EP3976001A1 - Formulations de comprimés d'aprémilast - Google Patents
Formulations de comprimés d'aprémilastInfo
- Publication number
- EP3976001A1 EP3976001A1 EP20813638.2A EP20813638A EP3976001A1 EP 3976001 A1 EP3976001 A1 EP 3976001A1 EP 20813638 A EP20813638 A EP 20813638A EP 3976001 A1 EP3976001 A1 EP 3976001A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- tablet formulation
- formulation according
- tablet
- mixtures
- sodium
- 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.)
- Pending
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
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
- A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
- A61K31/4035—Isoindoles, e.g. phthalimide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- 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
- A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
- A61K9/2806—Coating materials
- A61K9/2833—Organic macromolecular compounds
- A61K9/286—Polysaccharides, e.g. gums; Cyclodextrin
- A61K9/2866—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
Definitions
- the present invention relates to tablet formulations of apremilast or a pharmaceutically acceptable salt, solvate or polymorph thereof used for the treating or preventing of psoriatic arthritis and/or psoriasis. It further relates to processes of preparation of the formulations and the method of use for these formulations.
- Psoriatic arthritis is a chronic immune disease which is a type of arthritis that develops in some people with the skin condition psoriasis. Manifestations of PsA include swollen and tender joints, pain, and enthesitis and dacylitis, which are associated with impaired physical function and health-related quality of life.
- Psoriasis is a chronic, non-contagious skin disorder that appears in many different forms and can affect any part of the body.
- the most common type of psoriasis is plaque psoriasis, occurring in 80% of people suffering from the disease.
- Plaque psoriasis is characterized by red patches and lesions that are covered by a build-up of skin cells that are often called scales, and most commonly seen on the elbows, knees, scalp and back.
- Psoriasis is classified as mild, moderate, or severe, depending on the percentage of body surface involved and severity of the disease.
- OTEZLA® tablets are supplied in 10, 20, and 30 mg strengths for oral administration. OTEZLA® tablets are indicated for the treatment of patients with active psoriatic arthritis and for the treatment of patients with moderate to severe psoriasis who are candidates for phototherapy or systemic therapy.
- PDE4 phosphodiesterase-4
- cAMP cyclic adenosine monophosphate
- Apremilast is a substance that is very poorly soluble in water and has low permeability according to Biopharmaceutical Classification System (i.e. BCS Class 4).
- Apremilast is an optically pure form was first described in the patent application W02003080049.
- An experiment conducted according to an example included in this application provided apremilast form B.
- This form is described with the use of X-ray powder diffraction and thermal methods in the following patent application W02009120167, which describes forms A to G and an amorphous form.
- Forms A, B and F are described as pure polymorphic forms of apremilast, forms C, D, E and G as solvates of apremilast (form C - toluene, form D - dichloromethane, form E - acetonitrile, form G - ethyl acetate).
- WO2017168433A1 patent application discloses a topical pharmaceutical composition of apremilast.
- WO 20171 18447 patent application discloses a method for preparing amorphous apremilast from crystalline form I of apremilast and a formulation comprising amorphous apremilast and at least one pharmaceutically acceptable excipient.
- a solid form of apremilast should exhibit at least one of the following properties: adequate dissolution properties; stability and be easily prepared with good content uniformity.
- the main object of the present invention is to provide a formulation with high stability, having the desired level of dissolution rate and desired compressibility which overcomes the above described problems in the prior art and have additive advantages over them.
- apremilast is used in form B. So, the mentioned disadvantage of apremilast disappeared.
- the tablet formulation comprises apremilast form B with at least one pharmaceutically acceptable excipient and at least one disintegrant whose total amount in the tablet is between 6.0% and 30.0% by weight.
- the used disintegrant rate is very important in the tablet formulation. Dissolution problems are solved and surprisingly better dissolution profile is gained.
- the amount of disintegrant is between 6.0% and 20.0% or between 10.0% and 17.0% or between 1 1.0% and 15.0% by weight of the total formulation.
- Suitable disintegrants are selected from the group comprising croscarmellose sodium, sodium starch glycolate, alginic acid, crospovidone, sodium alginate, starch or mixtures thereof.
- the disintegrant is croscarmellose sodium.
- the amount of apremilast form B in the tablet is 3.0% to 25.0%, preferably 5.0% to 20.0%, more preferably 7.0% to 13.0% by weight.
- the tablet formulation comprises at least one pharmaceutically acceptable excipient which is selected from fillers, binders, lubricants, coating agents or mixtures thereof.
- Suitable fillers are selected from the group comprising microcrystalline cellulose, lactose, lactose anhydrous, lactose monohydrate, mannitol, spray-dried mannitol, starch, dextrose, sucrose, fructose, maltose, sorbitol, xylitol, inositol, kaolin, inorganic salts, calcium salts, polysaccharides, dicalcium phosphate, sodium chloride, dextrates, lactitol, maltodextrin, sucrose-maltodextrin mixture, trehalose, sodium carbonate, sodium bicarbonate, calcium carbonate, polyols, dextrose, maltitol or mixtures thereof.
- the filler is microcrystalline cellulose or lactose or lactose anhydrous or lactose monohydrate or mixtures thereof.
- the amount of the total fillers is between 50.0% to 85.0%, preferably between 65.0% to 80.0% by weight of the total tablet formulation.
- Suitable binders are selected from the group comprising polyvinylpyrrolidone, starch, dibasic calcium phosphate, tribasic calcium phosphate, isomalt, sodium carbonate, sodium bicarbonate, calcium carbonate, carboxymethyl cellulose, polydextrose, polyethylene oxide, hydroxypropyl methyl cellulose, methyl cellulose, polyethylene glycol or mixtures thereof.
- the binder is polyvinylpyrrolidone.
- the amount of binder is between 1 .0% and 15.0%, preferably between 1.0% and 10.0% by weight of the total formulation.
- Suitable lubricants are selected from the group comprising magnesium stearate, silica colloidal anhydrous, sodium stearyl fumarate, talc, polyethylene glycol, stearic acid, aluminum silicate or mixtures thereof.
- the lubricant is magnesium stearate or silica colloidal anhydrous or mixtures thereof.
- the amount of lubricant is between 1 .0% and 5.0% by weight of the total formulation.
- Suitable coating agents are selected from the group comprising hydroxypropyl cellulose, hydroxypropyl methylcellulose, polymethacrylates, talc, polyvinyl alcohol (PVA), polyethylene glycol (PEG), talc, polyvinyl alcohol-polyethylene glycol copolymers (Kollicoat® IR), ethylcellulose dispersions (Surelease®), polyvinylpyrrolidone-vinyl acetate copolymer (PVP- VA), titanium dioxide, iron oxide yellow, quinoline yellow aluminum, all kinds of Opadry®, pigments, dyes or mixtures thereof.
- the present tablet formulation comprises the coating agents to protect the formulation against the moisture and light, so it provides better stability.
- the coating agents to protect the formulation against the moisture and light, so it provides better stability.
- the desired stability is provided.
- the amount of coating agents is between 1.0% and 6.0% by weight of the total formulation.
- the tablet formulation of the present invention is prepared, using standard techniques and manufacturing processes well known in the art, such as direct compression, wet or dry granulation, hot melt granulation, hot melt extrusion, fluidized bed granulation, extrusion/spheronization, slugging, spray drying and solvent evaporation.
- the tablet formulation comprising apremilast form B is for use intreating or preventing arthritic conditions.
- Example 1 The tablet formulation processed with direct compression
- Example 2 The tablet formulation processed with direct compression
- Example 3 The tablet formulation processed with direct compression
- Example 4 The tablet formulation processed with direct compression Process for example 1 or 2 or 3 or 4:
- a process for preparing the tablet formulation comprising apremilast for B in example 1 or 2 comprises the following steps:
- Example 5 The tablet formulation processed with wet granulation
- Example 6 The tablet formulation processed with wet granulation
- Example 7 The tablet formulation processed with wet granulation
- Example 8 The tablet formulation processed with wet granulation Process for example 5 or 6 or 7 or 8:
- a process for preparing the tablet formulation comprising apremilast for B in example 3 or 4 comprises the following steps:
Landscapes
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical & Material Sciences (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Physical Education & Sports Medicine (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Rheumatology (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Preparation (AREA)
Abstract
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
TR2019/08440A TR201908440A2 (tr) | 2019-05-31 | 2019-05-31 | Apremi̇lastin tablet formülasyonlari |
PCT/TR2020/050318 WO2020242414A1 (fr) | 2019-05-31 | 2020-04-15 | Formulations de comprimés d'aprémilast |
Publications (2)
Publication Number | Publication Date |
---|---|
EP3976001A1 true EP3976001A1 (fr) | 2022-04-06 |
EP3976001A4 EP3976001A4 (fr) | 2023-04-26 |
Family
ID=73553856
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP20813638.2A Pending EP3976001A4 (fr) | 2019-05-31 | 2020-04-15 | Formulations de comprimés d'aprémilast |
Country Status (3)
Country | Link |
---|---|
EP (1) | EP3976001A4 (fr) |
TR (1) | TR201908440A2 (fr) |
WO (1) | WO2020242414A1 (fr) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP4183389A1 (fr) | 2021-11-18 | 2023-05-24 | KRKA, d.d., Novo mesto | Composition pharmaceutique comprenant de l'aprémilast |
CN114533691A (zh) * | 2022-03-21 | 2022-05-27 | 成都百裕制药股份有限公司 | 一种阿普米司特片剂及其工业化制备方法 |
CN116531326B (zh) * | 2023-04-26 | 2023-11-14 | 广东嘉博制药有限公司 | 一种阿普米司特的口服乳剂及其制备方法 |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2017083348A1 (fr) * | 2015-11-11 | 2017-05-18 | Celgene Corporation | Formes pharmaceutiques orales à libération contrôlée de médicaments faiblement solubles et leurs utilisations |
EP3455209A1 (fr) * | 2016-05-12 | 2019-03-20 | Zaklady Farmaceutyczne Polpharma SA | Formes cristallines de l'aprémilast |
CN107115310A (zh) * | 2017-04-12 | 2017-09-01 | 广州艾格生物科技有限公司 | 一种阿普斯特口服固体制剂及其制备方法 |
WO2019073477A1 (fr) | 2017-10-10 | 2019-04-18 | Mankind Pharma Ltd. | Composition pharmaceutique d'aprémilast à libération prolongée |
-
2019
- 2019-05-31 TR TR2019/08440A patent/TR201908440A2/tr unknown
-
2020
- 2020-04-15 EP EP20813638.2A patent/EP3976001A4/fr active Pending
- 2020-04-15 WO PCT/TR2020/050318 patent/WO2020242414A1/fr unknown
Also Published As
Publication number | Publication date |
---|---|
EP3976001A4 (fr) | 2023-04-26 |
WO2020242414A1 (fr) | 2020-12-03 |
TR201908440A2 (tr) | 2020-12-21 |
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Legal Events
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STAA | Information on the status of an ep patent application or granted ep patent |
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PUAI | Public reference made under article 153(3) epc to a published international application that has entered the european phase |
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Effective date: 20211129 |
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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 |
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DAV | Request for validation of the european patent (deleted) | ||
DAX | Request for extension of the european patent (deleted) | ||
A4 | Supplementary search report drawn up and despatched |
Effective date: 20230323 |
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RIC1 | Information provided on ipc code assigned before grant |
Ipc: A61K 9/28 20060101ALI20230317BHEP Ipc: A61P 19/02 20060101ALI20230317BHEP Ipc: A61K 31/4035 20060101ALI20230317BHEP Ipc: A61K 9/20 20060101AFI20230317BHEP |
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P01 | Opt-out of the competence of the unified patent court (upc) registered |
Effective date: 20230708 |