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WO2003005995A1 - Preparation de noyau comprenant un hydrochlorure de pioglitazone et un biguanide - Google Patents

Preparation de noyau comprenant un hydrochlorure de pioglitazone et un biguanide Download PDF

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Publication number
WO2003005995A1
WO2003005995A1 PCT/US2001/021615 US0121615W WO03005995A1 WO 2003005995 A1 WO2003005995 A1 WO 2003005995A1 US 0121615 W US0121615 W US 0121615W WO 03005995 A1 WO03005995 A1 WO 03005995A1
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WO
WIPO (PCT)
Prior art keywords
formulation
glucopyranosyl
patient
metformin
core
Prior art date
Application number
PCT/US2001/021615
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English (en)
Inventor
Akwete L. Adjei
Yaping Zhu
Anthony J. Cutie
Original Assignee
Aeropharm Technology Incorporated
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 Aeropharm Technology Incorporated filed Critical Aeropharm Technology Incorporated
Priority to MXPA04000180A priority Critical patent/MXPA04000180A/es
Priority to PCT/US2001/021615 priority patent/WO2003005995A1/fr
Priority to AU2001273289A priority patent/AU2001273289B2/en
Priority to CA002453775A priority patent/CA2453775A1/fr
Priority to JP2003511802A priority patent/JP2004536843A/ja
Priority to EP01952548A priority patent/EP1429747A4/fr
Publication of WO2003005995A1 publication Critical patent/WO2003005995A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/155—Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
    • 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
    • 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
    • A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
    • A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
    • A61K9/167—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction with an outer layer or coating comprising drug; with chemically bound drugs or non-active substances on their surface
    • 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
    • A61K9/501—Inorganic compounds
    • 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
    • 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

  • This invention relates to a core formulation, and, more particularly, to a core formulation comprising a first layer comprising pioglitazone, which covers at least a portion of a core comprising a biguanide, metformin (i.e., glucophage), with a modulating release polymer comprising a silicate.
  • a core formulation comprising a first layer comprising pioglitazone, which covers at least a portion of a core comprising a biguanide, metformin (i.e., glucophage), with a modulating release polymer comprising a silicate.
  • Metformin and pioglitazone are two active ingredients of anti-diabetic drugs that are used to treat diabetic patients, e.g. human beings. These two active agents are administered orally to patients in need thereof in protocols calling for the single administration of either ingredient.
  • a core formulation is advantageous to patients and prescribers because both medicaments are synergistic to each other in the body when used in the management of blood glucose control, i.e., diabetes.
  • a modulating agent like silica gel, in the preparation, controls the rate of drug release over a clinically meaningful period to enable better control of the effect of the medicinal agents in such preparation.
  • This invention relates to a core formulation, and, more particularly, to a core formulation comprising a first layer comprising pioglitazone hydrochloride, which covers at least a portion of a core comprising a biguanide, e.g. metformin, one or both of which are intimately dispersed in a silicate based modulating agent.
  • a biguanide e.g. metformin
  • a typical biguanide is metformin. It typically is used clinically as a pharmaceutically acceptable salt, preferably the hydrochloride salt.
  • a commercial form of metformin hydrochloride is available as glucophage.
  • Metformin hydrochloride is a hydrochloride salt of metformin base, and as used herein, "metformin” means the base compound as well as its pharmaceutically acceptable salts.
  • Metformin is used clinically to manage non-insulin dependent diabetes mellitus or "NIDDM", particularly in patients who are not effectively treated with a sulfonylurea. While it is not chemically related to the sulfonylureas, it is routinely utilized in combination with a sulfonylurea, and has been shown to be synergistic in some cases. Other biguanides such as phenformin, buformin etc. can also be used. Additionally, in the treatment of a diabetic patient the metformin, for example, and the pioglitazone hydrochloride are present in effective amounts to provide such treatment.
  • Metformin is an active ingredient for a commercially available drug employed to treat diabetes mellitus in a host or mammal, e.g. a human being, another animal.
  • the typical daily effective dose for the oral treatment of a mammal, i.e., a human ranges from about 500 mg to about 2550 mg.
  • the dose is a single dose of about 500 mg to about 850 mg.
  • Pioglitazone hydrochloride (ACTOS®), is an active ingredient for a commercially available drug employed to treat diabetes mellitus in a host, e.g. a human being.
  • the typical daily effective dose for the oral administration to a mammal, e.g. a human being ranges from aboutl5 mg to about 45 mg, given as a , single dose.
  • Silicates are pharmaceutical excipients generally regarded as safe and used therefore to prepare a variety of pharmaceutical systems well documented in the patent literature. In this regard, reference is made to Remington's Pharmaceutical Sciences, 18 t l Edition, Inorganic Pharmaceutical Chemistry, Silicon, pp 340-341, 1990.
  • the silicates have not been shown to modulate the release of the hypoglycemic drugs metformin and pioglitazone hydrochloride when administered together to try to improve the control and effectiveness of either drug, although co-administration of the two has been proposed [Whitcomb; et al., United States Patent No. 6,011,049].
  • a combined form of the drugs i.e. a single integral unit thereof has not heretofore been reported.
  • the present invention provides such a single integral unit in the form of a core formulation.
  • a typical silicate for this purpose is Purified Siliceous Earth (National Formulary XVI), also known in some forms as silica gel or fumed silica. It is typically used in oral pharmaceutical preparations as a bulking agent.
  • silicate means silicic acid, disilicic acid, tricisilic acid, metasilicic acid, and orthosilicic acid in their free or salt forms; silicon dioxide in either of its amporphous, crystalline, or precipitated forms; diatomacous earth; Fuller's earth, Kieselhurh, Celite; talc; attapulgite; micas; clays such as montmorilonite (MontmoriloniteTM), kaolin, aluminum oxide (Hydrargilite), bentone (BentoniteTM), bentonite (Bentonite MagmaTM) and pumice; silanes and siloxanes. These are used typically as adsorbents, carriers, dispersants, fillers, thickeners.
  • the relative concentrations of each drug is such that a first layer comprising pioglitazone hydrochloride is prepared.
  • the first layer covers at least a portion of a core comprising metformin with a portion or all of the amount of the silicate.
  • the first layer may cover only a portion of the core or encompass the entire core. For example, one quarter of the core to about three fourths of the tablet core.
  • the first layer should comprise pioglitazone hydrochloride with or without any silicate, because its dose requirement is lower compared to metformin.
  • pioglitazone hydrochloride is slightly non-polar, its solubility rate is slower, and its absorption rate thus is dependent on its dissolution rate in the contents of the gastrointestinal tract compared with metformin.
  • either the first layer or the core may additionally contain a mixture of the two active ingredients or both the first layer and the core may contain the two active ingredients with different and varying concentrations of one or both active ingredients.
  • the first layer of the core comprises pioglitazone hydrochloride in an amount of about 0.01 % to about 20% of the total weight of the core formulation, whereas, the metformin in the core is present in an amount of about 10% to about 97.5% of the total weight of the core formulation.
  • the amounts of pioglitazone hydrochloride range from about 1 mg to about 45 mg whereas the metformin ranges from about 100 mg to about 2550 mg.
  • a drug such as for example a sulfonylurea,an ⁇ -glucosidase inhibitor , a meglitinide, and an ACE inhibitor may be employed in an admixture with the active ingredients in the first layer and/or the core.
  • alpha.-glucosidase inhibitors [Jean-Bernard Ducep et al., US Patent No. 5,504,078], bisglucosylmoranoline derivatives [UK Patent No. GB 2 088 365 A], and glucosylmoranoline derivatives [European Patent No.
  • 87112480.6 include the following medicaments: 1.5-Dideoxy-4-O(.alpha.,D-glucopyranosyl)- l,5-[6,7-dideoxy-7-D-glucoheptopyranosyl)imino]-D-glucitol; 1.5-Dideoxy-4- O(.alpha.,D-glucopyranosyl)-l,5-[(l-deoxy-D-fructofuranosyl)imino]-D-glucitol; 1.5-Dideoxy-4-O(.alpha.,D-glucopyranosyl)-l,5-[(4-deoxy-4-D- glucopyranosyl)imino]-D-glucitol; 1.5-Dideoxy-4-O(.alpha.,D-glucopyranosyl)-N- [6-deoxy-l-(6-O-D-glucopyranosyl)-.alpha.-D-glucopy
  • the list of medicaments includes acid addition salt forms with such inorganic acids, such as, for example, hydrochloric, hydrobromic, sulfuric, phosphoric and like acids; with organic carboxylic acids such as, for example, acetic, propionic, glycolic, lactic, pyruvic, malonic, succinic, fumaric, maleic, tartaric, citric, ascorbic, maleic, hydroxymaleic, dihydroxymaleic, benzoic, 2- acetoxybenzoic, mandelic and like acids; and with organic sulfonic acids such as methanesulfonic acid and p-toluenesulfonic acid.
  • the sulfonylureas are a class of compounds that have been widely employed to treat diabetes.
  • sulfonylureas to be employed in the combinations or core formulations of this invention are glyburide, gliquidone, glipizide, tolbutamide, tolazamide, glisoxepid, chlorpropamide, glibornuride, gliclazide, glimepiride, phenbutamide, and tolcyclamide.
  • Other medicaments such as, for example, an antibiotic, a vitamin, a drug that works on the heart or in the liver, may be admixed with the active ingredients in the first layer and/or the core.
  • the modylating silicate polymer e.g. silica gel
  • the modylating silicate polymer e.g. silica gel
  • the type of association as well as the concentration of the modulating agent is dependent upon the concentrations of the core active ingredient, and the layer active ingredient, the degree of coverage of the core by the first layer and the desired rate of administration of every active ingredient.
  • the resultant core having the first layer thereon is prepared by any conventional means known in the pharmaceutical art, e.g. compression, tabletting technology, spraying technology, or encapsulation in a pharmaceutically acceptable presentation, such as a gelatin capsule.
  • the core formulation of the present invention is preferably fabricated by compression into a tablet.
  • the resultant core formulation of the present invention is useful to treat diabetes mellitus.
  • the resultant core formulation of the invention is as user friendly and clinically effective as compared to the administration of metformin alone or pioglitazone hydrochloride alone as demonstrated by co- administration of the two agents [Wltitcomb; et al., United States Patent No. 6,011,049], where in general, the incidence of adverse events was not influenced by age or menopausal status; and further, patients treated with the combination therapy attained better glycemic control than with either monotherapy.
  • the core formulation of the present invention may be administered orally, for example, with inert diluent or with an edible carrier.
  • the core formulation may have other excipients incorporated therein.
  • the subject core formulation may also contain the following adjuvants: a binder such as microcrystalline cellulose, gum tragacanth or gelatin; an excipient such as starch or lactose, a disintegrating agent such as alginic acid, Primogel®, corn starch and the like; a lubricant such as magnesium stearate or
  • Sterotex a glidant such as colloidal silicon dioxide; and a sweetening agent such as sucrose or saccharin may be added or a flavoring agent such as peppermint, methyl salicylate or orange flavoring.
  • a glidant such as colloidal silicon dioxide
  • a sweetening agent such as sucrose or saccharin
  • a flavoring agent such as peppermint, methyl salicylate or orange flavoring.
  • the subject core formulation of the invention may contain other various materials which modify the physical form of the dosage unit (the subject core formulation), for example, as coatings.
  • the subject core formulation of the present invention may be coated with sugar, shellac or other enteric coating agents. Materials used in preparing these various compositions should be pharmaceutically pure and non-toxic in the amounts used.
  • the resultant core formulation (having a first layer completely or partially covering the core), is treated whereby an outer shell is formed, at least a portion of which comprises the biodegradable modulating silicate material is presemt in an amount having a predetermined rate of degradation or metabolism in the host being present treated.
  • the silicate material is a high molecular weight compound, which is physiologically acceptable and excreted from the body of the human being or other animal almost intact.
  • the biodegradable silicate material comprising the outer shell, having a predetermined rate of degradation or metabolism or break down, is selected from silic acid and its derivatives, examples of which include those listed previously.
  • Other materials well known in the art, which do not react with metformin and/or pioglitazone hydrochloride such as biodegradable polymers, like polyorthoesters, polyanhydrides, polyamides based on glutamic acid, polyalkyl cyanoacrylates, polyesters of lactic and glycolic acid, polyactide polymers, cellulosic polymers, polyvinyl acetate, polyvinyl alcohol, polyvinylchloride, natural and synthetic rubbers, polyacrylates, polystyrene, etc. may be used.
  • U.S. Patents Nos. 4,166,800, and 4,389,330 which disclose additional shell forming materials and are incorporated hereinto by reference in their entirety.
  • the shell encapsulating the particles of pioglitazone hydrochloride of the first layer and/or the particles of metformin of the core is obtained by any conventional microencapsulation process whereby microspheres of metformin and/or pioglitazone hydrochloride are formed, e.g. a solvent removal process, a phase separation technique, coacervation etc.
  • a solvent removal process e.g. a solvent removal process, a phase separation technique, coacervation etc.
  • the resultant core formulation is treated whereby only the top surface area of the first layer comprising pioglitazone hydrochloride has a shell coating thereon.
  • U.S. Patent No. 5,916,584, incorporated hereinto by reference in its entirety which describes the process for forming such a shell.
  • the resulting core formulation having the first layer encapsulated by the shell comprising the shell material is one which provides a delay time prior to release of the active ingredients, i.e. pioglitazone hydrochloride and metformin, to the patient being treated for diabetes mellitus.
  • the resultant core formulation (having a first layer completely or partially covering the core) is treated whereby an outer shell comprising a natural polysaccaride, in its free acid a or salt form such as guar gum; gum arabic; gum karaya; gum Benjamin, plantago ovata gum; agar; carrageenan; cellulose; gelatin; pectin; or galacturonic acid is formed which encloses the particles of the first layer and/or the core.
  • Silicates are naturally occurring polymers consisting of silicon chains. These polymers have the propensity to absorb water thus swelling to become gel-like structures in solution. The gel dissolves slowly thus releasing its drug payloads in a dissolution controlled manner.
  • the silicate shell provides excellent stability to the core formulation while at the same time modulates drug release.
  • the silicate shell swells to become a gel-like structure in solution in the body of the patient, e.g. the stomach.
  • the gel ultimately dissolves slowly, e.g. typically, in several minutes to a few hours, usually within a day, releasing its drug payload, e.g. metformin and/or pioglitazone hydrochloride in a dissolution controlled manner.
  • the shell is formed using any conventional coating technique, as previously discussed, see U.S. Patents Nos. 4,166,800 and 4,839,177.
  • the rate of release is dependent on the shell's thickness and amount of the polymeric material contained therein for a particular medicament formulation. Typically, for a release of of about 2 to 6 hours, the thickness ranges from about 0.0001 mm to about 1 mm with a concentration of the polymeric material ranging from about 10 ppm to about 100,000 ppm.
  • the polysaccharide polymeric material e.g. silicate
  • the first layer comprising metformin and/or the core of pioglitazone in an effective amount to provide the desired stability and controlled release of these medicaments.
  • the silicate is provided in an amount ranging from about 10 ppm to about 100,000 ppm,in one both or of the medicaments to effect a desired release profile e.g. 15 minutes to about 12 hours of one or both of the medicaments of the core.
  • the resultant core formulation may be treated with the polymeric material whereby only the top surface area of the first layer comprising poglitazone hydrochloride has a coating hereon.
  • U.S. Patent No. 5,916,584. Thus as described above a delay time is provided prior to release of the release of the medicaments.
  • any pharmaceutically acceptable form thereof can be employed. Such a form encompasses the free acids, free bases, salts and various hydrate forms, including semi-hydrate forms of these medicaments, as well as other pharmaceutical materials which are used in the formulation process as acceptable excipient materials generally known to those skilled in the art.
  • any one of the biguanides i.e. drugs having the action of the stimulation of anaerobic glycolysis
  • these, like metformin increase the sensitivity to insulin in peripheral tissues of the host, e.g. a human being or another animal.
  • These compounds also are involved in the inhibition of glucose absorption from the intestine, suppression of hepatic gluconeogenesis, and inhibition of fatty acid oxidation.
  • Examples of other typical biguanides included in this application are phenformin, buformin etc.

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  • Health & Medical Sciences (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Endocrinology (AREA)
  • Emergency Medicine (AREA)
  • Inorganic Chemistry (AREA)
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  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
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Abstract

La présente invention concerne une préparation modulante comprenant un hydrochlorure de pioglitazone et un biguanide, par exemple de la metformine, au moins une partie de celle-ci étant recouverte d'une couche de pioglitazone
PCT/US2001/021615 2001-07-10 2001-07-10 Preparation de noyau comprenant un hydrochlorure de pioglitazone et un biguanide WO2003005995A1 (fr)

Priority Applications (6)

Application Number Priority Date Filing Date Title
MXPA04000180A MXPA04000180A (es) 2001-07-10 2001-07-10 Formulacion de nucleo que comprende hidrocloruro de pioglitazona y una biguanida.
PCT/US2001/021615 WO2003005995A1 (fr) 2001-07-10 2001-07-10 Preparation de noyau comprenant un hydrochlorure de pioglitazone et un biguanide
AU2001273289A AU2001273289B2 (en) 2001-07-10 2001-07-10 Core formulation comprising pioglitazone hydrochloride and a biguanide
CA002453775A CA2453775A1 (fr) 2001-07-10 2001-07-10 Preparation de noyau comprenant un hydrochlorure de pioglitazone et un biguanide
JP2003511802A JP2004536843A (ja) 2001-07-10 2001-07-10 ピオグリタゾンおよびビグアナイドを含むコア製剤
EP01952548A EP1429747A4 (fr) 2001-07-10 2001-07-10 Preparation de noyau comprenant un hydrochlorure de pioglitazone et un biguanide

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/US2001/021615 WO2003005995A1 (fr) 2001-07-10 2001-07-10 Preparation de noyau comprenant un hydrochlorure de pioglitazone et un biguanide

Publications (1)

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WO2003005995A1 true WO2003005995A1 (fr) 2003-01-23

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EP (1) EP1429747A4 (fr)
JP (1) JP2004536843A (fr)
AU (1) AU2001273289B2 (fr)
CA (1) CA2453775A1 (fr)
MX (1) MXPA04000180A (fr)
WO (1) WO2003005995A1 (fr)

Cited By (8)

* Cited by examiner, † Cited by third party
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WO2004006921A1 (fr) * 2002-07-11 2004-01-22 Takeda Pharmaceutical Company Limited Procede de production d'une preparation recouverte
EP1429732A4 (fr) * 2001-07-10 2005-01-26 Kos Life Sciences Inc Formulation de noyau
WO2005013942A1 (fr) * 2003-07-19 2005-02-17 Warren Ward Compositions comprenant des composants enrobes d'une couche permeable aux gaz mais impermeables aux liquides, leur utilisation pour le traitement d'affections de la peau et de la glande exocrine
WO2005021542A3 (fr) * 2003-08-28 2005-05-19 Ranbaxy Lab Ltd Procede pour la preparation de pioglitazone
WO2007073136A1 (fr) * 2005-12-20 2007-06-28 World-Trade Import-Export, Wtie, Ag. Compositions pharmaceutiques comprenant des substances derivees de la thiazolidinedione combinees au biguanide utilisees contre le diabete sucre de type 2
EA011854B1 (ru) * 2003-07-19 2009-06-30 Варрен Уорд Применение хлорида натрия, препарат на его основе, устройство для удерживания препарата и способ изготовления лекарства
US7976853B2 (en) 2003-01-29 2011-07-12 Takeda Pharmaceutical Company Limited Process for producing coated preparation
EP1838273A4 (fr) * 2005-01-10 2013-02-20 Elc Man Llc Revetement de surface discontinue pour particules

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US6358531B1 (en) * 1999-02-01 2002-03-19 The Curators Of The University Of Missouri Method for preparing porous shells or gels from glass particles
US6451342B2 (en) * 2000-05-01 2002-09-17 Aeropharm Technology Incorporated Core formulation comprised of troglitazone and a biguanide
US6780432B1 (en) * 2000-05-01 2004-08-24 Aeropharm Technology, Inc. Core formulation
WO2003005991A1 (fr) * 2001-07-10 2003-01-23 Aeropharm Technology Incorporated Formulation de noyau

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Non-Patent Citations (1)

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Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1429732A4 (fr) * 2001-07-10 2005-01-26 Kos Life Sciences Inc Formulation de noyau
WO2004006921A1 (fr) * 2002-07-11 2004-01-22 Takeda Pharmaceutical Company Limited Procede de production d'une preparation recouverte
US7976853B2 (en) 2003-01-29 2011-07-12 Takeda Pharmaceutical Company Limited Process for producing coated preparation
WO2005013942A1 (fr) * 2003-07-19 2005-02-17 Warren Ward Compositions comprenant des composants enrobes d'une couche permeable aux gaz mais impermeables aux liquides, leur utilisation pour le traitement d'affections de la peau et de la glande exocrine
EA011854B1 (ru) * 2003-07-19 2009-06-30 Варрен Уорд Применение хлорида натрия, препарат на его основе, устройство для удерживания препарата и способ изготовления лекарства
AU2004262969B2 (en) * 2003-07-19 2010-08-12 Warren Ward Compositions comprising components coated with a liquid impermeable but gas permeable layer, use thereof for treating cutaneous and other exocrine gland diseases
KR101231542B1 (ko) 2003-07-19 2013-02-07 워렌 워드 액체 불침투성이지만 기체 침투성인 층으로 코팅된성분들을 포함하는 조성물들과, 피부 질환들과 다른외분비선 질환들을 치료하기 위한 그들의 사용
CN102973946A (zh) * 2003-07-19 2013-03-20 瓦伦·沃德 包含由液体不可透过但气体可透过层包被的组分的组合物及其用于医学治疗的用途
CN102973946B (zh) * 2003-07-19 2015-03-18 瓦伦·沃德 包含由液体不可透过但气体可透过层包被的组分的组合物
WO2005021542A3 (fr) * 2003-08-28 2005-05-19 Ranbaxy Lab Ltd Procede pour la preparation de pioglitazone
EP1838273A4 (fr) * 2005-01-10 2013-02-20 Elc Man Llc Revetement de surface discontinue pour particules
WO2007073136A1 (fr) * 2005-12-20 2007-06-28 World-Trade Import-Export, Wtie, Ag. Compositions pharmaceutiques comprenant des substances derivees de la thiazolidinedione combinees au biguanide utilisees contre le diabete sucre de type 2

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AU2001273289B2 (en) 2004-10-07
EP1429747A4 (fr) 2005-01-05
EP1429747A1 (fr) 2004-06-23
JP2004536843A (ja) 2004-12-09
CA2453775A1 (fr) 2003-01-23
MXPA04000180A (es) 2004-11-22

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