DE2836447A1 - Pharmaceutical preparations in retard form - with active materials in core having semipermeable coating of film former and polymer - Google Patents

Pharmaceutical preparations in retard form - with active materials in core having semipermeable coating of film former and polymer

Info

Publication number
DE2836447A1
DE2836447A1 DE19782836447 DE2836447A DE2836447A1 DE 2836447 A1 DE2836447 A1 DE 2836447A1 DE 19782836447 DE19782836447 DE 19782836447 DE 2836447 A DE2836447 A DE 2836447A DE 2836447 A1 DE2836447 A1 DE 2836447A1
Authority
DE
Germany
Prior art keywords
core
bunitrolol
form according
tablets
release
Prior art date
Legal status (The legal status 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 status listed.)
Withdrawn
Application number
DE19782836447
Other languages
German (de)
Inventor
Bernhard Dr Freund
Volkmar Dipl Chem Haeselbarth
Heribert Harwalik
Herbert Dr Stricker
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
CH Boehringer Sohn AG and Co KG
Original Assignee
CH Boehringer Sohn AG and Co KG
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 CH Boehringer Sohn AG and Co KG filed Critical CH Boehringer Sohn AG and Co KG
Priority to DE19782836447 priority Critical patent/DE2836447A1/en
Priority to DD79214300A priority patent/DD146547A5/en
Priority to PL21711379A priority patent/PL217113A1/xx
Priority to SE7906119A priority patent/SE7906119L/en
Priority to GB7924504A priority patent/GB2025227B/en
Priority to NL7905484A priority patent/NL7905484A/en
Priority to IT49752/79A priority patent/IT1116877B/en
Priority to IL57796A priority patent/IL57796A0/en
Priority to FR7918301A priority patent/FR2430766A1/en
Priority to DK296979A priority patent/DK296979A/en
Priority to NO792335A priority patent/NO792335L/en
Priority to PT69922A priority patent/PT69922A/en
Priority to BE0/196306A priority patent/BE877706A/en
Priority to LU81503A priority patent/LU81503A1/en
Priority to FI792204A priority patent/FI792204A/en
Priority to ZA00793542A priority patent/ZA793542B/en
Priority to GR59598A priority patent/GR71195B/el
Priority to AU48947/79A priority patent/AU4894779A/en
Priority to CA331,894A priority patent/CA1126156A/en
Publication of DE2836447A1 publication Critical patent/DE2836447A1/en
Priority to US06/273,643 priority patent/US4361546A/en
Priority to US06/409,131 priority patent/US4459279A/en
Priority to US06/604,830 priority patent/US4578264A/en
Withdrawn legal-status Critical Current

Links

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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • 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
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/2853—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers, poly(lactide-co-glycolide)
    • 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
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2806—Coating materials
    • A61K9/2833—Organic macromolecular compounds
    • A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
    • A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • 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

Abstract

Pharmaceutical prepn. in retard form comprises a core contg. >=1 active substance together with a carrier or excipient. The core is coated with a semipermeable coating of 20-90% water-insoluble film former (I) (e.g. ethyl cellulose) and 10-80% water-soluble polymer (II), e.g. PVP, PEG or methyl cellulose. The release of active substance is independent of pH in the body fluid over the whole period of its activity. The core pH may be reduced by inclusion of acidic material to reduce disintegration time. Dosage regimens are simplified, and initial very high blood levels may be avoided. The core may be in the form of a tablet. The coating pref. has the same permeability over its whole surface. The core may contain an organic food acid to reduce the disintegration time of the core, e.g. citric or tartaric acid is used. The coating may also contain up to 70% water insol. polymer e.g. cellulose acetate.

Description

Neue Bunitrolol-RetardformNew prolonged-release bunitrolol form

Die Erfindung betrifft eine neue Dunitrolol-Reterdform, bei welcher in einer Gelatine-Kapsel Retardtabletten verschiedener Verzögerun6sstufen sowie gegebenenfalls unverzögerte sog. Initialtabletten zu einer Einheit zusammengefaßt sind und welche dadurch gekennzeichnet ist, daß die Retardtabletten eine unter Standardbedingungen aufgetragene Diffusionshülle bestimmter auf den Xirkstoff abgestimmter Zusammensetzung und Dicke aufweisen.The invention relates to a new dunitrolol Reterdform, in which in a gelatin capsule prolonged-release tablets of various delay levels as well if necessary, immediate so-called initial tablets combined into one unit are and which is characterized in that the prolonged-release tablets are under standard conditions applied diffusion shell of a specific composition tailored to the active substance and thickness.

Die ideale orale Depotform muß ähnlich wirken wie eine intravenöse Dauerinfusion, d.h. sie muß (nach zunächst raschem Anstieg) für die gewünschte Wirkungsdauer des Medikamentes einen möglichst konstanten Blutspiegel (ein sog. "Plateau't) aufrechterhalten.The ideal oral depot form must have a similar effect to an intravenous one Continuous infusion, i.e. it must (after initially rapid increase) for the desired duration of action Maintain a blood level of the drug that is as constant as possible (a so-called "plateau").

Die Annäherung an dieses Ideal wird in der Praxis durch die verschiedensten Faktoren erschwert, die (im Unterschied zur intravenösen Verabreichung) auf ein oral einzunehmendes Präparat während des Durchlaufens des Magen-Darm-Trakts einwirken. Zu nennen sind hier beispielsweise der pH-Gradient, die Motilität, der Enzymgehalt sowie der Elektrolyt- und Wassergehalt des Magen-Darm-Trakts.The approach to this ideal is in practice by the most diverse Factors that make it difficult (in contrast to intravenous administration) to a Oral preparation act during passage through the gastrointestinal tract. Examples include the pH gradient, motility and enzyme content as well as the electrolyte and water content of the gastrointestinal tract.

Eine gute Methode, von diesen Einflußparametern möglichst unabhängig zu werden und Schwankungen in der Freigabegeschwindigkeit möglichst auszugleichen, besteht darin, in einer Hartgelatine-Steckkapsel eine oder mehrere sog.A good method, as independent as possible from these influencing parameters and to compensate for fluctuations in the release speed as far as possible, consists in placing one or more so-called

Initialtabletten mit weiteren Tabletten, welche aufgrund unterschiedlicher Zusammensetzung und Dicke der Diffusionshülle unterschiedliche Freigabegeschwindigkeiten aufweisen, zu einer Dosierungseinheit zusammenzufassen. Die Annäherung an den idealen Freigabeverlauf wird dabei wesentlich mitbestimmt von der stofflichen Zusammensetzung sowie der Dicke der Diffusionshülle, welche auf die Art und Menge des zu verzögernden Wirkstoffs ahgestimmt sein müssen.Initial tablets with additional tablets, which are due to different Composition and thickness of the diffusion shell different release rates have to be combined into a dosage unit. The approach to the ideal The release process becomes essential co-determined by the material Composition and the thickness of the diffusion envelope, which depends on the type and amount of the active substance to be delayed must be correct.

Bei dem unter der Kurzbezeichnung Bunitrolol bekannten ß-Adrenolyticum 1- (2-Cyanophenoxy)-3tert .butylaminopropanel(2) handelt es sich um eine in Salzform (z.B. als Hydrochlorid) gut wasserlösliche Substanz.In the case of the ß-adrenolytic, known under the abbreviation Bunitrolol 1- (2-Cyanophenoxy) -3tert .butylaminopropanel (2) is in salt form (e.g. as hydrochloride) a readily water-soluble substance.

Es wurde nun gefunden, daß es gelingt, eine optimale Freigabekurve für den Wirkstoff Bunitrolol im Dosisbereich 10-150 mg zu erhalten, wenn man bei einer Retardform, welche Retardtabletten verschiedener Verzögerungsstufen sowie gegebenenfalls unverzögerte Tabletten in einer Kapsel besteht, die iietardtabletten mit einer Lackhülle aus 20-90 5o', vorzugsweise 40-70 % Äthylcellulose und 10-80 96, vorzugsweise 30-60 % Polyäthylenglykol unter Standardbedingungen bis zu einer Hüllendicke von 5-30 %, bezogen auf das Gewicht der Preßlinge, überzieht. Hierbei erhalten die Retardtabletten höhere Verzögerungsstufen entsprechend dickere Hüllen als diejenigen niedriger Verzögerungsstufen.It has now been found that an optimal release curve is achieved for the active ingredient Bunitrolol in the dose range 10-150 mg to be obtained if one is at a sustained-release form, which sustained-release tablets of various delay levels as well if necessary, immediate tablets in a capsule, the iietardtabletten with a coating of 20-90 50 ', preferably 40-70% ethyl cellulose and 10-80 96, preferably 30-60% polyethylene glycol under standard conditions up to one Shell thickness of 5-30%, based on the weight of the compacts, coated. Here If the prolonged-release tablets are given higher delay levels, correspondingly thicker shells than those of lower delay levels.

Besonders günstige Ergebnisse (z.B. eine besonders geringe Standardabweichung der Hullen-Permeabilität vom Mittelwert) ergeben sich, wenn bestimmte Herstellbedingungen stets konstant gehalten werden. Auf diese Weise ergibt sich ein reproduzierbarer Einbau des wasserlöslichen Polyäthylenglykols in die wasserunlösliche Äthylcellulose, was nach dem Herauslösen des ersteren zu einer gut reproduzierbaren Hüllenporosität führt.Particularly favorable results (e.g. a particularly low standard deviation the Hullen permeability from the mean value) result when certain manufacturing conditions always be kept constant. This results in a reproducible Incorporation of the water-soluble polyethylene glycol into the water-insoluble ethyl cellulose, which after the removal of the former results in a well reproducible shell porosity leads.

Hierbei haben sich das Lirmalten einer hohen SprEhgeschwindigkeit, ernönte Sprühtemperatur sowie die Standardisierung des Wassergehalts in dem zum Auftragen der Hülle benützten Lösungsmittel als besonders vorteilhaft erwiesen.Here, the whirling of a high spraying speed, the spray temperature and the standardization of the water content in the Applying the shell used solvents proved to be particularly advantageous.

Die neue Form eignet sich auch für die Herstellung von Kombinationspräparaten des Bunitrolols, z.B. mit Antihypertonica wie Hydrochlorothiazid und/oder Triamteren, oder gefäßerweiternden Mitteln wie Isosorbiddinitrat.The new shape is also suitable for the production of combination products of bunitrolol, e.g. with antihypertensive drugs such as hydrochlorothiazide and / or triamterene, or vasodilators such as isosorbide dinitrate.

Die Dosis der genannten Antihypertonica kann bei einem solchen Präparat bei 5-50 mg bzw. 10-50 mg liegen.The dose of the antihypertensive drugs mentioned can be varied with such a preparation 5-50 mg and 10-50 mg respectively.

(Bunitrolol: 10-150 mg, vorzugsweise 30 mg). Bei der Kombination mit Isosorbiddinitrat kann eine Dosis von 10-150 mg, vorzugsweise 30 mg Bunitrolol mit 5-100 mg, vorzugsweise 15 mg Isosorbiddinitrat kombiniert werden.(Bunitrolol: 10-150 mg, preferably 30 mg). When combined with Isosorbide dinitrate can contain a dose of 10-150 mg, preferably 30 mg of bunitrolol 5-100 mg, preferably 15 mg, of isosorbide dinitrate can be combined.

Es genügt, der vorstehend beschriebenen bunitrolol-Retardeinheit eine bzw. auch weitere Initialtabletten mit den zusätzlichen Wirkstoffen hinzuzufügen.It is sufficient to use the bunitrolol retard unit described above or also to add further initial tablets with the additional active ingredients.

Eine optimale Freigabekurve wird erreicht, wenn man die Gesamtdosis von 30 mg Bunitrolol auf eine Initialtablette sowie zwei mäßig verzögerte Retardtabletten verteilt (siehe nachstehendes Beispiel 1). Auf diese Weise erhält man einen raschen Plasmaspiegel-Anstieg mit verlängerter Plateaubildung. Die so erhaltene Dosiereinheit vereinfacht das Dosierschema des ß-Adrenolyticums wesentlich und reduziert die Gefahr der unfreiwilligen Uberdosierung, die bei B-Adrenolytica nicht zu unterschätzen ist. Sie führt ferner zu einem Abbau der (auf Plasma-Spitzen zurückgehende) Nebenwirkungen wie zu starke Absenkung des Blutdrucks oder starke Bradycardie.An optimal release curve is achieved when you consider the total dose from 30 mg bunitrolol to an initial tablet and two moderately delayed prolonged-release tablets distributed (see example 1 below). That way you get a quick one Rise in plasma level with prolonged plateau formation. The thus obtained dosing unit simplifies the dosing scheme of the ß-adrenolytic drug significantly and reduces the risk involuntary overdose, which should not be underestimated with B-adrenolytics is. It also leads to a reduction in side effects (due to plasma peaks) such as hypotensive blood pressure or severe bradycardia.

Die folgenden Beispiele erläutern die Erfindung, ohne sie zu beschränken: Beispiel 1 Bunitrolol-Retardform Die Herstellung der Tablettenkerne (Preßlinge) erfolgt in der üblichen Weise durch Zusammenmischen des Wirkstoffs mit üblichen Hilfsstoffen wie Lactose, Polyvinylpyrrolidon und einem Farbstoff, Feuchtgranulieren und Verpressen.der homogenen Mischung zu gewölbten Preßlingen von ca. 5 mm Durchmesser. (Herstellung sog. "Lösetabletten" ohne Sprengmittelzusatz). Für die Initialtablette stellt man einen Preßling mit 10 mg Wirkstoff her und überzieht ihn mit einem in wäßrigem Medium schnell zerfallenden Überzug aus Hydroxypropylmethylcellulose (20-90 z) und Polyäthylenglykol (10-80 96). Anschließend wird getrocknet.The following examples illustrate the invention without restricting it: example 1 Bunitrolol sustained-release form The tablet cores (pellets) are manufactured in the usual way by mixing the active ingredient with the usual excipients such as lactose, polyvinylpyrrolidone and a dye, wet granulation and compression homogeneous mixture to form curved compacts approx. 5 mm in diameter. (Manufacture so-called "dissolving tablets" without the addition of disintegrants). For the initial tablet, make a compact with 10 mg of active ingredient and coated it with an aqueous medium rapidly disintegrating coating made of hydroxypropylmethylcellulose (20-90 z) and polyethylene glycol (10-80 96). Then it is dried.

Des weiteren werden pro Initialtablette zwei Retardtabletten hergestellt. Sie enthalten jeweils 10 mg Wirkstoff und werden mittels einer üblichen SprühpiFtole mit einer Sprühlösung überzogen, die folgende Zusammensetzung aufweist Äthylcellulose N 14 5 Teile Polyäthylenglykol 6000 5 Teile Äthanol (vergällt) 45 Teile Methylenchlorid 45 Teile Für die verwendete Verzögerungsstufe 1 wird eine Lackmenge von 6 mg aufgetragen. Anschließend werden die Filmtabletten getrocknet.In addition, two prolonged-release tablets are produced for each initial tablet. They each contain 10 mg of active ingredient and are injected using a conventional spray gun coated with a spray solution having the following composition: ethyl cellulose N 14 5 parts of polyethylene glycol 6000 5 parts of ethanol (denatured) 45 parts of methylene chloride 45 parts For the delay level 1 used, a paint quantity of 6 mg is applied. The film-coated tablets are then dried.

Als letzter Schritt folgt das einkapselt der Initialtablette zusammen mit Je zwei Retardtabletten der hergestellten Verzöfrerungsstufe in Hartgelatine-Steckkapseln mittels einer Kapselfüllmaschine.The last step is to encapsulate the initial tablet together with two prolonged-release tablets each of the prepared delay stage in hard gelatin push-fit capsules by means of a capsule filling machine.

beispiel 2 Retardform einer Kombination Bunitrolol/Hydrochlorothiazid/rnjri amteren Die Herstellung der Bunitrolol-Preßlinge erfolgt lil cer gleichen reise wie in Beispiel 1 angegeben. Zusätzlich zu den 3 Bunitrolol-Preßlingen mit je 10 mg Wirkstoff stellt man einen weiteren Preßling mit 12,5 mg Hydrochlorothiazid sowie einen Preßling mit 25 mg Tria:nteren her, indem man Jeweils den Wirkstoff zusammen mit Milchzucker, Maisstärke sowie Magnesiumstearat und Farbstoff mischt und verpreßt.Example 2 Retard form of a combination of bunitrolol / hydrochlorothiazide / rnjri Officials The Bunitrolol pellets are produced in the same voyage as indicated in Example 1. In addition to the 3 bunitrolol tablets each with 10 mg of active ingredient is placed in another compact with 12.5 mg of hydrochlorothiazide as well a pellet with 25 mg Tria: nteren by combining the active ingredient in each case mixed with milk sugar, corn starch as well as magnesium stearate and coloring agent and pressed.

Auch die Herstellung der Überzüge erfolgt in der in Beispiel 1 angegebenen eise. Dabei werden der die zusätzlichen Wirkstoffe enthaltenden Preßiinge in der gleichen Weise überzogen wie die Bunitrolol-Initialtablette. Das Überziehen der Bunitrolol-Retardt2bletten sowie das Einfüllen der fertigen Tabletten in Kapseln erfolgt analog Beispiel 1, wobei Kapseln verwendet werden, die insgesamt 5 Tabletten mit 5 mm Durchmesser aufnehmen können.The coatings are also produced in the manner indicated in Example 1 ice. The pressed parts containing the additional active ingredients are in the coated in the same way as the bunitrolol initial tablet. Covering the Bunitrolol-Retardt2bletten as well as the filling of the finished tablets in capsules takes place analogously to Example 1, using capsules that contain a total of 5 tablets with a diameter of 5 mm.

Claims (7)

PatentansDrüche 1. Neue Bunitrolol-Retardform, bei welcher in einer Kapsel Retardtabletten verschiedener Verzögerungsstufen sowie gegebenenfalls unverzögerte Tabletten zu einer Einheit zusammengefaßt sind, dadurch gekennzeichnet, daß die Retardtabletten unter Standardbedingungen mit einer Hülle von 5-30 vo Gewicht, bezogen auf das Gewicht der Tablettenkerne überzogen sind, welche aus 20-90 L/O Äthylcellulose und 10-80 ß Polyäthylenglykol besteht.Patent claims 1. New Bunitrolol sustained release form, in which in a Capsule prolonged-release tablets of various delay levels and, if necessary, instantaneous Tablets are combined into a unit, characterized in that the Extended-release tablets under standard conditions with an envelope of 5-30% by weight are coated on the weight of the tablet cores, which are made of 20-90 L / O ethyl cellulose and 10-80 ß polyethylene glycol. 2. Retardform nach Anspruch 1, dadurch gekennzeichnet, daß sie eine Wirkstoffdosis von 10-150 mg enthält.2. Retard form according to claim 1, characterized in that it has a Contains active ingredient dose of 10-150 mg. 3. Retardform nach einem der vorhergehenden Ansprüche, dadurch gekennzeichnet, daß die Hülle der Retardtabletten aus 40-70 % Äthylcellulose und 30-60 % Polyäthylenglykol besteht.3. Retard form according to one of the preceding claims, characterized in that that the shell of the prolonged-release tablets made of 40-70% ethyl cellulose and 30-60% polyethylene glycol consists. 4. Retardform nach einem der vorhergehenden Ansprüche, dadurch gekennzeichnet, daß sie zusätzlich eine oder mehrere weitere Initialtabletten mit einem oder mehreren physiologisch mit Bunitrolol zusammenwirkenden Stoff enthält.4. Retard form according to one of the preceding claims, characterized in that that they also have one or more additional initial tablets with one or more Contains substance that interacts physiologically with bunitrolol. 5. Retardform nach Anspruch 4, dadurch gekennzeichnet, daß der (die) weitere Stoff(e) Hydrochlorothiazid und/oder Triamteren ist (sind).5. Retard form according to claim 4, characterized in that the (the) other substance (s) is (are) hydrochlorothiazide and / or triamterene. 6. Verfahren zur Herstellung einer neuen Bunitrolol-Petardform nach einem der vorhergehenuen hnsprtiche, dadurch gekennzeichnet, daß man heim Auftragen der Hülle den Wassergehalt der verwendeten Sprillösung standardisiert 6. Process for the production of a new Bunitrolol petard form according to one of the previous injuries, characterized in that one applies home the shell standardized the water content of the spray solution used 7. Verfahren zur Herstellung einer neuen Bunitrolol-Retardform nach einem der vorhergehenden Ansprüche, dadurch gekennzeichnet, daß man beim Auftragen der Hülle eine hohe Sprühgeschwindigkeit sowie erhöhte Sprühtemperatur anwendet.7th Process for the production of a new Bunitrolol sustained release form according to one of the preceding Claims, characterized in that a high spray speed is used when applying the casing as well as applying increased spray temperature.
DE19782836447 1978-07-15 1978-08-19 Pharmaceutical preparations in retard form - with active materials in core having semipermeable coating of film former and polymer Withdrawn DE2836447A1 (en)

Priority Applications (22)

Application Number Priority Date Filing Date Title
DE19782836447 DE2836447A1 (en) 1978-08-19 1978-08-19 Pharmaceutical preparations in retard form - with active materials in core having semipermeable coating of film former and polymer
DD79214300A DD146547A5 (en) 1978-07-15 1979-07-12 MEDICINAL RETARDANT SHAPE WITH UNFORGETTABLE POROESEN DIFFUSION SHELLS
PT69922A PT69922A (en) 1978-07-15 1979-07-13 MEDICAMENT RETARD FORM WITH UNLIMITED POROSEN DIFFUSION ZIPS
LU81503A LU81503A1 (en) 1978-07-15 1979-07-13 MEDICINAL PRODUCT RETARD FORM WITH INSOLUBLE POROUS DIFFUSION CASES
GB7924504A GB2025227B (en) 1978-07-15 1979-07-13 Pharmaceutical preparations in retard form
NL7905484A NL7905484A (en) 1978-07-15 1979-07-13 MEDICINE WITH DELAYED DELIVERY WITH INSOLUBLE POROUS DIFFUSION COVERS.
IT49752/79A IT1116877B (en) 1978-07-15 1979-07-13 PHARMACEUTICAL FORM FOR DELAYED DELIVERY OF MEDICINAL SUBSTANCES WITH INSOLUBLE POROUS SHELL AND HYDRATION PROCEDURE
IL57796A IL57796A0 (en) 1978-07-15 1979-07-13 Pharmaceutical compositions having retarded release of the active substance
FR7918301A FR2430766A1 (en) 1978-07-15 1979-07-13 DELAYED DRUG FORM COMPRISING AN INSOLUBLE POROUS BROADCASTING ENVELOPE
DK296979A DK296979A (en) 1978-07-15 1979-07-13 RETARDED RELEASE MEDICINE
NO792335A NO792335L (en) 1978-07-15 1979-07-13 PHARMACEUTICAL RETARD FORM WITH INSULABLE, POROUS DIFFUSION COATERS
PL21711379A PL217113A1 (en) 1978-07-15 1979-07-13
BE0/196306A BE877706A (en) 1978-07-15 1979-07-13 DELAYED DRUG FORM COMPRISING AN INSOLUBLE POROUS BROADCASTING ENVELOPE
SE7906119A SE7906119L (en) 1978-07-15 1979-07-13 TOXIC RETARD FORM WITH INSULABLE POROSA DIFFUSION WRAP
FI792204A FI792204A (en) 1978-07-15 1979-07-13 RETARD DOSERINGSFORM FOER CEILING MODEL MED EN LOESLIGT POROEST DIFFUSIONSSKAL
ZA00793542A ZA793542B (en) 1978-07-15 1979-07-13 Pharmaceutical preparations
GR59598A GR71195B (en) 1978-07-15 1979-07-13
AU48947/79A AU4894779A (en) 1978-07-15 1979-07-16 Retard compositions
CA331,894A CA1126156A (en) 1978-07-15 1979-07-16 Retard form of pharmaceuticals with insoluble porous diffusion-coats
US06/273,643 US4361546A (en) 1978-07-15 1981-06-15 Retard form of pharmaceuticals with insoluble porous diffusion coatings
US06/409,131 US4459279A (en) 1978-07-15 1982-08-18 Retard form of pharmaceuticals with insoluble porous diffusion coatings
US06/604,830 US4578264A (en) 1978-07-15 1984-04-27 Retard form of pharmaceuticals with insoluble porous diffusion coatings

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
DE19782836447 DE2836447A1 (en) 1978-08-19 1978-08-19 Pharmaceutical preparations in retard form - with active materials in core having semipermeable coating of film former and polymer

Publications (1)

Publication Number Publication Date
DE2836447A1 true DE2836447A1 (en) 1980-02-28

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Application Number Title Priority Date Filing Date
DE19782836447 Withdrawn DE2836447A1 (en) 1978-07-15 1978-08-19 Pharmaceutical preparations in retard form - with active materials in core having semipermeable coating of film former and polymer

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DE (1) DE2836447A1 (en)

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19724696A1 (en) * 1997-06-12 1998-12-24 Hexal Ag Pharmaceutical preparation with three types of pellets
DE19820529A1 (en) * 1998-05-08 1999-11-11 Lohmann Therapie Syst Lts Oral or mucosal preparation with controlled release of active agents by coated particles

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19724696A1 (en) * 1997-06-12 1998-12-24 Hexal Ag Pharmaceutical preparation with three types of pellets
DE19820529A1 (en) * 1998-05-08 1999-11-11 Lohmann Therapie Syst Lts Oral or mucosal preparation with controlled release of active agents by coated particles
US6635276B1 (en) 1998-05-08 2003-10-21 Kts Kignabb Therapie-Systeme Ag Oral or mucosal preparation containing an active ingredient, with controlled active ingredient release, and its use

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