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WO2004062667A1 - Forme amorphe du maleate de rosiglitazone et procede de preparation - Google Patents

Forme amorphe du maleate de rosiglitazone et procede de preparation Download PDF

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Publication number
WO2004062667A1
WO2004062667A1 PCT/US2004/000277 US2004000277W WO2004062667A1 WO 2004062667 A1 WO2004062667 A1 WO 2004062667A1 US 2004000277 W US2004000277 W US 2004000277W WO 2004062667 A1 WO2004062667 A1 WO 2004062667A1
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WIPO (PCT)
Prior art keywords
rosiglitazone maleate
solid
amoφhous
rosiglitazone
compound
Prior art date
Application number
PCT/US2004/000277
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English (en)
Inventor
Manne Satyanarayana Reddy
Gudipati Srinivasulu
Mandava Venkata Naga Brahmeshwar Rao
Banda Goverdhan Reddy
Original Assignee
Dr. Reddy's Laboratories Limited
Dr. Reddy's Laboratories, Inc.
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 Limited, Dr. Reddy's Laboratories, Inc. filed Critical Dr. Reddy's Laboratories Limited
Publication of WO2004062667A1 publication Critical patent/WO2004062667A1/fr

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics

Definitions

  • Rosiglitazone 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]-benzyl]-2,4- thiazolidinedione maleate is a highly selective and potent agonist for the peroxisome proliferators-activated receptor-gamma (PPAR ⁇ ).
  • Rosiglitazone maleate is used for the management of type 2 diabetes mellitus, also called non-insulin-dependent diabetes mellitus (NIDDM). Rosiglitazone maleate is believed to act primarily by increasing insulin sensitivity and improving glycemic control while reducing circulating insulin levels.
  • amorphous forms of certain drugs exhibit distinct dissolution characteristics and in some cases distinct bioavailability patterns compared to the crystalline form.
  • the dissolution rate may favor one formulation over another.
  • one formulation may be favored over another.
  • one formulation may be more suitable for treating certain patient populations. Therefore, it is desirable to have a procedure for making amorphous product or for converting a crystalline form of the drug to the amorphous form.
  • the invention relates to an amorphous form of rosiglitazone maleate.
  • the amorphous form of rosiglitazone maleate may have substantially the same X-ray diffraction pattern as shown in Figure 1.
  • the invention also relates to a composition that includes rosiglitazone maleate in a solid form, wherein at least 80 % by weight of the solid rosiglitazone maleate is in an amo ⁇ hous form.
  • the invention also relates to a process for preparation of an amorphous form of rosiglitazone maleate.
  • the invention also relates to a pharmaceutical composition that includes an amorphous form of rosiglitazone maleate and one or more pharmaceutically acceptable carriers or diluents.
  • the pharmaceutical composition include comprise one or more additional active ingredients in addition to rosiglitazone maleate.
  • the pharmaceutical composition is in a solid dosage form for oral administration, such as a tablet.
  • the invention also relates to a method for treatment or prophylaxis of diabetes mellitus, conditions associated with diabetes mellitus and complication thereof in a mammal.
  • Embodiments of the invention are not mutually exclusive, but may be implemented in various combinations. The described embodiments of the invention and the disclosed examples are given for the purpose of illustration rather than limitation of the invention as set forth the appended claims.
  • “Pharmaceutically acceptable” means that which is useful in preparing a pharmaceutical composition that is generally non-toxic and is not biologically undesirable and includes that which is acceptable for veterinary use and/or human pharmaceutical use.
  • composition includes, but is not limited to, a powder, a suspension, an emulsion and/or mixtures thereof.
  • composition is intended to encompass a product containing the specified ingredients in the specified amounts, as well as any product, which results, directly or indirectly, from combination of the specified ingredients in the specified amounts.
  • a “composition” may contain a single compound or a mixture of compounds.
  • a “compound” is a chemical substance that includes molecules of the same chemical structure regardless of its three dimensional orientation. Thus, it may be used to indicate racemates, stereoisomers, or both.
  • composition is intended to encompass a product including the active ingredient(s), pharmaceutically acceptable excipients that make up the carrier, as well as any product which results, directly or indirectly, from combination, complexation or aggregation of any two or more of the ingredients, or from dissociation of one or more of the ingredients, or from other types of reactions or interactions of one or more of the ingredients.
  • pharmaceutical compositions of the present invention encompass any composition made by admixing the active ingredient, additional active ingredient(s), and pharmaceutically acceptable excipients.
  • excipient means a component of a pharmaceutical product that is not the active ingredient, such as filler, diluent, carrier, and so on.
  • the excipients that are useful in preparing a pharmaceutical composition are preferably generally safe, non-toxic and neither biologically nor otherwise undesirable, and are acceptable for veterinary use as well as human pharmaceutical use.
  • a pharmaceutically acceptable excipient as used in the specification and claims includes both one and more than one such excipient.
  • proliferaxis of conditions associated with diabetes mellitus includes the treatment of conditions such as insulin resistance, impaired glucose tolerance, hyperinsulinaemia and gestational diabetes.
  • isolated is used to indicate separation of the compound being isolated regardless of the purity of the isolated compound from any unwanted substance, which is present with the compound as a mixture.
  • substantially free of in reference to a composition means that the absent substance cannot be detected in the composition by methods known to those skilled in the art at the time of the filing of this application.
  • Rosiglitazone maleate has the chemical structure:
  • Rosiglitazone maleate compound itself may be prepared according to known procedures such as those disclosed in U.S. Patent. Nos 5,002,953; 5,646,169; 5,741,803; and 6,288,095 of which the disclosures are incorporated herein by reference.
  • rosiglitazone in an amorphous form.
  • Amorphous materials do not exhibit the three-dimensional long-range order found in crystalline materials but are structurally more similar to liquids where the arrangement of molecules is random.
  • Amorphous solids are not crystalline and therefore do not give a definitive x-ray diffraction pattern (XRD), in addition they do not give rise to a melting point and tend to liquefy at some point beyond the glass transition point (Hancock and Zografi, (1997) J. Pharm. Sci., 86:1-12).
  • XRD definitive x-ray diffraction pattern
  • a sample of an XRD spectra of rosaglidazone maleate obtained by the inventors is shown in Fig. 1.
  • a particular process for preparation of the amorphous form of rosiglitazone maleate includes: a) providing rosiglitazone maleate solution in a nitrile solvent, an alcoholic solvent or a mixture thereof; b) removing the solvent to form a solid residue; and c) isolating the solid residue to obtain the amorphous form of rosiglitazone maleate.
  • the preferred nitrile solvents include this acetonitrile, and propionitrile.
  • the preferred alcoholic solvents include methanol, ethanol, isopropyalcohol, n-butyl alcohol, t-butyl alcohol and mixtures thereof.
  • the removal of the solvent from the rosiglitazone maleate solution may be affected at an increased temperature, preferably at reflux temperature, and/or reduced pressure.
  • the removal of the solvent may be carried out preferably below 75 °C, more preferably at about 40°C-75°C, yet more preferably at about 60°C-75°C, yet
  • the solid residue obtained after solvent removal may be isolated and dried using conventional methods.
  • the advantages of the process include simplicity, ecofriendliness and suitability for commercial use.
  • the amorphous form of rosiglitazone maleate shown in Fig. 1 is produced by described process.
  • the invention also relates to a composition of solid rosiglitazone maleate wherein at least 80% of the total weight of rosiglitazone maleate is in the amo ⁇ hous form.
  • the solid rosiglitazone maleate is suitable for use as a bulk active ingredient in formulating pharmaceutical products.
  • the remainder of the solid rosiglitazone maleate in the composition i.e., 20% or less of the total weight of rosiglitazone maleate, maybe other forms of rosiglitazone maleate, e.g. crystalline forms or polymo ⁇ hs.
  • the composition may include at least 95% of the amo ⁇ hous form of rosiglitazone maleate with respect to total weight of the solid rosiglitazone maleate in the composition.
  • the composition may include at least 99% of the amo ⁇ hous form of rosiglitazone maleate with respect to total weight of the solid rosiglitazone maleate in the composition.
  • the composition is substantially free of any forms of rosiglitazone maleate other than its amo ⁇ hous form.
  • amo ⁇ hous rosiglitazone maleate is X-ray powder diffraction (XPD).
  • XPD X-ray powder diffraction
  • amo ⁇ hous rosiglitazone maleate is characterized in providing an X-ray powder diffraction pattern containing one or more broad diffuse halos having very low counts (i.e. see FIG. 1) in contrast to the sha ⁇ diffraction peaks characteristic of crystalline materials.
  • X-ray diffraction also provides a convenient and practical means for quantitative determination of the relative amounts of crystalline and/or amo ⁇ hous forms in a solid mixture.
  • X-ray diffraction is adaptable to quantitative applications because the intensities of the diffraction peaks of a given compound in a mixture are proportional to the fraction of the corresponding powder in the mixture.
  • the percent composition of amo ⁇ hous or crystalline forms of rosiglitazone maleate in an unknown composition can be determined.
  • the measurements are made on solid powder rosiglitazone maleate.
  • the X- ray powder diffraction patterns of an unknown composition can be compared to known quantitative standards containing pure crystalline forms of rosiglitazone maleate to identify the percent ratio of a particular crystalline form. This is done by comparing the relative intensities of the peaks from the diffraction pattern of the unknown solid powder composition with a calibration curve derived from the X-ray diffraction patterns of pure known samples. The curve can be calibrated based on the X-ray powder diffraction pattern for the strongest peak from a pure sample of crystalline forms of rosiglitazone maleate. The calibration curve may be created in a manner known to those of skill in the art.
  • five or more artificial mixtures of crystalline forms of rosiglitazone maleate may be prepared.
  • such mixtures may contain, 2%, 5%, 7%, 8%, and 10% of rosiglitazone maleate for each crystalline form.
  • X-ray diffraction patterns are obtained for each artificial mixture using standard X-ray diffraction techniques. Slight variations in peak positions, if any, may be accounted for by adjusting the location of the peak to be measured. The intensities of the selected characteristic peak(s) for each of the artificial mixtures are then plotted against the known weight percentages of the crystalline form.
  • the resulting plot is a calibration curve that allows determination of the amount of the crystalline forms of rosiglitazone maleate in an unknown sample.
  • the intensities of the selected characteristic peak(s) in the mixture may be used to determine the percentage of the given crystalline form in the composition, with the remainder determined to be the amo ⁇ hous material.
  • amo ⁇ hous rosiglitazone maleate In addition to X-ray powder diffraction, amo ⁇ hous rosiglitazone maleate, or the presence of some amo ⁇ hous rosiglitazone maleate, can be distinguished from crystalline rosiglitazone maleate, using Raman spectroscopy, solution calorimetry, differential scanning calorimetry, solid state nuclear magnetic resonance spectra (ssNMR) or infrared spectroscopy. Each of these techniques is well established in the art. Amo ⁇ hous rosiglitazone maleate can also be identified based on the mo ⁇ hology of the particles seen under an electron microscope.
  • amo ⁇ hous rosiglitazone maleate is likely to be much more soluble than crystalline rosiglitazone maleate because the former is lack of lattice energy, providing another means of discriminating between the crystalline and amo ⁇ hous rosiglitazone forms, or detecting an amount of amo ⁇ hous form within a rosiglitazone maleate preparation.
  • the preferred method of differentiating amo ⁇ hous rosiglitazone from other crystalline and non-crystalline forms of rosiglitazone is X-ray powder diffraction (XPD).
  • mixtures comprising substantially crystalline or other solid forms of rosiglitazone maleate with amo ⁇ hous rosiglitazone maleate will, depending on the amount of amo ⁇ hous product present, may also possess varying degrees of increased solubility.
  • Such mixtures comprising amo ⁇ hous rosiglitazone maleate can be prepared, for example, by mixing amo ⁇ hous rosiglitazone maleate prepared according to the present invention with other solid forms of rosiglitazone, such as crystalline form, prepared according to prior art methods.
  • a mixture might also be prepared if the manufacturing process is incomplete, or inco ⁇ orates steps that allow or cause amo ⁇ hous product to be formed.
  • rosiglitazone maleate examples include, but are not limited to, crystalline rosiglitazone maleate, and other polymo ⁇ hs.
  • a detectable amount of amo ⁇ hous rosiglitazone maleate is an amount that can be detected using conventional techniques, such as FT-IR, Raman spectroscopy, XPD, TMA, DSC and the like.
  • the limits of detection by solid state NMR is reported to be approximately 5-10% according to Saindonet al., (Pharmaceutical Research, 10:197-203,1993).
  • the limits of detection by near infra red spectroscopy is reported to be approximately 2-5% according to Blanco and Villar (Analyst, 125:2311-2314, 2000).
  • the limits of detection by Modulated Differential Scanning Calorimetry (MDSC) is reported to be approximately 6% according to Saklatvala et al., (International Journal of Pharmaceutics, 192: 55-62, 1999).
  • the limits of detection by FTRaman spectroscopy is reported to be approximately 2% according to Taylor and Zografi (Pharm. Res. 15:755- 761, 1998).
  • the invention provides pharmaceutical compositions comprising the amo ⁇ hous form of rosiglitazone maleate, which can be formulated with a one or more pharmaceutically acceptable carriers, also known as excipients, which ordinarily lack pharmaceutical activity, but have various useful properties which may, for example, enhance the stability, sterility, bioavailability, and ease of formulation of a pharmaceutical composition.
  • pharmaceutically acceptable carriers also known as excipients, which ordinarily lack pharmaceutical activity, but have various useful properties which may, for example, enhance the stability, sterility, bioavailability, and ease of formulation of a pharmaceutical composition.
  • These carriers are pharmaceutically acceptable, meaning that they are not harmful to humans or animals when taken appropriately and are compatible with the other ingredients in a given formulation.
  • the carriers may be solid, semi-solid, or liquid, and may be formulated with the compound in bulk.
  • the resulting mixture may be manufactured in the form of a unit-dose formulation (i.e., a physically discrete unit containing a specific amount of active ingredient) such as a tablet or capsule.
  • a unit-dose formulation i.e., a physically discrete unit containing a specific amount of active ingredient
  • the pharmaceutical compositions may include, in addition to a compound of this invention, one or more active pharmaceutical compounds.
  • the pharmaceutical compositions of the present invention may include one or more additional medicaments in combination with the amo ⁇ hous form of rosiglitazone maleate.
  • the pharmaceutical compositions of the invention may be prepared by uniformly admixing the active ingredient with liquid or solid carriers and then shaping the product into the desired form.
  • the pharmaceutical compositions may be in the form of suspensions, solutions, elixirs, aerosols, or solid dosage forms. Because of their ease of administration, tablets and capsules represent the most advantageous oral dosage unit form, in which case solid pharmaceutical carriers are employed.
  • a preferred oral solid preparation is a tablet.
  • a tablet may be prepared by direct compression, wet granulation, or molding, of the active ingredient(s) with a carrier and other excipients in a manner known to those skilled in the art.
  • Compressed tablets may be prepared by compressing in a suitable machine the active ingredient in a free-flowing form such as powder or granules, optionally mixed with a binder, lubricant, inert diluent, surface active agent or dispersing agent. Molded tablets may be made on a suitable machine.
  • a mixture of the powdered compound moistened with an inert liquid diluent is suitable in the case of oral solid dosage forms (e.g., powders, capsules, and tablets). If desired, tablets may be coated by standard techniques.
  • the compounds of this invention may be formulated into typical disintegrating tablets, or into controlled or extended release dosage forms.
  • compositions of the invention are contemplated in various formulations suitable for various modes of administration, including but not limited to inhalation, oral, rectal, parenteral (including subcutaneous, intradermal, intramuscular, intravenous), implantable, intravaginal and transdermal administration.
  • parenteral including subcutaneous, intradermal, intramuscular, intravenous
  • implantable implantable, intravaginal and transdermal administration.
  • the most suitable route of administration in any given case depends on the duration of the subject's condition, the length of treatment desired, the nature and severity of the condition being treated, and the particular formulation that is being used.
  • the formulations may be in bulk or in unit dosage form.
  • a pharmaceutical composition of the invention will generally include about 0.1% by weight to about 99% by weight of active ingredient, preferably about 1% by weight to 50% by weight for oral administration and about 0.2% by weight to about 20% by weight for parenteral administration.
  • Formulations suitable for oral administration include capsules (hard and soft), cachets, lozenges, syrups, suppositories, and tablets, each containing a pre-determined amount of the active compound; as a powder or granules; as a solution or a suspension in an aqueous or non-aqueous liquid; or as an oil-in-water or water-in-oil emulsion.
  • Such formulations may be prepared by any suitable method of pharmacy that includes the step of bringing into association the active compound and a suitable carrier or carriers.
  • the amount of active ingredient per unit dosage of solid formulations may be as described in prior art for preparations of rosiglitazone maleate.
  • a preferable amount is from about 2% by weight to about 20% by weight.
  • Suitable carriers include but are not limited to fillers, binders, lubricants, inert diluents, surface active/dispersing agents, flavorants, antioxidants, bulking and granulating agents, adsorbants, preservatives, emulsifiers, suspending and wetting agents, glidants, disintegrants, buffers and pH-adjusting agents, and colorants.
  • Examples of carriers include celluloses, modified celluloses, cyclodextrins, starches, oils, polyols, sugar alcohols and sugars, and others.
  • sugar, sugar alcohols, ethanol, water, glycerol, and poyalkylene glycols are particularly suitable, and may also be used in solid formulations.
  • Cyclodextrins may be particularly useful for increasing bioavailability.
  • Formulations for oral administration may optionally include enteric coatings known in the art to prevent degradation of the formulation in the stomach and provide release of the drug in the small intestine.
  • enteric coatings known in the art to prevent degradation of the formulation in the stomach and provide release of the drug in the small intestine.
  • One example of pharmaceutical tablet of the amo ⁇ hous rosiglitazone maleate may include, as inactive ingredients, hypromellose 2910, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol 3000, sodium starch glycolate, titanium dioxide, triacetin and 1 or more of synthetic red and yellow iron oxides and talc.
  • Formulations suitable for buccal or sub-lingual administration include lozenges comprising the active compound in a flavored base, usually sucrose and acacia or tragacanth, although other agents are also suitable, and pastilles comprising the compound in an inert base such as gelatin and glycerin or sucrose and acacia.
  • Formulations suitable for rectal administration are preferably presented as unit dose suppositories. These may be prepared by admixing the active compound with one or more conventional solid carriers, e.g., cocoa butter, and then shaping the resulting mixture.
  • conventional solid carriers e.g., cocoa butter
  • the effective amount (i.e., dosage) of active compound for treatment will vary depending on the route of administration, the condition being treated, its severity, and duration, and the state and age of the subject. A skilled physician will monitor the progress of the subject and will adjust the dosage accordingly, depending on whether the goal is to eliminate, alleviate, or prevent a given condition. Generally, the dosage should be considered in proportion to the subject's weight.
  • the daily dose of particular formulations of active compound may be divided among one or several unit dose administrations. For example therapeutic administration about fifteen to thirty minutes before main meals is preferable (i.e. three times daily), although administration of the active compounds may be carried out prophylactically, and may be maintained for prolonged periods of time. One skilled in the art will take such factors into account when determining dosage.
  • Unit dosage of active ingredient may range from about 0.1 mg to about 2 g, preferably from about lmg to about lg, more preferably from about 1 mg to about 10 mg, even more preferably from about 2 mg to about 8 mg.
  • the invention also provides methods of for treatment or
  • prophylaxis of diabetes mellitus conditions associated with diabetes mellitus and complication thereof in a mammal, comprising administering to a patient in need of such treatment an effective amount of a composition comprising the amo ⁇ hous form of rosiglitazone maleate and one or more pharmaceutically acceptable carrier.
  • Conditions associated with diabetes include hyperglycaemia and insulin resistance, especially acquired insulin resistance and obesity. Further conditions associated with diabetes include hypertension, cardiovascular disease, especially atherosclerosis, certain eating disorders, in particular the regulation of appetite and food intake in subjects suffering from disorders associated with under-eating ,such as anorexia nervosa, and disorders associated with over-eating, such as obesity and anorexia bulimia. Additional conditions associated with diabetes include polycystic ovarian syndrome and steroid induced insulin resistance.
  • the complications of conditions associated with diabetes mellitus encompassed herein includes renal disease, especially renal disease associated with the development of Type II diabetes including diabetic nephropathy, glomerulonephritis, glomerular sclerosis, nephrotic syndrome, hypertensive nephrosclerosis and end stage renal disease.
  • the invention also provides a use of the amo ⁇ hous rosiglitazone maleate along with one or more additional medicaments. Since rosiglitazone maleate is an insulin sensitivity enhancer, a combination therapy with one or more other medicaments may be particularly desirable.
  • the medicaments that can be used with the amo ⁇ hous rosiglitazone maleate include metformin, sulfonylurea, their pharmaceutically acceptable salts, insulin, and combinations thereof.
  • the medicament is metformin hydrochloride.
  • the additional medicaments may be admixed with the amo ⁇ hous rosiglitazone maleate to form a single pharmaceutical dosage form, for example, such as tablets or may be prepared as a separate pharmaceutical dosage form, which can be administered to a patient along with the pharmaceutical dosage form of the amo ⁇ hous rosiglitazone at the same time or with a time interval depending upon the patients conditions and the additional medicaments being used for the combination therapy.
  • the pharmaceutical dosage forms may include any forms of drug, which are suitable transport the medicaments into body as noted hereinabove.
  • One example of such pharmaceutical dosage form of the combination therapy is a tablet, which may contain rosiglitazone maleate and metformin hydrochloride equivalent to: 1 mg rosiglitazone with 500 mg metformin hydrochloride, 2 mg rosiglitazone maleate with 500 mg metformin hydrochloride, or 4 mg rosiglitazone maleate with 500 mg metformin hydrochloride in addition to inactive ingredients such as hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol 400, povidone 29-32, sodium starch glycolate, titanium dioxide and one or more of red and yellow iron oxides.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Diabetes (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Hematology (AREA)
  • Obesity (AREA)
  • Emergency Medicine (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Endocrinology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention se rapporte à un maléate de rosiglitazone amorphe, et à la préparation et aux utilisations de ce dernier dans une composition pharmaceutique, et à un procédé de traitement médical comprenant une thérapie combinée.
PCT/US2004/000277 2003-01-08 2004-01-08 Forme amorphe du maleate de rosiglitazone et procede de preparation WO2004062667A1 (fr)

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005021541A2 (fr) * 2003-08-29 2005-03-10 Cipla Limited Processus
WO2005065663A1 (fr) * 2003-12-31 2005-07-21 Alpharma, Inc. Preparations de rosiglitazone et de metformine
WO2005065654A2 (fr) * 2003-12-31 2005-07-21 Alpharma, Inc. Preparations de rosiglitazone
WO2006090150A1 (fr) * 2005-02-24 2006-08-31 Smithkline Beecham Corporation Composition pharmaceutique comprenant de la rosiglitazone amorphe
CZ298424B6 (cs) * 2005-05-24 2007-09-26 Zentiva, A. S. Zpusob krystalizace rosiglitazonu a jeho derivátuze smesných rozpouštedel
US7358366B2 (en) 1999-04-23 2008-04-15 Smithkline Beecham P.L.C. Thiazolidinedione derivative and its use as antidiabetic

Citations (4)

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Publication number Priority date Publication date Assignee Title
WO1994005659A1 (fr) * 1992-09-05 1994-03-17 Smithkline Beecham Plc Derives substitues de la thiazolidenedione
WO2000064893A2 (fr) * 1999-04-23 2000-11-02 Smithkline Beecham Plc Nouvel agent pharmaceutique
WO2002026737A1 (fr) * 2000-09-26 2002-04-04 Dr. Reddy's Research Foundation Nouvelles formes polymorphes de 5-[4-[2-[n-methyl-n-(2-pyridyl)amino]ethoxy]benzyl] thiazolidine-2,4-dione maleate et procede de preparation associe
WO2002051823A1 (fr) * 2000-12-26 2002-07-04 Torrent Pharmaceuticals Ltd Procede de preparation de maleate de rosiglitazone

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1994005659A1 (fr) * 1992-09-05 1994-03-17 Smithkline Beecham Plc Derives substitues de la thiazolidenedione
WO2000064893A2 (fr) * 1999-04-23 2000-11-02 Smithkline Beecham Plc Nouvel agent pharmaceutique
WO2002026737A1 (fr) * 2000-09-26 2002-04-04 Dr. Reddy's Research Foundation Nouvelles formes polymorphes de 5-[4-[2-[n-methyl-n-(2-pyridyl)amino]ethoxy]benzyl] thiazolidine-2,4-dione maleate et procede de preparation associe
WO2002051823A1 (fr) * 2000-12-26 2002-07-04 Torrent Pharmaceuticals Ltd Procede de preparation de maleate de rosiglitazone

Cited By (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7358366B2 (en) 1999-04-23 2008-04-15 Smithkline Beecham P.L.C. Thiazolidinedione derivative and its use as antidiabetic
WO2005021541A2 (fr) * 2003-08-29 2005-03-10 Cipla Limited Processus
WO2005021541A3 (fr) * 2003-08-29 2005-05-06 Cipla Ltd Processus
GB2421504A (en) * 2003-08-29 2006-06-28 Cipla Ltd Process for the production of polymorphs of rosiglitazone maleate
GB2421504B (en) * 2003-08-29 2008-12-03 Cipla Ltd Process for the production of polymorphs of rosiglitazone maleate
WO2005065663A1 (fr) * 2003-12-31 2005-07-21 Alpharma, Inc. Preparations de rosiglitazone et de metformine
WO2005065654A2 (fr) * 2003-12-31 2005-07-21 Alpharma, Inc. Preparations de rosiglitazone
WO2005065654A3 (fr) * 2003-12-31 2006-09-28 Alpharma Inc Preparations de rosiglitazone
WO2006090150A1 (fr) * 2005-02-24 2006-08-31 Smithkline Beecham Corporation Composition pharmaceutique comprenant de la rosiglitazone amorphe
JP2008531534A (ja) * 2005-02-24 2008-08-14 スミスクライン・ビーチャム・コーポレイション 無定形のロシグリタゾンを含む医薬組成物
CZ298424B6 (cs) * 2005-05-24 2007-09-26 Zentiva, A. S. Zpusob krystalizace rosiglitazonu a jeho derivátuze smesných rozpouštedel

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