EP3976001A1 - Tablet formulations of apremilast - Google Patents

Tablet formulations of apremilast

Info

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
Application number
EP20813638.2A
Other languages
German (de)
French (fr)
Other versions
EP3976001A4 (en
Inventor
Gulcin TOK
Ediz Yildirim
Merve USTUN OZDEMIR
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.)
Sanovel Ilac Sanayi ve Ticaret AS
Original Assignee
Sanovel Ilac Sanayi ve Ticaret 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 Sanovel Ilac Sanayi ve Ticaret AS filed Critical Sanovel Ilac Sanayi ve Ticaret AS
Publication of EP3976001A1 publication Critical patent/EP3976001A1/en
Publication of EP3976001A4 publication Critical patent/EP3976001A4/en
Pending 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
    • A61K9/205—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:

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  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Immunology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Rheumatology (AREA)
  • Medicinal Preparation (AREA)

Abstract

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.

Description

TABLET FORMULATIONS OF APREMILAST
Field of the Invention
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.
Background of the Invention
Psoriatic arthritis (PsA) 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.
No cure for psoriatic arthritis exists, so the focus is on controlling symptoms and preventing damage to your joints. Without treatment, psoriatic arthritis may be disabling.
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.
Apremilast is at present available only as an oral formulation, marketed by Celgene Corp, under the trade name of OTEZLA®. 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.
Apremilast is an orally-active small molecule which inhibits phosphodiesterase-4 (PDE4). When PDE4 is inhibited in immune cells, it results in elevation of intracellular cyclic adenosine monophosphate (cAMP) levels, which can regulate inflammatory mediators. Clinical trials have demonstrated its efficacy and safety in psoriatic arthritis (PsA) and psoriasis. Established therapeutic options have variable effectiveness across the different domains of psoriatic disease. Apremilast is chemically identified as N-[2-[ (1 S)-1 -(3- ethoxy- 4- methoxyphenyl)-2- (methylsulfonyl) ethyl]-2,3-dihydro-1 ,3-dioxo-1 H-isoindol-4-yl]acetamide. The chemical structure is shown in Formula I.
Formula I
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.
There remains a need in the art for pharmaceutical composition of apremilast with improved properties. In particular, 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.
It has now surprisingly been found that at least one of the above properties can be achieved by the solid forms of the present invention. Detailed Description of the Invention
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 a substance that is very poorly soluble in water and low permeability according to Biopharmaceutical Classification System (i.e. BCS Class 4). So, the main effort is focused on finding a form that would be soluble in water as much as possible, thus showing the highest bioavailability of the drug in the organism.
According to one embodiment of the present invention, apremilast is used in form B. So, the mentioned disadvantage of apremilast disappeared.
According to the main embodiment of the present invention, 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.
Considering the properties of the active substance, the used disintegrant rate is very important in the tablet formulation. Dissolution problems are solved and surprisingly better dissolution profile is gained.
According to one embodiment of the present invention, 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.
According to one embodiment of the present invention, the disintegrant is croscarmellose sodium.
According to one embodiment of the present invention, 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. According to one embodiment of the present invention, 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.
According to one embodiment of the present invention, the filler is microcrystalline cellulose or lactose or lactose anhydrous or lactose monohydrate or mixtures thereof.
According to one embodiment of the present invention, 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.
According to one embodiment of the present invention, the binder is polyvinylpyrrolidone.
According to one embodiment of the present invention, 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.
According to one embodiment of the present invention, the lubricant is magnesium stearate or silica colloidal anhydrous or mixtures thereof.
According to one embodiment of the present invention, 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.
According to one embodiment of the present invention, the present tablet formulation comprises the coating agents to protect the formulation against the moisture and light, so it provides better stability. Especially, when hydroxypropyl cellulose, hydroxypropyl methylcellulose is used as coating agents, the desired stability is provided.
According to one embodiment of the present invention, 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:
- Sieving apremilast for B, lactose, microcrystalline cellulose, croscarmellose sodium and mixing them for 15 minutes
- Adding magnesium stearate and silica colloidal anhydrous and mixing them
- Compressing the total mixture into tablets
- Coating* the tablets. * The coating:
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:
- Adding apremilast for B, lactose monohydrate, microcrystalline cellulose, a part of croscarmellose sodium (1/3), polyvinylpyrrolidone and mixing them for 10 minutes
- Adding water into the mixture to obtained granules
- Then, drying the granules
- Adding the remained of croscarmellose sodium and mixing
- Adding magnesium stearate and silica colloidal anhydrous and mixing them
- Compressing the total mixture into tablets
- Coating* the tablets.
* The coating

Claims

1 . A tablet formulation comprising apremilast form B, 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 of the total tablet.
2. The tablet formulation according to claim 1 , wherein the amount of disintegrant is between 6.0% and 20.0% by weight of the total tablet.
3. The tablet formulation according to claim 2, wherein the amount of disintegrant is between 10.0% and 17.0% by weight of the total tablet.
4. The tablet formulation according to claim 1 , wherein the disintegrants are selected from the group comprising croscarmellose sodium, sodium starch glycolate, alginic acid, crospovidone, sodium alginate, starch or mixtures thereof.
5. The tablet formulation according to claim 1 , wherein the amount of apremilast form B in the tablet is 3.0% to 25.0% by weight.
6. The tablet formulation according to claim 1 , further comprising at least one pharmaceutically acceptable excipient which is selected from fillers, binders, lubricants, coating agents or mixtures thereof.
7. The tablet formulation according to claim 6, wherein the 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.
8. The tablet formulation according to claim 6, wherein the 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.
9. The tablet formulation according to claim 6, wherein the 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.
10. The tablet formulation according to claim 6, wherein the coating agents are selected from the group comprising hydroxypropyl cellulose, hydroxypropyl methylcellulose, polymethacrylates, talc, polyvinyl alcohol, polyethylene glycol, talc, polyvinyl alcohol- polyethylene glycol copolymers, ethylcellulose dispersions, polyvinylpyrrolidone-vinyl acetate copolymer, titanium dioxide, iron oxide yellow, quinoline yellow aluminum or mixtures thereof.
1 1. The tablet formulation according to claim 10, wherein the coating agent is hydroxypropyl cellulose or hydroxypropyl methylcellulose or mixtures thereof.
12. The tablet formulation according to claim 1 , for use intreating or preventing arthritic conditions.
EP20813638.2A 2019-05-31 2020-04-15 TABLET FORMULATIONS OF APREMILAST Pending EP3976001A4 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TR2019/08440A TR201908440A2 (en) 2019-05-31 2019-05-31 APREMILASTIN TABLET FORMULATIONS
PCT/TR2020/050318 WO2020242414A1 (en) 2019-05-31 2020-04-15 Tablet formulations of apremilast

Publications (2)

Publication Number Publication Date
EP3976001A1 true EP3976001A1 (en) 2022-04-06
EP3976001A4 EP3976001A4 (en) 2023-04-26

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
EP20813638.2A Pending EP3976001A4 (en) 2019-05-31 2020-04-15 TABLET FORMULATIONS OF APREMILAST

Country Status (3)

Country Link
EP (1) EP3976001A4 (en)
TR (1) TR201908440A2 (en)
WO (1) WO2020242414A1 (en)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP4183389A1 (en) 2021-11-18 2023-05-24 KRKA, d.d., Novo mesto Pharmaceutical composition comprising apremilast
CN114533691A (en) * 2022-03-21 2022-05-27 成都百裕制药股份有限公司 Apremilast tablet and industrial preparation method thereof
JP2023140859A (en) * 2022-03-23 2023-10-05 東和薬品株式会社 Method for manufacturing tablets containing apremilast, tablets containing apremilast, and method for improving tableting properties of tablets containing apremilast
CN116531326B (en) * 2023-04-26 2023-11-14 广东嘉博制药有限公司 Oral emulsion of apremilast and preparation method thereof

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3373916A1 (en) * 2015-11-11 2018-09-19 Celgene Corporation Controlled release oral dosage forms of poorly soluble drugs and uses thereof
EP3455209A1 (en) * 2016-05-12 2019-03-20 Zaklady Farmaceutyczne Polpharma SA Crystalline forms of apremilast
CN107115310A (en) * 2017-04-12 2017-09-01 广州艾格生物科技有限公司 A kind of Apremilast oral solid formulation and preparation method thereof
US20200330433A1 (en) 2017-10-10 2020-10-22 Mankind Pharma Ltd. Extended release pharmaceutical composition of apremilast

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EP3976001A4 (en) 2023-04-26
WO2020242414A1 (en) 2020-12-03

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