WO2021096444A1 - Compositions pharmaceutiques comprenant du ticagrelor - Google Patents

Compositions pharmaceutiques comprenant du ticagrelor Download PDF

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Publication number
WO2021096444A1
WO2021096444A1 PCT/TR2019/050944 TR2019050944W WO2021096444A1 WO 2021096444 A1 WO2021096444 A1 WO 2021096444A1 TR 2019050944 W TR2019050944 W TR 2019050944W WO 2021096444 A1 WO2021096444 A1 WO 2021096444A1
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WO
WIPO (PCT)
Prior art keywords
ticagrelor
pharmaceutical composition
composition according
croscarmellose sodium
hydroxypropyl cellulose
Prior art date
Application number
PCT/TR2019/050944
Other languages
English (en)
Inventor
Ersin Yildirim
Bayram Kanik
Fatma ÖZTÜRK
Tansel AKTAŞ
Filiz ÖZYÜREK
Original Assignee
Santa Farma İlaç Sanayi̇ A.Ş.
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 Santa Farma İlaç Sanayi̇ A.Ş. filed Critical Santa Farma İlaç Sanayi̇ A.Ş.
Priority to EP19952515.5A priority Critical patent/EP4058025A4/fr
Priority to PCT/TR2019/050944 priority patent/WO2021096444A1/fr
Publication of WO2021096444A1 publication Critical patent/WO2021096444A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2009—Inorganic compounds
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose

Definitions

  • the present invention relates to a pharmaceutical composition, comprising ticagrelor, wherein the pharmaceutical composition is in a solid dosage form having proper correlation between in vitro dissolution release profile and in vivo release profile.
  • Ticagrelor is a platelet aggregation inhibitor that acts by inhibition of adenosine 5- diphosphate.
  • Ticagrelor is a reversible, selective P2Y 12-receptor antagonist. Its chemical name is (lS,2S,3R,5S)-3-(7- ⁇ [(lR,2S)-2-(3,4-Diflourophenyl)cyclopropyl]amino ⁇ -5- (propylsulfanyl)-3H-[l,2,3]triazol[4,5-d]pyrimidine-3-yl)-5-(2-hydroxyethoxy)cyclopentane- 1,2-diol and its chemical structure is given below. Its CAS Number is 274693-27-5.
  • Ticagrelor has a low and pH-independent solubility in aqueous media as well as a low permeability.
  • Ticagrelor may exist in various crystalline forms, including solvated forms.
  • Ticagrelor presents polymorphic characteristic. In addition to various crystalline forms, amorphous form is also available.
  • Ticagrelor is a reversible, selective P2Y 12-receptor antagonist (antiplatelet agent) being developed to reduce thromboembolic events in patients with atherosclerosis. It is orally active and does not require metabolic activation.
  • Ticagrelor co administered with acetylsalicylic acid (ASA)
  • ASA acetylsalicylic acid
  • thrombotic events cardiac death, myocardial infarction and stroke
  • Acute Coronary Syndromes unstable angina, non ST elevation Myocardial Infarction [NSTEMI] or ST elevation Myocardial Infarction [STEMI]
  • PCI percutaneous coronary intervention
  • CABG coronary artery by pass grafting
  • the dosing regimen is an initial single 180 mg loading dose (two tablets of 90 mg) and then continued at 90 mg twice daily. Treatment is recommended for at least 12 months unless discontinuation of ticagrelor is clinically indicated.
  • Ticagrelor is a cyclo-pentyltriazolo-pyrimidine that reversibly inhibits the P2Y12 receptor which is a protein found mainly but not exclusively on the surface of blood platelets and which is an important regulator in blood clotting.
  • Ticagrelor has 6 stereocenters and due to that there are many crystalline and also amorphous forms. Especially, four non- solvated crystalline forms are available, named as Polymorph I, II, III and IV. They all present different physical and chemical properties.
  • Ticagrelor is marketed by AstraZeneca with trade names of Brilinta and Brilique.
  • BRILINTA is an oral antiplatelet treatment that works by inhibiting platelet activation. For at least the first 12 months following Acute Coronary Syndrome (ACS), it is superior to other antithrombotic agents like clopidogrel. BRILINTA also reduces the rate of stent thrombosis in patients who have been stented for the treatment of ACS. In the management of ACS, the recommended maintenance dose of BRILINTA is 90mg twice daily during the first year after an ACS event. After one year, patients with a history of heart attack can now be treated with 60mg twice daily. BRILINTA should be used with a daily maintenance dose of aspirin of 75 - 100 mg.
  • ACS Acute Coronary Syndrome
  • WO9905143 discloses [4,5-d]pyrimidine compounds and its derivatives, including Ticagrelor.
  • WOO 192262 discloses various crystalline forms I, II, III and IV and amorphous forms of Ticagrelor.
  • Pharmaceutical compositions comprising ticagrelor are disclosed in W02008024044 and W02008024045. Oral pharmaceutical compositions which can comprise 20-45% by weight of the active ingredient are explained and they release all the active ingredient substantially.
  • a pharmaceutical composition comprises active ingredient, a filler/diluent consisting essentially of a mixture of mannitol and dibasic calcium phosphate dihydrate, a binder consisting essentially of hydroxypropyl cellulose, a disintegrant consisting essentially of sodium starch glycolate, and one or more lubricants. Wet granulation process is preferred as the manufacturing method.
  • W02015001489 relates to oral pharmaceutical compositions comprising amorphous ticagrelor and processes for their preparation.
  • TR2017/15203 discloses a method of manufacture for a formulation comprising ticagrelor, characterized in that the step of granulating the solid mixture wherein the mixture comprises the active agent ticagrelor and at least one water-soluble binder and at least one water-soluble filler that is granulated with a suitable granulation solution.
  • TR2016/01835 discloses a process for producing a formulation comprising ticagrelor or a pharmaceutically acceptable salt thereof, characterized in that the ticagrelor or pharmaceutically acceptable salt is dissolved and / or dispersed in a solvent or solvent mixture during manufacture.
  • EP3332769 relates to a solid oral pharmaceutical composition, comprising ticagrelor or a pharmaceutically acceptable salt thereof with at least one hydrophilic polymer wherein the composition is substantially free of calcium salts and their derivatives.
  • WO20 14059955 relates to a solid oral pharmaceutical formulation containing ticagrelor as the active pharmaceutical constituent wherein the pharmaceutical composition contains at least one the non-hygroscopic binder, at least one the non-hygroscopic filler and at least one lubricant and substantially no disintegrant.
  • WO20 18229785 relates to oral pharmaceutical compositions comprising ticagrelor and pharmaceutically acceptable polymer in a ratio of 1:0.1 to 1:1 in the form of solid dispersion.
  • WO2015110952 relates to a composition comprising ticagrelor or salt thereof in an amount less than 20% of the weight of total composition, wherein the composition is devoid of water- insoluble fillers.
  • CN107397717 discloses a solid preparation of ticagrelor or a pharmaceutically acceptable salt thereof which comprises filler, disintegrant, lubricant, additive and high polymer.
  • the solid preparation is prepared by mixing a filler and ticagrelor or its pharmacy or it is acceptable to salt, adding a lubricant and a disintegrant respectively and mixing the additive and the polymer to form a suitable solid preparation.
  • CN109700773 relates to a pharmaceutical composition comprising ticagrelor wherein the percentage the ticagrelor of weight at the formulation composition is 2%.
  • CN201310432438 discloses a solid dispersion comprising ticagrelor in which ticagrelor is dispersed in a carrier material to solve the problem of solubility.
  • CN106265557 discloses a dispersible tablet formulation comprising ticagrelor in which ticagrelor is in an amount of the total tablet weight 20 to 50% by weight.
  • WO201 1076749 numbered patent document discloses solid dosage forms comprising ticagrelor, characterized in that at least 90% by volume of ticagrelor particles have a particle size in the range of 1 pm to 150 pm. It further discloses that ticagrelor, being poorly soluble, presents a significant problem in the design of pharmaceutical compositions. Further, in order to exhibit good bioavailability, it is desirable to formulate dosage forms showing fast dissolution of the drug. However, it is stated that these effects are observable only if the ratio of ticagrelor is more that 50% by weight in the composition with the particle size of the drug and by the use of hydrophilic polymers/emulsifiers in the dosage form. Ticagrelor is classified as a BCS class IV compound, exhibiting low solubility and low permeability. This property leads to an undesirable dissolution profile and hence poor bioavailability. It also leads to high intra-subject and inter-subject variability following oral administration.
  • the patent application no. EP2056832 discloses an oral pharmaceutical composition comprising ticagrelor and other excipients.
  • the composition is presented as enhancing the bioavailability through increasing the release of the active agent due to the formulation comprising at least one filler, one disintegrant, one diluent, one binder and one lubricant.
  • Ticagrelor has a low aqueous solubility and this characteristic property brings bioavailability and dissolution release profile problems regarding decreases in the solubility of solid formulations.
  • several methods are followed, different forms of ticagrelor and different excipients are composed to overcome some of these problems.
  • pharmaceutical preparations that have proper dissolution release profile in correlation with in vivo release profile with improved flow character and compressibility properties.
  • compositions comprising ticagrelor or salt thereof and one or more pharmaceutically acceptable excipients with proper dissolution release profile and in vivo release profile.
  • an oral dosage form composition in concurrent use of acetylsalicylic acid for the treatment of the prevention of atherothrombotic events in adult patients with - acute coronary syndromes (ACS) or
  • MI myocardial infarction
  • in another aspect of this invention is to develop an immediate-release solid pharmaceutical formulation comprising ticagrelor or a pharmaceutically acceptable salt thereof, which has improved blend properties prior to tablet compression or filling into the capsule.
  • an immediate release solid oral composition comprising only ticagrelor as active substance and one or more acceptable excipients manufactured by using optimised wet granulation process.
  • a solid oral pharmaceutical composition comprising ticagrelor or salt thereof, which composition is in the form of a tablet.
  • a solid oral pharmaceutical composition comprising ticagrelor or salt thereof, which composition is in the form of a capsule.
  • One or more pharmaceutically acceptable excipients may be present in the tablets, e.g. at least one filler, at least one binder, at least one disintegrant, at least one glidant, and at least one lubricant, and optionally a coating comprising film forming polymer.
  • a solid oral pharmaceutical composition comprising ticagrelor or salt thereof with one or more pharmaceutically acceptable excipients, wherein the composition comprises no more than 80% pharmaceutically acceptable excipients by weight of the composition.
  • Ticagrelor has 6 stereocenters and due to that there are many crystalline and also amorphous forms. Especially, four non- solvated crystalline forms are available, named as Polymorph I, II, III and IV. They all present different physical and chemical properties.
  • the active agent is crystalline ticagrelor.
  • the active agent is ticagrelor polymorph II presenting X-ray powder diffraction pattern containing specific peaks at 5.5° ( ⁇ 0.1°), 6.8° ( ⁇ 0.1°), 10.6° ( ⁇ 0.1°), 13.5° ( ⁇ 0.1°), 14.9° ( ⁇ 0.1°), 18.3° ( ⁇ 0.1°), 19.2° ( ⁇ 0.1°), 22.7° ( ⁇ 0.1°), 24.3° ( ⁇ 0.1°) and 27.G ( ⁇ 0.1°) 2Q.
  • the active agent is ticagrelor polymorph II which is also used in innovator drug product and declared that it is the most stable crystalline form of ticagrelor hat has desired thermodinamic and chemical characteristics.
  • In another object of the present invention is provide a pharmaceutical compositions containing ticagrelor wherein the total weight of the ticagrelor is between 20 - 30% w/w per solid dosage form.
  • In another object of the present invention is to obtain a bioequivalent pharmaceutical composition with improved dissolution release profile containing ticagrelor with optimized amounts of excipients manufactured by using optimized parameters of wet granulation method.
  • the present invention provides a solid oral dosage form comprising ticagrelor and optimized amounts of pharmaceutically acceptable excipients manufactured by using the most proper manufacturing method.
  • the present invention relates to an immediate release solid oral composition comprising ticagrelor and one or more acceptable excipients manufactured by using optimised wet granulation process.
  • Another object of the present invention is to provide a preparation method of a pharmaceutical composition of ticagrelor wherein the pharmaceutical compositions herein disclosed can be manufactured into solid dosage forms, such as tablet, film coated tablet, sachet, capsule having improved granule characteristics and the desired dissolution profiles.
  • Another object of the present invention is to provide a pharmaceutical compositions containing ticagrelor manufactured by using wet granulation process wherein provided for the manufacture of tablets containing the active ingredient, filler(s), diluent(s), disintegrant(s), glidant(s), and lubricant(s) etc.
  • the present invention is related to a pharmaceutical composition manufactured by using wet granulation method comprising Ticagrelor, Microcrystalline cellulose, Silicon dioxide in the extragranular phase, Dibasic calcium phosphate in the intragranular phase, wherein lubrication time is between 6 to 12 minutes.
  • the composition is in a solid dosage form.
  • crystalline ticagrelor can be used as ticagrelor.
  • ticagrelor is in crystalline form. More preferably crystalline ticagrelor is in the form of polymorph II has a X-ray powder diffraction pattern containing specific peaks at 5.5°, 6.8° , 10.6°, 13.5°, 14.9°, 18.3°, 19.2° , 22.7°, 24.3° and 27.G ( ⁇ 0.1° 2Q).
  • composition preferably further comprises at least one excipient selected from fillers, diluents, disintegrants, binders and lubricants.
  • the composition comprises mannitol as a diluent.
  • Disintegrant is preferably selected from croscarmellose sodium, crospovidone, low- substituted hydroxypropyl cellulose, starch, sodium starch glycolate, carmellose and mixtures thereof. More preferably the disintegrant is croscarmellose sodium.
  • Binder is preferably selected from hypromellose, hydroxypropyl cellulose, povidone, starch, sucrose, polyethylene glycol, or mixtures thereof. More preferably, the binder is hydroxypropyl cellulose.
  • Lubricant is preferably selected from sodium stearyl fumarate, magnesium stearate, calcium stearate talc, stearic acid and mixtures thereof. More preferably, the lubricant is magnesium stearate.
  • the present invention is also provides a wet granulation manufacturing process for the pharmaceutical composition comprising ticagrelor, preferably crystalline ticagrelor as polymorph II, comprising the following steps: a. Ticagrelor, mannitol, dibasic calcium phosphate, specified amount of croscarmellose sodium were stirred in high-shear granulator for 5 minutes. b. Hydroxypropyl cellulose was dissolved in deionised water and added on the powder blend in step a and granulation process was performed with stirring. c. Granule obtained in step b was sifted and dried at a specified temperature. d.
  • step d Dried granule was sifted and silicon dioxide, microcrystalline cellulose and the remaining amount of croscarmellose sodium was added through screening.
  • step d Powder blend obtained in step d was lubricated with magnesium stearate for 6 to 12 minutes.
  • Final blend in step e was subjected to tablet compression process.
  • Tablets obtained in step f were coated with a proper film coating agent.
  • Quality by Design (QbD) principles were applied to the development of the ticagrelor comprising pharmaceutical composition.
  • the critical quality attributes that have the potential to affect product performance have been identified using the principles as outlined in ICH Q8 and Q9 guidelines.
  • Solubility of ticagrelor is very low (not ionised in the pysiological pH range) and exhibits a moderate intrinsic permeability, there is potentially a higher risk that changes in formulation and processing parameters can affect clinical performance, and this was taken into account during development. Moreover, this low aqueous solubility of ticagrelor leads to an increase of relevance of particle size. Solubility studies in human intestinal fluids, bulk-tapped density, compressibility index, Hausner ratio, flowability studies of drug substance were performed prior to beginning of the development process of pharmaceutical drug product.
  • ticagrelor solubility is very low in pysiological pH range.
  • Ticagrelor containing pharmaceutical drug products are designed based on all investment studies explained above. Micronizing particle size values and designation of polymorphism are the main approaches to improve physicochemical and biopharmaceutical properties of the poorly soluble drugs, thereby improving their solubility. These approaches are used for ticagrelor also.
  • suitable fillers may comprise but not limited to dibasic calcium phosphate, polysaccharides, primarily microcrystalline cellulose, lactose, mannitol, sugars, sorbitol, sucrose, inorganic salts, primarily calcium salts and the like and mixtures thereof.
  • the most preferred filler is microcrystalline cellulose.
  • the pharmaceutical composition comprises at least a disintegrant, preferably, it is selected from croscarmellose sodium, crospovidone, low-substituted hydroxypropyl cellulose, starch, sodium starch glycolate, carmellose and mixtures thereof. More preferably, the disintegrant is croscarmellose sodium.
  • suitable diluents may comprise but not limited to dibasic calcium phosphate, polysaccharides, primarily microcrystalline cellulose, lactose, mannitol, sugars, sorbitol, sucrose, inorganic salts, primarily calcium salts and the like and mixtures thereof.
  • the most preferred diluent is mannitol, silicon dioxide and dibasic calcium phosphate or a mixture thereof, preferably is a mixture thereof.
  • the binder may be, for example, hypromellose, cellulose or cellulose derivatives, povidone, starch, sucrose, polyethylene glycol, or mixtures thereof.
  • the binder is dissolved in a solvent, for instance, water, an alcohol, or mixtures thereof.
  • the binder solution is hydroxypropyl cellulose dissolved in water.
  • the pharmaceutical composition comprises at least a lubricant, preferably, it is selected from sodium stearyl fumarate, magnesium stearate, calcium stearate talc, stearic acid and mixtures thereof. More preferably, the lubricant is magnesium stearate.
  • formulation design begins from the well-known prior art documents and based on experimental studies, multiple formulations were designed to overcome challenges directly affects dissolution profile and granule characteristics of pharmaceutical compositions comprising ticagrelor.
  • formulation design
  • Ticagrelor, mannitol, dibasic calcium phosphate, croscarmellose sodium were stirred in high-shear granulator for 5 minutes.
  • Hydroxypropyl cellulose was dissolved in sufficient quantity of deionised water.
  • step 3 The solution obtained in step 2 was added on the powder blend in step 1 and granulation process was performed with stirring. 4. Granule obtained in step 3 was sifted and dried at a specified temperature.
  • step 5 Final blend in step 5 was subjected to tablet compression process.
  • step 6 Tablets obtained in step 6 were coated with a proper film coating agent.
  • Formulation I was analyzed for granule properties, such as bulk density, tapped-density. Moreover, Hausner ratio, Carr index (compressibility index) were calculated by using bulk density, tapped-density and specified.
  • Diluents used in the formulation I were dibasic calcium phosphate and mannitol.
  • a third diluent was planned to be added into the granulation process which is silicon dioxide. It is known from the prior art that silicon dioxide helps to improve the flowability of powders by acting to counteract different mechanisms. The nature of silicon dioxide allows it to attract and preferentially bind moisture, helping to eliminate liquid bridges between solid particles that hinder powder flow.
  • Silicon dioxide incorporated in powder during the granulation means uniform flow through the equipment. This can boost consistency during the tabletting process and provide improvement in the physico-chemical properties like friability, hardness, structural stability with content uniformity, easy tabletting processes and high resistance to sticking. Moreover, the large internal porosity silicon dioxide provides greater capacity for water included in the formulation.
  • hydroxypropyl cellulose that was used in the formulation as binder was planned to be in solution form as dissolving into the deionized water.
  • hydroxypropyl cellulose that was used in the formulation as binder was planned to be in solution form as dissolving into the deionized water.
  • Ticagrelor, mannitol, dibasic calcium phosphate, specified amount of croscarmellose sodium were stirred in high-shear granulator for 5 minutes.
  • Hydroxypropyl cellulose was dissolved in deionised water and added on the powder blend in step 1 and granulation process was performed with stirring.
  • step 2 Granule obtained in step 2 was sifted and dried at a specified temperature. 4. Dried granule was sifted and silicon dioxide, microcrystalline cellulose and the remaining amount of croscarmellose sodium was added through screening.
  • step 5 Powder blend obtained in step 4 was lubricated with magnesium stearate for 3 minutes and then extra 6 minutes. Lubrication time was totally 9 minutes. 6. Final blend in step 5 was subjected to tablet compression process.
  • step 6 Tablets obtained in step 6 were coated with a proper film coating agent.
  • Dissolution conditions are as in the following:
  • Dissolution medium Water + 0.2% Polysorbate 80
  • volume of dissolution medium 900 ml
  • Formulation III In another embodiment designated as Formulation III, was designed to optimize lubrication time in manufacturing process of formulation II. Manufacturing method: 1. Ticagrelor, mannitol, dibasic calcium phosphate, specified amount of croscarmellose sodium were stirred in high-shear granulator for 5 minutes.
  • step 2 Hydroxypropyl cellulose was dissolved in deionised water and added on the powder blend in step 1 and granulation process was performed with stirring. 3. Granule obtained in step 2 was sifted and dried at a specified temperature.
  • step 4 Powder blend obtained in step 4 was lubricated with magnesium stearate for a specied range of duration to get two more different types of the formulation. 6. Final blend in step 5 was subjected to tablet compression process.
  • step 6 Tablets obtained in step 6 were coated with a proper film coating agent. minutes.
  • Formulation III_A Same manufacturing method with Formulation III with lubrication time of 6 minutes.
  • Formulation III_B Same manufacturing method with Formulation III with lubrication time of 12 minutes.
  • PK parameters (AUQ and C max ) are in line with the specifications based on Guideline on the Investigation on Bioequivalence.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
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  • General Health & Medical Sciences (AREA)
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  • Veterinary Medicine (AREA)
  • Inorganic Chemistry (AREA)
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Abstract

La présente invention concerne une composition pharmaceutique, comprenant du ticagrelor, la composition pharmaceutique étant fabriquée par utilisation d'un procédé de granulation par voie humide présentant des propriétés d'écoulement et de compressibilité améliorées ; la composition comprenant de la cellulose microcristalline, et du dioxyde de silicium conjointement dans la phase extragranulaire et du phosphate de calcium dibasique dans une phase intragranulaire ayant une plage de temps de lubrification optimisée comprise entre 6 et 12 minutes.
PCT/TR2019/050944 2019-11-13 2019-11-13 Compositions pharmaceutiques comprenant du ticagrelor WO2021096444A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP19952515.5A EP4058025A4 (fr) 2019-11-13 2019-11-13 Compositions pharmaceutiques comprenant du ticagrelor
PCT/TR2019/050944 WO2021096444A1 (fr) 2019-11-13 2019-11-13 Compositions pharmaceutiques comprenant du ticagrelor

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/TR2019/050944 WO2021096444A1 (fr) 2019-11-13 2019-11-13 Compositions pharmaceutiques comprenant du ticagrelor

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WO2021096444A1 true WO2021096444A1 (fr) 2021-05-20

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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023222184A1 (fr) * 2022-05-16 2023-11-23 Hyloris Developments Sa Solution aqueuse de ticagrelor, procédé de fabrication et utilisations
WO2023222660A1 (fr) * 2022-05-16 2023-11-23 Hyloris Developments Sa Solution aqueuse de ticagrelor, procédé de fabrication et utilisations

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US20110104271A1 (en) * 2009-11-05 2011-05-05 Fmc Corporation Microcrystalline Cellulose and Calcium Phosphate Compositions Useful as Pharmaceutical Excipients
US20170296666A1 (en) * 2016-04-18 2017-10-19 Amneal Pharmaceuticals Company Gmbh Stable Pharmaceutical Composition Of Amorphous Ticagrelor
EP3266447A1 (fr) * 2016-02-12 2018-01-10 Ali Raif Ilac San. A.S. Procédé de production de formulations contenant du ticagrelor
WO2018229785A1 (fr) * 2017-06-15 2018-12-20 Natco Pharma Limited Compositions pharmaceutiques de ticagrélor

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TR201617983A2 (tr) * 2016-12-07 2018-06-21 Sanovel Ilac Sanayi Ve Ticaret Anonim Sirketi Ti̇cagrelorun kati oral farmasöti̇k bi̇leşi̇mleri̇
WO2021080529A1 (fr) * 2019-10-26 2021-04-29 Santa Farma İlaç Sanayi̇ A.Ş. Formulations pharmaceutiques solides comprenant du ticagrelor

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Publication number Priority date Publication date Assignee Title
US20110104271A1 (en) * 2009-11-05 2011-05-05 Fmc Corporation Microcrystalline Cellulose and Calcium Phosphate Compositions Useful as Pharmaceutical Excipients
EP3266447A1 (fr) * 2016-02-12 2018-01-10 Ali Raif Ilac San. A.S. Procédé de production de formulations contenant du ticagrelor
US20170296666A1 (en) * 2016-04-18 2017-10-19 Amneal Pharmaceuticals Company Gmbh Stable Pharmaceutical Composition Of Amorphous Ticagrelor
WO2018229785A1 (fr) * 2017-06-15 2018-12-20 Natco Pharma Limited Compositions pharmaceutiques de ticagrélor

Non-Patent Citations (2)

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Title
ALJABERI AHMAD, CHATTERJI ASHISH, SHAH NAVNIT H., SANDHU HARPREET K.: "Functional performance of silicified microcrystalline cellulose versus microcrystalline cellulose: a case study", DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY, vol. 35, no. 9, September 2009 (2009-09-01), pages 1066 - 1071, XP055823099 *
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Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2023222184A1 (fr) * 2022-05-16 2023-11-23 Hyloris Developments Sa Solution aqueuse de ticagrelor, procédé de fabrication et utilisations
WO2023222660A1 (fr) * 2022-05-16 2023-11-23 Hyloris Developments Sa Solution aqueuse de ticagrelor, procédé de fabrication et utilisations

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EP4058025A1 (fr) 2022-09-21

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