OA11306A - Composition comprising 5-Ä4-Ä2-(n-2-pyridyl) amino) ethoxyÜbenzylÜbenzylÜthiazolidine-2, 4-dione - Google Patents

Composition comprising 5-Ä4-Ä2-(n-2-pyridyl) amino) ethoxyÜbenzylÜbenzylÜthiazolidine-2, 4-dione Download PDF

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Publication number
OA11306A
OA11306A OA9900267A OA9900267A OA11306A OA 11306 A OA11306 A OA 11306A OA 9900267 A OA9900267 A OA 9900267A OA 9900267 A OA9900267 A OA 9900267A OA 11306 A OA11306 A OA 11306A
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compound
composition
pharmaceutically acceptable
acceptable form
composition according
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OA9900267A
Inventor
Jai Patel
Hamish Ross
Jeffrey Roger Granett
Robin Price
Paul Nigel Wray
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Smithkline Beecham Corp Smithk
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Priority claimed from GBGB9712851.6A external-priority patent/GB9712851D0/en
Application filed by Smithkline Beecham Corp Smithk filed Critical Smithkline Beecham Corp Smithk
Publication of OA11306A publication Critical patent/OA11306A/en

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    • 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
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • 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
    • A61P3/06—Antihyperlipidemics
    • 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

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

Abstract

A pharmaceutical composition comprising Compound (I), characterised in that the composition comprises 2 to 12 mg of Compound (I) in a pharmaceutically acceptable form and optionally a pharmaceutically acceptable carrier therefor, the use of such a composition in medicine, processes for the preparation of such a composition and intermediate composition useful in such a process.

Description

1 011306
COMPOSITION
This invention relates to a composition, in particular to a pharmaceutical composition, and to the use of such a composition in medicine, to processes forthe préparation of such a composition and to a composition useful in such aprocess.
European Patent Application, Publication Number 0,306,228 relates tocertain thiazolidinedione dérivatives disclosed as having hypoglycaemic andhypolipidaemic activity. One particular thiazolidinedione disclosed in EP0306228 is 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine- 2,4-dione (hereinafter 'Compound (I)'). International Patent Application,publication number-WO94/05659 discloses certain salts of Compound (I),including the maleate sait at Example 1 thereof.
It is now surprisingly indicated that a discrète and particular daily dosageof Compound (I) provides an especially bénéficiai effect on glycaemic control andis therefore particularly useful for treatment of diabètes mellitus, especially TypeII diabètes and conditions associated with diabètes mellitus.
We hâve also discovered a new and advantageous method for preparingpharmaceutical compositions, especially unit dosage compositions, containingCompound (I). The new method involves the préparation of a pre-administrationconcentrate of Compound (I) which thereafter is formulated into the required unitdose in an efficient and economical manner. The new process is particularlyadvantageous for the préparation of tablets of Compound (I).
Accordingly, in a first aspect the présent invention provides apharmaceutical composition, suitably in unit dosage form, comprising Compound(I), characterised in that the composition comprises 2 to 12 mg of Compound (I)in a pharmaceutically acceptable form and optionally a pharmaceuticallyacceptable carrier therefor.
Suitable pharmaceutically acceptable forms of Compound (I) includepharmaceutically acceptable salted forms and pharmaceutically acceptablesolvated forms, including pharmaceutically acceptable solvated forms ofpharmaceutically acceptable salts.
Suitable compositions comprise 2, 3, 4, 5, 6, 7, 8, 9, 10,11 or 12 mg ofCompound (I) in a pharmaceutically acceptable form. 2 011306
Particular compositions comprise 2 to 4mg of Compound (I) in apharmaceutically acceptable form.
Particular compositions comprise 4 to 8mg of Compound (I) in apharmaceutically acceptable form.
Particular compositions comprise 8 to 12 mg of Compound (I) in apharmaceutically acceptable form.
One composition comprises 2 mg of Compound (I) in a pharmaceuticallyacceptable form.
Preferred compositions comprise 4 mg of Compound (I) in apharmaceutically acceptable form.
Preferred compositions comprise 8 mg of Compound (I) in apharmaceutically acceptable form.
Suitable pharmaceutically acceptable salted forms of Compound (I)include those described in EP 0306228 and WO94/05659. A preferredpharmaceutically acceptable sait is a maleate.
Suitable pharmaceutically acceptable solvated forms of Compound (I)include those described in EP 0306228 and WO94/05659, in particular hydrates.
Compound (I) or a pharmaceutically acceptable sait thereof, or apharmaceutically acceptable solvaté thereof, may be prepared using knownmethods, for example those disclosed in EP 0306228 and WO94/05659. Thedisclosures of EP 0306228 and WO94/05659 are incorporated herein by reference.
Compound (I) may exist in one of several tautomeric forms, ail of whichare encompassed by the term ‘Compound (I)’ as individual tautomeric forms or asmixtures thereof.
Compound (I) contains a chiral carbon atom, and hence can exist in up totwo stereoisomeric forms, the term Compound (I) encompasses ail of theseisomeric forms whether as individual isomers or as mixtures of isomers, includingracemates.
When used herein the term 'conditions associated with diabètes' includesthose conditions associated with the pre-diabetic State, conditions associated withdiabètes mellitus itself and complications associated with diabètes mellitus.
When used herein the term 'conditions associated with the pre-diabetic state' includes conditions such as insulin résistance, including hereditary insulin résistance, impaired glucose tolérance and hyperinsulinaemia. 3 011306 'Conditions associated with diabètes mellitus itself includehyperglycaemia insulin résistance, including acquired insulin résistance andobesity. Further conditions associated with diabètes mellitus itself includehypertension, cardiovascular disease, especially atherosclerosis, certain eatingdisorders, in particular those requiring the régulation of appetite and food intake,such as disorders associated with under-eating, for example anorexia nervosa anddisorders associated with over-eating, for example obesity and anorexia bulimia.Additional conditions associated with diabètes mellitus itself include polycysticovarian syndrome and steroid induced insulin résistance and gestational diabètes. 'Complications associated with diabètes mellitus' includes rénal disease,especially rénal disease associated with Type II diabètes, including diabeticnephropathy, glomerulonephritis, glomerular sclerosis, nephrotic syndrome,hypertensive nephrosclerosis and end stage rénal disease.
As used herein the term 'pharmaceutically acceptable' embraces bothhuman and veterinary use: for example the term 'pharmaceutically acceptable'embraces a veterinarily acceptable compound.
As used herein the term concentrate with respect to Compound (I) in apharmaceutically acceptable form means a proportionate amount of Compound (I)in a pharmaceutically acceptable form greater than that présent in anadministerable composition.
For the avoidance of doubt, when reference is made herein to scalaramounts, including mg amounts and % weight amounts, of'Compound (I) in apharmaceutically acceptable form', the scalar amount referred to is made inrespect of Compound (I) per se\ For example 2 mg of Compound (I) in the formof the maleate sait is that amount of maleate sait which contains 2 mg ofCompound (I).
Diabètes mellitus is preferably Type II diabètes.
In a further aspect, the invention provides a process for preparing apharmaceutical composition comprising 2 to 12 mg of Compound (I) in apharmaceutically acceptable form, and a pharmaceutically acceptable carriertherefor, which process comprises admixing 2 to 12 mg of Compound (I) in apharmaceutically acceptable form and the pharmaceutically acceptable carrier andoptionally thereafter formulating the composition produced into an administerableform. 4 011306
As indicated above the invention also provides a further process forpreparing a pharmaceutical composition comprising Compound (I) in apharmaceutically acceptable form which is particularly suitable for preparing arange of unit dosage forms of Compound (I). Accordingly, the invention furtherprovides a process for preparing a pharmaceutical composition of Compound (I)in a pharmaceutically acceptable form and a pharmaceutically acceptable carrier,which process comprises: (i) preparing a first composition comprising Compound (I) in a pharmaceuticallyacceptable form and a first pharmaceutically acceptable carrier; (ii) admixing the first composition with a second pharmaceutically acceptablecarrier to provide the required composition of Compound (I) and optionallythereafter formulating the composition produced into an administerable form. A preferred administerable form of the pharmaceutical composition ofCompound (I) is a unit dose composition.
Unless otherwise specified, suitable unit doses comprise up to 12 mg, suchas 1 to 12 mg, of Compound (I) in a pharmaceutically acceptable form.
Other unit doses include those mentioned herein. A key component of the last above mentioned process is the firstcomposition. Accordingly, the présent invention also provides a composition foruse as a first composition in a process for preparing a unit dose of Compound (I)in a pharmaceutically acceptable form.
The invention also provides a composition comprising Compound (I) in apharmaceutically acceptable form and optionally a pharmaceutically acceptablecarrier, characterised in that the composition is a pharmaceutically acceptable,pre-administration composition. A suitable pharmaceutically acceptable, pre-administration composition isa concentrate, preferably a granular concentrate, of Compound (I) in apharmaceutically acceptable form. The granular concentrate is particularly welladapted to be diluted to provide a composition for administration, preferably atablet.
In a further aspect the invention provides a composition comprising
Compound (I) in a pharmaceutically acceptable form and a pharmaceutically acceptable carrier, characterised in that the composition is a concentrate of
Compound (I) in a pharmaceutically acceptable form, adapted to be diluted so as to provide a composition for administration. 5 011306
Suitably, the fîrst composition, pre-administration compositionor dilutable composition (hereinafter referred to for convenience as ‘the fîrstcomposition’) contains up to 50% by weight, for example an amount in the rangeof from 2 to 50% by weight, of Compound (I) in a pharmaceutically acceptableform.
Favourably, the fîrst composition contains an amount of Compound (I) ina pharmaceutically acceptable form in the range of from 5 to 20% by weight, inparticular 5%, 10% or 15% by weight, for example 10% by weight.
The processes of the invention can provide pharmaceutical compositionsof Compound (I) in any conventionally administerable form, including orally orparenterally adminsterable forms. They are particularly well adapted forpreparing orally administrable forms, especially tablet forms of Compound (I) in apharmaceutically acceptable form.
The fîrst pharmaceutically acceptable carrier can comprise anyconventional pharmaceutically acceptable carrier comprising conventionalpharmaceutically acceptable excipients, including those disclosed in the referencetexts mentioned below. However, as it is not essential that the fîrstpharmaceutically acceptable carrier is in an administerable form, then it need notcontain excipients solely associated with administration. For example the fîrstpharmaceutically acceptable carrier need not contain a lubricant.
The second pharmaceutically acceptable carrier includes any conventionalpharmaceutically acceptable carrier comprising any conventionalpharmaceutically acceptable excipient, including disintegrants, diluents andlubricants, including those disclosed in the reference texts mentioned below.
One particular fîrst composition comprises Compound (I) in apharmaceutically acceptable form, a disintegrant, a binder and a diluent. A suitable disintegrant is sodium starch glycollate. A suitable binder is a methyl cellulose binder, such as hydroxypropylmethylcellulose 2910.
Suitable diluents include cellulose, for example a microcrystallinecellulose, and lactose monohydrate. A suitable lubricant is magnésium stéarate.
We hâve found that a particularly advantageous fîrst composition contains
Compound (I) in a pharmaceutically acceptable form, sodium starch glycollate, hydroxypropyl methylcellulose 2910, microcrystalline cellulose and lactose 6 011306 monohydrate, especially when in a granular form. This granular form has beenfound to be particularly stable.
When the first composition contains about 10% by weight of Compound(I) in a pharmaceutically acceptable form, it is readily dilutable to give unit dosecompositions comprising in the range of between 2 to 12 mg , especially 2 to 8mg, 2 to 4mg, 4 to 8 mg and 8 to 12 mg of Compound (I) in a pharmaceuticallyacceptable form.
The préparation of the first composition is suitably carried using anyconventional method appropriate to the nature of the said first composition, forexample wet granulation methods provide the first composition in granular form.
Methods for formulating the compositions of the invention intoadministerable forms include conventional formulation methods as disclosed inthe reference texts cited herein, including tabletting methods.
The administerable compositions of the invention are preferably adaptedfor oral administration. However, they may also be adapted for other modes ofadministration, for example parentéral administration, sublingual or transdermaladministration.
The administerable compositions may be in the form of tablets, capsules,powders, granules, lozenges, suppositories, reconstitutable powders, or liquidpréparations, such as oral or stérile parentéral solutions or suspensions.
In order to obtain consistency of administration it is preferred that acomposition of the invention is in the form of a unit dose.
Unit dose présentation forms for oral administration may bç tablets andcapsules and may contain conventional excipients such as binding agents, forexample syrup, acacia, gelatin, sorbitol, tragacanth, or polyvinylpyrrolidone;fillers, for example lactose, sugar, maize-starch, calcium phosphate, sorbitol orglycine; tabletting lubricants, for example magnésium stéarate; disintegrants, forexample starch, polyvinylpyrrolidone, sodium starch glycollate ormicrocrystalline cellulose; or pharmaceutically acceptable wetting agents such assodium lauryl sulphate.
Unless otherwise prescribed, compositions of the invention arepreferably in unit dosage form in an amount appropriate for the relevant dailydosage, suitable unit dosages comprise 1, 2, 3, 4, 5, 6, 7, 8, 9,10, 11 or 12 mg ofCompound (I) in a pharmaceutically acceptable form.
The solid compositions for example the oral compositions may be prepared by conventional methods of blending, filling or tabletting. As required repeated blending operations may be used to distribute the active agent throughout those compositions employing large quantifies of fillers. Such operations are of course conventional in the art. The tablets may be coated according to methods 7 011306 well known in normal pharmaceutical practice, in particular with an aqueous filmcoating.
Liquid compositions, for example oral liquid compositions, may be inthe form of émulsions, syrups, or élixirs, or they may be in a dry product form tobe reconstituted with water or other suitable vehicle before use. Such liquidpréparations may contain conventional additives such as suspending agents, forexample sorbitol, syrup, methyl cellulose, gelatin, hydroxyethylcellulose,carboxymethylcellulose, aluminium stéarate gel, hydrogenated edible fats;emulsifying agents, for example lecithin, sorbitan monooleate, or acacia;non-aqueous vehicles (which may include edible oils), for example almond oil,fractionated coconut oil, oily esters such as esters of glycérine, propylene glycol,or ethyl alcohol; preservatives, for example methyl or propyl p-hydroxybenzoateor sorbic acid; and if desired conventional flavouring or colouring agents.
Parentéral compositions, including parentéral administrationcompositions for example unit dosage compositions, comprise the activecompound and a stérile vehicle, and, depending upon the concentration used, canbe either suspended or dissolved in the vehicle. In preparing solutions forparentéral administration the composition of the invention may be dissolved inwater for injection and filter sterilized before filling into a suitable vial orampoule and sealing. Advantageously, adjuvants such as a local anaesthetic, apreservative and buffering agents can be dissolved in the vehicle. To enhance thestability, the composition can be ffozen after filling into the vial and the waterremoved under vacuum. Parentéral suspensions are prepared in substantially thesame manner, except that the active compound is suspended in the vehicle insteadof being dissolved, and sterilization cannot be accomplished by filtration. Thecompound can be sterilized by exposure to ethylene oxide before suspending inthe stérile vehicle. Advantageously, a surfactant or wetting agent is included inthe composition to facilitate uniform distribution of the compound.
Unless otherwise specified the compositions of the invention may containfrom 0.1% to 99% by weight, preferably from 10-60% by weight, of the activematerial, depending upon the method of administration.
The composition may, if desired, be in the form of a pack accompaniedby written or printed instructions for use.
The compositions of the invention may be prepared and formulatedaccording to conventional methods, such as those disclosed in standard referencetexts, for example the British and US Pharmacopoeias, Remington'sPharmaceutical Sciences (Mack Publishing Co.), Martindale The ExtraPharmacopoeia (London, The Pharmaceutical Press) and Harry's Cosmeticology(Leonard Hill Books). 8 011306
The présent invention also provides a pharmaceutical compositioncomprising 2 to 12 mg of Compound (I) and a pharmaceutically acceptable carriertherefor, for use as an active therapeutic substance.
In particular, the présent invention provides a pharmaceuticalcomposition comprising 2 to 12 mg of Compound (I) in a pharmaceuticallyacceptable form, for use in the treatment of diabètes mellitus, especially Type IIdiabètes, and conditions associated with diabètes mellitus..
The composition of the invention may be administered from 1 to 6 timesa day, but most preferably 1 or 2 times per day.
Accordingly, in a further aspect the invention provides a method fortreatment of diabètes mellitus, especially Type II diabètes and conditionsassociated with diabètes mellitus, in a mammal such as a human, which methodcomprises administering per day 2 to 12 mg of Compound (I) in apharmaceutically acceptable form, to a mammal in need thereof.
Particularly, the method comprises the administration of 2 to 4,4 to 8 or8 to 12 mg of Compound (I) in a pharmaceutically acceptable form.
Particular dosages are 2mg/day, 4mg/day, including 2mg twice per day,and 8 mg/day, including 4mg twice per day.
Particularly, the method comprises the administration of 2 to 4mg ofCompound (I) in a pharmaceutically acceptable form.
Particularly, the method comprises the administration of 4 to 8mg ofCompound (I) in a pharmaceutically acceptable form.
Particularly, the method comprises the administration of 8 to 12 mg ofCompound (I) in a pharmaceutically acceptable form.
Preferably, the method comprises the administration of 2 mg ofCompound (I) in a pharmaceutically acceptable form.
Preferably, the method comprises the administration of 4 mg ofCompound (I) in a pharmaceutically acceptable form.
Preferably, the method comprises the administration of 8 mg ofCompound (I) in a pharmaceutically acceptable form. A range of 2 to 4mg includes a range of 2.1 to 4, 2.2 to 4, 2.3 to 4, 2.4to 4, 2.5 to 4,2.6 to 4, 2.7 to 4, 2.8 to 4,2.9 to 4 or 3 to 4mg. A range of 4 to 8mg includes a range of 4.1 to 8,4.2 to 8, 4.3 to 8, 4.4 to8, 4.5 to 8,4.6 to 8, 4.7 to 8,4.8 to 8,4.9 to 8, 5 to 8, 6 to 8 or 7 to 8mg. A range of 8 to 12 mg includes a range of 8.1 to 12, 8.2 to 12, 8.3 to 12, 8.4 to 12, 8.5 to 12, 8.6 to 12, 8.7 to 12, 8.8 to 12, 8.9 to 12, 9 to 12, 10 to 12 or 11 to 12mg.
No adverse toxicological effects hâve been established for the compositions or methods of the invention in the abovementioned dosage ranges. 9 011306
The following examples illustrate the invention but do not limit it in any way.
Example 1 : Concentrate Préparation
Approximately two thirds of the lactose monohydrate is passed through a suitablescreen and blended with the milled maleate sait of Compound (I).
Sodium starch glycollate, hydoxypropyl methylcellulose, microcrystallinecellulose and the remaining lactose are passed through a suitable screen and addedto the mixture. Blending is then continued. The resulting mixture is then wetgranulated with purified water. The wet granules are then screened, dried on afluid bed drier and the dried granules are passed through a further screen andfinally homogenised.
% COMPOSITION OF GRANULAR CONCENTRATE
Ingrédient Quantity (%) Milled Compound (I) as maleatesait 13.25 (puremaleate sait) Sodium Starch Glycollate 5.00 Hydoxypropyl Methylcellulose2910 5.00 Microcrystalline Cellulose 20.0 Lactose Monohydrate, regulargrade to 100 Purified water * * Removed during processing. 10 011306
Example 2: Formulation of the concentrate into tablets.
The granules from Example 1 are placed into a tumble blender. Approximatelytwo thirds of the lactose is screened and added to the blender. Themicrocrystalline cellulose, sodium starch glycollate, magnésium stéarate andremaining lactose are screened and added to the blender and the mixture blendedtogether. The resulting mix is then compressed on a rotary tablet press to a targetweight of 150mg for the 1,2 and 4mg tablets and to a target weight of 300mg forthe 8mg tablets.
The tablet cores are then transferred to a tablet coating machine, pre-warmed with warm air (approximately 65°C) and film coated until the tabletweight has increased by 2.0% to 3.5%.
Quantity (mg per Tablet)
Tablet Strength l.Omg 2.0mg 4.0mg 8.0mg Active Ingrédient: Compound (I) maleate Concentrate granules 10.00 20.00 40.00 80.00 Other Ingrédients: Sodium Starch Glycollate 6.96 6.46 5.46 10.92 Microcrystalline Cellulose 27.85 25.85 21.85 43.70 Lactose monohydrate 104.44 96.94 81.94 163.88 Magnésium Stéarate 0.75 0.75 0.75 1.50 Total Weight of Tablet Core 150.0 150.0 150.0 300.0 Aqueous film coating material 4.5 4.5 4.5 9.0 Total Weight of Film Coated Tablet 154.5 154.5 154.5 309.0

Claims (21)

11 011306 Claims:
1. A pharmaceutical composition comprising 5-[4-[2-(N-methyl-N-(2-pyridyl)amino)ethoxy]benzyl]thiazolidine-2,4-dione (hereinafter 'Compound (I)’),characterised in that the composition comprises 2 to 12 mg of Compound (I) in apharmaceutically acceptable form and optionally a pharmaceutically acceptablecarrier therefor.
2. A composition according to claim 1, which comprises 2 to 4mg ofCompound (I) in a pharmaceutically acceptable form.
3. A composition according to claim 1, which comprises 4 to 8mg ofCompound (I) in a pharmaceutically acceptable form.
4. A composition according to claim 1, which comprises 8 to 12 mg ofCompound (I) in a pharmaceutically acceptable form.
5. A composition according to claim 1, which comprises 2 mg ofCompound (I) in a pharmaceutically acceptable form'
6. A composition according to claim 1, which comprises 4 mg ofCompound (I) in a pharmaceutically acceptable form.
7. A composition according to claim 1, which comprises 8 mg ofCompound (I) in a pharmaceutically acceptable form.
8. A composition according to any one of claims 1 to 7, which comprises themaleate sait of Compound (I)
9. A process for preparing a pharmaceutical composition comprising 2 to 12mg of Compound (I) in a pharmaceutically acceptable form, and apharmaceutically acceptable carrier therefor, which process comprises admixing 2to 12 mg of Compound (I) in a pharmaceutically acceptable form and thepharmaceutically acceptable carrier. 12 011306
10. A process for preparing a pharmaceutical composition of Compound (I) ina pharmaceutically acceptable form and a pharmaceutically acceptable carrier,which process comprises: (i) preparing a first composition comprising Compound (I) in a pharmaceuticallyacceptable form and a first pharmaceutically acceptable carrier; (ii) admixing the first composition with a second pharmaceutically acceptablecarrier to provide the required composition of Compound (I) and optionallythereafter formulating the composition produced into an administerable form.
11. A process according to claim 9 or claim 10, wherein the compositionprepared is in unit dosage form.
12. A process according to claim 9 or claim 10, wherein the compositionprepared is a tablet.
13. A composition for use as a first composition in a process according toclaim 10, for preparing a unit dose of Compound (I) in a pharmaceuticallyacceptable form.
14. A composition comprising Compound (I) in a pharmaceutically acceptableform and optionally a pharmaceutically acceptable carrier, characterised in thatthe composition is a pharmaceutically acceptable, pre-administration composition.
15. A pre-administration composition according to claim 13, which is aconcentrate of Compound (I) in a pharmaceutically acceptable form.
16. A composition comprising Compound (I) in a pharmaceutically acceptableform and a pharmaceutically acceptable carrier, characterised in that thecomposition is a concentrate of Compound (I) in a pharmaceutically acceptableform, adapted to be diluted so as to provide a composition for administration.
17. A composition according to any one of daims 13 to 16, which contains upto 50% by weight of Compound (I) in a pharmaceutically acceptable form. 13 011306
18. A composition according to any one of daims 13 to 17, which contains anamount of Compound (I) in a pharmaceutically acceptable form in the range offrom 5 to 20% by weight.
19. A composition according to any one of daims 13 to 18, which contains 5%, 10% or 15% by weight of Compound (I) in a pharmaceutically acceptable form.
20. A composition according to any one of daims 13 to 19, which contains Compound (I) in a pharmaceutically acceptable form, sodium starch glycollate, hydroxypropyl methylcellulose 2910, microcrystalline cellulose and lactose monohydrate.
21. A composition according to any one of daims 13 to 20, in granular form.
OA9900267A 1997-06-05 1999-12-02 Composition comprising 5-Ä4-Ä2-(n-2-pyridyl) amino) ethoxyÜbenzylÜbenzylÜthiazolidine-2, 4-dione OA11306A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB9711683.4A GB9711683D0 (en) 1997-06-05 1997-06-05 Composition
GBGB9712851.6A GB9712851D0 (en) 1997-06-18 1997-06-18 Composition

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OA11306A true OA11306A (en) 2003-10-22

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US7045519B2 (en) 1998-06-19 2006-05-16 Chiron Corporation Inhibitors of glycogen synthase kinase 3
UA67844C2 (en) * 1999-04-23 2004-07-15 Смітклайн Бічам Плс A polymorph of 5-[4-[2-(n-methyl-n-(2-pyridyl)amino)ethoxy]benzyl] thiazolidine-2,4-dione of maleic acid salt
US20040248945A1 (en) 1999-04-23 2004-12-09 Smithkline Beecham P.L.C. Thiazolidinedione derivative and its use as antidiabetic
DE60004658T2 (en) 1999-04-23 2004-06-24 Smithkline Beecham Plc, Brentford THIAZOLIDINDEDE DERIVATIVE AND ITS USE AS ANTIDIBLE
GB0021978D0 (en) 2000-09-07 2000-10-25 Smithkline Beecham Plc Novel pharmaceutical
GB0127805D0 (en) * 2001-11-20 2002-01-09 Smithkline Beecham Plc Pharmaceutical composition
GB0129876D0 (en) * 2001-12-13 2002-02-06 Smithkline Beecham Plc Novel pharmaceutical
GB0129871D0 (en) * 2001-12-13 2002-02-06 Smithkline Beecham Plc Novel pharmaceutical
WO2003050112A1 (en) * 2001-12-13 2003-06-19 Smithkline Beecham Plc Toluenesulfonate hydrates of a thiazolidinedione derivative
GB0130509D0 (en) * 2001-12-20 2002-02-06 Smithkline Beecham Plc Novel pharmaceutical
DE06252444T8 (en) * 2006-05-09 2009-03-19 Teva Pharmaceutical Industries Ltd. 2-N- {5 - [[4- [2- (Methyl-2-pyridinylamino) -ethoxy] -phenyl] -methyl] -2,4-thiazolidinedione-succinic acid, method of preparation and compositions with rosiglitazone maleate
US7435741B2 (en) 2006-05-09 2008-10-14 Teva Pharmaceutical Industries, Ltd. 2-N{5-[[4-[2-(methyl-2-pyridinylamino) ethoxy] phenyl]methyl]-2,4-thiazolidinedione} butanedioic acid, methods of preparation and compositions with rosiglitazone maleate
WO2015008234A1 (en) * 2013-07-17 2015-01-22 Glenmark Pharmaceuticals S.A. Bicyclic heterocyclic compounds as ror gamma modulators

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SG59988A1 (en) * 1987-09-04 1999-02-22 Beecham Group Plc Substituted thiazolidinedione derivatives
GB9218830D0 (en) * 1992-09-05 1992-10-21 Smithkline Beecham Plc Novel compounds
MX9603338A (en) * 1994-02-10 1997-03-29 Smithkline Beecham Plc Use of insulin sensitisers for treating renal diseases.
JPH11510508A (en) * 1995-08-10 1999-09-14 ワーナー−ランバート・コンパニー Methods for reducing the amount of exogenous insulin administered to non-insulin dependent diabetes mellitus patients
WO1997018811A1 (en) * 1995-11-17 1997-05-29 Warner-Lambert Company A method of treating myotonic dystrophy
NZ314406A (en) * 1996-03-18 2000-12-22 Sankyo Co Treatment or prophylaxis of pancreatitis with a medicament containing an insulin sensitiser including oxazoles and thiazoles
EP0921798A1 (en) * 1996-07-12 1999-06-16 Smithkline Beecham Plc Novel treatment of leptine resistance

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