)

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003070227A1 (en) * 2002-02-21 2003-08-28 Lts Lohmann Therapie-Systeme Ag Taste-masked film-type or wafer-type medicinal preparation
WO2011134962A3 (en) * 2010-04-27 2012-05-03 Bayer Pharma Aktiengesellschaft Orally disintegrating tablet containing acarbose
KR101421330B1 (en) * 2008-12-17 2014-07-18 사토 세이야쿠 가부시키가이샤 A disintegrating tablet
CN104013590A (en) * 2014-05-09 2014-09-03 万特制药(海南)有限公司 Acarbose-containing medicinal composition and preparation method thereof
WO2016097170A1 (en) * 2014-12-17 2016-06-23 Empros Pharma Ab A modified release composition of orlistat and acarbose for the treatment of obesity and related metabolic disorders
WO2018064795A1 (en) * 2016-10-05 2018-04-12 Boai Nky Pharmaceuticals Ltd. Tablet compositions containing crosslinked polyvinylpyrrolidone and their use in beverage applications

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2367900A (en) * 1998-12-18 2000-07-03 Bayer Corporation Chewable drug delivery system
RU2010128019A (en) * 2007-12-08 2012-01-20 Байер Шеринг Фарма Акциенгезельшафт (DE) ORAL DISPERSABLE TABLET
TR201100150A2 (en) * 2011-01-06 2012-07-23 Bi̇lgi̇ç Mahmut Water soluble dosage forms
WO2013115745A1 (en) * 2012-01-31 2013-08-08 Mahmut Bilgic A process for production of pharmaceutical (effervescent) composition comprising alpha - glucosidase inhibitor (e.g. vogliobose and metformin)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0226121A2 (en) * 1985-12-13 1987-06-24 Bayer Ag Composition containing very pure acarbose
EP0638317A1 (en) * 1993-08-05 1995-02-15 F. Hoffmann-La Roche Ag Pharmaceutical composition

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0226121A2 (en) * 1985-12-13 1987-06-24 Bayer Ag Composition containing very pure acarbose
EP0638317A1 (en) * 1993-08-05 1995-02-15 F. Hoffmann-La Roche Ag Pharmaceutical composition

Cited By (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003070227A1 (en) * 2002-02-21 2003-08-28 Lts Lohmann Therapie-Systeme Ag Taste-masked film-type or wafer-type medicinal preparation
US7615235B2 (en) 2002-02-21 2009-11-10 Lts Lohmann Therapie-Systeme Ag Film-shaped or wafer-shaped pharmaceutical preparation with masked taste
KR101421330B1 (en) * 2008-12-17 2014-07-18 사토 세이야쿠 가부시키가이샤 A disintegrating tablet
WO2011134962A3 (en) * 2010-04-27 2012-05-03 Bayer Pharma Aktiengesellschaft Orally disintegrating tablet containing acarbose
CN104013590A (en) * 2014-05-09 2014-09-03 万特制药(海南)有限公司 Acarbose-containing medicinal composition and preparation method thereof
CN107405309A (en) * 2014-12-17 2017-11-28 安普洛德制药公司 The tune of orlistat and acarbose for treating obesity and related metabolic disturbance releases composition
WO2016097170A1 (en) * 2014-12-17 2016-06-23 Empros Pharma Ab A modified release composition of orlistat and acarbose for the treatment of obesity and related metabolic disorders
CN107405309B (en) * 2014-12-17 2019-04-16 安普洛德制药公司 Tune for the orlistat and acarbose for the treatment of obesity and related metabolic disturbance releases composition
EA033448B1 (en) * 2014-12-17 2019-10-31 Empros Pharma Ab Modified release composition of orlistat and acarbose for the treatment of obesity and related metabolic disorders
US10561617B2 (en) 2014-12-17 2020-02-18 Empros Pharma Ab Modified release composition of orlistat and acarbose for the treatment of obesity and related metabolic disorders
EP3943076A3 (en) * 2014-12-17 2022-04-13 Empros Pharma AB A modified release composition of orlistat and acarbose for the treatment of obesity and related metabolic disorders
US11975105B2 (en) 2014-12-17 2024-05-07 Empros Pharma Ab Modified release composition of orlistat and acarbose for the treatment of obesity and related metabolic disorders
WO2018064795A1 (en) * 2016-10-05 2018-04-12 Boai Nky Pharmaceuticals Ltd. Tablet compositions containing crosslinked polyvinylpyrrolidone and their use in beverage applications
CN109803931A (en) * 2016-10-05 2019-05-24 博爱新开源医疗科技集团股份有限公司 Tablet composition containing crosslinked polyvinylpyrrolidone and its purposes in beverage application
US11535740B2 (en) 2016-10-05 2022-12-27 Boai Nky Medical Holdings Ltd. Tablet compositions containing crosslinked polyvinylpyrrolidone and their use in beverage applications

Also Published As

Publication number Publication date
AU2517199A (en) 1999-08-09
DE19802700A1 (en) 1999-07-29

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