WO1995008988A1 - Tablet containing a basic material possibly containing active substances and active substance containing microparticles - Google Patents

Tablet containing a basic material possibly containing active substances and active substance containing microparticles Download PDF

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Publication number
WO1995008988A1
WO1995008988A1 PCT/EP1994/003166 EP9403166W WO9508988A1 WO 1995008988 A1 WO1995008988 A1 WO 1995008988A1 EP 9403166 W EP9403166 W EP 9403166W WO 9508988 A1 WO9508988 A1 WO 9508988A1
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WO
WIPO (PCT)
Prior art keywords
microparticles
tablet according
tablet
active ingredient
eudragit
Prior art date
Application number
PCT/EP1994/003166
Other languages
German (de)
French (fr)
Inventor
Werner Korsatko
Brigitte Korsatko
Wolfram Tritthart
Original Assignee
Werner Korsatko
Brigitte Korsatko
Wolfram Tritthart
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 Werner Korsatko, Brigitte Korsatko, Wolfram Tritthart filed Critical Werner Korsatko
Priority to AU78088/94A priority Critical patent/AU7808894A/en
Priority to EP94928795A priority patent/EP0715515A1/en
Publication of WO1995008988A1 publication Critical patent/WO1995008988A1/en

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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
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets
    • A61K9/2081—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets with microcapsules or coated microparticles according to A61K9/50
    • 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
    • A61K9/2077—Tablets comprising drug-containing microparticles in a substantial amount of supporting matrix; Multiparticulate tablets

Definitions

  • the invention relates to a novel tablet for use as a chewing and / or disintegrating tablet.
  • the active ingredient is usually incorporated into matrix tablets, film-coated tablets or retard pellets, the pellets then being filled into capsules or compressed into swallowing tablets.
  • the size of the tablets or capsules is naturally limited to a weight of approximately 0.6 g. Even tablets or capsules with this weight have considerable difficulties in swallowing. Both tablets and capsules cannot be bitten before swallowing, as this would destroy the pellets and matrices and the sustained-release effect would be lost.
  • the invention is therefore based on the object of providing a novel chewing and / or disintegrating tablet which enables a delayed release of active substance while avoiding the disadvantages of the prior art.
  • this object is achieved in that active ingredient-containing microparticles with retarding properties are present in a conventional base composition which is suitable for biting and / or disintegrating in liquid, which, because of their elasticity and strength, do not destroy when the tablet is bitten and / or disintegrates become.
  • the base composition has at least one additional active ingredient, which, in the event that the microparticles contain sodium fluorophosphate or sodium fluoride, contains at least one calcium salt or a calcium complex.
  • the invention further proposes that the base mass contains the same active ingredient (s) as the microparticles.
  • the amount of active ingredient in the base mass can preferably be set so that it acts as an initial dose and the amount in the microparticles so that it acts as a maintenance dose.
  • the microparticles consist of a retarding, elastic, active substance-containing matrix and a retarding and likewise elastic shell.
  • the elastic matrix can be made from an Eudragit derivative or a composition of various Eudragit derivatives, cellulose derivatives such as methyl cellulose, hydroxyethyl cellulose or hydroxypropyl cellulose or other conventional retarding adjuvants high proportion of plasticizing components, while the shell is preferably made of polyacrylates, such as ⁇ ⁇
  • Eudragit or Eudragit compositions or of cellulose derivatives, such as ethyl cellulose, cellulose acetate phthalate or hydroxypropyl ethyl cellulose phthalate, optionally with the addition of plasticizing auxiliaries.
  • the invention relates to a tablet with microparticles with a content of 0.3 to 3.0 mm, preferably 0.3 to 1.0 mm.
  • the invention also relates to tablets containing sodium fluorophosphate or sodium fluoride in the microparticles and optionally at least one calcium salt or calcium complex in the base material, for the prevention or therapy of osteoporosis.
  • the invention relates to a tablet containing naftidrofuryl salt e.g. Naftidrofuryl hydrogen oxalate in the microparticles, for blood circulation and / or vasodilation.
  • naftidrofuryl salt e.g. Naftidrofuryl hydrogen oxalate in the microparticles
  • the invention also relates to a tablet with a content of diclofenac or its salt in the microparticles, as an anti-inflammatory and / or anti-rheumatic.
  • the invention relates to a tablet containing cimetidine or ranitidine or their salts in the microparticles as an H 2 blocker.
  • the invention also relates to a tablet containing pentoxyfylline in the microparticles as a vasodilatane. Furthermore, the invention relates to a tablet containing loratadine as an antiallergic.
  • the invention also relates to a tablet containing ⁇ -blockers, such as propanolol and atenolol, or ⁇ -blockers, such as clonidine, or their salts in the microparticles, as an antihypertensive.
  • ⁇ -blockers such as propanolol and atenolol
  • ⁇ -blockers such as clonidine
  • the invention relates to a tablet containing furosemide or hydrochlorothiazide in the microparticles as a diuretic.
  • the measures according to the invention provide for the first time a chewing and / or disintegrating tablet in which the active ingredient or combination of active ingredients is released in a retarded manner.
  • a particular advantage here is that the active ingredient contained in the microparticles can be metered in such a way that it was not possible when incorporating them into previously used oral retardation systems.
  • the active ingredient or combination of active ingredients is present exclusively in the microparticles.
  • Particularly high-dose active ingredients which, according to the state of knowledge, could not be applied or could only be applied in a retarded form to a limited extent, can thus be taken in the form of a chewing tablet and / or disintegration tablet.
  • the incorporation of the active ingredient or combination of active ingredients into the microparticles designed according to the invention does not adversely affect the retarding properties when the tablet is chewed and / or disintegrated, since the microparticles are not destroyed due to their elasticity and strength when they are chewed and / or disintegrated.
  • Depending on the structure of the retard Systems of the microparticles result in a delayed release at a later point in time, for example in the gastrointestinal tract after passage through the stomach.
  • the active ingredient or combination of active ingredients is contained both in the microparticles and in the base material, the amounts then being able to be adjusted so that the active ingredient is contained in the basic mass, which is released immediately, acts as an initial dose, while the amount of active ingredient in the microparticles, which is released only after a delay, acts as a maintenance dose.
  • the elastic retard matrix is made of cellulose
  • compositions built up The terms Avicel, Methocel and Eudragit used in this context are registered trademarks.
  • tablets are also provided according to the invention in which, as an initial dose, part of the active ingredient is present in the base material and another part, as a maintenance dose, is present in the microparticles.
  • calcium salts can be provided in the base composition in order to provide a combination preparation for the treatment of osteoporosis.
  • MFP in microparticles 50 mg MFP MFP in basic mass 50 mg MFP calcium salts 500 mg approx
  • MFP in microparticles 140 mg MFP MFP in basic mass 60 mg MFP calcium salts 500 mg approx
  • tablets constructed according to the invention with the active ingredient sodium fluoride can also be used in the microparticles, an example of a possible composition being given in Table 2 below.
  • composition of a tablet according to the invention contains naftidrofuryl hydrogen oxalate as an active ingredient, which promotes blood circulation and vasodilator.
  • ® is embedded, is based on an Eudragit composition, while the tablet base (as shown) can have different compositions.
  • Table 4 shows a tablet according to the invention in which the microparticles contain the active ingredient diclofenac, which has an anti-inflammatory and anti-rheumatic effect.
  • the elastic matrix in which this active ingredient is embedded in the microparticles also consists of the cellulose derivative Avicel.
  • FIG. 2 shows the in vitro liberation of the active ingredient diclofenac from the tablets described above.
  • game 6 shows the in vitro liberation of the active ingredient diclofenac from the tablets described above.
  • the chewing tablets described in Examples 1 to 5 above can be used as disintegration tablets without changing the composition.
  • Corresponding investigations have shown that when these tablets are placed in a glass filled with water (e.g. 50 ml), they largely disintegrate there within a period of about 3 minutes to form an ingestible suspension.
  • the structure of the tablets according to the invention therefore not only provides a chewing tablet, but also a disintegrating tablet with delayed release of active ingredient, which avoids the disadvantages of conventional swallowing tablets described at the outset.
  • Vasodilatants e.g.
  • ⁇ -blockers such as propranolol, atenolol + magnesium salts
  • ⁇ -blockers such as clonidine + magnesium salts + potassium salts

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  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • Nutrition Science (AREA)
  • Physiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

A tablet that may be chewed and/or dissolved contains active substance containing microparticles with retarding properties in a usual basic material suitable for chewing and/or for being dissolved in a liquid. Because of their elasticity and solidity, said microparticles are not destroyed when the tablet is chewed and/or dissolved.

Description

Tablette enthaltend eine möglicherswelse wirkstoffhaltige Grundmasse und wirkr stoffhaltige MikropartikelTablet containing a possible basic substance containing active substance and microparticles containing active substance
Die Erfindung betrifft eine neuartige Tablette zur Verwen¬ dung als Zerbeiß- und/oder Zerfallstablette.The invention relates to a novel tablet for use as a chewing and / or disintegrating tablet.
Üblicherweise wird bei peroralen Retard-Arzneiformen der Wirkstoff in Matrixtabletten, Filmtabletten oder Retard¬ pellets eingearbeitet, wobei die Pellets anschließend in Kapseln abgefüllt oder zu Schlucktabletten verpreßt werden. Die Tabletten oder Kapseln sind naturgemäß in ihrer Größe beschränkt auf ein Gewicht von ca. 0,6 g. Bereits bei Tabletten oder Kapseln mit diesem Gewicht treten beträcht¬ liche Schwierigkeiten beim Schlucken auf. Sowohl Tabletten als auch Kapseln können dabei vor dem Schlucken nicht zerbissen werden, da auf diese Weise die Pellets und Matrizes zerstört würden und der Retardeffekt verloren ginge.In the case of oral sustained-release pharmaceutical forms, the active ingredient is usually incorporated into matrix tablets, film-coated tablets or retard pellets, the pellets then being filled into capsules or compressed into swallowing tablets. The size of the tablets or capsules is naturally limited to a weight of approximately 0.6 g. Even tablets or capsules with this weight have considerable difficulties in swallowing. Both tablets and capsules cannot be bitten before swallowing, as this would destroy the pellets and matrices and the sustained-release effect would be lost.
Der Erfindung liegt daher die Aufgabe zugrunde, eine neu¬ artige Zerbeiß- und/oder Zerfallstablette zur Verfügung zu stellen, die unter Vermeidung der Nachteile des Standes der Technik eine verzögerte Wirkstoff-Freisetzung ermög¬ licht. Erfindungsgemäß wird diese Aufgabe dadurch gelöst, daß in einer üblichen Grundmasse, die zum Zerbeißen und/oder zum Zerfallen in Flüssigkeit geeignet ist, wirkstoffhaltige Mikropartikel mit retardierenden Eigenschaften vorhanden sind, die aufgrund ihrer Elastizität und Festigkeit beim Zerbeißen und/oder Zerfallen der Tablette nicht zerstört werden.The invention is therefore based on the object of providing a novel chewing and / or disintegrating tablet which enables a delayed release of active substance while avoiding the disadvantages of the prior art. According to the invention, this object is achieved in that active ingredient-containing microparticles with retarding properties are present in a conventional base composition which is suitable for biting and / or disintegrating in liquid, which, because of their elasticity and strength, do not destroy when the tablet is bitten and / or disintegrates become.
In einer bevorzugten Ausführungsform der Erfindung weist die Grundmasse mindestens einen zusätzlichen Wirkstoff auf, wobei dieser, für den Fall, daß die Mikropartikel Natriumfluorophosphat oder Natriumfluorid enthalten, min¬ destens ein Calciumsalz oder einen Calciumkomplex enthält.In a preferred embodiment of the invention, the base composition has at least one additional active ingredient, which, in the event that the microparticles contain sodium fluorophosphate or sodium fluoride, contains at least one calcium salt or a calcium complex.
Die Erfindung schlägt weiterhin vor, daß die Grundmasse den (die) gleichen Wirkstoff(e) wie die Mikropartikel ent¬ hält.The invention further proposes that the base mass contains the same active ingredient (s) as the microparticles.
Dabei kann die Menge an Wirkstoff in der Grundmasse bevor¬ zugt so eingestellt sein, daß sie als Initialdosis wirkt und die Menge in den Mikropartikeln so, daß sie als Erhal¬ tungsdosis wirkt.The amount of active ingredient in the base mass can preferably be set so that it acts as an initial dose and the amount in the microparticles so that it acts as a maintenance dose.
Erfindungsgemäß ist in der bevorzugten Ausführungsform weiter vorgesehen, daß die Mikropartikel aus einer retar¬ dierenden, elastischen, Wirkstoffhaltigen Matrix und einer retardierenden und ebenfalls elastischen Hülle bestehen.According to the invention, it is further provided in the preferred embodiment that the microparticles consist of a retarding, elastic, active substance-containing matrix and a retarding and likewise elastic shell.
®®
Dabei kann die elastische Matrix aus einem Eudragit -Deri- vat oder einer Zusammensetzung verschiedener Eudragit -De¬ rivate, Cellulosederivaten wie z.B. Methylcellulose, Hy- droxyethylcellulose oder Hydroxypropylcellulose oder anderen üblichen, retardierenden Hilfsstoffen mit einem hohen Anteil an plastifizierenden Bestandteilen, bestehen, während die Hülle vorzugsweise aus Polyacrylaten, wie β βThe elastic matrix can be made from an Eudragit derivative or a composition of various Eudragit derivatives, cellulose derivatives such as methyl cellulose, hydroxyethyl cellulose or hydroxypropyl cellulose or other conventional retarding adjuvants high proportion of plasticizing components, while the shell is preferably made of polyacrylates, such as β β
Eudragit oder Eudragit -Zusammensetzungen, oder aus Cellu- losederivaten, wie Ethylcellulose, Celluloseacetatphthalat oder Hydroxypropyl ethylcellulosephthalat, ggf. unter Zusatz plastifizierender Hilfsstoffe, besteht.Eudragit or Eudragit compositions, or of cellulose derivatives, such as ethyl cellulose, cellulose acetate phthalate or hydroxypropyl ethyl cellulose phthalate, optionally with the addition of plasticizing auxiliaries.
Die Erfindung betrifft in einer besonderen Ausführungsform eine Tablette mit Mikropartikeln mit einem Gehalt von 0,3 bis 3,0 mm, bevorzugt 0,3 bis 1,0 mm besitzen.In a particular embodiment, the invention relates to a tablet with microparticles with a content of 0.3 to 3.0 mm, preferably 0.3 to 1.0 mm.
Die Erfindung betrifft außerdem Tablette, mit einem Gehalt von Natriumfluorophosphat oder Natriumfluorid in den Mi¬ kropartikeln und gegebenenfalls mindestens einem Calcium- salz oder einem Calciumkomplex in der Grundmasse, zur Prä¬ vention oder Therapie von Osteoporose.The invention also relates to tablets containing sodium fluorophosphate or sodium fluoride in the microparticles and optionally at least one calcium salt or calcium complex in the base material, for the prevention or therapy of osteoporosis.
Desweiteren betrifft die Erfindung eine Tablette, mit einem Gehalt an Naftidrofurylsalz z.B. Naftidrofuryl- hydrogenoxalat in den Mikropartikeln, zur Durchblutungs¬ förderung und/oder Gefäßerweiterung.Furthermore, the invention relates to a tablet containing naftidrofuryl salt e.g. Naftidrofuryl hydrogen oxalate in the microparticles, for blood circulation and / or vasodilation.
Die Erfindung betrifft auch eine Tablette, mit einem Ge¬ halt an Diclofenac bzw. dessen Salz in den Mikropartikeln, als Antiphlogistikum und/oder Antirheumatikum.The invention also relates to a tablet with a content of diclofenac or its salt in the microparticles, as an anti-inflammatory and / or anti-rheumatic.
Desweiteren betrifft die Erfindung eine Tablette, mit einem Gehalt an Cimetidin oder Ranitidin bzw. deren Salzen in den Mikropartikeln, als H2-Blocker.Furthermore, the invention relates to a tablet containing cimetidine or ranitidine or their salts in the microparticles as an H 2 blocker.
Die Erfindung betrifft außerdem eine Tablette, mit einem Gehalt an Pentoxyfyllin in den Mikropartikeln, als Vasodi- latans. Desweiteren betrifft die Erfindung eine Tablette, mit einem Gehalt an Loratadin, als Antiallergikum.The invention also relates to a tablet containing pentoxyfylline in the microparticles as a vasodilatane. Furthermore, the invention relates to a tablet containing loratadine as an antiallergic.
Die Erfindung betrifft außerdem eine Tablette, mit einem Gehalt an ß-Blocker, wie Propanolol und Atenolol, oder α-Blocker, wie Clonidin, bzw. deren Salze in den Mikro¬ partikeln, als Antihypertonikum.The invention also relates to a tablet containing β-blockers, such as propanolol and atenolol, or α-blockers, such as clonidine, or their salts in the microparticles, as an antihypertensive.
Schließlich betrifft die Erfindung eine Tablette, mit einem Gehalt an Furosemid oder Hydrochlorothiazid in den Mikropartikeln, als Diuretikum.Finally, the invention relates to a tablet containing furosemide or hydrochlorothiazide in the microparticles as a diuretic.
Durch die erfindungsgemäßen Maßnahmen wird erstmalig eine Zerbeiß- und/oder Zerfallstablette zur Verfügung gestellt, bei der der Wirkstoff oder die Wirkstoffkombination retar¬ diert freigesetzt wird. Dabei besteht ein besonderer Vor¬ teil darin, daß der in den Mikropartikeln enthaltende Wirkstoff so dosiert werden kann, wie es bei Einarbeitung in bisher übliche perorale Retardsysteme nicht möglich war.The measures according to the invention provide for the first time a chewing and / or disintegrating tablet in which the active ingredient or combination of active ingredients is released in a retarded manner. A particular advantage here is that the active ingredient contained in the microparticles can be metered in such a way that it was not possible when incorporating them into previously used oral retardation systems.
Bei einer Alternative der erfindungsgemäßen Zerbeiß- und/- oder Zerfallstablette ist der Wirkstoff oder die Wirk- stoffkombination ausschließlich in den Mikropartikeln vor¬ handen. Besonders hoch dosierte Wirkstoffe, die nach dem Stand des Wissens nicht oder nur bedingt in retardierter Form appliziert werden konnten, können so in Form einer Zerbeiß- und/oder Zerfallstablette eingenommen werden. Durch die Einarbeitung des Wirkstoffes oder der Wirk- stoffkombination in die erfindungsgemäß ausgebildeten Mikropartikel erfolgt beim Zerbeißen und/oder Zerfallen der Tablette keine Beeinträchtigung der retardierenden Eigenschaften, da die Mikropartikel aufgrund ihrer Elastizität und Festigkeit beim Zerbeißen und/oder Zer¬ fallen nicht zerstört werden. Je nach Aufbau des Retard- Systems der Mikropartikel erfolgt eine verzögerte Frei¬ setzung zu einem späteren Zeitpunkt, beispielsweise im Gastrointestinaltrakt nach der Magenpassage.In an alternative of the chewing and / or disintegrating tablet according to the invention, the active ingredient or combination of active ingredients is present exclusively in the microparticles. Particularly high-dose active ingredients which, according to the state of knowledge, could not be applied or could only be applied in a retarded form to a limited extent, can thus be taken in the form of a chewing tablet and / or disintegration tablet. The incorporation of the active ingredient or combination of active ingredients into the microparticles designed according to the invention does not adversely affect the retarding properties when the tablet is chewed and / or disintegrated, since the microparticles are not destroyed due to their elasticity and strength when they are chewed and / or disintegrated. Depending on the structure of the retard Systems of the microparticles result in a delayed release at a later point in time, for example in the gastrointestinal tract after passage through the stomach.
In einer weiteren Alternative ist es möglich, neben dem in den Mikropartikeln enthaltenen Wirkstoff, der verzögert freigesetzt werden soll, in die Grundmasse einen weiteren Wirkstoff einzuarbeiten, der sofort, z.B. beim Zerbeißen der Tablette oder nach dem Zerfallen in Flüssigkeit, freigesetzt werden kann und soll. Als Beispiel hierfür wäre ein Kombinationspräparat zur Behandlung von Osteo- porose zu nennen, das Natriumfluorophosphat oder Natrium- fluorid in Form von retardierenden Mikropartikeln, ein¬ gebettet in eine calciumhaltige Grundmasse, aufweist.In a further alternative, it is possible, in addition to the active ingredient contained in the microparticles, which is to be released with a delay, to incorporate a further active ingredient into the base material, which immediately, e.g. when the tablet is chewed or after disintegrating into liquid, can and should be released. An example of this would be a combination preparation for the treatment of osteoporosis which contains sodium fluorophosphate or sodium fluoride in the form of retarding microparticles embedded in a calcium-containing matrix.
In einer weiteren Alternative der erfindungsgemäßen Zer¬ beiß- und/oder Zerfallstablette kann weiter vorgesehen sein, daß der Wirkstoff oder die Wirkstoffkombination sowohl in den Mikropartikeln als auch in der Grundmasse enthalten ist, wobei die Mengen dann so eingestellt werden können, daß der Wirkstoff in der Grundmasse, der sofort, freigesetzt wird, als Initialdosis wirkt, während die Menge an Wirkstoff in den Mikropartikeln, die erst ver¬ zögert freigesetzt wird, als Erhaltungsdosis wirkt.In a further alternative of the chewing and / or disintegrating tablet according to the invention, it can further be provided that the active ingredient or combination of active ingredients is contained both in the microparticles and in the base material, the amounts then being able to be adjusted so that the active ingredient is contained in the basic mass, which is released immediately, acts as an initial dose, while the amount of active ingredient in the microparticles, which is released only after a delay, acts as a maintenance dose.
In den Zeichnungen stelltIn the drawings
Fig. 1 die in-vitro-Liberation von Natriumfluoro phosphat aus erfindungsgemäßen Tabletten; und1 shows the in vitro liberation of sodium fluorophosphate from tablets according to the invention; and
Fig. 2 die in-vitro-Liberation von Diclofenac aus erfindungsgemäßen Tabletten dar. Zur Veranschaulichung der Erfindung sind im folgenden Bei¬ spiele für die verschiedenen Alternativen der erfindungs¬ gemäßen Tablette detaillierter angegeben.2 shows the in vitro liberation of diclofenac from tablets according to the invention. To illustrate the invention, examples are given in more detail below for the various alternatives of the tablet according to the invention.
BEISPIELEEXAMPLES
Beispiel 1example 1
MFP-ZerbeißtablettenMFP chewable tablets
Im folgenden (Tabelle 1) sind Zusammensetzung und Retar- dierungsdauer verschiedener erfindungsgemäßer Tabletten angeführt, die als Wirkstoff in den Mikropartikeln Natri- umfluorophosphat (= Monofluorophosphat, MFP) enthalten.The following (Table 1) lists the composition and duration of retardation of various tablets according to the invention which contain sodium fluorophosphate (= monofluorophosphate, MFP) as active ingredient in the microparticles.
Die elastische Retardmatrix ist dabei aus Cellulosederi-The elastic retard matrix is made of cellulose
® vaten bzw. Cellulosederivaten in Kombination mit Eudragit -® vaten or cellulose derivatives in combination with Eudragit -
Zusammensetzungen aufgebaut. Die in diesem Zusammenhang verwendeten Bezeichnungen Avicel, Methocel und Eudragit sind eingetragene Warenzeichen. Compositions built up. The terms Avicel, Methocel and Eudragit used in this context are registered trademarks.
Tabelle 1Table 1
Zusammensetzung Retardie-Composition retardation
[%] rungsdauer[%] duration
Mikrooartikel:Micro articles:
MFP 42,0 6 StundenMFP 42.0 6 hours
Lactose 8,0Lactose 8.0
Avicel PH 101 27,0Avicel PH 101 27.0
Methocel K 100 premium 8,0Methocel K 100 premium 8.0
Hydroxypropylmethylcellulose- phthalat 12,0Hydroxypropyl methyl cellulose phthalate 12.0
Diethylphthalat 3,0Diethyl phthalate 3.0
Tablettenbasis:Tablet base:
TricalciumcitratTricalcium citrate
CitronensäureCitric acid
SorbitSorbitol
AspartameAspartame
OrangenaromaOrange aroma
MagnesiumstearatMagnesium stearate
Mikropartikel:Microparticles:
MFP 21,0 8 StundenMFP 21.0 8 hours
Lactose 12,0Lactose 12.0
Avicel PH 101 29,0Avicel PH 101 29.0
Methocel K 100 premium 19,0Methocel K 100 premium 19.0
Eudragit RS 100 1,5Eudragit RS 100 1.5
Eudragit L 30 D 15,0Eudragit L 30 D 15.0
Talcum 2,0Talcum 2.0
Triethylcitrat 0,5Triethyl citrate 0.5
Tablettenbasis:Tablet base:
MPFMPF
CalciumphosphatCalcium phosphate
TricalciumcitratTricalcium citrate
CalciumcarbonatCalcium carbonate
SorbitSorbitol
CitronenaromaLemon flavor
BoesonBoeson
Talcum Tabelle 1 (Fortsetzung)Talcum Table 1 (continued)
Mikropartikel:Microparticles:
MFP 40,0 7 StundenMFP 40.0 7 hours
Lactose 4,5Lactose 4.5
Avicel PH 101 25,0Avicel PH 101 25.0
Eudragit RS PO 12,0Eudragit RS PO 12.0
Eudragit RS 30 D 1,5Eudragit RS 30 D 1.5
Eudragit RS 100 1,5Eudragit RS 100 1.5
Eudragit L 30 D 15,0Eudragit L 30 D 15.0
Dibutylphthalat 0,5Dibutyl phthalate 0.5
Tablettenbasis:Tablet base:
Calciu phosphatCalciu phosphate
TricalciumcitratTricalcium citrate
SorbitSorbitol
MannitMannitol
PfefferminzaromaPeppermint flavor
Magnesiums earatMagnesium earat
Mikropartikel:Microparticles:
MFP 20,0 8 StundenMFP 20.0 8 hours
Lactose 8,0Lactose 8.0
Avicel PH 101 34,0Avicel PH 101 34.0
Eudragit RS PO 22,0Eudragit RS PO 22.0
Eudragit RS 30 D 1,5Eudragit RS 30 D 1.5
Eudragit S 100 12,0Eudragit S 100 12.0
Talcum 2,0Talcum 2.0
Triethylcitrat 0,5Triethyl citrate 0.5
Tablettenbasis:Tablet base:
CalciumcarbonatCalcium carbonate
CalciumhydrogencitratCalcium hydrogen citrate
SorbitSorbitol
Saccharin-NatriumSodium saccharine
AromaAroma
Polyethylenglycol Beispiel 2Polyethylene glycol Example 2
Kombinierte MFP-ZerbeißtablettenCombined MFP chewable tablets
Wie bereits dargelegt, sind erfindungsgemäß auch Tabletten vorgesehen, bei denen, als Initialdosis, ein Teil des Wirk¬ stoffes in der Grundmasse und ein anderer Teil, als Erhaltungsdosis, in den Mikropartikeln vorliegt. Außerdem können erfindungsgemäß in der Grundmasse Calciumsalze vor¬ gesehen sein, um ein Kombinationspräparat zur Behandlung von Osteoporose bereitzustellen.As already explained, tablets are also provided according to the invention in which, as an initial dose, part of the active ingredient is present in the base material and another part, as a maintenance dose, is present in the microparticles. In addition, according to the invention, calcium salts can be provided in the base composition in order to provide a combination preparation for the treatment of osteoporosis.
Dabei können beispielsweise folgende Kombinationen vor¬ gesehen sein:The following combinations can be provided, for example:
1. MFP in Mikropartikeln 50 mg MFP MFP in Grundmasse 50 mg MFP Calciumsalze 500 mg Ca1. MFP in microparticles 50 mg MFP MFP in basic mass 50 mg MFP calcium salts 500 mg approx
2. MFP in Mikropartikeln 140 mg MFP MFP in Grundmasse 60 mg MFP Calciumsalze 500 mg Ca2. MFP in microparticles 140 mg MFP MFP in basic mass 60 mg MFP calcium salts 500 mg approx
3. MFP in Mikropartikeln 200 mg MFP Calciumsalze 500 mg Ca3. MFP in microparticles 200 mg MFP calcium salts 500 mg approx
Zur weiteren Veranschaulichung der Erfindung wird auf Fig. 1 verwiesen, in der die in-vitro-Liberation von MFP aus kombinierten Tabletten gemäß der oben angegebenen Zu¬ sammensetzung 1 dargestellt ist. Beispiel 3For a further illustration of the invention, reference is made to FIG. 1, in which the in vitro liberation of MFP from combined tablets according to the composition 1 indicated above is shown. Example 3
Für ähnliche Einsatzzwecke wie in Beispiel 1 und 2 be¬ schriebenen MFP-Tabletten können auch erfindungsgemäß auf¬ gebaute Tabletten mit dem Wirkstoff Natriumfluorid in den Mikropartikeln eingesetzt werden, wobei in der folgenden Tabelle 2 ein Beispiel für eine mögliche Zusammensetzung angegeben ist.For similar purposes as described in Examples 1 and 2 MFP tablets, tablets constructed according to the invention with the active ingredient sodium fluoride can also be used in the microparticles, an example of a possible composition being given in Table 2 below.
Tabelle 2Table 2
Zusammensetzungcomposition
[%][%]
Mikropartikel:Microparticles:
Natriumfluorid 20,0Sodium fluoride 20.0
Avicel PH 101 48,0Avicel PH 101 48.0
Eudragit RS PO 10,0Eudragit RS PO 10.0
Eudragit RS 30 D 2,0Eudragit RS 30 D 2.0
Eudragit L 30 D 15,0Eudragit L 30 D 15.0
Dibutylphthalat 5,0Dibutyl phthalate 5.0
Tablettenbasis:Tablet base:
SorbitSorbitol
MannitMannitol
Bolus albaBolus alba
AvicelAvicel
WeinsäureTartaric acid
OrangenaromaOrange aroma
Magnesiumstearat Beispiel 4Magnesium stearate Example 4
Tabletten mit Naftidrofurylhvdroαenoxalat als WirkstoffTablets with Naftidrofurylhvdroαenoxalat as active ingredient
Die im folgenden (Tabelle 3) detaillierter dargestellteThe ones shown in more detail below (Table 3)
Zusammensetzung einer erfindungsgemäßen Tablette enthält als Wirkstoff Naftidrofurylhydrogenoxalat, das durch- blutungsfördernd und gefäßerweiternd wirkt. Die elastischeThe composition of a tablet according to the invention contains naftidrofuryl hydrogen oxalate as an active ingredient, which promotes blood circulation and vasodilator. The elastic
Retardmatrix, in die dieser Wirkstoff in den MikropartikelnRetard matrix, in which this active ingredient in the microparticles
® eingebettet ist, beruht auf einer Eudragit -Zusammensetzung, während die Tablettenbasis (wie dargestellt) unterschiedlich zusammengesetzt sein kann. ® is embedded, is based on an Eudragit composition, while the tablet base (as shown) can have different compositions.
Tabelle 3Table 3
Zusammensetzungcomposition
[%][%]
Mikropartikel:Microparticles:
Naftidrofurylhydrogenoxalat 30,0Naftidrofuryl hydrogen oxalate 30.0
Eudragit RS PO 67,0Eudragit RS PO 67.0
Eudragit RS 100 2,5Eudragit RS 100 2.5
Triethylcitrat 0,5Triethyl citrate 0.5
Tablettenbasis:Tablet base:
MagnesiumoxidMagnesium oxide
MagnesiumeitratMagnesium citrate
Magnesiumasparat und andereMagnesium asparat and others
MagnesiumsalzeMagnesium salts
SorbitSorbitol
MannitMannitol
Süßstoffsweetener
AromaAroma
CitronensäureCitric acid
MagnesiumstearaMagnesium steara
oder Tablettenbasis:or tablet base:
SorbitSorbitol
MannitMannitol
AvicelAvicel
AromaAroma
WeinsäureTartaric acid
Magnesiumstearat Magnesium stearate
Beispiel 5Example 5
Tablette mit dem Wirkstoff Diclofenac NaTablet with the active ingredient Diclofenac Na
Im folgenden (Tabelle 4) ist eine erfindungsgemäße Tablette dargestellt, bei der die Mikropartikel den Wirk¬ stoff Diclofenac enthalten, der antiphlogistisch und antirheumatisch wirkt. Die elastische Matrix, in die dieser Wirkstoff in den Mikropartikeln eingebettet ist, besteht im weiteren aus dem Cellulosederivat Avicel.The following (Table 4) shows a tablet according to the invention in which the microparticles contain the active ingredient diclofenac, which has an anti-inflammatory and anti-rheumatic effect. The elastic matrix in which this active ingredient is embedded in the microparticles also consists of the cellulose derivative Avicel.
Tabelle 4Table 4
Zusammensetzungcomposition
[%][%]
Mikropartikel:Microparticles:
Diclofenac Na 25,0 %Diclofenac Na 25.0%
Avicel PH 101 37,0 %Avicel PH 101 37.0%
Lactose 35,0 %Lactose 35.0%
Aroma 1,0 %Aroma 1.0%
Kollidon 25 2,0 %Kollidon 25 2.0%
Tablettenbasis:Tablet base:
MagnesiumcarbonatMagnesium carbonate
MagnesiumoxidMagnesium oxide
MagnesiumeitratMagnesium citrate
MagnesiumasparatMagnesium asparat
KaliumcarbonatPotassium carbonate
CitronensäureCitric acid
In Entsprechung zu Fig. 1 ist in Fig. 2 die in-vitro-Libe¬ ration des Wirkstoffes Diclofenac aus den oben beschrie¬ benen Tabletten dargestellt. Bei spiel 6Corresponding to FIG. 1, FIG. 2 shows the in vitro liberation of the active ingredient diclofenac from the tablets described above. In game 6
Die in den vorangehenden Beispielen 1 bis 5 beschriebenen Zerbeißtabletten können ohne Änderung der Zusammensetzung als Zerfallstabletten eingesetzt werden. Bei entsprechenden Untersuchungen hat sich herausgestellt, daß diese Tabletten, wenn sie in ein beispielsweise mit Wasser gefülltes Glas (z.B. 50 ml) gegeben werden, dort innerhalb eines Zeitraumes von etwa 3 Minuten so weitgehend zerfallen, daß eine einnehm¬ bare Suspension entsteht. Durch den erfindungsgemäßen Aufbau der Tabletten wird daher nicht nur eine Zerbeißtablette zur Verfügung gestellt, sondern auch eine Zerfallstablette mit verzögerter Wirkstoff-Freisetzung, die die anfänglich beschriebenen Nachteile von üblichen Schlucktabletten vermeidet.The chewing tablets described in Examples 1 to 5 above can be used as disintegration tablets without changing the composition. Corresponding investigations have shown that when these tablets are placed in a glass filled with water (e.g. 50 ml), they largely disintegrate there within a period of about 3 minutes to form an ingestible suspension. The structure of the tablets according to the invention therefore not only provides a chewing tablet, but also a disintegrating tablet with delayed release of active ingredient, which avoids the disadvantages of conventional swallowing tablets described at the outset.
Als weitere Anwendungsbeispiele für kombinierte Zerbeiß- und/oder Zerfallstabletten sind die folgenden Kombinationen möglich, wobei der bei der angegebenen Indikation wirksame Wirkstoff in die Mikropartikel eingearbeitet wird und die übrigen Substanzen damit kombinierte Bestandteile in der Grundmasse darstellen.The following combinations are possible as further application examples for combined chewing tablets and / or disintegration tablets, the active ingredient which is active in the indicated indication being incorporated into the microparticles and the other substances thus constituting components in the basic composition.
____. H2~Blocker z.B.____. H2 ~ blocker e.g.
Cimetidin + SucralfatCimetidine + sucralfate
Ranitidin + Calciumcarbonat + MagnesiumoxidRanitidine + calcium carbonate + magnesium oxide
2. Vasodilatantien z.B.2. Vasodilatants e.g.
Pentoxyfyllin + Magnesiumasparat oder Magnesium¬ eitrat _____ Antiallergica z.B.Pentoxyfyllin + magnesium aspartate or magnesium eitrate _____ Antiallergica e.g.
Loratadin + Calciumsalze + TricalciumcitratLoratadine + calcium salts + tricalcium citrate
_____ Antihvpertonica z.B._____ Antihvpertonica e.g.
ß-Blocker wie Propranolol, Atenolol + Magnesium¬ salze α-Blocker wie Clonidin + Magnesiumsalze + Kaliumsalzeβ-blockers such as propranolol, atenolol + magnesium salts α-blockers such as clonidine + magnesium salts + potassium salts
5. Diuretica z.B.5. Diuretics e.g.
Furosemid, Hydrochlorothiazid + Magnesiumsalze + KaliumsalzeFurosemide, hydrochlorothiazide + magnesium salts + potassium salts
Die in der vorstehenden Beschreibung, in den Ansprüchen sowie in den Zeichnungen offenbarten Merkmale der Erfindung können sowohl einzeln als auch in beliebiger Kombination für die Verwirklichung der Erfindung in ihren verschiedenen Ausführungsformen wesentlich sein. The features of the invention disclosed in the above description, in the claims and in the drawings can be essential both individually and in any combination for realizing the invention in its various embodiments.

Claims

Ansprüche Expectations
1. Tablette zur Verwendung als Zerbeiß- und/oder Zer¬ fallstablette, dadurch gekennzeichnet, daß in einer üblichen Grundmasse, die zum Zerbeißen und/oder zum Zerfallen in Flüs¬ sigkeit geeignet ist, wirkstoffhaltige Mikropartikel mit re¬ tardierenden Eigenschaften vorhanden sind, die aufgrund ihrer Elastizität und Festigkeit beim Zerbeißen und/oder Zerfallen der Tablette nicht zerstört werden. 1. Tablet for use as a chewing and / or disintegrating tablet, characterized in that active ingredient-containing microparticles with retarding properties are present in a conventional matrix which is suitable for chewing and / or disintegrating in liquid due to their elasticity and strength, they cannot be destroyed when the tablet is bitten and / or disintegrates.
2. Tablette nach Anspruch 1, dadurch gekennzeichnet, daß die Grundmasse mindestens einen zusätzlichen Wirkstoff aufweist.2. Tablet according to claim 1, characterized in that the matrix has at least one additional active ingredient.
3. Tablette nach Anspruch 2, dadurch gekennzeichnet, daß die Grundmasse mindestens ein Calciu salz oder einen Calciumkomplex und die Mikropartikel Natriumfluoro- phosphat oder Natriumfluorid enthalten.3. Tablet according to claim 2, characterized in that the basic composition contains at least one calcium salt or a calcium complex and the microparticles contain sodium fluorophosphate or sodium fluoride.
4. Tablette nach einem der Ansprüche 1-3, dadurch gekenn¬ zeichnet, daß die Grundmasse den (die) gleichen Wirkstoff(e) wie die Mikropartikel enthält.4. Tablet according to any one of claims 1-3, characterized gekenn¬ characterized in that the matrix contains the same active ingredient (s) as the microparticles.
5. Tablette nach Anspruch 4, dadurch gekennzeichnet, daß die Menge an Wirkstoff in der Grundmasse so einge¬ stellt ist, daß sie als Initialdosis wirkt, und die5. Tablet according to claim 4, characterized in that the amount of active ingredient in the base is adjusted so that it acts as an initial dose, and the
Menge an Wirkstoff in den Mikropartikeln so eingestellt ist, daß sie als Erhaltungsdosis wirkt.Amount of active ingredient in the microparticles is set so that it acts as a maintenance dose.
6. Tablette nach einem der vorangehenden Ansprüche, da¬ durch gekennzeichnet, daß die Mikropartikel aus einer retardierenden, elastischen Wirkstoff altigen Matrix und einer retardierenden und ebenfalls elastischen Hülle bestehen. 6. Tablet according to one of the preceding claims, da¬ characterized in that the microparticles consist of a retarding, elastic active substance old matrix and a retarding and also elastic shell.
7. Tablette nach Anspruch 6, dadurch gekennzeichnet, daß7. Tablet according to claim 6, characterized in that
® die Matrix aus einem Eudragit -Derivat oder einer Zu-® the matrix from an Eudragit derivative or a
® sammensetzung verschiedener Eudragit -Derivate, Cellu¬ losederivaten wie z.B. Methylcellulose, Hydroxyethyl- cellulose oder Hydroxypropylcellulose, oder anderen üblichen, retardierenden Hilfsstoffen mit einem hohen Anteil an plastifizierenden Bestandteilen, besteht.® composition of various Eudragit derivatives, cellulose derivatives such as Methyl cellulose, hydroxyethyl cellulose or hydroxypropyl cellulose, or other conventional retarding auxiliaries with a high proportion of plasticizing constituents.
8. Tablette nach einem der Ansprüche 6 oder 7, dadurch gekennzeichnet, daß die Hülle aus Polyacrylaten, wie β8. Tablet according to one of claims 6 or 7, characterized in that the shell made of polyacrylates, such as β
Eudragit oder Eudragit -Zusammensetzungen, oder aus Cellulosederivaten, wie Ethylcellulose, Celluloseace- tatphthalaat oder Hydroxypropylmethylcellulosephtha- lat, ggf. unter Zusatz plastifizierender Hilfsstoffe, besteht.Eudragit or Eudragit compositions, or of cellulose derivatives, such as ethyl cellulose, cellulose sulfate phthalate or hydroxypropyl methyl cellulose phthalate, optionally with the addition of plasticizing auxiliaries.
9. Tablette nach einem der vorangehenden Ansprüche, da¬ durch gekennzeichnet, daß die Mikropartikel einen Durchmesser zwischen 0,3 und 3,0 mm besitzen.9. Tablet according to one of the preceding claims, da¬ characterized in that the microparticles have a diameter between 0.3 and 3.0 mm.
10. Tablette nach Anspruch 9, dadurch gekennzeichnet, daß die Mikropartikel einen Durchmesser von 0,3 bis 1,0 mm besitzen. 10. Tablet according to claim 9, characterized in that the microparticles have a diameter of 0.3 to 1.0 mm.
11. Tablette nach einem der vorangehenden Ansprüche mit einem Gehalt von Natriumfluorophosphat oder Natrium¬ fluorid in den Mikropartikeln und gegebenenfalls min¬ destens einem Calciumsalz oder Calciumkomplex in der Grundmasse, zur Prävention oder Therapie von Osteoporose.11. Tablet according to one of the preceding claims containing sodium fluorophosphate or sodium fluoride in the microparticles and optionally at least one calcium salt or calcium complex in the base material, for the prevention or therapy of osteoporosis.
12. Tablette nach einem der Ansprüche 1 bis 10, mit einem Gehalt an Naftidrofurylsalz, wie z.B. Naftidrofurylhy¬ drogenoxalat in den Mikropartikeln, zur Durchblutungs¬ förderung und/oder Gefäßerweiterung.12. Tablet according to one of claims 1 to 10, containing naftidrofuryl salt, such as e.g. Naftidrofurylhy¬ drug oxalate in the microparticles, to promote blood circulation and / or vasodilation.
13. Tablette nach einem der Ansprüche 1-10, mit einem Gehalt an Diclofenac bzw. dessen Salz in den Mikro¬ partikeln, als Antiphlogistikum und/oder Antirheuma- tikum.13. Tablet according to any one of claims 1-10, containing diclofenac or its salt in the microparticles, as an anti-inflammatory and / or anti-rheumatic.
14. Tablette nach einem der Ansprüche 1-10, mit einem Gehalt an Cimetidin oder Ranitidin bzw. deren Salzen in den Mikropartikeln, als H2-Blocker.14. Tablet according to any one of claims 1-10, containing cimetidine or ranitidine or their salts in the microparticles, as an H 2 blocker.
15. Tablette nach einem der Ansprüche 1-10, mit einem Ge¬ halt an Pentoxyfyllin in den Mikropartikeln, als Vaso- dilatans.15. Tablet according to any one of claims 1-10, with a Ge content of pentoxyfylline in the microparticles as Vasodilatans.
16. Tablette nach einem der vorangehenden Ansprüche 1-10, mit einem Gehalt an Loratadin in den Mikropartikeln, als Antiallergikum.16. Tablet according to one of the preceding claims 1-10, containing loratadine in the microparticles, as an antiallergic.
17. Tablette nach einem der vorangehenden Ansprüche 1-10, mit einem Gehalt an ß-Blocker, wie Propanolol und Atenolol, oder α-Blocker, wie Clonidin, in den Mikro¬ partikeln, als Antihypertonikum.17. Tablet according to one of the preceding claims 1-10, containing β-blockers, such as propanolol and atenolol, or α-blockers, such as clonidine, in the microparticles as an antihypertensive.
18. Tablette nach einem der Ansprüche 1-10, mit einem Ge¬ halt an Furosemid oder Hydrochlorothiazid in den Mikro¬ partikeln, als Diuretikum. 18. Tablet according to any one of claims 1-10, with a Ge content of furosemide or hydrochlorothiazide in the microparticles, as a diuretic.
PCT/EP1994/003166 1993-09-29 1994-09-22 Tablet containing a basic material possibly containing active substances and active substance containing microparticles WO1995008988A1 (en)

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DE19934333190 DE4333190C2 (en) 1993-09-29 1993-09-29 Bite-coated tablet with delayed release of active ingredient

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Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19648576A1 (en) * 1996-11-23 1998-06-04 Karsten Dr Cremer Lozenge for modified release of active substances in the gastrointestinal tract
WO2005074885A1 (en) * 2004-02-03 2005-08-18 Philippe Perovitch Method for the diffusion of molecules which are insoluble in an aqueous medium and composition using said method
US7125562B2 (en) 1997-08-22 2006-10-24 Smithkline Beecham Corporation Rapidly disintegrating methylcellulose tablets
US7132114B2 (en) 1997-08-22 2006-11-07 Smithkline Beecham Corporation Rapidly disintegrating methylcellulose tablets

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ES2206709T3 (en) * 1996-05-13 2004-05-16 Novartis Consumer Health S.A. ORAL SUPPLY SYSTEM.

Citations (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2047096A (en) * 1979-04-09 1980-11-26 Sanofi Sa Naftidrofuryl composition for immediate and delayed release
EP0153104A2 (en) * 1984-02-10 1985-08-28 Benzon Pharma A/S Diffusion coated multiple-units dosage form
EP0207405A2 (en) * 1982-07-27 1987-01-07 Mylan Pharmaceuticals, Inc. Method for making pharmaceutical combination composition in granularly heterogenous solid unit dosage form with enhanced bioavailability
WO1987002240A1 (en) * 1985-10-11 1987-04-23 Aktiebolaget Hässle New drug preparation with controlled release of the active compound, a method for the manufacture thereof and the use of the new preparation
EP0294933A2 (en) * 1987-05-08 1988-12-14 Smith Kline & French Laboratories Limited Pharmaceutical compositions
EP0355247A2 (en) * 1988-08-22 1990-02-28 Ss Pharmaceutical Co., Ltd. Compressed-molded preparations
EP0381219A2 (en) * 1989-02-02 1990-08-08 Warner-Lambert Company Modified release gemfibrozil composition
WO1991017743A1 (en) * 1990-05-17 1991-11-28 Europharmaceuticals S.A. Slow release pharmaceutical compositions to be orally administered, and method for preparing same
EP0503425A1 (en) * 1991-03-14 1992-09-16 MERCK PATENT GmbH Pellets containing sodium monofluorophosphate
FR2679451A1 (en) * 1991-07-22 1993-01-29 Prographarm Laboratoires MULTIPARTICLE TABLET WITH RAPID DELIVERY.
EP0525388A1 (en) * 1991-07-01 1993-02-03 Gerhard Dr. Gergely Suckable or chewable tablet

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4861590A (en) * 1986-09-25 1989-08-29 Colgate-Palmolive Company Sustained release fluoride and calcium composition
DE4236090C1 (en) * 1992-10-26 1994-01-05 Asta Medica Arzneimittel Pharmaceutical preparation for fluoride ion supply

Patent Citations (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2047096A (en) * 1979-04-09 1980-11-26 Sanofi Sa Naftidrofuryl composition for immediate and delayed release
EP0207405A2 (en) * 1982-07-27 1987-01-07 Mylan Pharmaceuticals, Inc. Method for making pharmaceutical combination composition in granularly heterogenous solid unit dosage form with enhanced bioavailability
EP0153104A2 (en) * 1984-02-10 1985-08-28 Benzon Pharma A/S Diffusion coated multiple-units dosage form
WO1987002240A1 (en) * 1985-10-11 1987-04-23 Aktiebolaget Hässle New drug preparation with controlled release of the active compound, a method for the manufacture thereof and the use of the new preparation
EP0294933A2 (en) * 1987-05-08 1988-12-14 Smith Kline & French Laboratories Limited Pharmaceutical compositions
EP0355247A2 (en) * 1988-08-22 1990-02-28 Ss Pharmaceutical Co., Ltd. Compressed-molded preparations
EP0381219A2 (en) * 1989-02-02 1990-08-08 Warner-Lambert Company Modified release gemfibrozil composition
WO1991017743A1 (en) * 1990-05-17 1991-11-28 Europharmaceuticals S.A. Slow release pharmaceutical compositions to be orally administered, and method for preparing same
EP0503425A1 (en) * 1991-03-14 1992-09-16 MERCK PATENT GmbH Pellets containing sodium monofluorophosphate
EP0525388A1 (en) * 1991-07-01 1993-02-03 Gerhard Dr. Gergely Suckable or chewable tablet
FR2679451A1 (en) * 1991-07-22 1993-01-29 Prographarm Laboratoires MULTIPARTICLE TABLET WITH RAPID DELIVERY.
WO1993001805A1 (en) * 1991-07-22 1993-02-04 Laboratoires Prographarm Rapidly disintegratable multiparticulate tablet

Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19648576A1 (en) * 1996-11-23 1998-06-04 Karsten Dr Cremer Lozenge for modified release of active substances in the gastrointestinal tract
DE19648576C2 (en) * 1996-11-23 1999-08-12 Lohmann Therapie Syst Lts Lozenge for modified release of active substances in the gastrointestinal tract
US7125562B2 (en) 1997-08-22 2006-10-24 Smithkline Beecham Corporation Rapidly disintegrating methylcellulose tablets
US7132114B2 (en) 1997-08-22 2006-11-07 Smithkline Beecham Corporation Rapidly disintegrating methylcellulose tablets
WO2005074885A1 (en) * 2004-02-03 2005-08-18 Philippe Perovitch Method for the diffusion of molecules which are insoluble in an aqueous medium and composition using said method
US8846083B2 (en) 2004-02-03 2014-09-30 Philippe Perovitch Method for the diffusion of molecules which are insoluble in an aqueous medium and composition using said method

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DE4333190A1 (en) 1995-03-30
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DE4333190C2 (en) 1996-05-30

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