WO2016114726A1 - Comprimé de prednisone à libération retardée régulée dans le temps - Google Patents

Comprimé de prednisone à libération retardée régulée dans le temps Download PDF

Info

Publication number
WO2016114726A1
WO2016114726A1 PCT/TR2015/000007 TR2015000007W WO2016114726A1 WO 2016114726 A1 WO2016114726 A1 WO 2016114726A1 TR 2015000007 W TR2015000007 W TR 2015000007W WO 2016114726 A1 WO2016114726 A1 WO 2016114726A1
Authority
WO
WIPO (PCT)
Prior art keywords
coating
core
tablet
axis
prednisone
Prior art date
Application number
PCT/TR2015/000007
Other languages
English (en)
Inventor
Hatice Öncel
Yilmaz Çapan
Onur PINARBAŞLI
Sibel AKANSEL
Original Assignee
Ilko Ilaç Sanayi Ve Ticaret Anonim Şirketi
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 Ilko Ilaç Sanayi Ve Ticaret Anonim Şirketi filed Critical Ilko Ilaç Sanayi Ve Ticaret Anonim Şirketi
Priority to PCT/TR2015/000007 priority Critical patent/WO2016114726A1/fr
Publication of WO2016114726A1 publication Critical patent/WO2016114726A1/fr

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
    • A61K9/28—Dragees; Coated pills or tablets, e.g. with film or compression coating
    • A61K9/2893—Tablet coating processes
    • 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
    • A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
    • A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
    • A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
    • 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
    • A61K9/2813—Inorganic compounds
    • 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
    • A61K9/282—Organic compounds, e.g. fats
    • 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
    • A61K9/284—Organic macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone

Definitions

  • the present invention is related to time-controlled delayed release tablet comprising prednisone whose release active ingredient from core after a lag time wherein said, time-controlled delayed release tablets are press-coated tablets comprising a core and a coating covering said core.
  • Prednisone is an active substance used as anti-inflammatory or immunosupresant and prodrug of prednisolone.
  • the chemical name for prednisone is 1 ,4-Pregnadiene- 17alpha,21-diol-3,11,20-trione. It is white, odourless and very slightly soluble in water and is available.
  • the structural formula is represented below:
  • Prednisone is generally recommended in the treatment of immunoinflamatory disorders like, ulcerative colitis, osteoarthritis, psoriasis, rheumatoid arthritis, Crohn's disease, ankylosing spondylit, fibromyalgia and autoimmune diseases such as asthma, type I diabetes, multiple sclerosis, systemic lupus erythematosus, scleroderma, atopic dermatitis and acquired hemolytic anemia.
  • immunoinflamatory disorders like, ulcerative colitis, osteoarthritis, psoriasis, rheumatoid arthritis, Crohn's disease, ankylosing spondylit, fibromyalgia and autoimmune diseases such as asthma, type I diabetes, multiple sclerosis, systemic lupus erythematosus, scleroderma, atopic dermatitis and acquired hemolytic anemia.
  • Time-controlled release formulations are known in the art that are able to deliver drug substances with a defined release rate after a lag time during which no drug substance is released.
  • the coating acts as a barrier to the ingress of aqueous media into an active- agent-containing core and thereby creating a lag time during which no drug substance is released.
  • the coating acts as a medium through which drug is released in a delayed or modified manner.
  • Time-controlled delayed release tablets allow treatment of diseases according to circadian rhythm. Especially if symptoms a disease become apparent at night, or in the early hours at morning, the time when a patient must take its medication in order to affect the best clinical outcome requires detailed consideration. For example, stiffnes and pain associated with rheumatoid arthritis and osteoarthritis occur in the early waking hours, which is believed to be as a result of the secretion of lnterleukin-6 (IL-6) in the early hours of the morning, e.g.
  • IL-6 lnterleukin-6
  • Time controlled delayed release formulations are known in the art that are able to deliver drug substances with a defined release after a lag time during which no drug substance is released.
  • Press-coated tablet is a type of these formulations.
  • Press-coated tablet consist of a core (fast disintegration or modified release) which is coated by compression with a solid barrier.
  • the barrier could contain polymeric material, diluents (as a release modifier).
  • Press- coated tablets could be modulated to provide different release patterns depending on the drug distribution and also with different type of controlling polymer used in core and coat. Based on this concept, the possibly obtainable modified drug releases are extended release and delayed release (time, pH and microbially control) for specific region of gastrointestinal tract.
  • a delayed release tablet consist of a drug core which is press-coated with different polymeric (pH independent) barriers. This delayed drug release is programmed for the treatment of disease that depends on circadian rhythms.
  • the lag time of drug release is controlled by the compression coating, which prevents drug release from the core until the polymer coat is completely eroded, swollen or ruptured. Drug release pattern depends on the compression-coat properties.
  • the press-coating could be performed with water soluble polymers (hydroxypropylcellulose, hydroxypropylmethylcellulose, pectin, polyethylene oxide), water insoluble polymer (ethylcellulose) and wax (Behenic acid).
  • Such a dosage form is disclosed in WO 02/072033.
  • This dosage form is characterized by a coating containing a natural or synthetic gum that gels in the presence of aqueousmedia.
  • the gellable coating act as a medium through which drug is released in a delayed or modified manner.
  • US 6,365,185 relates to tablets which are time-controlled to release active agent at different rates in different regions of the digestive tract in order to maintain a substantially constant concentration in the blood.
  • a modified release drug delivery system for once a day peroral use, consist of a solid core comprising an active agent together with hydrogel, with the solid core being coated with a semi-permeable, self destructing membrane which is optionally drilled to provide a release orifice, and then optionally further coated with the same or different active agent material.
  • the device delivers the active agent in a substantially constant effective dose for the duration of the transit through the stomach and small intestine, followed by accelerated release when reaching the large intestine.
  • EP1631251 B1 discloses the delayed release tablet core with a defined geometry.
  • the characteristic of the formulation is that, the coatingruptures upon immersion in an aqueous medium after a period of between about 2 to 6 hours to release the drug and the core being disposedwithin said coating such that the coating thickness about an axis (X- Y) is thicker than the coating about an axis (AB)orthogonal to (X-Y), and wherein the thickness of the coating about the axis (X-Y), wherein the axis (A-B) is the axis of the direction of movement of the punch used in the press-coating of the tablet.
  • the inventors also assert that the thickness of the coating around or about the axis (A-B) is not critical for controlling the lag time.
  • EP1615626 (Jagotec AG) is related to Prednisone delayed release tablet formulation with colored core. This patents relates to the use' of a colouring agent or excipient in such tablets to determine whether the core is centrally located within the core, to check the integrity of the core, and to ensure that there is no contaminating core material on or near the surface of the coating. Description of the Invention:
  • EP1631251 B1 discloses the coating ruptures upon immersion in an aqueous medium after a period of between about 2 to 6 hours to release the drug and the core being disposed within said coating such that the coating thickness about an axis (X- Y) is thicker than the coating about an axis (A-B) orthogonal to (X-Y), and wherein the thickness of the coating about the axis (X-Y), wherein the axis (A-B) is the axis of the direction of movement of the punch used in the press-coating of the tablet.
  • the inventors also assert that the thickness of the coating around or about the axis (A-B) is not critical for controlling the lag time.
  • the core tablet size and also the coating material amount related to release of drug substance are critical controlling the lag time likewise the coating about the axis (X-Y). Because, the lag time depends on the ratio of the coating's and core tablet's surface areas. In addition, the coating's and core tablet's surface areas are related with coating and core tablet weight, respectively. In this aspect, the applicant developed formulations that the coating thickness about an axis (A-B) is thicker than or equal the coating about an axis (X-Y).
  • the thickness of the coating about the axis (A-B) is about 1.85 to about 2.125 mm.
  • the coating thickness either side of the core on the axis (A-B) may or may not be equal.
  • the coating on a first side of the core (A-core) may have a thickness of about 1.80 to 2.00 mm, more preferably 1.95 to 2.05 mm, whereason the other side of the core (B-core) the thickness may be about 1.8 to 1.90 mm, more preferably 1.85 to 1.90 mm.
  • the coating thickness about an axis (A-B) is 1.85mm- 2.125mm and the coating an axis (X-Y) is 1.6-1.9 mm, about 1.75 mm.
  • core tablet shape is round and flat
  • press-coated tablet shape is round and biconvex.
  • the diameter and thickness of core tablet is about 5.5 mm and about 2mm, respectively.
  • the diameter and thickness of press-coated tablet is about 9mm and about 5.85 mm, preferably 5.75-6.25mm respectively.
  • the core tablet size alters the coating material amount needed to targeted lag time.
  • the core tablet size should belarge enough to press and placed precisely in the center of the die. And it should be small enough to require less coating material needed to targeted lag time and also swallow offinal tablet.
  • the present invention also provides for a press-coated tablet having an in vitro dissolution profile which is a median lag time of about 4 hours (3.5 - 4.5 hours) and at least about % 90 of prednisone is released after 5 hours.
  • the present invention provides press-coated tablet comprising a core comprising prednisone and a coating around said core, wherein said core is released drug substance 2-6 hours, preferably 4 hours, after oral administration.
  • the present invention provides press-coated tablet comprising a core comprising prednisone and a coating around said core, wherein said prednisone from 4 to 17 % by weight oftotal core tablet.
  • the weight of the core tablet is 50-80mg, preferably about 60mg.
  • the present invention also provides for a press-coated tablet comprising a core comprising prednisone and a coating around said core, wherein said the amount of coating from 3 to 10 fold, preferably 5-7 fold, more preferably about 6 fold by weight of core tablet.
  • the amount of coating is 300-380mg, preferably 320-360mg, more preferably about 340mg.
  • the core tablet comprising prednisone and a one or more pharmaceutically acceptable excipients selected from the group consisting of diluents, fillers, disintegrants, lubricants, glidants, colorants, or combination thereof.
  • the coating is water ' insoluble or substantially water insoluble, hydrophobic and may contain one or more of the excipients selected from cellulose derivatives such as hydroxypropyl cellulose, hydroxypropylmethyl cellulose, carboxymethyl cellulose, and derivatives thereof; fatty acids or their esters or salts; long chain fatty alcohols; polyoxyethylene alkyl ethers; polyoxyethylene stearates and like.
  • cellulose derivatives such as hydroxypropyl cellulose, hydroxypropylmethyl cellulose, carboxymethyl cellulose, and derivatives thereof
  • fatty acids or their esters or salts long chain fatty alcohols
  • polyoxyethylene alkyl ethers polyoxyethylene stearates and like.
  • hydrophobic excipients for coatings may be selected from any waxy substance known for use as tablet excipients. Preferably they have a HLB value of less than 5, and more preferably about 2.
  • Suitable hydrophobic agents include waxy substances such as carnauba wax, parafin, microcrystalline wax, beeswax, cetyl ester wax and the like; or non-fatty hydrophobic substances such as calcium phosphate salts, e.g. dibasic calcium phosphate.
  • the coating contains a calcium phosphate salt, glyceryl behenate, and polyvinyl pyrollidone, or mixtures thereof, and one or more adjuvants, diluents, lubricants or fillers.
  • Cores are preferably formed according to wet granulation techniques generally known in the art. Prednisone and pharmaceutically acceptable excipients are sieved and blended. Water is then added to the blend and the mixture and the mixture is homogenized to form a granulate, which is then dried to obtain a granulate with requisite residual moisture. Preferably residual moisture content is from 0.8- to 3.0 %by weight. The granulate is then sized by passing it through screens of desired aperture. The obtained granules are lubricated and pressed into tablets.
  • Coating are preferably formed according to wet granulation techniques generally known in the art. Hydrophobic polymer and suitable excipients are mixed and granulated with water. Then granules are dried and sieved. The obtained granules are lubricated and with core tablets pressed into press-coated tablets.
  • the hardness of a press-coated tablet at least 60 Newtons, and more particularly 65 to 75 Newtons.
  • the delayed release prednisone tablets comprise 1 mg to 5mgprednisone.
  • Prednisone Delayed Release Tablet is prepared according to the unit formula below:
  • Prednisone, lactose, polyvinyl pyrrolidone and crospovidone is sieved through a 0.8 mm sieve and prepared for wet granulation by adding water.After the sieving and drying of wet granulates, they are mixed with magnesium stearate and compressed as tablets.
  • glyceryl behenate, polyvinyl pyrrolidone and dibasic calcium hydrogen phosphate is sieved through a 0.8 mm sieve and prepared for wet granulation by adding water. After the sieving and drying of wet granulates, they are mixed with magnesium stearate.
  • Dissolution Medium ' and Method: Water, App. II (Paddle) with sinker, 500 ml_, 100 rpm

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Inorganic Chemistry (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne un comprimé à libération retardée régulée dans le temps comprenant de la prednisone, qui libère l'ingrédient actif du noyau après un temps de latence, ce temps de latence dépendant de la taille du comprimé à noyau, de la quantité de matériau de revêtement et du rapport du matériau de revêtement à la superficie du comprimé à noyau, lesdits comprimés à libération retardée régulée dans le temps étant des comprimés enrobés à la presse comprenant un noyau et un revêtement recouvrant ledit noyau.
PCT/TR2015/000007 2015-01-12 2015-01-12 Comprimé de prednisone à libération retardée régulée dans le temps WO2016114726A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/TR2015/000007 WO2016114726A1 (fr) 2015-01-12 2015-01-12 Comprimé de prednisone à libération retardée régulée dans le temps

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/TR2015/000007 WO2016114726A1 (fr) 2015-01-12 2015-01-12 Comprimé de prednisone à libération retardée régulée dans le temps

Publications (1)

Publication Number Publication Date
WO2016114726A1 true WO2016114726A1 (fr) 2016-07-21

Family

ID=52484542

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/TR2015/000007 WO2016114726A1 (fr) 2015-01-12 2015-01-12 Comprimé de prednisone à libération retardée régulée dans le temps

Country Status (1)

Country Link
WO (1) WO2016114726A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004093843A1 (fr) * 2003-04-24 2004-11-04 Jagotec Ag Comprime a action retardee et a geometrie de noyau definie
WO2013030726A1 (fr) * 2011-08-26 2013-03-07 Wockhardt Limited Diffusion de médicament programmé
US20130243861A1 (en) * 2012-03-16 2013-09-19 Cadila Healthcare Limited Press-coated tablets of prednisone

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004093843A1 (fr) * 2003-04-24 2004-11-04 Jagotec Ag Comprime a action retardee et a geometrie de noyau definie
WO2013030726A1 (fr) * 2011-08-26 2013-03-07 Wockhardt Limited Diffusion de médicament programmé
US20130243861A1 (en) * 2012-03-16 2013-09-19 Cadila Healthcare Limited Press-coated tablets of prednisone

Similar Documents

Publication Publication Date Title
ES2911800T3 (es) Formulaciones de liberación modificada de pridopidina
PT1623703E (pt) Formulações de hidrocodona de libertação controlada
CZ176493A3 (en) Pharmaceutical preparation with controlled release of oxycodon
JP2021038224A (ja) 特に注意欠陥障害の治療のための方法および組成物
EP2187874A2 (fr) Compositions à libération prolongée de trimétazidine et procédé de préparation
US20130243861A1 (en) Press-coated tablets of prednisone
Hadi et al. Formulation and evaluation of mini-tablets-filled-pulsincap delivery of lornoxicam in the chronotherapeutic treatment of rheumatoid arthritis.
AU2017252410A1 (en) Oral pharmaceutical compositions of mesalazine
JP2014196334A (ja) クエチアピンを含む徐放性医薬組成物
AU2016347352B2 (en) Optimised high-dose mesalazine-containing tablet
JP5697668B2 (ja) 口腔内崩壊錠剤
CA3021066C (fr) Compositions pharmaceutiques orales de nicotinamide
KR20000071245A (ko) 활성 물질의 방출이 조절되는 진통제
Moon et al. Formulation and evaluation of press-coated indomethacin tablets for pulsatile drug delivery system
KR20160012706A (ko) 서방성 제제
WO2010084397A2 (fr) Compositions pharmaceutiques solides à libération modifiée à base de trimétazidine et procédé associé
EP2503996A2 (fr) Compositions pharmaceutiques à libération contrôlée de galantamine
KR20090086128A (ko) 메만틴 약학 조성물
RU2411035C2 (ru) Лекарственная форма с модифицированным высвобождением 6-метил-2-этил-3-гидроксипиридина сукцината
WO2016114726A1 (fr) Comprimé de prednisone à libération retardée régulée dans le temps
AU2014295098B2 (en) Anti-tuberculosis stable pharmaceutical composition in a form of a coated tablet comprising granules of isoniazid and granules of rifapentine and its process of preparation
ES2954286T3 (es) Composiciones de piridostigmina de liberación sostenida
WO2015115586A1 (fr) Formulation à libération prolongée
WO2023089553A1 (fr) Formulations à libération contrôlée de flavoxate et procédé de préparation de celles-ci
RU2744270C2 (ru) Прессованный фармацевтический препарат

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: 15705401

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: 15705401

Country of ref document: EP

Kind code of ref document: A1