WO1998052564A1 - Composition pharmaceutique contenant du benzimidazole et procede de preparation - Google Patents

Composition pharmaceutique contenant du benzimidazole et procede de preparation Download PDF

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Publication number
WO1998052564A1
WO1998052564A1 PCT/GB1998/001465 GB9801465W WO9852564A1 WO 1998052564 A1 WO1998052564 A1 WO 1998052564A1 GB 9801465 W GB9801465 W GB 9801465W WO 9852564 A1 WO9852564 A1 WO 9852564A1
Authority
WO
WIPO (PCT)
Prior art keywords
benzimidazole
moisture resistant
resistant coating
core
composition according
Prior art date
Application number
PCT/GB1998/001465
Other languages
English (en)
Inventor
Yusuf Khwaja Hamied
Vinay G. Nayak
Geena Malhotra
Original Assignee
Cipla Limited
Wain, Christopher, Paul
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 Cipla Limited, Wain, Christopher, Paul filed Critical Cipla Limited
Priority to EP98922927A priority Critical patent/EP0983067A1/fr
Priority to CA002290824A priority patent/CA2290824A1/fr
Priority to AU75390/98A priority patent/AU729038B2/en
Priority to GB9927132A priority patent/GB2343117B/en
Publication of WO1998052564A1 publication Critical patent/WO1998052564A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
    • A61K9/5078—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings with drug-free core
    • 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
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole

Definitions

  • the present invention relates to a pharmaceutical composition and to a process of preparation thereof, and more particularly to a pharmaceutical composition containing a benzimidazole.
  • Benzirnidazole derivatives such as omeprazole, lansoprazole and timoprazole, etc.
  • omeprazole lansoprazole
  • timoprazole timoprazole
  • Benzirnidazole derivatives are known potent proton pump inhibitors with powerful inhibitory action against the secretion of gastric acid (Lancet, Nov. 27, 1982, pages 1223 - 1224). They are used in the treatment of Zollinger- Ellison syndrome and stress related oesophagitis ulceration.
  • the derivatives are well known and are described, for example, in EP-A-0005129.
  • EP-A-0247983 describes an oral pharmaceutical preparation of omeprazole which is composed of a core material in the form of small beads or tablets containing omeprazole together with an alkaline reacting compound, the core material having one or more inert reacting subcoating layers thereon.
  • the alkaline reacting compounds can be chosen among but are not restricted to substances such as the sodium, potassium, calcium, magnesium and aluminium salts of phosphoric acid, carbonic acid, citric acid or other suitable weak inorganic or organic acids; substances normally used in antacid preparations such as alurriinium, calcium and magnesium hydroxides; magnesium oxide or composite substances, such as Al 2 0 3 .6MgO.C0 2 .12H 2 0, (Mg 6 Al 2 (OH) 16 C0 3 .4H 2 0), MgO.Al 2 0 3 .2Si0 2 .nH 2 0 or similar compounds; organic pH-buffering substances such as trmydroxymethylaminomethane or other similar, pharmaceutically acceptable pH-buffering substances.
  • substances such as the sodium, potassium, calcium, magnesium and aluminium salts of phosphoric acid, carbonic acid, citric acid or other suitable weak inorganic or organic acids
  • substances normally used in antacid preparations such as alurriin
  • alkaline reacting salt of omeprazole such as the sodium, potassium, magnesium, calcium or ammonium salt of omeprazole (which are described in EP-A-0124495) is used, this can be in place of or in addition to the alkaline reacting compound.
  • TW289733 describes a process of preparing pellets containing omeprazole.
  • the process comprises spraying a solution comprising omeprazole, excipient, ethanol, water, ammonia and binder on an inert core; granulating; spraying an intermediate coating solution comprising excipient, ethanol, water, ammonia and binder on the granules; and providing a final outer coating.
  • US4786505 describes pharmaceutical preparations containing omeprazole in an alkali environment as the core material, one or more inert subcoating layers which are water soluble and an outer enteric coating.
  • compositions which is a solid pellet comprising an inert core, a benzimidazole in or on the core, a moisture resistant coating around the core, the moisture resistant coating comprising at least one hydrophobic material, and an enteric coating around the moisture resistant coating.
  • a process of preparing a composition substantially as described above comprises providing an inert core having a benzimidazole therein or thereon, applying a moisture resistant coating around the core, the moisture resistant coating comprising at least one hydrophobic material, and applying an enteric coating around the moisture resistant coating.
  • the benzimidazole in or on the core is present in an alkaline environment, and more particularly the benzimidazole is present as an intimate mixture with at least one alkali.
  • the alkali is ammonia or a solution of ammonia or ammonium carbonate.
  • a process according to the present invention therefore preferably further comprises formulating the benzimidazole in an alkaline environment substantially as herein described.
  • an alkali employed in the present invention comprises an aqueous solution of ammonia (i.e. ammonium hydroxide) or ammonium carbonate, although it is of course also possible to use liquid ammonia or ammonia gas.
  • the benzimidazole may be formulated under an ammonia atmosphere, for example, and the gas may be absorbed, such as by dissolution in any aqueous material present.
  • the pH of the benzimidazole- containing part of any formulation is preferably from above 7 to 10, and is more preferably in the range 8 to 9.
  • an ammonia solution is used, the solution preferably containing from 20 to 40wt% ammonia, more preferably about 30 wt% ammonia.
  • the invention is applicable to pharmaceutically active benzimidazole derivatives. Particularly useful such derivatives are the alkali metal salts of the benzimidazole. Examples of specific useful derivatives are omeprazole, lansoprazole, timoprazole, pariprazole and pantoprazole, in particular omeprazole.
  • the hydrophobic material of the coating is present in sufficient amount to ensure that the coating substantially repels water therefrom.
  • the hydrophobic material can be solid or liquid, and is desirably selected from the group consisting of a polyalkylsiloxane, castor oil, mineral oil, isopropyl myristate, stearic acid, cetyl alcohol or the like.
  • the hydrophobic material comprises a polyalkylsiloxane, and it is particularly preferred that the hydrophobic material comprises polydimethylsiloxane.
  • the moisture resistant coating may further comprise at least one binding agent.
  • the binding agent may be hydrophobic or hydrophilic. In the latter case, the binding agent is incorporated in the moisture resistant coating in an amount which ensures that the water repellent properties of the latter (as provided by the hydrophobic material substantially as described above), are substantially unaffected by the hydrophilic nature of the binding agent.
  • the binding agent is preferably selected from the group consisting of a sugar, polyvinyl-pyrrolidone, shellac and gums, such as xanthan gum, or the like. It is especially preferred that the binding agent comprises a sugar, such as sucrose or the like.
  • a binding agent is employed in the moisture resistant coating when the hydrophobic material is a liquid.
  • a preferred moisture resistant coating comprises an emulsion of a polyalkylsiloxane (especially polydimethylsiloxane) or an admixture thereof, with the binding agent.
  • the moisture resistant coating may contain one or more other conventional additives that typically aid in the process of adhesion onto the inert core.
  • the moisture resistant coating may also be useful in benzimidazole pharmaceutical compositions that do not have an alkaline binder.
  • the moisture resistant coating can be typically applied by spraying, using conventional equipment.
  • a further moisture resistant coating can be provided over the enteric coating.
  • enteric coatings may be employed in the present invention, including for example: cellulose acetate phthalate; hydroxypropyl methyl cellulose phthalate (HPMCP); hydroxypropyl cellulose acetyl succinate; polyvinyl acetate phthalate; copolymerised methacrylic acid/methacrylic acid methyl esters, such as Eudragit L 12-5, Eudragit L 100 55 or Eudragit S 100; and mixtures thereof.
  • the enteric coating may contain conventional plasticisers, pigments and/or dispersants, including for example polyethylene glycols, triacetin, triethyl citrate, and Citroflex, dibutyl sebacate.
  • the enteric coating can be applied in any suitable manner, for example in the form of an aqueous dispersion in water, or other dispersing medium, or in the form of a solution. It is preferred that a dispersion or solution of the enteric coating is treated with an alkali in order to neutralise at least part of any free acid content.
  • the alkali may be, for example, a carbonate or hydroxide of sodium, potassium, magnesium or calcium.
  • the benzimidazole is present in the inert core.
  • the inert core of the pharmaceutical composition comprises a plurality of compressed granules of the benzimidazole.
  • This embodiment is particularly useful when it is desired to provide the pharmaceutical composition in tablet form, and there is further provided by the present invention a tablet which comprises a pharmaceutical composition substantially as herein described, wherein the inert core is formed from a plurality of granules comprising the benzimidazole, which granules are compressed together to form the core.
  • the moisture resistant coating is applied around the inert core, then the enteric coating is suitably provided around the moisture resistant coating on the inert core.
  • the benzimidazole is present on the inert core.
  • the second embodiment of the present invention is particularly applicable for the inclusion of a plurality of pellets substantially as herein before described in a capsule.
  • the inert cores of the pellets may typically be non-pareils, and suitably provided in the form of sugar beads or sugar/starch beads.
  • a capsule which comprises a capsule shell containing a plurality of pellets substantially as herein before described.
  • the moisture resistant coating is applied around the inert core of each of the pellets to be provided in a capsule, and the enteric coating is suitably provided around the moisture resistant coating on each of the inert cores.
  • compositions according to the present invention may comprise one or more additives.
  • particularly useful additives include a solubiliser to aid solubilisation of the pharmaceutically active ingredient, and a lubricant to aid flow of the active ingredient during manufacture.
  • the solubiliser may be, for example, a sugar, which is preferably in pulverised form.
  • An example of a suitable sugar is sucrose.
  • the lubricant may be, for example, starch and/or talcum. It will be appreciated that the pharmaceutical compositions of the invention may contain any one or more other additives conventionally used in the formulation of pharmaceutical compositions.
  • compositions of the invention may be used to treat conditions in the same manner as the prior known benzimidazole compositions.
  • the pharmaceutical compositions may be formulated for oral, topical, parenteral or rectal administration. Oral administration is preferred.
  • the pharmaceutical compositions may take the form of, for example, a tablet or peltab (e.g. comprising a plurality of granules comprising a benzimidazole, together with conventional excipients, such as disintegrants and binders, compressed into a tablet) or a capsule (e.g. containing a plurality of individual pellets comprising a benzimidazole disposed within the capsule shell).
  • a tablet or peltab e.g. comprising a plurality of granules comprising a benzimidazole, together with conventional excipients, such as disintegrants and binders, compressed into a tablet
  • a capsule e.g. containing a plurality of individual pellets comprising a benzimidazole disposed within the capsule shell.
  • the pharmaceutical composition may include conventional excipients.
  • Tablets to be employed in compositions of the invention can be made, for example, by using equipment known as a marumerizer (which is also called a spheronizer).
  • a marumerizer which is also called a spheronizer
  • core ingredients including the benzimidazole
  • the granules may be compressed by conventional means in order to form a solid core, and subsequently coated with a moisture resistant coating and an enteric coating as herein before described.
  • the pellets comprise benzimidazole loaded onto a plurality of inert cores suitable for inclusion in a capsule
  • the benzimidazole can be supplied as a spray, for example.
  • the benzimidazole may be mixed with one or more additives before being loaded on the inert cores.
  • the additives may include, for example, a solubiliser and/or a lubricant.
  • the inert cores can be loaded with the benzimidazole (together with any additives), and sprayed with a binder, in a centrifugal coating apparatus.
  • Non-pareil seeds 95.00 mg
  • Particles were also made of the above materials with the addition of 30% by weight ammonia solution in an amount to provide a pH of 8.0-9.0.
  • the active drug, the sucrose, the corn starch and the talcum were blended thoroughly to yield a dusting powder.
  • the non-pareil seeds were loaded into a centrigual coater and then coated with the dusting powder while spraying the HPMC (hydroxypropyl methyl cellulose) solution, with the ammonia solution when used. This resulted in the production of a plurality of discrete particles containing the active ingredient.
  • the particles so obtained were dried using conventional tray dryers/fluid bed dryers to an outlet temp, of 45 °C.
  • a plurality of particles containing the active drug were prepared as follows:
  • Non-pareil seeds 95.00 mg Active drug 20.00 mg Sucrose 32.00 mg Corn starch 32.00 mg Talcum 10.00 mg HPMC 1.00 mg
  • Particles were also made of the above materials with the addition of 3.00 mg ammonium carbonate.
  • the active drug, the sucrose, the corn starch, the ammonium carbonate (when present) and the talcum were blended thoroughly to yield a dusting powder.
  • the non-pareil seeds were loaded into the centrifugal coater and then coated with the dusting powder while spraying the HPMC (hydroxypropyl methyl cellulose) solution. This resulted in the production of a plurality of discrete particles containing the active ingredient.
  • the particles so obtained were dried using conventional tray dryers/fluid bed dryers to an outlet temp, of 45 °C.
  • a plurality of particles containing the active drug were prepared from the following materials:
  • Particles were also made of the above materials but with the addition of 3.00 mg ammonium carbonate.
  • the active drug, the sucrose, the corn starch, the ammonium carbonate (when present) and the talcum were blended thoroughly to yield a dusting powder.
  • the non-pareil seeds were loaded into the centrifugal coater and then coated with the dusting powder while spraying the HPC-L Klucel (hydroxypropyl cellulose) solution. This resulted in the production of a plurality of discrete particles containing the active ingredient.
  • the particles so obtained were dried using conventional tray dryers/fluid bed dryers to an outlet temp, of 45°C.
  • a plurality of tablet cores containing an active drug were prepared from the following materials:
  • Particles were also made of the above materials but with the addition of 30% by weight solution of ammonia to give a pH of 8.0-9.0.
  • the active drug was blended with the sucrose and the corn starch in a suitable mixer.
  • the blend containing the active drug was then granulated with a solution of the gelatine binder (with the ammonia when present).
  • the granules were dried using conventional means, then lubricated with the talcum and magnesium stearate. Finally, the granules were compressed into a suitable shape for a tablet core using conventional compression equipment.
  • a plurality of tablet cores containing an active drug were prepared from the following materials:
  • Particles were also made of the above materials but also including 3.00 mg ammonium carbonate.
  • the active drug was blended with the sucrose, corn starch and the ammonium carbonate (when present) in a suitable mixer.
  • the blend containing the active drug was then granulated with a solution of the gelatine binder.
  • the granules were dried using conventional means, then lubricated with the talcum and magnesium stearate. Finally, the granules were compressed into a suitable shape for a tablet core using conventional compression equipment.
  • Example 7 A plurality of tablet cores containing an active drug were prepared from the following materials:
  • Particles were also made of the above materials but also including 2.00 mg ammonium carbonate.
  • the active drug was blended with the mannitol, and then granulated with a solution of PVP-K30 containing ammonium carbonate (when present).
  • the granules were dried using conventional means, then lubricated with the talcum, magnesium stearate, PEG 6000 and Crospovidone. Finally, the granules were compressed into a suitable shape for a tablet core using conventional compression equipment.
  • Example 8 A plurality of tablet cores containing an active drug were prepared from the following materials:
  • Particles were also made of the above materials but including 30% by weight ammoma solution to a pH of 8.0-9.0.
  • the active drug was blended with the mannitol. It was then granulated with the ammoma solution (when present). The granules were dried using conventional means, then lubricated with the talcum, magnesium stearate, PEG 6000 and Crospovidone. Finally, the granules were compressed into a suitable shape for a tablet core using conventional compression equipment.
  • Intermediate Example 16 The 190.00 mg particles formed in Intermediate Example 5 were coated with 3.00 mg polydimethylsiloxane to produce a moisture resistant coating around each particle.
  • the 190.00 mg particles formed in Intermediate Example 4 were also treated with 20.00 mg of an emulsion of 4.27 mg of polydimethylsiloxane, and 15.73 mg sucrose along with other conventional coating additives to produce a moisture resistant coating around each particle.
  • the 190.00 mg particles formed in Intermediate Example 5 were also treated with 20.00 mg of an emulsion of 4.27 mg of polydimethylsiloxane, and 15.73 mg sucrose along with other conventional coating additives to produce a moisture resistant coating around each particle.
  • the 193.00 mg particles formed in Intermediate Example 6 were also treated with 20.00 mg of an emulsion of 4.27 mg of polydimethylsiloxane, and 15.73 mg sucrose along with other conventional coating additives to produce a moisture resistant coating around each particle.
  • the 190.00 mg particles formed in Intermediate Example 4 were coated with polydimethylsiloxane, and an amount of 30% by wt. ammonia solution, to produce a moisture resistant coating around each particle.
  • the 190.00 mg particles formed in Intermediate Example 5 were coated with polydimethylsiloxane, and an amount of 30% by wt. ammonia solution, to produce a moisture resistant coating around each particle.
  • a plurality of particles containing the active drug were prepared from the following materials:
  • a plurality of particles containing the active drug were made from the following materials:
  • Non-pareil seeds 95.00 mg
  • Particles were also made of the above materials with the addition of 30% by weight solution of ammoma to pH 8.0-9.0.
  • a plurality of particles containing the active drug were prepared from the following materials:
  • Non-pareil seeds 108.00 mg Active drug 20.00 mg Sucrose 35.90 mg Corn Starch 21.10 mg Talcum 2.00 mg
  • Particles were also made of the above materials with the addition of 30% by weight solution of ammonia to pH 8.0-9.0.
  • compositions obtained in Intermediate Examples 1 - 8 and 23, 24, 25 were treated with 11.00 mg of a mixture comprising of 2.85 mg of an emulsion of polydimethylsiloxane with 9.00 mg of a binding agent as described earlier (Sucrose/Polyvinylpyrrolidone/Shellac/Xanthan Gum), along with 1 mg of talc.
  • the coating was carried out using a fluidised bed coater. Alternately, it could have been carried out using a conventional coating pan. This produced a moisture resistant coating around each composition of the respective examples.
  • Example 1 Example 1
  • the particles formed in Intermediate Examples 9 to 14 were provided with an enteric coating to yield compositions according to the present invention. Some were coated with cellulose acetate phthalate, some with HPMCP and some with Eudragit L 100 55. In each case, 500.00 g of the particles were each coated with 55.00 g of the respective enteric coating polymer.
  • the enteric coating polymer was deposited using a conventional coating process.
  • the particles formed in Intermediate Examples 15 to 22 were each coated with an enteric coating polymer to yield tablet compositions according to the present invention. Some were coated with cellulose acetate phthalate, some with HPMCP and some with Euragdit L 100 55. In each case, the enteric coating polymer was deposited using a conventional process for coating.
  • Example 1 500.00 g of the enteric coated particles from Example 1 were coated with 3.00 mg per unit dosage form of a moisture resistant coating of polydimethylsiloxane. The moisture resistant coating was sprayed onto the particles.
  • Example 5 500.00 g of the enteric coated particles from Example 1 were coated with 20.00 mg of an emulsion containing 4.27 mg of polydimethylsiloxane, and 15.73 mg sucrose per unit dosage form to give a moisture resistant coating. The moisture resistant coating was sprayed onto the particles.
  • Example 5 500.00 g of the enteric coated particles from Example 1 were coated with 20.00 mg of an emulsion containing 4.27 mg of polydimethylsiloxane, and 15.73 mg sucrose per unit dosage form to give a moisture resistant coating. The moisture resistant coating was sprayed onto the particles.
  • Example 2 500.00 g of the enteric coated tablets from Example 2 were each coated with 3.00 mg per unit dosage form of a moisture resistant coating of polydimethylsiloxane. The moisture resistant coating was sprayed onto the tablets.
  • Example 2 500.00 g of the enteric coated tablets from Example 2 were each coated with 20.00 mg of an emulsion containing 4.27 mg of polydimethylsiloxane, and 15.73 mg sucrose per unit dosage form to give a moisture resistant coating. The moisture resistant coating was sprayed onto the tablets.
  • Enteric coatings included cellulose acetate phthalate, HPMCP and Euragdit L 100

Abstract

L'invention concerne une composition pharmaceutique qui est un pellet solide contenant un noyau inerte; un benzimidazole situé dans ou sur ledit noyau; un enrobage résistant à l'humidité recouvrant ledit noyau et contenant au moins une matière hydrophobe; et un revêtement gastro-résistant recouvrant ledit enrobage résistant à l'humidité.
PCT/GB1998/001465 1997-05-23 1998-05-21 Composition pharmaceutique contenant du benzimidazole et procede de preparation WO1998052564A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
EP98922927A EP0983067A1 (fr) 1997-05-23 1998-05-21 Composition pharmaceutique contenant du benzimidazole et procede de preparation
CA002290824A CA2290824A1 (fr) 1997-05-23 1998-05-21 Composition pharmaceutique contenant du benzimidazole et procede de preparation
AU75390/98A AU729038B2 (en) 1997-05-23 1998-05-21 Benzimidazole pharmaceutical composition and process of preparation
GB9927132A GB2343117B (en) 1997-05-23 1998-05-21 Benzimidazole pharmaceutical composition and process of preparation

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9710800.5 1997-05-23
GBGB9710800.5A GB9710800D0 (en) 1997-05-23 1997-05-23 Pharmaceutical composition and method of preparing it

Related Child Applications (2)

Application Number Title Priority Date Filing Date
US09424024 A-371-Of-International 2000-02-25
US09/900,200 Continuation US20010053387A1 (en) 1997-05-23 2001-07-09 Benzimidazole pharmaceutical composition and process of prepatation

Publications (1)

Publication Number Publication Date
WO1998052564A1 true WO1998052564A1 (fr) 1998-11-26

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PCT/GB1998/001465 WO1998052564A1 (fr) 1997-05-23 1998-05-21 Composition pharmaceutique contenant du benzimidazole et procede de preparation

Country Status (6)

Country Link
EP (1) EP0983067A1 (fr)
AU (1) AU729038B2 (fr)
CA (1) CA2290824A1 (fr)
GB (2) GB9710800D0 (fr)
WO (1) WO1998052564A1 (fr)
ZA (1) ZA984266B (fr)

Cited By (20)

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WO1999029299A1 (fr) * 1997-12-08 1999-06-17 Byk Gulden Lomberg Chemische Fabrik Gmbh Nouvelle forme de suppositoire renfermant un compose actif acidolabile
WO1999038511A1 (fr) * 1998-01-30 1999-08-05 Ethypharm Microgranules d'omeprazole gastroproteges, procede d'obtention et preparations pharmaceutiques
FR2793688A1 (fr) * 1999-05-21 2000-11-24 Ethypharm Lab Prod Ethiques Microgranules gastroproteges, procede d'obtention et preparations pharmaceutiques
WO2001032185A1 (fr) * 1999-11-02 2001-05-10 Cipla Ltd. Composition pharmaceutique renfermant au moins un acide bisphosphonique ou un de ses sels et son procede de preparation
US6245913B1 (en) 1999-06-30 2001-06-12 Wockhardt Europe Limited Synthetic procedure for 5-methoxy-2-[(4-methoxy-3,5-dimethyl-2-pyridinyl)-methylthio]-IH-benzimidazole hydrochloride and its conversion to omeprazole
DE19959419A1 (de) * 1999-12-09 2001-06-21 Ratiopharm Gmbh Stabile galenische Zubereitungen umfassend ein Benzimidazol und Verfahren zu ihrer Herstellung
EP1222922A1 (fr) * 1999-10-20 2002-07-17 Eisai Co., Ltd. Procede de stabilisation de composes benzimidazoles
US6676965B1 (en) 1999-10-20 2004-01-13 U&I Pharmaceuticals Ltd. Enteric coated formulation for bisphosphonic acids and salts thereof
US6780436B1 (en) 1999-09-13 2004-08-24 Laboratorios Del Dr. Esteve, Sa Solid oral pharmaceutical formulation of modified release that contains an acid labile benzimidazole compound
WO2004075881A1 (fr) * 2003-02-28 2004-09-10 Ranbaxy Laboratories Limited Compositions pharmaceutiques stables de rabeprazole et leurs procedes de fabrication
WO2005027876A1 (fr) * 2003-08-28 2005-03-31 Ranbaxy Laboratories Limited Compositions pharmaceutiques de benzimidazole et leurs procedes de preparation
WO2005107721A2 (fr) 2004-05-07 2005-11-17 Altana Pharma Ag Forme galenique pharmaceutique et procede de fabrication de celle-ci
WO2006011159A2 (fr) * 2004-06-21 2006-02-02 Torrent Pharmaceuticals Limited Composition pharmaceutique stabilisee contenant du sodium de rabeprazole presentant une biodisponibilite amelioree
EP1667681A1 (fr) * 2003-10-03 2006-06-14 Astron Research Pvt. Ltd Nouveau systeme d'administration transmucosale
WO2008065107A1 (fr) * 2006-11-28 2008-06-05 Monteresearch S.R.L. Comprimés stables au stockage à base de dérivés de benzimidazole enrobés d'un film gastro-résistant
US7785630B2 (en) 1999-06-07 2010-08-31 Nycomed Gmbh Preparation and administration form comprising an acid-labile active compound
CN101822671A (zh) * 2009-03-06 2010-09-08 信谊药厂 雷贝拉唑组合物及其制备方法
CN102772387A (zh) * 2012-08-09 2012-11-14 广东帅广医药有限公司 兰索拉唑组合物肠溶胶囊及其制备方法
CN103202818A (zh) * 2012-01-15 2013-07-17 山东新时代药业有限公司 一种含有右旋雷贝拉唑或其可药用盐的肠溶片剂及其制备方法
EP3292862A1 (fr) 2016-09-07 2018-03-14 Sandoz Ag Formulations d'oméprazole

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US6328993B1 (en) 1997-12-08 2001-12-11 Byk Gulden Lomberg Chemische Fabrik Gmbh Oral administration form for an acid liable active proton pump inhibitor
WO1999029320A1 (fr) * 1997-12-08 1999-06-17 Byk Gulden Lomberg Chemische Fabrik Gmbh Nouvelle forme galenique comprenant un compose actif acido-labile
EP1371361A1 (fr) * 1997-12-08 2003-12-17 ALTANA Pharma AG Nouvelle forme de suppositoire renfermant un composé actif acidolabile
US6607742B2 (en) 1997-12-08 2003-08-19 Altana Pharma Ag Suppository composition which is a spray-dried suspension of an acid-labile proton pump inhibitor in a solvent solution of a sterol and polymer
US6884437B2 (en) 1997-12-08 2005-04-26 Byk Gulden Lomberg Chemische Fabrik Gmbh Administration form comprising an acid-labile active compound
WO1999029299A1 (fr) * 1997-12-08 1999-06-17 Byk Gulden Lomberg Chemische Fabrik Gmbh Nouvelle forme de suppositoire renfermant un compose actif acidolabile
US6383510B1 (en) 1997-12-08 2002-05-07 Byk Gulden Lomberg Chemische Fabrik Gmbh Suppository form comprising an acid-labile active compound
CN1114405C (zh) * 1998-01-30 2003-07-16 埃法尔姆公司 胃保护性奥美拉唑微粒、其制备方法及药物制剂
US6551621B1 (en) 1998-01-30 2003-04-22 Ethypharm Gastroprotected omeprazole microgranules, method for obtaining same and pharmaceutical preparations
WO1999038511A1 (fr) * 1998-01-30 1999-08-05 Ethypharm Microgranules d'omeprazole gastroproteges, procede d'obtention et preparations pharmaceutiques
US8409612B1 (en) 1999-05-21 2013-04-02 Ethypharm Microgranules insoluble in gastric fluid, method for obtaining same and pharmaceutical preparations
WO2000071121A1 (fr) * 1999-05-21 2000-11-30 Laboratoires Des Produits Ethiques Ethypharm Microgranules gastroproteges, procede d'obtention et preparations pharmaceutiques
FR2793688A1 (fr) * 1999-05-21 2000-11-24 Ethypharm Lab Prod Ethiques Microgranules gastroproteges, procede d'obtention et preparations pharmaceutiques
AU771759B2 (en) * 1999-05-21 2004-04-01 Laboratoires Des Produits Ethiques Ethypharm Microgranules insoluble in gastric fluid, method for obtaining same and pharmaceutical preparations
US7794752B1 (en) 1999-06-07 2010-09-14 Nycomed Gmbh Preparation and administration form comprising an acid-labile active compound
US7790198B2 (en) 1999-06-07 2010-09-07 Nycomed Gmbh Preparation and administration form comprising an acid-labile active compound
US7785630B2 (en) 1999-06-07 2010-08-31 Nycomed Gmbh Preparation and administration form comprising an acid-labile active compound
US6245913B1 (en) 1999-06-30 2001-06-12 Wockhardt Europe Limited Synthetic procedure for 5-methoxy-2-[(4-methoxy-3,5-dimethyl-2-pyridinyl)-methylthio]-IH-benzimidazole hydrochloride and its conversion to omeprazole
US6780436B1 (en) 1999-09-13 2004-08-24 Laboratorios Del Dr. Esteve, Sa Solid oral pharmaceutical formulation of modified release that contains an acid labile benzimidazole compound
EP1222922A1 (fr) * 1999-10-20 2002-07-17 Eisai Co., Ltd. Procede de stabilisation de composes benzimidazoles
US7011847B2 (en) 1999-10-20 2006-03-14 U & I Pharmaceuticals Ltd. Enteric coated formulation for bisphosphonic acids and salts thereof
EP1222922A4 (fr) * 1999-10-20 2006-04-12 Eisai Co Ltd Procede de stabilisation de composes benzimidazoles
US6676965B1 (en) 1999-10-20 2004-01-13 U&I Pharmaceuticals Ltd. Enteric coated formulation for bisphosphonic acids and salts thereof
US7220762B1 (en) 1999-10-20 2007-05-22 Eisai R&D Management Co., Ltd. Methods for stabilizing benzimidazole compounds
WO2001032185A1 (fr) * 1999-11-02 2001-05-10 Cipla Ltd. Composition pharmaceutique renfermant au moins un acide bisphosphonique ou un de ses sels et son procede de preparation
DE19959419A1 (de) * 1999-12-09 2001-06-21 Ratiopharm Gmbh Stabile galenische Zubereitungen umfassend ein Benzimidazol und Verfahren zu ihrer Herstellung
US7105180B2 (en) 1999-12-09 2006-09-12 Ratiopharm Gmbh Stable galenic preparations comprising a benzimidazole and method for the production thereof
WO2004075881A1 (fr) * 2003-02-28 2004-09-10 Ranbaxy Laboratories Limited Compositions pharmaceutiques stables de rabeprazole et leurs procedes de fabrication
WO2005027876A1 (fr) * 2003-08-28 2005-03-31 Ranbaxy Laboratories Limited Compositions pharmaceutiques de benzimidazole et leurs procedes de preparation
EP1667681A4 (fr) * 2003-10-03 2009-09-30 Astron Res Pvt Ltd Nouveau systeme d'administration transmucosale
EP1667681A1 (fr) * 2003-10-03 2006-06-14 Astron Research Pvt. Ltd Nouveau systeme d'administration transmucosale
WO2005107721A2 (fr) 2004-05-07 2005-11-17 Altana Pharma Ag Forme galenique pharmaceutique et procede de fabrication de celle-ci
WO2006011159A3 (fr) * 2004-06-21 2006-07-06 Torrent Pharmaceuticals Ltd Composition pharmaceutique stabilisee contenant du sodium de rabeprazole presentant une biodisponibilite amelioree
WO2006011159A2 (fr) * 2004-06-21 2006-02-02 Torrent Pharmaceuticals Limited Composition pharmaceutique stabilisee contenant du sodium de rabeprazole presentant une biodisponibilite amelioree
WO2008065107A1 (fr) * 2006-11-28 2008-06-05 Monteresearch S.R.L. Comprimés stables au stockage à base de dérivés de benzimidazole enrobés d'un film gastro-résistant
CN101822671A (zh) * 2009-03-06 2010-09-08 信谊药厂 雷贝拉唑组合物及其制备方法
CN103202818A (zh) * 2012-01-15 2013-07-17 山东新时代药业有限公司 一种含有右旋雷贝拉唑或其可药用盐的肠溶片剂及其制备方法
CN102772387A (zh) * 2012-08-09 2012-11-14 广东帅广医药有限公司 兰索拉唑组合物肠溶胶囊及其制备方法
EP3292862A1 (fr) 2016-09-07 2018-03-14 Sandoz Ag Formulations d'oméprazole
WO2018046498A1 (fr) 2016-09-07 2018-03-15 Sandoz Ag Formulations d'oméprazole

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CA2290824A1 (fr) 1998-11-26
AU7539098A (en) 1998-12-11
GB9710800D0 (en) 1997-07-23
EP0983067A1 (fr) 2000-03-08
GB2343117A (en) 2000-05-03
GB2343117B (en) 2001-07-25
GB9927132D0 (en) 2000-01-12
ZA984266B (en) 1999-01-20
AU729038B2 (en) 2001-01-25

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