WO2003013480A1 - Preparation enterique de fluoxetine - Google Patents

Preparation enterique de fluoxetine Download PDF

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Publication number
WO2003013480A1
WO2003013480A1 PCT/IB2002/001268 IB0201268W WO03013480A1 WO 2003013480 A1 WO2003013480 A1 WO 2003013480A1 IB 0201268 W IB0201268 W IB 0201268W WO 03013480 A1 WO03013480 A1 WO 03013480A1
Authority
WO
WIPO (PCT)
Prior art keywords
fluoxetin
enteric
formulation
group
layer
Prior art date
Application number
PCT/IB2002/001268
Other languages
English (en)
Inventor
Abhijit Mukund Deshmukh
Ujwal Damu Kolhe
Vipin Tatyasaheb Dhanorkar
Mailatur Sivaraman Mohan
Original Assignee
Dr. Reddy's Laboratories Ltd.
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 Dr. Reddy's Laboratories Ltd. filed Critical Dr. Reddy's Laboratories Ltd.
Priority to US10/486,157 priority Critical patent/US20040170688A1/en
Priority to CA002457385A priority patent/CA2457385A1/fr
Publication of WO2003013480A1 publication Critical patent/WO2003013480A1/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
    • 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
    • A61K9/2886—Dragees; Coated pills or tablets, e.g. with film or compression coating having two or more different drug-free coatings; Tablets of the type inert core-drug layer-inactive layer
    • 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
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5026—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, 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
    • A61K9/48—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
    • A61K9/5005—Wall or coating material
    • A61K9/5021—Organic macromolecular compounds
    • A61K9/5036—Polysaccharides, e.g. gums, alginate; Cyclodextrin
    • A61K9/5042—Cellulose; Cellulose derivatives, e.g. phthalate or acetate succinate esters of hydroxypropyl methylcellulose

Definitions

  • the present invention belongs to the field of Pharmaceutical Sciences and provides an industrially advantageous improved formulation of Fluoxetin or a pharmaceutically acceptable salt, solvate, enantiomer or mixtures thereof including racemic mixture, which is designed for once a week dosing.
  • active ingredient is in the form of pluralities of particles as spherical, cylindrical or elliptical units, pellets, minitablets, tablets or capsules, which can be enteric coated with enteric polymers with an optional smoothening layer.
  • the enteric polymer can be applied in a manner, which does not require any neutralization or reduction of free acidic groups.
  • Fluoxetin N-Methyl-3-phenyl-3-[( ⁇ , ⁇ , ⁇ -trifluoro-4-tolyl) oxyl] propylamine, is an antidepressant drug, which is disclosed in U.S. Patent No. 4,314,081, 4,626,549 and 5,847,217.
  • the teaching for (S) and (R) enantiomeric forms of Fluoxetin is found in U.S. Patent No. 5,889,186 and 5,708,035 respectively.
  • Method and formulation for treating depression using optically pure Fluoxetin is disclosed in U.S. Patent No. 5,104,899.
  • the drug coated core is then optionally coated with a separating layer comprising of non reducing sugar, sucrose along with one or more pharmaceutically acceptable excipients and coated with hydroxypropylmethylcellulose acetate succinate as enteric coating polymer along with one or more pharmaceutically acceptable excipients and finally coated with finishing layer hydroxypropylmethylcellulose and talc.
  • a separating layer comprising of non reducing sugar, sucrose along with one or more pharmaceutically acceptable excipients and coated with hydroxypropylmethylcellulose acetate succinate as enteric coating polymer along with one or more pharmaceutically acceptable excipients and finally coated with finishing layer hydroxypropylmethylcellulose and talc.
  • the separating layer is also used to provide smooth surface for the enteric coat, to improve the acid resistance of the pellets. It has been noted that the use of sucrose in separating layer has surprisingly improved the acid resistance of the pellets and successfully prevented the direct contact of core pellets with enteric polymer.
  • One of the further objectives of the smoothening layer described in U.S. Patent No. 5,910,319 is to improve the coverage of enteric layer and to avoid thin spots in it caused by bumps and irregularities on the core.
  • the U.S. Patent No. 5,985,322 discloses the use of hydroxypropylmethylcellulose acetate succinate as most preferred enteric polymer in view of 4% to 28 % of succinoyl groups, which are the only free carboxylic groups in the compound. It is disclosed that the enteric polymer must be the one having only small number of carboxylic acid groups per unit weight or repeating units of the polymers so as to decrease the chances of reaction of Fluoxetin and enteric polymer to form a slowly dissolving or even insoluble coating.
  • Fluoxetin does not require the reduction of particle size of Fluoxetin to less than 50 ⁇ m before using. Moreover Fluoxetin has a particle size wherein 90% particles are of size less than 229 microns, 50% particles are of size less than 90 microns and 10% particles are of size less than 23 microns.
  • the smoothening coat is an optional feature of the invention. Particularly when the formulation is in the form of capsule the gelatin capsule shell itself act as a separating layer and avoids the extra processing steps in the enteric formulation and enables the formulator to incorporate enteric polymer with substantially high number or free carboxylic acid groups.
  • the present invention also avoids the usual long processing time required for the coating of drug layer over non-pareil seeds thus saving the processing time and production cost. Likewise, the usual problems of drug loss, which occurs during the coating of drug on the inert non-pareil seeds as described in U.S. Patent 5,985,322 and 5,910,319 are avoided.
  • the formulation of the present invention comprises;
  • a core comprising Fluoxetin or a pharmaceutically accepted salt, solvate, enantiomers or mixtures thereof including racemic mixture, in an amount of 90 mg base equivalent of Fluoxetin;
  • an enteric coating layer comprising an at least one enteric coating polymers selected from the group consisting of Eudragit L100-55, Eudragit L 100, Eudragit S 100, hydroxypropyl methyl cellulose pthalate, cellulose acetate pthalate, polyvinyl acetate pthalate; an at least one plasticisers selected from the group consisting of triethyl citrate, polyethylene glycol, diethyl phthalate or dibutyl phthalate; an at least one lubricant or glidants selected from the group consisting of talc, magnesium stearate, kaolin or colloidal silicon dioxide.
  • enteric coating polymers selected from the group consisting of Eudragit L100-55, Eudragit L 100, Eudragit S 100, hydroxypropyl methyl cellulose pthalate, cellulose acetate pthalate, polyvinyl acetate pthalate
  • an at least one plasticisers selected from the group consisting of triethyl citrate,
  • the present invention is designed in the form of enteric formulations manufactured in such a way that the product passes unchanged through the stomach of the patient, and dissolves and releases the active ingredient quickly when it leaves the stomach and enters the small intestine.
  • enteric formulations of the present invention are in the form of tablet or capsule wherein, the active ingredient, Fluoxetin or a pharmaceutically accepted salts, solvates, enantiomers or mixtures thereof including racemic mixture, is in the inner part of the tablet, minitablets, pellet or pluralities of particles as spherical, elliptical or cylindrical units, enclosed with a film or envelope called as the "enteric coating", which is insoluble in acid environments, such as the stomach, but is soluble in near-neutral environments such as the small intestine.
  • the capsules When the enteric formulation is in the form of capsule, the capsules are banded/sealed with gelatin solution followed by enteric coating, such that the capsule shell itself acts as separating layer to avoid the possible reaction of the active ingredient and the enteric polymer. Such a presence of natural separating coat avoids the excess manufacturing steps required in earlier inventions. Further it has been noted that the capsules enteric coated in the said manner are found to be therapeutically equivalent to the commercially available product Prozac ® Weekly 90 mg capsule and have acceptable stability as per ICH guidelines.
  • active ingredient refers to Fluoxetin or a pharmaceutically accepted salts, solvates, enantiomers or mixtures thereof including racemic mixture.
  • enteric formulations comprising Fluoxetin preferably as hydrochloride salts, however as will be appreciated by those skilled in the art, other salt form or free base form could be used to obtain the same beneficial feature of the invention.
  • the present invention utilizes Fluoxetin in the range of particle size wherein 90% particles are of size less than 229 microns, 50%> particles are of size less than 90 microns and 10% particles are of size less than 23 microns.
  • the present enteric coated formulations can be prepared by coating the enteric polymer having substantially high free carboxylic acid, groups and does not require to limit the free carboxylic acid group in the range of from 4% to 28%.
  • the active ingredient is in the form of pluralities of particles as spherical, elliptical or cylindrical units.
  • the delivery system in the fo ⁇ n of plurality of single units offers many clinical advantages. Each of the single units act as a separate entity therefore the chances of dose dumping or unpredictable transit across the gastrointestinal tract due to variable gastric or intestinal residence time is overcome by using plurality of single units.
  • the present invention describes the manufacturing of core of active material in the form of mini-tablets or pluralities of particles as spherical, elliptical or cylindrical units, either by compressing the active agent with one or more of the pharmaceutically acceptable excipients on tablet compression machine or by extrusion-spheronization technique.
  • the present invention describes an improved enteric formulation containing Fluoxetin or pharmaceutically accepted salts or solvates thereof, in the dosage range of 60-120 mg, preferably 90-120 mg and most preferably 90 mg base equivalent of Fluoxetin.
  • the enteric formulations according to the present invention are designed for the treatment of various depressive disorders known in the art with a dosing frequency of once every seven days.
  • the formulation of the present invention is in the form of capsules or tablets comprising pluralities of particles as spherical, elliptical or cylindrical units or in the form of mini-tablets.
  • the size of such particles ranges from 0.5mm to 3.0 mm.
  • the size of such minitablets is in the range of from 0.5mm to 6 mm preferably 0.5 mm to 4 mm.
  • the size of such tablets is in the range of 6mm to 16 mm preferably 8 mm to 14 mm more preferably 8mm to 11mm.
  • These pluralities of particles as spherical, elliptical or cylindrical units are filled in the hard gelatin capsules of size ranging from 3 to 000.
  • the hard gelatin capsules are then sealed with the gelatin solution in water in the concentration of 5-50% w/w at temperature ranging from 37°C to 70°C using hard gelatin capsule band sealing machine known to the pharmaceutical Industry.
  • the sealing can be done using aqueous or nonaqueous solution of any of the polymers selected from hydroxypropylmethylcellulose, hydroxypropyl cellulose or hydroxyethylcellulose.
  • sealing and banding are used interchangeably in this description, which means applying a "band" of cohesive or polymeric materials as aqueous or non-aqueous solution to fuse the cap and the body of the capsule.
  • Sealing of hard gelatin capsules with a band of gelatin or other cellulosic materials is known to the pharmaceutical industry since long and is very common technique employed in order to make the capsules tamperproof.
  • the object of applying such a sealing or banding of the capsules according to the present invention is to prevent the migration of enteric solution to the interior of the capsule thus avoiding the contact of active ingredient with the enteric coating.
  • the capsules are sealed to fuse the cap and body of the gelatin shell to provide uniform surface for subsequent coatings.
  • smoothening layer/coat When the active ingredient is in the form of tablets it is preferred that smoothening layer/coat is applied.
  • said smoothening coat/layer is composed of cohesive or polymeric material with finely divided solid excipients, which constitute fillers.
  • the polymeric or cohesive materials can be selected from any of the polymeric materials selected from hydroxypropylmethylcellulose, polyvinylpyrrolidone, hydroxypropylcellulose, polyethylene glycol, sodium alginate, Eudragit RD 100, combination of N- vinyl pyrollidone and vinyl acetate, combination of microcrystalline cellulose and carragenan etc. Hydroxypropylmethylcellulose and polyethylene glycol are the preferred material for smoothening layer as per present description.
  • the fillers used are those commonly used in pharmaceutical industries like finely powdered talc, silicon dioxide etc.
  • the preferred aspect of the present invention is to avoid the use of sucrose in said smoothening layer, the use of which may be detrimental to the patients having history of hyperglycemia.
  • enteric formulation When enteric formulation is in the form of capsule the smoothening layer may be applied to facilitate more even enteric coat.
  • the capsule shell itself acts as separating barrier (separating coat), which prevents the interaction of acidic enteric polymer with the active ingredient in the core.
  • separating barrier means a capsule shell with or without a band.
  • the formulation of the present invention avoids the need of separating layer between the enteric layer and the core containing active ingredient (Fluoxetin it pharmaceutically accepted salt, solvates, enantiomers and mixtures thereof including racemic mixture) thus reduces the extra processing steps needed to manufacture such formulations containing separating layer.
  • the enteric layer is composed of a water-insoluble polymer together with a plasticizer and one or more pharmaceutically accepted excipients.
  • the polymers used for enteric coating as per the present invention are selected from the group consisting of Eudragit LI 00-55, Eudragit L 100, Eudragit S 100, hydroxypropyl methyl cellulose pthalate, cellulose acetate pthalate, polyvinyl acetate pthalate etc.
  • the preferred polymer is Eudragit L100-55.
  • the coating process can be as follows.
  • the Eudragit L 100-55 is dissolved in solvent such as isopropyl alcohol and triethyl citrate and magnesium stearate are added to it.
  • the resulting solution is sprayed on the tablets or capsules using coating pan.
  • aqueous dispersion of Eudragit L 100-55 (Spray dried Eudragit L30D-55 which can be reconstituted for aqueous formulations) can also be used for coating.
  • Eudragit L 100-55, Triethyl citrate or magnesium stearate can be replaced by the functionally equivalent ingredients as described in this specification.
  • the pluralities of particles as spherical, elliptical or cylindrical units are prepared by using wet granulation with or without use of binders like N-vinyl pyrollidone, hydroxypropyl methyl cellulose (5 cps-100 cps), hydroxypropylcellulose, pregelatinized starch, starch paste, combination of N-vinyl pyrollidone and vinyl acetate and gelatin in the concentration range of 2% to 20%.
  • binders like N-vinyl pyrollidone, hydroxypropyl methyl cellulose (5 cps-100 cps), hydroxypropylcellulose, pregelatinized starch, starch paste, combination of N-vinyl pyrollidone and vinyl acetate and gelatin in the concentration range of 2% to 20%.
  • the said formulation also contains one or more of the pharmaceutically accepted diluents like sorbitol, mannitol, microcrystalline cellulose, dicalcium phosphate or combination thereof .
  • the formulation of the present invention also contains surfactants like sodium lauryl sulphate, poloxamer 407, Tween 20/40/60/80, Span 20/40/60/80, Cremophor RH 40 or combination thereof.
  • the said formulation also contains one or more of the pharmaceutically accepted disintegrants selected from crosscarmellose sodium, crosspovidone, sodium carboxymethylcellulose, sodium starch glycolate or such like.
  • the percentage of water with respect to weight of powder mass ranges from 10% to 50% w/w.
  • the moisture content of the wet mass ranges from 10% to 50%.
  • the pluralities of particles are manufactured by extrusion of wet mass of Fluoxetin and one or more pharmaceutically acceptable excipients followed by spheronization.
  • hydroxypropyl methylcellulose 5 cps
  • All the ingredients except hydroxypropyl methylcellulose were weighed and blended together for 15-30 minutes. The blend was then sifted through 40 # screen. The sifted powder mass was then granulated with hydroxypropylmethylcellulose solution in water. The wet mass was then passed through extruder. The extrudes were then spheronized in spheronizer at speed ranging from 200 rpm to 1500 m for the period of 2 minutes to 15 minutes. The pellets were then dried for sufficient period of time till the loss on drying of pellets was not more than 1.5 % w/w.
  • Core Pellet (Plurality of particles as spherical, elliptical or cylindrical units)
  • Core pellet (Plurality of particles as spherical, elliptical or cylindrical units)
  • Core pellet (Plurality of particles as spherical, elliptical or cylindrical units)
  • the mini-tablets are prepared either by using wet granulation or direct compression or dry granulation method with or without use of binders like N-vinyl pyrrolidone, hydroxypropylmethyl cellulose (5 cps to 100 cps) hydroxypropylcellulose, pregelatinized starch, starch paste, combination of N-vinyl pyrrolidone and vinyl acetate and gelatin in the concentration range of 2% to 20 %.
  • the Said formulation also contains one or more of the pharmaceutically accepted excipients like mannitol, sorbitol, microcrystalline cellulose, dicalcium phosphate or combination thereof as diluents.
  • Magnesium stearate, stearic acid, lubritab, talc and silicon dioxide are used as lubricants and glidants.
  • the said pharmaceutical excipients also contain disintegrants like hydroxy propyl cellulose, crosspovidone, sodium starch glycolate, crosscarmellose sodium or combination thereof.
  • the said formulation also contains surfactants like sodium lauryl sulphate, poloxamer 407,Tween 0/40/60/80, Span 20/40/60/80, Cremophor RH 40 or combination thereof.
  • magnesium stearate and talc were weighed accurately and sifted through 40 # screen. The sifted materials were then blended for 5-60 minutes in a suitable blender. Magnesium stearate and talc were weighed and sifted through 40 # screen and added to other ingredients and blended for 5-20 minutes before compressing into mini-tablets. Alternatively all the excipients except magnesium stearate, talc and polyvinyl pyrollidone were weighed accurately and sifted through 40 # screen and were granulated while polyvinylpyrrolidone solution in water. The wet mass was then optionally milled and dried or dried directly till the loss on drying was 0.3% to 5 % w/w. The dried granules were again milled and mixed with magnesium stearate. Talc is weighed and sifted separately. The lubricated granules were mixed for 5 minutes to 20 minutes and compressed into tablets or mini-tablets.
  • the core of the present invention can be coated with film coating polymers like N-vinyl pyrrolidone (PVP K-30/K-90), polyethylene glycol, hydroxypropylmethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, sodium alginate, EUDRAGIT® RD 100, combination of N-vinyl pyrrolidone and vinyl acetate along with one or more pharmaceutically acceptable excipients like plasticisers, glidants, anti adherent agents to improve the process of capsule filling Example 4.
  • film coating polymers like N-vinyl pyrrolidone (PVP K-30/K-90), polyethylene glycol, hydroxypropylmethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, sodium alginate, EUDRAGIT® RD 100, combination of N-vinyl pyrrolidone and vinyl acetate along with one or more pharmaceutically acceptable excipients like plasticisers, glidants, anti adherent agents to improve the process of capsule
  • Hard Gelatin Capsule Sealing The core in the form of pluralities of particles as spherical, elliptical or cylindrical units are filled in hard gelatin capsules of size ranging from 3 to 000. The hard gelatin capsules are then sealed with gelatin solution in water in the concentration range of 5-50 % w/w at temperature ranging from 37°C to 70°C using hard gelatin capsule band sealing machine. The sealing of capsules is done to fuse the cap and body of capsules to provide uniform surface for the further functional coating and also to prevent the possible ingress of solvent during coating.
  • the smoothening coat when applied is optional with an object of providing a smooth surface for the enteric coating.
  • the optional smoothening coat can be applied using one or more of the agents like N-vinyl pyrrolidone (PVP K-30/K-90), polyethylene glycol, hydroxypropylmethylcellulose, hydroxypropylcellulose, hydroxyethylcellulose, sodium alginate, Eudragit RD100, combination of N- vinyl pyrrolidone and vinyl acetate (Plasdone S-630), Opadry AMB along with one or more pharmaceutically acceptable excipients like plasticisers selected from triethyl citrate, polyethylene glycol, diethyl phthalate, dibutyl phthalate, glidants, antiadherents like talc, magnesium stearate, kaolin, colloidal silicon dioxide, which are commonly known to those skilled in the art.
  • These agents are applied in the range of 0.5 to 9 mg/cm 2 surface area corresponding to 0.5 to 7 %
  • the agents which inhibits the release of drug in stomach and releases the same once the pH in the body reaches 5.0 to 7.5 are sodium alginate, cellulose acetate, copolymers derived from methacrylic acid/ethyl acrylate, anionic methacrylic acid and methacrylic acid esters, cellulose acetate phthalate, polyvinyl acetate phthalate and hydroxypropylmethylcellulose phthalate or combination thereof.
  • the coating solution/suspension also contains excipients like plasticisers selected from triethyl citrate, polyethylene glycol, diethyl phthalate, dibutyl phthalate, glidants, antiadherents like talc, magnesium stearate, kaolin or colloidal silicon dioxide and such like.
  • the finishing coat can be optionally applied with an object to improve the elegance of the product.
  • the agents which constitute the finishing coat includes various grades and colours of commercial product Opadry of M/s Colorcon which consists of hydroxy propyl methylcellulose along with one or more pharmaceutically acceptable excipients.
  • the assay and related substances show that the Fluoxetin 90 mg capsules and tablets are substantially stable over the storage period of 3 months and 6 months respectively at the storage conditions of 40°C and 75% RH (relative humidity).
  • gelatin shell acts as natural separating barrier/coat to prevent the interaction between Fluoxetin and enteric coating polymers (or polymers used for site specific coating as described in this specification) containing even substantially high percentages of free carboxylic acid groups.
  • enteric Fluoxetin formulations of present invention was found to be substantially stable and therapeutically equivalent to the commercially available formulation Prozac ® Weekly 90 mg capsules.
  • the examples given above are for the purpose of illustration only and not to be construed as limitations thereon. Many variation of the present invention mentioned in the detailed description are obvious to those skilled in the art and are contemplated to be within the scope of the present invention.

Abstract

L'invention concerne une préparation entérique de fluoxétine avantageuse sur le plan industriel n'impliquant pas l'utilisation de saccharose et de succinate d'acétate d'hydroxypropylméthylcellulose. Cette invention a également trait à des préparations entériques de fluoxétine sous forme de comprimés ou de gélules pourvues d'une couche de séparation facultative. Lorsque ces préparations se présentent sous forme de gélules, la couche de séparation est la coque de la gélule même, ce qui permet de réduire l'étape de traitement desdites préparations entériques. La préparation de cette invention, ainsi que la fluoxétine ou ses sels acceptables pharmaceutiquement, les solvates, les enantiomères ou les mélanges correspondants contenant un mélange racémique sont également considérés comme étant dans la portée de cette invention.
PCT/IB2002/001268 2001-08-06 2002-04-19 Preparation enterique de fluoxetine WO2003013480A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US10/486,157 US20040170688A1 (en) 2001-08-06 2002-04-19 Enteric formulation of fluoxetin
CA002457385A CA2457385A1 (fr) 2001-08-06 2002-04-19 Preparation enterique de fluoxetine

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN647/MAS/2001 2001-08-06
IN647MU2001 2001-08-06

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WO2003013480A1 true WO2003013480A1 (fr) 2003-02-20

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Cited By (5)

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Publication number Priority date Publication date Assignee Title
WO2004058228A1 (fr) * 2002-12-24 2004-07-15 Lupin Limited Composition de fluoxetine a enrobage enterique
EP1502587A1 (fr) * 2003-07-30 2005-02-02 Pharmathen S.A. Formulation à libération prolongée du chlorhydrate de Venlafaxine
WO2009006299A2 (fr) * 2007-06-29 2009-01-08 Dr. Reddy's Laboratories Ltd. Systèmes à multiples particules
EP2946774A1 (fr) * 2014-05-19 2015-11-25 Tillotts Pharma AG Capsules enrobées à libération modifiée
JP2017515879A (ja) * 2014-05-19 2017-06-15 ティロッツ・ファルマ・アクチエンゲゼルシャフトＴｉｌｌｏｔｔｓ Ｐｈａｒｍａ Ａｇ 放出調節コーティングカプセル

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US4626549A (en) 1974-01-10 1986-12-02 Eli Lilly And Company Treatment of obesity with aryloxyphenylpropylamines
US5104899A (en) 1990-08-13 1992-04-14 Sepracor, Inc. Methods and compositions for treating depression using optically pure fluoxetine
US5708035A (en) 1991-02-04 1998-01-13 Sepracor Inc. Methods of use and compositions of R(-) fluoxetine
US5889186A (en) 1994-12-16 1999-03-30 Uop Process for preparation of the pharmaceutically desired (S)-oxetine enantiomers
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WO2004058228A1 (fr) * 2002-12-24 2004-07-15 Lupin Limited Composition de fluoxetine a enrobage enterique
EP1502587A1 (fr) * 2003-07-30 2005-02-02 Pharmathen S.A. Formulation à libération prolongée du chlorhydrate de Venlafaxine
WO2005009414A1 (fr) * 2003-07-30 2005-02-03 Pharmathen S.A. Formulation a liberation prolongee pour chlorhydrate de venlafaxine
AU2004258732B2 (en) * 2003-07-30 2009-06-11 Pharmathen S.A. Sustained release formulation for venlafaxine hydrochloride
WO2009006299A2 (fr) * 2007-06-29 2009-01-08 Dr. Reddy's Laboratories Ltd. Systèmes à multiples particules
WO2009006299A3 (fr) * 2007-06-29 2009-02-19 Reddys Lab Ltd Dr Systèmes à multiples particules
CN106456559A (zh) * 2014-05-19 2017-02-22 蒂洛特斯制药股份有限公司 调节释放的包衣胶囊
WO2015177025A1 (fr) * 2014-05-19 2015-11-26 Tillotts Pharma Ag Capsules enrobées à libération modifiée
EP2946774A1 (fr) * 2014-05-19 2015-11-25 Tillotts Pharma AG Capsules enrobées à libération modifiée
JP2017515880A (ja) * 2014-05-19 2017-06-15 ティロッツ・ファルマ・アクチエンゲゼルシャフトＴｉｌｌｏｔｔｓ Ｐｈａｒｍａ Ａｇ 放出調節コーティングカプセル
JP2017515879A (ja) * 2014-05-19 2017-06-15 ティロッツ・ファルマ・アクチエンゲゼルシャフトＴｉｌｌｏｔｔｓ Ｐｈａｒｍａ Ａｇ 放出調節コーティングカプセル
AU2015263308B2 (en) * 2014-05-19 2020-01-16 Tillotts Pharma Ag Modified release coated capsules
JP2020063290A (ja) * 2014-05-19 2020-04-23 ティロッツ・ファルマ・アクチエンゲゼルシャフトＴｉｌｌｏｔｔｓ Ｐｈａｒｍａ Ａｇ 放出調節コーティングカプセル
EP3145497B1 (fr) * 2014-05-19 2020-10-28 Tillotts Pharma AG Capsules enrobées à libération modifiée
US11160762B2 (en) 2014-05-19 2021-11-02 Tillotts Pharma Ag Modified release coated capsules
US11266605B2 (en) 2014-05-19 2022-03-08 Tillotts Pharma Ag Modified release coated capsules
JP7041334B2 (ja) 2014-05-19 2022-03-24 ティロッツ・ファルマ・アクチエンゲゼルシャフト 放出調節コーティングカプセル
JP7041333B2 (ja) 2014-05-19 2022-03-24 ティロッツ・ファルマ・アクチエンゲゼルシャフト 放出調節コーティングカプセル
CN114983971A (zh) * 2014-05-19 2022-09-02 蒂洛特斯制药股份有限公司 调节释放的包衣胶囊

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