[go: up one dir, main page]

WO2020130960A1 - Compositions pharmaceutiques orales d'eslicarbazépine - Google Patents

Compositions pharmaceutiques orales d'eslicarbazépine Download PDF

Info

Publication number
WO2020130960A1
WO2020130960A1 PCT/TR2018/050850 TR2018050850W WO2020130960A1 WO 2020130960 A1 WO2020130960 A1 WO 2020130960A1 TR 2018050850 W TR2018050850 W TR 2018050850W WO 2020130960 A1 WO2020130960 A1 WO 2020130960A1
Authority
WO
WIPO (PCT)
Prior art keywords
eslicarbazepine acetate
pharmaceutical composition
composition
binder
optionally
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.)
Ceased
Application number
PCT/TR2018/050850
Other languages
English (en)
Inventor
Mustafa Koksal ULGEN
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Mustafa Nevzat Ilac Sanayii AS
Original Assignee
Mustafa Nevzat Ilac Sanayii AS
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 Mustafa Nevzat Ilac Sanayii AS filed Critical Mustafa Nevzat Ilac Sanayii AS
Priority to PCT/TR2018/050850 priority Critical patent/WO2020130960A1/fr
Publication of WO2020130960A1 publication Critical patent/WO2020130960A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

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
    • A61K9/2022—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
    • 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
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • 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
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1635—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
    • A61K9/14—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
    • A61K9/1605—Excipients; Inactive ingredients
    • A61K9/1629—Organic macromolecular compounds
    • A61K9/1652—Polysaccharides, e.g. alginate, cellulose derivatives; Cyclodextrin
    • 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
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants

Definitions

  • the present invention relates to the pharmaceutical compositions comprising eslicarbazepine acetate; to the preparation processes of the pharmaceutical compositions comprising eslicarbazepine acetate; and to the pharmaceutical compositions comprising eslicarbazepine acetate for use as an anticonvulsant.
  • the present invention relates to a pharmaceutical composition of eslicarbazepine acetate, wherein the composition comprises a mixture of eslicarbazepine acetate, at least one binder and optionally at least one further pharmaceutically acceptable excipient subjected to at least two times compaction and dry granulation.
  • the present invention relates to a method of preparing a pharmaceutical composition of eslicarbazepine acetate, wherein the method comprises following steps:
  • the present invention relates to a pharmaceutical composition of eslicarbazepine acetate, wherein the composition comprises a mixture of eslicarbazepine acetate, at least one binder and optionally at least one further pharmaceutically acceptable excipient subjected to at least two times compaction and dry granulation, for use as an anticonvulsant.
  • Eslicarbazepine acetate is a dibenz[b,f]azepine-5-carboxamide derivative, which is chemically designated as (S)-10-Acetoxy-10,l l-dihydro-5H-dibenz[b,f]azepine-5-carboxamide and has the following structure: Compound I
  • Eslicarbazepine acetate represents a third-generation, single enantiomer member of the family of first-line dibenz[b,f]azepine antiepileptic drugs carbamazepine (first generation) and oxcarbazepine (second generation).
  • Eslicarbazepine acetate is a prodrug that is extensively converted to eslicarbazepine, the primary active metabolite in the body.
  • Eslicarbazepine acetate is an anticonvulsant medication approved for use as monotherapy or adjunctive therapy in the treatment of partial-onset seizures.
  • Eslicarbazepine acetate is currently available on the market as Aptiom in America and Canada; as Zebinix in Europe.
  • Currently available tablets contain 200, 400, 600 or 800 mg of eslicarbazepine acetate; and povidone, croscarmellose sodium, and magnesium stearate as inactive ingredients.
  • Eslicarbazepine acetate has been first disclosed in the PCT application WO 97/02250 Al.
  • Said invention provides 10-acyloxy-10,l l-dihydrodibenz/b,f/azepine-5-carboxamides useful for treating nervous system disorders; pharmaceutical compositions comprising these compounds and a pharmaceutically acceptable carrier; and the use of these compounds for the treatment of central and peripheric nervous system disorders.
  • any pharmaceutical composition comprising eslicarbazepine acetate has not been illustrated.
  • Said invention provides a pharmaceutical preparation comprising eslicarbazepine acetate in combination with a binder (povidone) and a disintegrant (croscarmellose sodium), wherein the eslicarbazepine acetate and part of the disintegrant are present in granules prepared by wet granulation, and the remaining part of the disintegrant is extragranular, and wherein the preparation has a bulk density of at least 0.3 g/mL.
  • a pharmaceutical preparation comprising eslicarbazepine acetate in combination with a binder (povidone) and a disintegrant (croscarmellose sodium), wherein the eslicarbazepine acetate and part of the disintegrant are present in granules prepared by wet granulation, and the remaining part of the disintegrant is extragranular, and wherein the preparation has a bulk density of at least 0.3 g/mL.
  • Said invention also provides a method of preparing a pharmaceutical preparation, and optionally an oral dosage form, comprising a binder and a disintegrant, the method comprising the steps of mixing eslicarbazepine acetate with part of the total amount of binder and part of the disintegrant; providing a granulation liquid; dissolving or dispersing the remaining proportion of the total amount of the binder in the granulation liquid; granulating the mixture from the mixing step using the granulation liquid produced in the dissolving or dispersing step to produce granules; contacting the granules with the remaining part of the disintegrant to form a preparation having a bulk density of at least 0.3 g/mL, and optionally forming an oral dosage form.
  • CN 105560251 A relates to an eslicarbazepine acetate pharmaceutical composition comprising pregelatinized starch in a specific weight ratio. Said pharmaceutical composition is prepared by wet granulation.
  • CN 106913550 A relates to a tablet composition comprising eslicarbazepine acetate, croscarmellose sodium, povidone, magnesium stearate, wherein part of the croscarmellose sodium is internally added and the remaining part is externally added; part of the povidone is internally added and the remaining part is externally added.
  • the preparation method comprises the steps of API crushing; mixing of granulating substances; wet granulation; drying; size stabilization; addition of excipients and mixing; and tabletting. Said pharmaceutical composition is prepared by wet granulation.
  • PCT application WO 2017/103876 A1 relates to a high drug load solid oral pharmaceutical composition
  • a high drug load solid oral pharmaceutical composition comprising eslicarbazepine acetate and at least one excipient, wherein binder is present either in intra-granular or in extra-granular part of composition; or wherein binder is present in intra-granular part of the composition in dispersion form (granulation liquid/binder solution); or wherein intra-granular part of the composition comprises disintegrant and optionally binder in dry powder form and/or dispersion form and extra-granular part of the composition is free of disintegrant and/or binder.
  • high drug load refers to eslicarbazepine acetate in the range of about 30% to about 97% by weight, preferably in the range of about 60% to about 95% by weight on the basis of the total weight of the composition.
  • High drug load solid oral pharmaceutical composition of the invention is prepared by any conventional wet or dry process. However, only the tablet dosage form prepared in Example 6 has been shown to exhibit a dissolution profile similar to that of the commercially available reference product, to be bioequivalent to the reference product and to be stable; and said dosage form is prepared by wet granulation.
  • wet granulation method has been preferred for the preparation of said pharmaceutical compositions.
  • wet granulation has benefits of good particle size distribution and good flow, it requires multiple time- consuming and expensive steps with a risk of over-granulation.
  • binder selection, method of addition of the binder, the effect of drying time and temperature on drug stability and its distribution within the solid mass are all the problems to be taken into consideration.
  • PCT application WO 2012/091593 A1 relates to solid pharmaceutical composition in the form of granules comprising eslicarbazepine acetate.
  • Granule formulation of the invention has been described as providing production of homogeneous colored granules, narrower particle size distribution and better flowability.
  • PCT application WO 2011/031176 A1 relates to oral suspension formulation comprising eslicarbazepine acetate.
  • Oral suspension formulation of the invention has been described as providing good physical stability properties such as low levels of sedimentation and easy re dispersion on agitation; a wide range of API particle sizes; good aspect such as low production of foam and homogeneity of suspension and low sediment compaction.
  • European patent application EP 2441438 A1 relates to oral water-dispersible pharmaceutical formulation comprising eslicarbazepine acetate.
  • Sachet formulation of the invention has been described as providing easy application, desired solubility and a dissolution rate, desired level of bioavailability and a formulation not leading to flowability -related problems.
  • Tablet forms are the most widely used solid dosage forms because of their advantages such as providing unit dosage forms with accurate and stable dose, great precision, less variability; protection of medicaments from atmospheric conditions like air, moisture and light; prolonged stability to medicaments with respect to physical, chemical and microbiological attributes; cheap oral dosage form due to the low manufacturing, packing and storage cost as compare to other solid dosage forms; easy to handle manufacturing; large scale production. Therefore, tablet forms are preferable compared to above-mentioned alternative dosage forms.
  • Eslicarbazepine acetate exhibits some problems on industrial-scale. Eslicarbazepine acetate has extremely low bulk density leading to poor flowability. When the particles are compressed, brittle behaviour has been observed. Due to its low plastic deformation ability, compressibility is low and flowability is very, very poor. Therefore, it can be difficult to handle and compress. Eslicarbazepine acetate is also reported to be poorly soluble in water which leads to poor dissolution and administration of a high dose of the drug in order to achieve desired therapeutic effect. Poor aqueous solubility, flowability, compressibility and high dose of the drug lead to technical challenges in the development of a desired formulation. These difficulties indicate that there is still a need for alternative formulations of eslicarbazepine acetate with enhanced solubility, flowability and compressibility together with stability and longer shelf life.
  • the present invention relates to a pharmaceutical composition of eslicarbazepine acetate, wherein the composition comprises a mixture of eslicarbazepine acetate, at least one binder and optionally at least one further pharmaceutically acceptable excipient subjected to at least two times compaction and dry granulation.
  • the present invention relates to a method of preparing a pharmaceutical composition of eslicarbazepine acetate, wherein the method comprises following steps:
  • the present invention relates to a pharmaceutical composition of eslicarbazepine acetate, wherein the composition comprises a mixture of eslicarbazepine acetate, at least one binder and optionally at least one further pharmaceutically acceptable excipient subjected to at least two times compaction and dry granulation, for use as an anticonvulsant.
  • Eslicarbazepine acetate has a low bulk density being 0.18 - 0.47 g/ml. It has been observed that particles of the active ingredient usually exhibit brittle behaviour when compressed. Because the active ingredient exhibits very little plastic deformation, compactibility characteristic is not good. Little or no powder flow has been observed. Because Carr’s index is greater than 42%, flowability is considered to be“very, very poor” (USP ⁇ 1174>). Even when the inventors tried to reduce the concentration of the active ingredient to 66.7%, powder could not flow through 15 mm funnel. Futhermore, bulk density of such a powder mixture being 0.35 - 0.45 g/ml had a volume of 2.7 - 3.4 ml. Accordingly, swallowing these large-sized tablets would be difficult. Therefore, direct powder mixing and direct compression methods were not suitable in the preparation of the pharmaceutical compositions of eslicarbazepine acetate.
  • Briquette press has been performed at the first trial of dry granulation method. However, powder flow was so poor that compressing the tablets under fixed compression force was not possible. Because the amount of the powder filled into die cavity was not consistent, some of the pressed tablets were hard, some were soft. Low-weight tablets were more friable. Inventors performed other trials in order to provide good flow, but failed. Accordingly, briquette press has not been found applicable.
  • the present invention relates to a pharmaceutical composition of eslicarbazepine acetate, wherein the composition comprises a mixture of eslicarbazepine acetate, at least one binder and optionally at least one further pharmaceutically acceptable excipient subjected to at least two times compaction and dry granulation.
  • compositions of the present invention include eslicarbazepine acetate preferably in an amount of about 20 to about 95 wt%, more preferably about 40 to about 92 wt%, most preferably about 60 to about 90 wt% of the composition.
  • compositions of the present invention include at least one further pharmaceutically acceptable excipient.
  • Further pharmaceutically acceptable excipients of the invention may be selected from the group comprising, without limitation, diluents, disintegrants, lubricants, glidants, or a combination thereof.
  • Binder(s) of the invention may include, but are not limited to, starches (pre-gelatinized starch, sodium starch glycolate, etc.), sugars (dextrin, maltodextrin, dextrose, polydextrose, maltose, sucrose, etc.), cellulose derivatives (carboxymethylcellulose calcium, carboxymethylcellulose sodium, low substituted hydroxypropyl cellulose, methylcellulose, ethylcellulose, hydroxyethyl cellulose, hydroxyethylmethyl cellulose, hydroxypropyl cellulose, hypromellose, microcrystalline cellulose, etc.), com sweeteners, natural and synthetic gums (acacia gum, guar gum, etc.), gelatin, povidone, polyethylene glycol, polyethylene oxide, polyvinyl alcohols, polymethacrylates, waxes, alginic acid, sodium alginate, cottonseed oil, hydrogenated vegetable oil, carbomer, magnesium aluminium silicate, stearic acid, alcohols, water,
  • Binder(s) of the invention preferably include povidone.
  • Pharmaceutical compositions of the invention comprise the binder preferably in an amount of about 0.5 to about 30 wt%, more preferably about 1 to about 20 wt%, most preferably about 2 to about 15 wt% of the composition.
  • Diluent(s) of the invention may include, but are not limited to, monosaccharides (fructose, galactose, glucose, dextrose, etc.), disaccharides (lactose, maltose, sucrose, trehalose, etc.), oligosaccharides (dextranes, dextrins, maltodextrins, etc.), polysaccharides (cellulose derivatives such as microcrystalline cellulose, starches such as pre-gelatinized starch, etc.), sugar alcohols (mannitol, sorbitol, xylitol, lactitol, etc.), amino acids (arginine, glycine, etc.), calcium carbonate, calcium sulphate, magnesium carbonate, magnesium oxide, dibasic calcium phosphate anhydrous, dibasic calcium phosphate dihydrate, tribasic calcium phosphate, kaolin, sodium alginate, sodium chloride and/or mixtures thereof.
  • monosaccharides fructos
  • Diluent(s) of the invention preferably include microcrystalline cellulose.
  • Pharmaceutical compositions of the invention comprise the diluent preferably in an amount of up to about 70 wt%, more preferably about 2 to about 50 wt%, most preferably about 5 to about 30 wt% of the composition.
  • Disintegrant(s) of the invention may include, but are not limited to, starches (pre-gelatinized starch, sodium starch glycolate, etc.), cellulose derivatives (carboxymethylcellulose calcium, carboxymethylcellulose sodium, low substituted hydroxypropyl cellulose, methylcellulose, microcrystalline cellulose, croscarmellose sodium, etc.), povidone, crospovidone, colloidal silicon dioxide, magnesium aluminum silicate, tribasic calcium phosphate, guar gum, clays, ion exchange resins, alginic acid, sodium alginate, and/or mixtures thereof.
  • Disintegrant(s) of the invention preferably include croscarmellose sodium.
  • Pharmaceutical compositions of the invention comprise the disintegrant preferably in an amount of about 0.5 to about 20 wt%, more preferably about 1 to about 15 wt%, most preferably about 2 to about 10 wt% of the composition.
  • Lubricant(s) of the invention may include, but are not limited to, sodium stearyl fumarate, stearic acid, metallic stearates (magnesium stearate, calcium stearate, zinc stearate, etc.), glyceryl monostearate, glyceryl palmitostearate, glyceryl behenate, metallic lauryl sulfates (sodium lauryl sulphate, magnesium lauryl sulphate, etc.), poloxamer, medium-chain triglycerides, fatty acids, fatty acid esters, fatty alcohols, paraffins, hydrogenated vegetable oils, hydrogenated castor oil, polyethylene glycols, boric acid, sodium benzoate, sodium acetate, sodium chloride, talc, and/or mixtures thereof.
  • Lubricant(s) of the invention preferably include magnesium stearate.
  • Pharmaceutical compositions of the invention comprise the lubricant preferably in an amount of about 0.1 to about 10 wt%, more preferably about 0.1 to about 5 wt%, most preferably about 0.1 to about 3 wt% of the composition.
  • Glidant(s) of the invention may include, but are not limited to, colloidal silicon dioxide, magnesium silicate, magnesium trisilicate, calcium silicate, tribasic calcium phosphate, cellulose, starch, talc, and/or mixtures thereof.
  • Pharmaceutical compositions of the invention comprise the glidant preferably in an amount of about 0.1 to about 10 wt%, more preferably about 0.1 to about 5 wt%, most preferably about 0.1 to about 3 wt% of the composition.
  • the pharmaceutical composition of eslicarbazepine acetate wherein the composition comprises a mixture of eslicarbazepine acetate, at least one binder and optionally at least one further pharmaceutically acceptable excipient subjected to at least two times compaction and dry granulation provided enhanced solubility, flowability and compressibility together with stability, longer shelf life and safety.
  • the extent of the invention should not be limited by the following examples of the pharmaceutical compositions and preparation method of these pharmaceutical compositions. The examples below are only given to illustrate the invention.
  • a method of preparing the pharmaceutical compositions of the invention comprises following steps:
  • compositions of the invention can be in the form of a solid oral dosage form, such as a tablet or capsule.
  • the step of forming an oral dosage form comprises compression into a tablet.
  • the step of forming an oral dosage form comprises filling a capsule.
  • compositions of the invention are suitable for use as an anticonvulsant.

Landscapes

  • Health & Medical Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • Epidemiology (AREA)
  • Pain & Pain Management (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

La présente invention concerne une composition pharmaceutique d'acétate d'eslicarbazépine, la composition comprenant un mélange d'acétate d'eslicarbazépine, d'au moins un liant et éventuellement d'au moins un autre excipient pharmaceutiquement acceptable soumis à un compactage au moins deux fois et à une granulation à sec ; un procédé de préparation d'une composition pharmaceutique d'acétate d'eslicarbazépine, le procédé comprenant les étapes de compactage au moins deux fois d'un mélange d'acétate d'eslicarbazépine, d'au moins un liant et éventuellement d'au moins un autre excipient pharmaceutiquement acceptable ; d'une granulation à sec du mélange compacté au moins deux fois ; et éventuellement de formation d'une forme posologique orale ; une composition pharmaceutique d'acétate d'eslicarbazépine, la composition comprenant un mélange d'acétate d'eslicarbazépine, d'au moins un liant et éventuellement d'au moins un autre excipient pharmaceutiquement acceptable soumis à un compactage au moins deux fois et à une granulation à sec, pour une utilisation en tant qu'anticonvulsivant.
PCT/TR2018/050850 2018-12-20 2018-12-20 Compositions pharmaceutiques orales d'eslicarbazépine Ceased WO2020130960A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/TR2018/050850 WO2020130960A1 (fr) 2018-12-20 2018-12-20 Compositions pharmaceutiques orales d'eslicarbazépine

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/TR2018/050850 WO2020130960A1 (fr) 2018-12-20 2018-12-20 Compositions pharmaceutiques orales d'eslicarbazépine

Publications (1)

Publication Number Publication Date
WO2020130960A1 true WO2020130960A1 (fr) 2020-06-25

Family

ID=71101516

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/TR2018/050850 Ceased WO2020130960A1 (fr) 2018-12-20 2018-12-20 Compositions pharmaceutiques orales d'eslicarbazépine

Country Status (1)

Country Link
WO (1) WO2020130960A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115192531A (zh) * 2021-04-14 2022-10-18 北京万全德众医药生物技术有限公司 一种醋酸艾司卡西平片制备及其制备方法

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017103876A1 (fr) * 2015-12-18 2017-06-22 Jubilant Generics Limited Formes galéniques solides orales de l'eslicarbazépine

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017103876A1 (fr) * 2015-12-18 2017-06-22 Jubilant Generics Limited Formes galéniques solides orales de l'eslicarbazépine

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
BULTMANN, J. M.: "Multiple compaction of microcrystalline cellulose in a roller compactor", EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, vol. 54, no. 1, 2002, pages 59 - 64, XP004367692, DOI: 10.1016/S0939-6411(02)00047-4 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN115192531A (zh) * 2021-04-14 2022-10-18 北京万全德众医药生物技术有限公司 一种醋酸艾司卡西平片制备及其制备方法

Similar Documents

Publication Publication Date Title
EP1410797B1 (fr) Formes orales solides comprenant du valsartan
CA2955495C (fr) Comprimes de rucaparib a dosage eleve
CA2722093C (fr) Compositions pharmaceutiques comprenant du brivaracetam
KR20110112266A (ko) 활성 성분의 방출을 조절할 수 있는 가분성 생약 형태
EP3402488B1 (fr) Formes galéniques solides orales de l'eslicarbazépine
EP2197428B1 (fr) Composition pharmaceutique amelioree contenant un agent anticonvulsif a base de pyrrolidone et son procede de preparation
JP2020070260A (ja) テネリグリプチン含有医薬組成物、テネリグリプチン含有医薬組成物の製造方法、テネリグリプチン含有錠剤及びテネリグリプチン含有錠剤の製造方法
US20130058876A1 (en) (trimethoxyphenylamino) pyrimidinyl formulations
JP2020114834A (ja) セリチニブ製剤
CN109875972B (zh) 一种奥美沙坦酯氨氯地平药物组合物
WO2020130960A1 (fr) Compositions pharmaceutiques orales d'eslicarbazépine
CA2677125A1 (fr) Preparations de matieres medicamenteuses, compositions pharmaceutiques et formes pharmaceutiques
ES2968510T3 (es) Forma de dosificación que proporciona liberación prolongada de sal de ácido fosfórico de Tapentadol
WO2006123213A1 (fr) Preparations a liberation modifiee de gliclazide
US20160022661A1 (en) Dosage Form Comprising Crizotinib
US20070059354A1 (en) Sustained release dosage forms of oxcarbazepine
EP2044933A1 (fr) Système de matrice à multi-particules contenant de la galantamine
KR101944085B1 (ko) 발사르탄 함유 고형 경구제형 및 그 제조방법
RU2214243C2 (ru) Твердая лекарственная форма на основе карведилола
WO2017163268A2 (fr) Forme d'administration pharmaceutique du divalproex à libération prolongée
JP2014040379A (ja) 疎水性薬物を含む錠剤製造方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 18943763

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 18943763

Country of ref document: EP

Kind code of ref document: A1