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WO1998003161A1 - Comprimes a liberation controlee - Google Patents

Comprimes a liberation controlee Download PDF

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Publication number
WO1998003161A1
WO1998003161A1 PCT/GB1997/001770 GB9701770W WO9803161A1 WO 1998003161 A1 WO1998003161 A1 WO 1998003161A1 GB 9701770 W GB9701770 W GB 9701770W WO 9803161 A1 WO9803161 A1 WO 9803161A1
Authority
WO
WIPO (PCT)
Prior art keywords
coating
controlled release
medium
active ingredient
rate
Prior art date
Application number
PCT/GB1997/001770
Other languages
English (en)
Inventor
Abraham Jacob Domb
Original Assignee
Dexcel Ltd.
Smith, Norman, Ian
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 Dexcel Ltd., Smith, Norman, Ian filed Critical Dexcel Ltd.
Priority to AU33522/97A priority Critical patent/AU3352297A/en
Publication of WO1998003161A1 publication Critical patent/WO1998003161A1/fr

Links

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
    • A61K9/28—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
    • A61K9/20—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
    • 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
    • A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone
    • A61K9/2846—Poly(meth)acrylates
    • 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
    • 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
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates

Definitions

  • the present invention relates to a controlled release tablet, which is useful for the oral administration of pharmaceutically active water soluble and water insoluble substances.
  • Drug release from a controlled release dosage form is generally controlled by a coating outside an active core.
  • the release can be achieved a) by diffusion: the coating swells in aqueous environment so that the active substance can diffuse through the stagnant liquid phase contained in the coating polymer; or b) by osmosis: the coating is semi-permeable, i.e. only water can penetrate the coating polymer and dissolve the active substance, this will lead to a pressure buildup inside the coating, in order to allow the active to be released from the unit a hole or channel with a well defined area must be formed in the coating, this can be achieved either by laser drilling (SE patent 435 897 - U.S. Pat.
  • a controlled release tablet for the oral administration of a pharmaceutically active ingredient comprising a) a controlled release core composition comprising a pharmaceutically active ingredient incorporated into a polymeric carrier and diffusable therefrom at a predetermined controlled rate upon contact with a medium of an environment of use, said polymer carrier being insoluble in said medium; and b) a release rate controlling coating surrounding said core, said coating comprising a water insoluble and water impermeable polymeric material having at least one channeling agent dispersed in said coating and constituting about 5-60 wt./wt.% of the total coating, said channeling agent being soluble in said medium and being leachable from said coating upon contact with said medium to form molecular channels in said coating for passive diffusion of said pharmaceutically active ingredient via said channels at a controlled rate predetermined by said channels.
  • the tablet of the present invention is made up of two components, a controlled release core matrix that releases the entrapped drug in the proper releasing medium at a controlled manner without being disintegrated , preferably at a rate of up to 55% during the first hour, up to 75% at the second hour and at least 70% of the drug during the next 5 hours.
  • the second component is a continuous polymeric coating that serves as a rate controlling membrane which releases the drug at a controlled rate of preferably not more than 70% of the drug within 6 hours and not less than 70% within 24 hours in the proper releasing medium.
  • the coating is preferably composed of a water insoluble polymer and a hydrophilic channeling agent that is leached out when exposed to the releasing medium.
  • the water insoluble polymer may be a hydrophobic polymer that does not swell in water or a polymer that may swell in water.
  • the channeling agent may be a water soluble small molecule such as sucrose and NaCI or a macromolecule such as polysaccharides, water soluble acrylic polymer, and other water soluble polymers.
  • said channeling agent is a polysaccharide, and especially preferred for use as said channeling agent is arabinogalactan.
  • a tablet that is composed of a slow release core matrix coated with a continuous water insoluble film containing a water soluble channeling agent that determines the drug release rate;
  • a tablet with a rate controlling film coating with a system that avoids an accidental burst release in case of a breakage of the coating
  • a tablet in which the channeling agent is a branched polysaccharide such as Arabinogalactan;
  • a tablet in which the coating is a water based dispersion of a water insoluble polymer with the channeling agent soluble in the water phase that form a continuous, uniform, stable, flexible and reproducible coating.
  • the pharmaceutically active ingredient in the formulations according to the present invention may be any active substance that is advantageously administered in a controlled release oral tablet formulation.
  • suitable active substance are found among almost all therapeutic groups, including diuretics, antiepileptics, sedative, antiahrrythmics, antirheumatics, b-blockers, vasodilators, oral antidiabetics, antihypertensives, analgesics, bro ⁇ chodilators, hormones, orally active peptides and proteins, vitamins, oral antidiabetics, antibiotics, antihypertensives, anti-inflammatory agents, steroids, antifungals, antidepressants, homeopathic agents and enzymes.
  • active substances may be mentioned Diltiazem, nifedipin, ibuprofen, indomethacine, clonidine, KCI, lithium carbonate, depyridamol, paracetamol, verapamii, paracetamol, morphine, nitroglycerine, captopril, dexamethasone, propranolol, furoseamide, digoxin, and diclofenac.
  • water soluble drugs should be retarded by the core matrix and being released in a controlled pattern before applying the rate controlling coating. Accordingly, the insoluble drugs should be released from the core matrix at a proper rate which require a way to increase the availability of the drug when placed in the proper releasing medium. For this, the insoluble drug will be treated by physical means to increase its availability for example, blending the drug with a water soluble carrier (sugar, PEG) at a molecular level to meet the release specifications for the core matrix.
  • a water soluble carrier sucgar, PEG
  • the core matrix is preferably in the shape of a common tablet (oval, circular, round edge rectangular) which is individually coated in the next step to provide the final tablet.
  • the surface area may be between 20 and 200 mm and thickness of 1 to 10 mm or by weight of the core matrix in the range of 100 mg and 1500 mg.
  • the composition of the core matrix depends on the nature of the drug.
  • a hydrophilic drug is formulated with hydrophobic polymers that retard their availability while insoluble drugs are formulated with hydrophilic polymers that enable them to be released from the matrix within the specification range.
  • Water soluble drugs are typically granulated or compressed with one or more water insoluble polymers described for the coating. Examples of polymers are copolymers of methacrylic acid-methyl methacrylate and ethyl cellulose.
  • a water insoluble drug may be first solubilized in an organic solution containing a hydrophilic carrier [i.e. polyethylene glycol, low molecular weight poly(vinyl pyrrolidone) (PVP)] and sprayed on sugar microparticles to form granules with improved drug availability when contact with the releasing medium.
  • a hydrophilic carrier i.e. polyethylene glycol, low molecular weight poly(vinyl pyrrolidone) (PVP)
  • the coating polymer should have good film forming and adhesive properties, that can be applied either from an organic solvent or from a water dispersion.
  • the amount of coating material applied on the core matrix is in the range of 5 to 50% of the weight of the matrix.
  • the polymer used must be insoluble in water and water impermeable in order to prevent dissolution thereof and/or the creation of osmotic pressure within the tablet.
  • Suitable polymers are non- swelling or slightly swelling cellulose alkyl ester or ether derivatives such as ethyl cellulose, methyl cellulose, cellulose acetate phthalate, methyl- hydroxypropyl cellulose; acrylic polymers such as copolymers of acrylic acid and Methylmethacrylate known as Eudragit family of polymers; vinyl polymers such as polyvinyl chloride, polystyrene, poly(vinyl acetate).
  • the preferred polymers are water dispersions of methacrylic/methyl methacrylate polymers, Eudragit 30SE and ethyl cellulose, Aquacoat, or their acetone or alcohol solutions.
  • plastisizers also are present in the coating.
  • the amount may vary between 1 and 30% by weight of the total coating solids, preferably between 5 and 20%.
  • suitable plastisizers are acetyltributyl citrate, tributyl citrate, triethyl citrate, blown castor oil, glyceryl triacetate, butyl sebacate and polyethylene glycol.
  • the coating may contain coloring agents, flavor and any minor agents that makes the tablet more attractive for use.
  • the coating preferably contains a channeling agent in the amount of between 5 and 60% of the total coating solids.
  • the channeling agent can be soluble in the coating liquid or microparticles dispersed in the coating liquid.
  • suitable channeling agents are pharmaceutically acceptable water soluble salts and sugars such as NaCI, boric acid, sodium borate, sucrose, lactose, and sodium lactate.
  • Hydrophilic polymers such as linear and branched natural and modified polysaccharides such as dextran, arabinogalactan, synthetic polymers such as homo- and copolymer of vinyl alcohol, homo- and copolymers of acrylic acid, poly(ethylene glycol), poly(ethylene-co-propylene glycol), and poly(vinylpyrrolidone).
  • the coating is commonly applied on the core matrix by pan coating with spraying the water base or organic base coating liquid on the compressed matrices.
  • Other methods such as fluidised bed and dipping methods may be used.
  • the channeling agent may be leached out to form channels through the film coating at different rates depending on the solubilization rate of the channeling agent in the releasing medium.
  • highly water soluble branched Arabinogalactan may be leached out from a coating more rapidly forming channels of a certain size and shape whereas less water soluble linear dextran may be leached out at a slower rate forming different channels which may affect the drug release rate.
  • the general procedure for producing the core matrix is by incorporating the pharmaceutically active ingredient in a mixture or granulate that will allow the controlled release of the active ingredient by passive diffusion at a specific rate predetermined by the core formulation by methods known per se from the core matrix.
  • the preparation of the core matrix generally involves the granulation of the drug with a hydrophobic polymer (for water soluble drugs) using common granulation methods and then mixing the granules with ingredients that further retard or enhance the drug release from the matrix, a lubricant, or a colorant and compressing into tablets using common tableting machines.
  • the general method of producing the coating according to the invention comprises the steps of dissolving or dispersing a hydrophobic polymer, channeling agent, plastisizer, colorant and other additives in water or in an organic solvent (alcohol, acetone). The coating dispersion is then applied on the core matrix tablets usually by a pan coating.
  • the core matrix is prepared by compression into a tablet granulates of the drug prepared from the drug and the retarding polymer.
  • Fig. 1A graphically illustrates the dissolution of Diltiazem from a coated tablet of Example 3a;
  • Fig. 1 B graphically illustrates the dissolution of Diltiazem from a coated tablet of Example 3b;
  • Fig. 1 C graphically illustrates the dissolution of Diltiazem from a coated tablet of Example 3c;
  • Fig. 1D graphically illustrates the dissolution of Diltiazem from a coated tablet of Example 3d;
  • Fig. 1 E presents the dissolution of Diltiazem from a coated tablet of Example 3d in tabular form
  • Fig. 1 F graphically illustrates the dissolution of Diltiazem from a coated tablet of Example 3e (31 % channeling agent) and 3f (33% channeling agent);
  • Fig. 1 G presents the data of Figure 1f in tabular form; and Figs. 1 H and 11 tabularly and graphically represent the dissolution of verapamil from a coated tablet of Example 5.
  • Dissolution release medium buffer pH6.8 using a dissolution system-peddle mixing at 100 rpm. The results are an average of 6 chamber with a narrow standard deviation (less than 10%).
  • Example 1 preparation of core matrix for Diltiazem:
  • Granules of Diltiazem are prepared by spray granulation (using a Glatt spray granulation instrument) of a water dispersion of a hydrophobic polymer such as Eudragit RS30D containing a plastisizer such as an ester of citric acid.
  • the drug may be mixed with hydrophobic or hydrophilic additives before granulation.
  • the granules are mixed with common ingredients such as lactose and magnesium stearate (lubricant) and compressed into tablets using a Potary press, punches 11.0 (Q), 9.5 (R) without dividing line, tablet weight 350 to 500 mg each.
  • Citroflex 2 (citrate ester plasticizer) 6mg system: Glatt spray granulator
  • Matrix composition Diltiazem granules: 279mg
  • Dissolution release rate 1h- 50 %, 2h- 68 %. 7h- 100 % carried out in a medium having a pH 2 for 2 hours, and then in a medium having a pH of 6.8 for an additional 5 hours using a dissolution system-peddle mixing.
  • Granulation Diltiazem hydrochloride 240mg
  • Matrix composition Diltiazem granules: 335mg
  • Dissolution release rate 1h-36 %, 2h-47 %. 7h-70 % carried out in a medium having a pH 2 for 2 hours, and then in a medium having a pH of 6.8 for an additional 5 hours using a standard dissolution system-peddle mixing at 00 rpm.
  • the results are an average of 6 chambers with a narrow standard deviation of less than 10%.
  • Matrix composition Diltiazem granules: 335mg
  • Dissolution release rate 1h-48 %, 2h- 64 %. 7h- 93 % carried out in a medium having a pH 2 for 2 hours, and then in a medium having a pH of 6.8 for an additional 5 hours using a dissolution system-peddle mixing.
  • Granulation Diltiazem hydrochloride 240mg
  • Matrix composition Diltiazem granules: 325mg
  • Dissolution release rate 1h- 48 %, 2h- 61 %. 7h- 87 % carried out in a medium having a pH 2 for 2 hours, and then in a medium having a pH of 6.8 for an additional 5 hours using a dissolution system-peddle mixing.
  • Matrix composition Diltiazem granules: 335mg
  • Dissolution release rate 1h- 52 %, 2h- 71 %. 7h- 100 % carried out in a medium having a pH 2 for 2 hours, and then in a medium having a pH of 6.8 for an additional 5 hours using a dissolution system-peddle mixing.
  • Example 2 Core matrix for poorly soluble drugs
  • Nifedipin is a water insoluble drug which has some solubility in 0.1N HCI.
  • the purpose of the granulation step is to increase the drug dissolution rate from the matrix to meet the release characteristic determined for the core matrix.
  • the granulation involve spraying an acetone solution of nifedipin with or without a hydrophilic component such poly(vinylpyrrolidone or poly(ethylene glycol) on a hydrophilic support such as lactose or avicel particles and compression molding the granules or mixtures containing the granules into tablets. The tablets are then coated with the rate limiting coating. Examples of granulation and tablet compositions are as follows: a.
  • Granulation solution Nifedipine 300g (30mg/tablet)
  • Povidone k-30 750g (75mg/tablet) support Lactose 100 mesh size 3.0kg (300mg/tablet) preparation: the solution was sprayed on the lactose particles at 50°C for 1.5 hours using a Glatt. The granules containing 3.5% water were compressed into tablets. Dissolution release rate in 0.1 N HCI: 1h- 24 %, 2h- 40 %. 7h- 74 % Granulation solution: Nifedipine 300g (30mg/tablet)
  • Dissolution release rate in 0.1 N HCI 1 h- 25 %, 2h- 43 %. 7h- 78 %
  • Granulation solution Nifedipine 300g (30mg/tablet)
  • Acetone 6 litter solvent support Lactose 100 mesh 3.0 kg (250mg/tablet) preparation: the solution was sprayed on the Lactose particles at
  • Dissolution release rate in 0.1 N HCI 1 h- 22 %, 2h- 47 %. 7h- 80 % d.
  • Granulation solution Nifedipine 300g (30mg/tablet)
  • Example 3 Coating of Diltiazem core matrix tablets:
  • the core tablet of example 1e where coated by either a water base dispersion or by an organic base polymer solution (ethanol, isopropanol, acetone, methylene chloride).
  • the channeling agents in this example are Siractan (a trade name for arabinogalactan) carried out in a dissolution release medium having a pH 2 for 2 hours, and then in a medium having a pH of 6.8 for an additional 5 hours, thereafter using a dissolution system- peddle mixing.
  • the results are an average of 6 chambers with a narrow standard deviation (less than 10%).
  • Typical compositions per tablet are as follows:
  • Dissolution rate 3h-10%; 6h- 35%; 10h- 50%; 24h-90%
  • Example 4 Coating of Nifedipine core matrix tablets of Example 2a:
  • compositions per tablet are as follows: a. Eudragit RS30D 8.0 parts Eudragit RL30D 2.0 parts Siractan 6.0 parts
  • Dissolution rate 3h-5 %; 6h- 16 %; 10h- 30 %; 24h- 72 %
  • Dissolution rate 3h- 15 %; 6h- 35 %; 10h- 60 %; 24h- 75 %
  • Example 5 preparation of a coated tablet for Verapamil:
  • Granules of Verapamil are prepared by spray or wet granulation (using a Glatt spray granulation instrument or wet granulation device).
  • the drug content in these tablets was 20 mg/tablet.
  • the drug may be mixed with hydrophobic or hydrophilic additives before granulation.
  • the granules are mixed with common ingredients such as lactose and magnesium stearate (lubricant) and compressed into tablets using a Potary press, punches 11.0 (Q), 9.5 (R) without dividing line, tablet weight 350 to 500 mg each.
  • the core tablet was coated by either a water base dispersion or by an organic base polymer solution (ethanol, isopropanol, acetone, methylene chloride).
  • the channeling agents in this example is Siractan (a trade name for arabinogalactan). Other channeling gents such as dextran can be used.
  • Methocel K4M hydroxypropyl methyl cellulose 25mg

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

La présente invention concerne un comprimé à libération contrôlée permettant l'administration par voie orale d'un principe actif. Un tel comprimé est constitué d'une composition de noyau à libération contrôlée où le principe actif est incorporé dans un excipient polymère à partir duquel il peut se diffuser selon un débit imposé dès qu'il entre en contact avec le milieu de mise en oeuvre, le polymère étant insoluble dans ce milieu. Un tel comprimé est également constitué, entourant le noyau, d'un enrobage de régulation du débit de libération. Cet enrobage est constitué d'un matériau polymère insoluble dans l'eau et imperméable à l'eau, lequel matériau polymère inclut en dispersion dans l'enrobage au moins un agent d'effet canal constituant environ 5 à 60 % de la masse totale de l'enrobage. Cet agent d'effet canal est soluble dans le milieu considéré et lixiviable de l'enrobage par contact avec le milieu considéré, de façon à constituer dans l'enrobage des canaux moléculaires permettant la diffusion passive du principe actif via les canaux selon un débit imposé par les canaux.
PCT/GB1997/001770 1996-07-24 1997-07-01 Comprimes a liberation controlee WO1998003161A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU33522/97A AU3352297A (en) 1996-07-24 1997-07-01 Controlled release tablets

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IL11893296A IL118932A0 (en) 1996-07-24 1996-07-24 Controlled release tablets
IL118932 1996-07-24

Publications (1)

Publication Number Publication Date
WO1998003161A1 true WO1998003161A1 (fr) 1998-01-29

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1997/001770 WO1998003161A1 (fr) 1996-07-24 1997-07-01 Comprimes a liberation controlee

Country Status (3)

Country Link
AU (1) AU3352297A (fr)
IL (1) IL118932A0 (fr)
WO (1) WO1998003161A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001001966A2 (fr) * 1999-07-01 2001-01-11 Abbott Laboratories Forme posologique a liberation continue a enrobage de latex et son procede de realisation
WO2004041244A2 (fr) * 2002-10-30 2004-05-21 Pharmacia Corporation Comprimes oraux a liberation etendue et procedes de fabrication et d'utilisation associes
US8282958B2 (en) 2003-12-23 2012-10-09 Ferring B.V. Coating method
US8697135B2 (en) 2001-10-15 2014-04-15 Ferring B.V. Method for the preparation of a pharmaceutical composition comprising 5-aminosalicylic acid for use in treatment of ulcerative colitis and Crohn's disease
US8858992B2 (en) 2003-04-23 2014-10-14 Ferring B.V. High drug load mesalazine sachet

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4445641A (en) * 1982-01-08 1984-05-01 Bend Research, Inc. Controlled-release dispenser
EP0314206A1 (fr) * 1987-09-24 1989-05-03 Merck & Co. Inc. Dispositif pour la distribution de médicaments à solubilité modulée
GB2218905A (en) * 1988-05-27 1989-11-29 Elan Corp Plc Controlled release potassium chloride tablet formulation
DE4230563A1 (de) * 1992-09-12 1994-03-17 Boehringer Ingelheim Kg Hochdosierte Kompaktgranulate und daraus hergestellte Tabletten
US5458887A (en) * 1994-03-02 1995-10-17 Andrx Pharmaceuticals, Inc. Controlled release tablet formulation

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4445641A (en) * 1982-01-08 1984-05-01 Bend Research, Inc. Controlled-release dispenser
EP0314206A1 (fr) * 1987-09-24 1989-05-03 Merck & Co. Inc. Dispositif pour la distribution de médicaments à solubilité modulée
GB2218905A (en) * 1988-05-27 1989-11-29 Elan Corp Plc Controlled release potassium chloride tablet formulation
DE4230563A1 (de) * 1992-09-12 1994-03-17 Boehringer Ingelheim Kg Hochdosierte Kompaktgranulate und daraus hergestellte Tabletten
US5458887A (en) * 1994-03-02 1995-10-17 Andrx Pharmaceuticals, Inc. Controlled release tablet formulation

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2001001966A2 (fr) * 1999-07-01 2001-01-11 Abbott Laboratories Forme posologique a liberation continue a enrobage de latex et son procede de realisation
US6251432B1 (en) 1999-07-01 2001-06-26 Abbott Laboratories Sustained release dosage form unit having latex coating and method of making the same
WO2001001966A3 (fr) * 1999-07-01 2001-07-26 Abbott Lab Forme posologique a liberation continue a enrobage de latex et son procede de realisation
US6620434B2 (en) 1999-07-01 2003-09-16 Abbott Laboratories Sustained release dosage form unit having latex coating and method of making the same
AU774671B2 (en) * 1999-07-01 2004-07-01 Abbott Laboratories Sustained release dosage form unit having latex coating and method of making the same
US8697135B2 (en) 2001-10-15 2014-04-15 Ferring B.V. Method for the preparation of a pharmaceutical composition comprising 5-aminosalicylic acid for use in treatment of ulcerative colitis and Crohn's disease
WO2004041244A3 (fr) * 2002-10-30 2004-07-15 Pharmacia Corp Comprimes oraux a liberation etendue et procedes de fabrication et d'utilisation associes
JP2006507298A (ja) * 2002-10-30 2006-03-02 ファルマシア コーポレーション 経口持続放出型錠剤、ならびにその製造法および使用法
WO2004041244A2 (fr) * 2002-10-30 2004-05-21 Pharmacia Corporation Comprimes oraux a liberation etendue et procedes de fabrication et d'utilisation associes
US8858992B2 (en) 2003-04-23 2014-10-14 Ferring B.V. High drug load mesalazine sachet
US9402815B2 (en) 2003-04-23 2016-08-02 Ferring B.V. High drug load mesalazine sachet
US8282958B2 (en) 2003-12-23 2012-10-09 Ferring B.V. Coating method
US8501226B2 (en) 2003-12-23 2013-08-06 Ferring B.V. Coating method

Also Published As

Publication number Publication date
AU3352297A (en) 1998-02-10
IL118932A0 (en) 1996-10-31

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