EP2729132A1 - Composition pharmaceutique et forme galenique solide a haute teneur en dronedarone et son procede de preparation - Google Patents
Composition pharmaceutique et forme galenique solide a haute teneur en dronedarone et son procede de preparationInfo
- Publication number
- EP2729132A1 EP2729132A1 EP12733700.4A EP12733700A EP2729132A1 EP 2729132 A1 EP2729132 A1 EP 2729132A1 EP 12733700 A EP12733700 A EP 12733700A EP 2729132 A1 EP2729132 A1 EP 2729132A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- dronedarone
- excipient
- composition according
- sodium
- equal
- Prior art date
- Legal status (The legal status 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 status listed.)
- Withdrawn
Links
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
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/343—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide condensed with a carbocyclic ring, e.g. coumaran, bufuralol, befunolol, clobenfurol, amiodarone
-
- 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
- A61K9/1682—Processes
- A61K9/1694—Processes resulting in granules or microspheres of the matrix type containing more than 5% of excipient
-
- 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
-
- 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
- A61K9/2027—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/06—Antiarrhythmics
Definitions
- the present invention relates to pharmaceutical compositions, intended to be used in solid dosage form for oral administration, mainly comprising dronedarone or at least one of its derivatives, as well as solid dosage forms as such made from said compositions, preferably tablets.
- the present invention also relates to a process for the preparation of such solid dosage forms based on said pharmaceutical compositions by the hot-melt route and also relates to the therapeutic application of such compositions or such solid dosage forms.
- Dronedarone and its method of preparation are described in patents EP 0 471 609 B1 and US 5,223,510.
- Dronedarone blocks potassium, sodium and calcium channels and also has anti-adrenergic properties.
- Dronedarone is an antiarrhythmic agent effective in maintaining sinus rhythm in patients with atrial fibrillation or atrial flutter. Dronedarone can be administered via dosage units containing an effective amount of said active ingredient, for example 400 mg of dronedarone for an adult.
- dronedarone or a derivative thereof is advantageously formulated in solid dosage forms administered orally, for example tablets.
- dronedarone present a real challenge in terms of the development of formulations adapted to the preparation of such solid dosage forms, combining both an effective amount of active ingredient and a size of said galenic form sufficiently reduced to be able to be easily swallowed.
- EP 1 007 030 B1 describes such a method.
- the addition of the excipients necessary for the compression of this grain and the assimilation of the dronedarone after absorption of a tablet lead to a final mass of 650 mg for one unit.
- the characteristics of dronedarone are among the factors limiting the possibilities of increasing its concentration in solid dosage forms.
- the dronedarone tablet on the market comprises a maximum of 65.54% by weight of dronedarone, in the form of dronedarone hydrochloride relative to the total weight of said tablet.
- wet granulation generates dust emission rates during the manufacture of unsatisfactory solid galenic forms following a drying phase which is essential in such a process.
- the applicant has surprisingly discovered a pharmaceutical composition and a solid dosage form that can be administered orally at high levels. dronedarone content and / or at least one of its derivatives.
- This ability to increase the content of dronedarone and / or at least one of its derivatives in solid dosage forms allows a reduction in the size of said forms, advantageously tablets, compared to the dosage form currently on the market.
- He has also discovered a process for the hot-melt manufacture of solid dosage forms from such a composition, having the advantage of allowing an increase in the concentration of active principle, advantageously a concentration greater than 80% by weight associated.
- This method via a hot-melt granulation has, moreover, the advantage of overcoming the problems usually encountered in the context of a process via wet granulation. Indeed, this method makes it possible to have a significantly reduced water content in the dosage form compared with the use of a conventional method, thus the drying step is avoided. This drying step in less simplifies the process and make it more energy efficient. This saves time and reduces costs.
- the reduction of the size of the dosage form has several advantages: it makes it possible to significantly improve the comfort of the patient and the observance of the treatment; in fact, the tablet is more easily ingested by the patient, it makes it possible to reduce the costs of industrial production, in particular by reducing the quantity of excipients used and reducing the number of cases and packaging and therefore the number of transport pallets.
- the subject of the invention is a pharmaceutical composition comprising: Up to 92% by weight, advantageously from 81 to 92% by weight, still more advantageously between 81 and 86% by weight, of dronedarone and / or at least one of its derivatives.
- At least one hot-melt excipient having a melting temperature or a glass transition temperature greater than or equal to approximately 35 ° C and less than or equal to approximately 120 ° C, preferably less than or equal to about 100 ° C and / or is greater than or equal to about 50 ° C, even greater than or equal to about 35 ° C and less than or equal to about 100 ° C, still more preferably greater than or equal to about 50 ° C and less than or equal to about 100 ° C;
- 0 to 20% advantageously from 0 to 1 1% by weight of at least one additional excipient, different from said hot melt excipient, and selected from disintegrants, lubricants, and flow agents, the percentages being expressed relative to total weight of said pharmaceutical composition.
- the invention more particularly relates to a pharmaceutical composition
- a pharmaceutical composition comprising:
- the dronedarone as well as the fusible excipient make up the internal phase of the formulation (components used for the formation of the grain). Any additional excipients used constituting the outer phase of the formulation.
- it also relates to a solid dosage form, administrable orally, formed from a pharmaceutical composition according to the invention.
- the invention further relates to a method for producing solid dosage forms comprising at least the following steps, in the indicated order:
- a granulation step B of said composition using a granulator to reach a temperature for melting or softening of the hot melt excipient.
- the method for manufacturing solid dosage forms comprises the following steps, in the indicated order:
- a step A of mixing a composition according to the invention ⁇ A step B of granulation of said composition using a granulator to reach a temperature for melting or softening of the hot melt excipient.
- the method is characterized in that it further comprises following step B, the following steps in the order indicated: ⁇ A step C of cooling the grains obtained at the end of the preceding granulation step at room temperature, preferably between about 20-25 ° C; A step D of grain calibration consisting of sieving said grains.
- the additional excipients used in the composition of the said invention will be added to the grains during this calibration step.
- the calibration takes place through a grid opening mesh less than about 2.0 mm;
- step E • Possibly a step E of mixing said grains if additional excipients are added in step D;
- the method is characterized in that the solid dosage forms are tablets and / or in that it is a continuous process.
- the invention relates to a solid dosage form having a composition according to the invention, administrable orally and obtainable at the end of the process according to the invention, advantageously (i) the process being a process continuously.
- compositions or the solid dosage forms according to the invention comprise dronedarone or at least one of its derivatives.
- Dronedarone derivatives Dronedarone compounds that may also exist in the form of bases or addition salts with acids. Such addition salts are part of the invention. These salts may be prepared with pharmaceutically acceptable acids, but the salts of other acids useful, for example, for the purification or isolation of the dronedarone compounds are also part of the invention.
- the dronedarone derivatives are advantageously addition salts with acids as defined above. More particularly, they are addition salts with pharmaceutically acceptable acids.
- the dronedarone derivative is hydrochloride of dronedarone.
- Excipient an inactive or inert substance that facilitates the preparation and administration of a drug
- Disintegrating an excipient which allows the satisfactory disintegration of the galenic form and thus the disintegration of the active principle in the stomach by increasing the friability and decreasing the hardness of the galenic form;
- Lubricant an excipient intended to facilitate the manufacturing steps of the galenic forms, thanks to their sliding role, ie to increase the fluidity of the particles in the tubes of the machines.
- Hot-Melt Excipient An excipient that softens or becomes fluid under the effect of heat. Such excipients have either a melting temperature: the temperature at which the crystalline solid state and the liquid state of the excipient coexist (measured at normal atmospheric pressure of 1 atmosphere), ie a glass transition temperature: temperature below wherein the excipient-forming molecules have a low relative mobility or temperature at which the excipient changes from the amorphous solid state to a viscous fluid state.
- a pharmaceutical composition or a solid dosage form according to the invention may comprise up to 92% by weight of dronedarone and / or at least one of its derivatives, advantageously between about 81% and 92% by weight, and even more advantageously between about 81% and 86% by weight, relative to the total weight of said composition or said dosage form.
- a pharmaceutical composition or a galenical form according to the invention further comprises at least one excipient, which is pharmaceutically acceptable and is heat-fusible at a temperature greater than or equal to approximately 35 ° C, advantageously greater than or equal to approximately 50 ° C and less than or equal to at about 120 ° C, preferably less than or equal to about 100 ° C.
- Tf melting temperatures
- Tg glass transition temperatures
- hot-melt excipient suitable for the invention mention may be made of citric acid monohydrate (Tf ⁇ 100 ° C), stearic acid (Tf ⁇ 54-67 ° C), palmitic acid (Tf ⁇ 63 -64 ° C).
- This hot-melt excipient may advantageously be chosen from binders, plasticizers and mixtures thereof. It is advantageously chosen from polyoxyethylene polyoxypropylene copolymers, abbreviated polyethylene glycol PEG, PEG3000 (mp 48-54 ° C), PEG4000 (mp 50-58 ° C), PEG 6000 (mp 55 ° -63 ° C.
- the hot-melt excipient or excipients are chosen from polyoxyethylene polyoxypropylene copolymers, and even more advantageously from polyoxyethylene polyoxypropylene hot-melt copolymers at a temperature of between about 50 ° C. and about 70 ° C.
- poloxamer 188 (mp 52-57 ° C), poloxamer 237 (mp 49 ° C), poloxamer 338 (mp 57 ° C), poloxamer 407 (mp 52 57 ° C).
- the hot-melt excipient is poloxamer 407.
- the content of the hot-melt excipient may be from about 7% to 20% by weight, preferably from about 7% to 10% by weight, based on the total weight of said composition or said dosage form.
- said content of hot melt excipient can also be expressed relative to the total weight of equivalent dronedarone base. It will then be between 1 and 20%, particularly between 5 and 15% and even more particularly 10% by weight relative to the total weight of dronedarone equivalent base.
- said content of hot-melt excipient can be defined both with respect to the total weight of the composition and relative to the total weight of the dronedarone equivalent base contained in the composition.
- equivalent basis we mean the amount corresponding to the amount of dronedarone base form, ie unsalified.
- the compositions or the galenic forms according to the invention may contain a disintegrant.
- This disintegrant may be chosen from crosslinked polyvinylpyrrolidone, crosslinked carboxymethylcellulose, alginic acid, sodium alginate, sodium carboxymethylcellulose, microcrystalline cellulose, cellulose powder, sodium croscarmellose, crospovidone and starch. pregelatinized, sodium starch glycolate, sodium carboxymethyl starch, starch and mixtures thereof. It is advantageously crospovidone, croscarmellose sodium or their mixtures.
- the disintegrating content may be between 0% and 10% by weight, advantageously between 3% and 10% by weight, and still more advantageously between 5% and 10% by weight, relative to the total weight of said composition or said galenic form. .
- compositions or dosage forms according to the invention may comprise, in addition, at least one additional excipient, different from said hot-melt excipient, and may advantageously have a melting point greater than about 100 ° C.
- the additional excipient (s) is (are) chosen from among the usual excipients known to those skilled in the art according to the pharmaceutical form and the desired mode of administration. This or these additional excipient (s) may or may be chosen for example from flow agents, lubricants and disintegrants.
- a pharmaceutical composition or a dosage form according to the invention may further comprise at least one lubricant.
- This lubricant may advantageously be chosen from magnesium stearate, stearic acid, glycerol tribehenate, sodium stearyl fumarate, calcium stearate, glyceryl monostearate, glyceryl palmitostearate, sodium lauryl sulfate, zinc stearate, and the like.
- stearic acid hydrogenated vegetable oils, polyethylene glycol, sodium benzoate, talc and mixtures thereof. It is advantageously magnesium stearate.
- the lubricant content can be between 0 and 1% by weight, more preferably between 0 and 0.5% by weight, relative to the total weight of lubricant in said composition or said dosage form.
- a pharmaceutical composition or a galenic form according to the invention may further comprise at least one flow agent. It is advantageously silicone dioxide.
- the content of flow agent may be between 0 and 1% by weight, advantageously between 0 and 0.4% by weight, relative to the total weight of said composition or said dosage form.
- the composition or the dosage form according to the invention comprises between 81 and 92% by weight of dronedarone hydrochloride, between 7 and 10% by weight of hot melt excipient, between 5 and 10% by weight of disintegrant, between 0 and 0.5% by weight of lubricant and between 0 and 0.4% by weight of flow agent, relative to the total weight of said composition or said dosage form.
- compositions of the present invention are generally formulated in dosage units for daily administration, one or more times per day.
- dosage unit means a solid dosage form that can be administered orally, advantageously a tablet.
- the dosage unit or solid dosage form for an adult, can have a mass of 466mg to 523mg, and contains 400mg of dronedarone equivalent base.
- compositions described above solid dosage forms according to the invention can be obtained by the following method.
- the process according to the invention for the manufacture of solid dosage forms, advantageously tablets, is carried out continuously.
- the method comprises the following steps:
- this granulation step C is conducted at a temperature of up to about 70 ° C. to 90 ° C. Said steps A, B can take place successively, one after the other, in the indicated order or at the same time. and then
- a calibration step D consisting of sieving the grains obtained in the previous step D through a mesh opening grid, advantageously less than 2 mm and / or greater than 1.0 mm, more advantageously equal to 1. 5mm. Possibly the additional excipients of the external phase being added during this step.
- step E when additional excipients are added in step D.
- This mixing step will lubricate the grains in the case where a lubricant is added, preferably magnesium stearate.
- Step F consists of a compression step by punching using a press and punches.
- the first step or step A of said process consists in mixing the ingredients of the same composition, manually or mechanically in batch or continuous mixers.
- step B can be done in a Continuous granulator with co-rotating screws rotating in a jacketed sleeve. This step can be done,
- a third step also called step C, then consists of a cooling which can take place for example by spreading the grains obtained in the granulation stage on a plate (or by transfer by extraction) at about 20-25 ° C.
- a fourth calibration step D is conducted, for example, on a Frewitt® TC150 calibrator equipped, for example, with a grid of 1.5 mm mesh aperture.
- the grid and in particular its mesh opening will be chosen according to the desired calibration.
- the components of the external phase will be added during this step.
- step E an optional step of mixing or step E to be done using a mixer by turning for example.
- the grains are finally subjected to galenic shaping, advantageously compression, using, for example, a Korsh® XL 100 rotary press between 10 and 20 KN with a D type punch, oblong with dimensions of 15.5 ⁇ 8. mm depending on the size and shape desired.
- galenic shaping advantageously compression
- the pharmaceutical compositions, dosage forms, and methods of manufacture according to the present invention may be plotted by the presence of the factors or combinations of factors set forth hereinafter. These include:
- hot-melt excipient for example Poloxamer
- the hot melt process makes it possible to have a water content that is significantly reduced in the galenic form compared with the use of a conventional method, for example a wet granulation process, for the same galenic form.
- the size of the tablet compared to its concentration of active ingredient, but also the concentration of active ingredient. Indeed, only the method according to the present invention allows our knowledge, with a single granulation step and without using organic solvents, to obtain after compression dronedarone concentrations up to 92%. Conventional processes, including for example the wet granulation method, require the use of a large amount of excipients to improve the wettability of the powder, the cohesion of the grain and the compressibility of the powder mixture, this amount being directly proportional to the amount of dronedarone implemented.
- the percentages of the ingredients of the compositions or of the galenic forms, according to the invention, are chosen so as to obtain a total of 100% by weight relative to the total weight of said composition or of said dosage form.
- compositions according to the invention By way of example, a pharmaceutical composition 1A and a pharmaceutical composition 1B according to the invention, comprising only dronedarone hydrochloride as active principle are indicated for illustrative purposes in Table 1 below. The nature of the components of these compositions is indicated in said table as well as the concentration of said components, expressed in% by weight of component relative to the total weight of the composition.
- a mixing step (step A) of said process consists in mixing with a Turbula® or Servolift®-type inversion mixer for about 210 turns the ingredients of the internal phase of one of the compositions defined above.
- step B a granulation step (step B) is carried out using a Consigma® 25 co-rotating screw granulator rotating in a jacketed sheath.
- the parameters are: a powder mixture rate of 5 to 6 kg / h, a screw speed of 250 to 300 rpm, a jacket temperature of 80 to 100 ° C, the temperature of the composition reaching a maximum of 86 ° C.
- a cooling step (step C) then consists of cooling to about 20-25 ° C by spreading on a tray or by pneumatic transport of said grains.
- step D a calibration step is conducted on a Frewitt® TC-150 calibrator using a grid of 1.5 mm mesh aperture.
- Magnesium stearate, silicon dioxide and crospovidone are optionally added to the grains in step D, if appropriate, the mixture of grains and additional excipients being carried out for about 210 turns in a mixer by inverting Turbula® or Servolift® type (step E).
- step F The grains finally undergo a compression step (step F) using a Korsh® XL 100 rotary press or a Kilian S100 rotary press between 10 and 25 KN with an oblong punch of 15.5 mm length and 8 mm width to form tablets.
- Table 2 below groups together characteristics of the tablets 1A and 1B obtained after a continuous process using the compositions respectively described above as well as the characteristics of the reference tablet obtained by wet granulation. Table 2 below indicates for each tablet, its total mass, its equivalent dronedarone base (eq-base).
- compositions according to the invention have a mass and a reduced size compared to the reference tablet.
- a tablet is placed in a container containing 1000 ml of phosphate buffer at pH 4.5 and at a temperature of 37 ° C. The whole is stirred at a speed of 75 rpm using a pallet and the amount of active ingredient dissolved is measured after 30 minutes.
- the weight percent of dronedarone dissolved for tablet 1B is 83.3%. It can be seen that the% of dronedarone dissolution is greater than or equal to 80% by weight of dronedarone relative to the total weight of dronedarone present in the tablet, which proves to be in accordance with the regulatory recommendations for immediate-release pharmaceutical forms. . 4. Evaluation of bioavailability
- the dose used is 60 mg / animal, whatever the period / condition corresponding to 6 mg / kg, (assuming a weight of 10 kg for a dog) and the dose of 400 mg given in humans (c ie, about 6 mg / kg for a human weight of 70 kg).
- the conditions of administration are as follows:
- Pentagastrin (6 mg / kg, 0.25 ml / kg) is administered intramuscularly and helps to maintain the animal's pH between 2-3, thus mimicking human conditions.
- the treatments are:
- Treatment 1 60 mg of dronedarone hydrochloride tablet (reference, Multaq®) under fasted conditions
- oral Treatment 2 60 mg tablet according to the invention of dronedarone hydrochlorate under fasting conditions
- oral Treatment 3 60 mg tablet according to the invention of dronedarone hydrochlorate under nourished conditions and rich in fat, orally
- Samples and analyzes Blood samples are collected in plastic tubes containing lithium heparin as anticoagulant at the following sampling times: before treatment and 0.5, 1, 2, 3, 4, 6, 8 and 24 hours after administration of each treatment.
- the plasma concentration of dronedarone is determined using an exploratory liquid chromatography-mass spectrometry (LC-MS / MS) assay method.
- the low limit of detection with this method for the compounds tested is 0.5 ng / mL.
- Pharmacokinetic parameters are calculated from individual concentrations by non-compartmental analysis using WinNonLin 5.2.1 software (Pharsight, USA) and using theoretical sampling times (provided that actual sampling times do not differ more 15% of theoretical times).
- AUCiast corresponds to the area under the curve or integral of the plasma concentration as a function of time t calculated by the trapezoidal method of t 0 until the time corresponding to the last quantifiable concentration.
- - AUC corresponds to the area under the curve or integral of plasma concentration as a function of time extrapolated to infinity. - T1 / 2z; terminal elimination half-life
- the C max is increased by a factor of 2.3, the AUCi ast by a factor of 1.5, and the AUC 1, 4.
Landscapes
- Health & Medical Sciences (AREA)
- Veterinary Medicine (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)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
Claims
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
FR1156153A FR2977495B1 (fr) | 2011-07-07 | 2011-07-07 | Composition pharmaceutique et forme galenique solide a haute teneur en dronedarone et son procede de preparation |
PCT/EP2012/063312 WO2013004830A1 (fr) | 2011-07-07 | 2012-07-06 | Composition pharmaceutique et forme galenique solide a haute teneur en dronedarone et son procede de preparation |
Publications (1)
Publication Number | Publication Date |
---|---|
EP2729132A1 true EP2729132A1 (fr) | 2014-05-14 |
Family
ID=46506382
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP12733700.4A Withdrawn EP2729132A1 (fr) | 2011-07-07 | 2012-07-06 | Composition pharmaceutique et forme galenique solide a haute teneur en dronedarone et son procede de preparation |
Country Status (6)
Country | Link |
---|---|
US (1) | US20140148507A1 (fr) |
EP (1) | EP2729132A1 (fr) |
KR (1) | KR20140046011A (fr) |
CN (1) | CN103764126A (fr) |
FR (1) | FR2977495B1 (fr) |
WO (1) | WO2013004830A1 (fr) |
Families Citing this family (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN105708809B (zh) * | 2015-05-09 | 2018-07-31 | 张秋野 | 一种控缓释剂药用辅料的热熔融制粒方法 |
FR3039990B1 (fr) * | 2015-08-10 | 2018-07-06 | Rhodia Operations | Procede d'encapsulation |
CN108042500A (zh) * | 2017-12-19 | 2018-05-18 | 佛山市弘泰药物研发有限公司 | 一种盐酸决奈达隆口崩片及其制备方法 |
CN112137999A (zh) * | 2020-09-30 | 2020-12-29 | 郑州大学 | 盐酸决奈达隆在制备抗消化道肿瘤药物中的应用 |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2599486A1 (fr) * | 2010-07-30 | 2013-06-05 | Jiangsu Hengrui Medicine Co. Ltd. | Dispersion solide de dronédarone et son procédé d'élaboration |
Family Cites Families (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2665444B1 (fr) | 1990-08-06 | 1992-11-27 | Sanofi Sa | Derives d'amino-benzofuranne, benzothiophene ou indole, leur procede de preparation ainsi que les compositions les contenant. |
DE69230372T2 (de) * | 1991-03-19 | 2000-06-15 | Cytrx Corp | Polyoxypropylen/polyoxyethylen copolymere mit verbesserter biologischer aktivität |
FR2764800B1 (fr) * | 1997-06-23 | 1999-09-10 | Sanofi Sa | Composition pharmaceutique solide contenant des derives de benzofuranne |
EP2133074A1 (fr) * | 2008-06-10 | 2009-12-16 | Sanofi-Aventis | Utilisation de dronédarone pour la préparation d'un médicament destiné à la prévention de la fibrillation auriculaire permanente |
CN102078307B (zh) * | 2009-12-01 | 2012-11-07 | 天津市汉康医药生物技术有限公司 | 一种盐酸决奈达隆固体分散体的药物组合物及其制备方法 |
WO2011135581A2 (fr) * | 2010-04-28 | 2011-11-03 | Cadila Healthcare Limited | Compositions pharmaceutiques de dronédarone |
-
2011
- 2011-07-07 FR FR1156153A patent/FR2977495B1/fr not_active Expired - Fee Related
-
2012
- 2012-07-06 WO PCT/EP2012/063312 patent/WO2013004830A1/fr active Application Filing
- 2012-07-06 EP EP12733700.4A patent/EP2729132A1/fr not_active Withdrawn
- 2012-07-06 KR KR1020147002922A patent/KR20140046011A/ko active Search and Examination
- 2012-07-06 CN CN201280042989.1A patent/CN103764126A/zh active Pending
- 2012-07-06 US US14/131,310 patent/US20140148507A1/en not_active Abandoned
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP2599486A1 (fr) * | 2010-07-30 | 2013-06-05 | Jiangsu Hengrui Medicine Co. Ltd. | Dispersion solide de dronédarone et son procédé d'élaboration |
Also Published As
Publication number | Publication date |
---|---|
WO2013004830A1 (fr) | 2013-01-10 |
KR20140046011A (ko) | 2014-04-17 |
CN103764126A (zh) | 2014-04-30 |
US20140148507A1 (en) | 2014-05-29 |
FR2977495B1 (fr) | 2014-03-07 |
FR2977495A1 (fr) | 2013-01-11 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US20210093575A1 (en) | Immediate release formulations and dosage forms of gamma-hydroxybutyrate | |
AU2010352575C1 (en) | Immediate release formulations and dosage forms of gamma-hydroxybutyrate | |
EP1007030B3 (fr) | Composition pharmaceutique solide contenant des derives de benzofuranne | |
US11925709B2 (en) | Tablet formulation for CGRP active compounds | |
JP5763063B2 (ja) | イルベサルタンおよびアムロジピンを含む固体医薬固定用量組成物、これらの調製ならびにこれらの治療用途 | |
NO320844B1 (no) | Celecoxibpreparat, fremgangsmate for fremstilling av dette og av farmasoytisk preparat som omfatter det og anvendelse av celeboxibpreparatet for fremstilling av preparat og medikament. | |
US20100196464A1 (en) | Orlistat pharmaceutical formulations | |
US20120276199A1 (en) | Taste masked pharmaceutical formulations | |
EP2729132A1 (fr) | Composition pharmaceutique et forme galenique solide a haute teneur en dronedarone et son procede de preparation | |
FR2999937A1 (fr) | Unite solide a haute teneur en fexofenadine et son procede de preparation | |
US8772346B2 (en) | Pharmaceutical composition | |
EP4076404B1 (fr) | Composition pharmaceutique de pyrazole | |
EP2793853B1 (fr) | Formulations pharmaceutiques de flurbiprofène et glucosamine | |
EP4062907A1 (fr) | Formulation par voie orale d'ivermectine et utilisations | |
US20070087051A1 (en) | Pharmaceutical composition | |
RU2707286C1 (ru) | Фармацевтическая противогрибковая композиция на основе производного хлорфенилбутандиона и способ её получения | |
WO2023198476A1 (fr) | Forme pharmaceutique vétérinaire molle à mâcher | |
EP2682104A1 (fr) | Formulations à désagrégation orale de dexketoprofen | |
RU2545833C1 (ru) | Фармацевтическая композиция с антиишемической и антиоксидантной активностью и способ ее получения | |
EP2682105A1 (fr) | Formulations à désagrégation orale de dexketoprofene | |
FR3060390A1 (fr) | Formulation comprenant de la pravastatine et de l'acide acetylsalycilique | |
KR20050035138A (ko) | 분무건조 공정에 의해 제조된 구강내 붕해 발데콕시브조성물 | |
EP1845959A2 (fr) | Medicament destine a etre administre par voie orale comprenant un inhibiteur de la cyclo-oxygenase-2, et son procede de preparation | |
WO2006025029A2 (fr) | Composition de divalproex a liberation prolongee |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
Free format text: ORIGINAL CODE: 0009012 |
|
17P | Request for examination filed |
Effective date: 20140207 |
|
AK | Designated contracting states |
Kind code of ref document: A1 Designated state(s): AL AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HR HU IE IS IT LI LT LU LV MC MK MT NL NO PL PT RO RS SE SI SK SM TR |
|
AX | Request for extension of the european patent |
Extension state: BA ME |
|
REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1192164 Country of ref document: HK |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: EXAMINATION IS IN PROGRESS |
|
17Q | First examination report despatched |
Effective date: 20180808 |
|
STAA | Information on the status of an ep patent application or granted ep patent |
Free format text: STATUS: THE APPLICATION IS DEEMED TO BE WITHDRAWN |
|
18D | Application deemed to be withdrawn |
Effective date: 20200603 |
|
REG | Reference to a national code |
Ref country code: HK Ref legal event code: WD Ref document number: 1192164 Country of ref document: HK |