WO2016120746A1 - Composition pharmaceutique comprenant du roflumilast - Google Patents

Composition pharmaceutique comprenant du roflumilast Download PDF

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Publication number
WO2016120746A1
WO2016120746A1 PCT/IB2016/050221 IB2016050221W WO2016120746A1 WO 2016120746 A1 WO2016120746 A1 WO 2016120746A1 IB 2016050221 W IB2016050221 W IB 2016050221W WO 2016120746 A1 WO2016120746 A1 WO 2016120746A1
Authority
WO
WIPO (PCT)
Prior art keywords
pharmaceutical composition
roflumilast
maize starch
composition according
lactose monohydrate
Prior art date
Application number
PCT/IB2016/050221
Other languages
English (en)
Inventor
Pankaj Sharad MANDPE
Vikas Dinanath YANDE
Sandip Ashok PAWAR
Original Assignee
Micro Labs Limited
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 Micro Labs Limited filed Critical Micro Labs Limited
Publication of WO2016120746A1 publication Critical patent/WO2016120746A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • 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
    • A61K9/2013—Organic compounds, e.g. phospholipids, fats
    • A61K9/2018—Sugars, or sugar alcohols, e.g. lactose, mannitol; Derivatives thereof, e.g. polysorbates
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4858—Organic compounds

Definitions

  • the present invention relates to a pharmaceutical composition comprising Roflumilast.
  • the present invention provides a pharmaceutical composition in the form of a tablet or a capsule comprising Roflumilast and pharmaceutically acceptable excipients and a process for preparing the same.
  • Background of the invention :
  • COPD chronic obstructive pulmonary disease
  • chronic bronchitis is an inflammation of the lining of bronchial tubes. Emphysema occurs when the air sacs (alveoli) at the end of the smallest air passages (bronchioles) in the lungs are gradually destroyed.
  • Roflumilast is a pharmaceutical agent that is used to treat severe exacerbations caused by COPD. It is a phosphodiesterase type 4 inhibitor, commonly referred to as a PDE4 inhibitor. It blocks the degradative action of PDE4 on cyclic adenosine monophosphate (cAMP). cAMP acts as a messenger which is responsible for many biological processes. Roflumilast exerts its effect on the body by its active metabolite
  • Roflumilast N-(3, 5- dichloropyridin-4-yl)-3-cyclopropylmethoxy-4-difluoromethoxy-benzamide. Its empirical formula is C17H CI2F2N2O3 and the molecular weight is 403.22.
  • the chemical structure is:
  • Roflumilast N-oxide 3-(Cyclopropylmethoxy)- N-(3, 5-dichloro-1 -oxido-4-pyridinyl)-4-(difluoromethoxy) benzamide; N-(3,5- Dichloro -1 -oxopyridin-4-yl)-4-difluoromethoxy-3-cyclopropyl- methoxy benzamide and the chemical structure is:
  • ROFLUMILAST N-OXIDE Roflumilast is available as Daliresp® tablets (by Forest
  • Daliresp® contains the following inactive ingredients: Lactose monohydrate, corn starch, povidone and magnesium stearate.
  • US5712298 discloses Roflumilast generically.
  • US8431 154 discloses a dosage form of Roflumilast for oral administration in the form of a tablet or pellet form which is prepared using the aqueous solution of polyvinyl pyrrolidone.
  • US20130345265 discloses a dosage form of Roflumilast along with excipients like polyvinyl pyrrolidone, lactose, corn starch and magnesium stearate.
  • WO2013030789 discloses dosage form of Roflumilast with pharmaceutically acceptable excipients wherein the binder is selected from a saccharide, protein or synthetic polymer.
  • Roflumilast poorly water soluble drug like Roflumilast which can be economical.
  • the present inventors have developed a pharmaceutical composition comprising Roflumilast along with pharmaceutically acceptable excipients like maize starch, lactose monohydrate, hydroxypropyl cellulose and magnesium stearate wherein the weight ratio of maize starch to lactose is 1 :1 to 2:1 .
  • the present invention relates to a pharmaceutical composition comprising Roflumilast.
  • the present invention relates to a pharmaceutical composition
  • a pharmaceutical composition comprising Roflumilast along with pharmaceutically acceptable excipients like maize starch, lactose monohydrate, hydroxypropylcellulose and magnesium stearate wherein the weight ratio of maize starch to lactose is 1 :1 to 2:1 .
  • the pharmaceutical composition is in the form of a tablet or a capsule.
  • the pharmaceutical composition comprises lactose monohydrate with typical particle size distribution wherein
  • the pharmaceutical composition comprises maize starch wherein particle size of maize starch is between 1 ⁇ to 500 ⁇ .
  • the pharmaceutical composition comprises roflumilast in an amount of 0.1 %-1 .4% by weight, lactose in an amount of 15%-60% by weight, hydroxypropylcellulose in an amount of 1 .5%-3.5% by weight, maize starch in an amount of 25%-75% by weight and magnesium stearate in an amount of 0.5%-2% by weight.
  • a process for preparing a pharmaceutical composition comprising the steps of:
  • step (c) granulating the dry mix of step (b) with the solution prepared in step (a) to form granules;
  • the present invention relates to a pharmaceutical composition comprising Roflumilast.
  • a pharmaceutical composition denotes a composition which shows immediate release.
  • active ingredient (used interchangeably with “active” or “active substance” or “drug”) as used herein includes Roflumilast or its pharmaceutically acceptable salt.
  • pharmaceutically acceptable inert excipients denotes any of the components of a pharmaceutical composition other than the active and which are approved by regulatory authorities or are generally 'regarded as safe' for human or animal use.
  • a pharmaceutical composition comprises roflumilast and pharmaceutically acceptable excipients like maize starch, lactose monohydrate, hydroxypropylcellulose and magnesium stearate wherein the weight ratio of maize starch to lactose is 1 :1 to 2:1 .
  • inert excipients examples include, but are not limited to diluents, lubricants, binders, wetting agents, antifoaming agents, solvents and plasticizers. A combination of excipients may also be used. The amount of excipient(s) employed will depend upon how much active agent is to be used. One excipient can perform more than one function.
  • Binders include, but are not limited to, starches such as potato starch, wheat starch, corn starch (maize starch); microcrystalline cellulose such as products known under the registered trademarks Avicel, Filtrak, Heweten or Pharmacel; celluloses such as hydroxypropyl cellulose, hydroxyethyl cellulose, hydroxypropyl methylcellulose (HPMC), ethyl cellulose, sodium carboxymethylcellulose; natural gums like acacia, alginic acid, guar gum; liquid glucose, dextrin, povidone, syrup, polyethylene oxide, polyvinylpyrrolidone, poly-N-vinyl amide, polyethylene glycol, gelatin, poly propylene glycol, tragacanth and other materials known to one ordinarily skilled in the art and mixtures thereof.
  • starches such as potato starch, wheat starch, corn starch (maize starch); microcrystalline cellulose such as products known under the registered trademarks Avicel, Filtrak, Heweten or Pharmacel
  • Hydroxypropyl cellulose is nonionic water-soluble cellulose ether. It combines organic solvent solubility, thermoplasticity and surface activity with the aqueous thickening and stabilizing properties. Hydroxypropyl cellulose is available in various grades with corresponding varying viscosities and molecular weights. Depending on the necessity of the composition, suitable grade of hydroxypropyl cellulose can be incorporated.
  • Diluents which include, but are not limited to confectioner's sugar, compressible sugar, dextrates, dextrin, dextrose, fructose, lactitol, mannitol, sucrose, starch, lactose, xylitol, sorbitol, talc, microcrystalline cellulose, calcium carbonate, calcium phosphate dibasic or tribasic, calcium sulphate and other materials known to one ordinarily skilled in the art and mixtures thereof.
  • Lubricants may be selected from, but are not limited to, those conventionally known in the art such as Mg, Al or Ca or Zn stearate, polyethylene glycol, glyceryl behenate, mineral oil, sodium stearyl fumarate, stearic acid, hydrogenated vegetable oil, talc and other materials known to one ordinarily skilled in the art and mixtures thereof.
  • Glidants include, but are not limited to, silicon dioxide; magnesium trisilicate, powdered cellulose, starch, talc and tribasic calcium phosphate, calcium silicate, magnesium silicate, colloidal silicon dioxide, silicon hydrogel and other materials known to one ordinarily skilled in the art and mixtures thereof.
  • Solvents include, but are not limited to purified water, acetone, ethyl alcohol, isopropyl alcohol dichloromethane and other materials known to one ordinarily skilled in the art and mixtures thereof.
  • additives there is considerable overlap between the above-listed additives in common usage, since a given additive is often classified differently by different practitioners in the field, or is commonly used for any of several different functions.
  • the above-listed additives should be taken as merely exemplary, and not limiting, of the types of additives that can be included in compositions of the present invention.
  • One or more of these additives can be selected and used by the skilled artisan having regard to the particular desired properties of the dosage form by routine experimentation without any undue burden.
  • the amount of each type of additive employed may vary within ranges conventional in the art.
  • the extended release pharmaceutical composition is in form of a tablet or a capsule.
  • tablet or a capsule include tablet, capsules, pills, granules, tablets in capsules, caplets, mini- tablets or a combination thereof.
  • the pharmaceutical composition comprises lactose monohydrate with typical particle size distribution wherein (a) 50%-65% particles are smaller than 45 ⁇ ;
  • Lactose monohydrate is a white, almost white crystalline powder freely but soluble in water, practically insoluble in ethanol. Particle size distribution can be determined by various methods like Sieve analysis, Microscopy, Laser diffraction method, sedimentation techniques and many more.
  • the pharmaceutical composition comprises maize starch wherein particle size of maize starch is between 1 ⁇ to 500 ⁇ .
  • Starch occurs as an odorless and tasteless, fine, white to off-white powder. It consists of very small spherical or ovoid granules or grains whose size and shape are characteristic for each botanical variety.
  • the pharmaceutical composition comprises roflumilast in an amount of 0.1 %-1 .4% by weight, lactose in an amount of 15%-60% by weight, hydroxypropylcellulose in an amount of 1 .5%-3.5% by weight, maize starch in an amount of 25%-75% by weight and magnesium stearate in an amount of 0.5%-2% by weight.
  • a process for preparing a pharmaceutical composition comprising the steps of:
  • step (c) granulating the dry mix of step (b) with the solution prepared in step (a) to form granules;
  • Example 1 Pharmaceutical composition comprising Roflumilast
  • step (c) Solution of step (b) was added into solution of step (a) under continuous stirring.
  • Granules obtained in step 3 were lubricated with magnesium stearate & the mixture was compressed.

Abstract

La présente invention concerne une composition pharmaceutique comprenant du roflumilast. En particulier, la présente invention concerne une composition pharmaceutique sous la forme d'un comprimé ou d'une capsule comprenant du roflumilast et des excipients pharmaceutiquement acceptables et un procédé de préparation de ceux-ci.
PCT/IB2016/050221 2015-01-29 2016-01-18 Composition pharmaceutique comprenant du roflumilast WO2016120746A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN299/MUM/2015 2015-01-29
IN299MU2015 2015-01-29

Publications (1)

Publication Number Publication Date
WO2016120746A1 true WO2016120746A1 (fr) 2016-08-04

Family

ID=56542538

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2016/050221 WO2016120746A1 (fr) 2015-01-29 2016-01-18 Composition pharmaceutique comprenant du roflumilast

Country Status (1)

Country Link
WO (1) WO2016120746A1 (fr)

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003070279A1 (fr) * 2002-02-20 2003-08-28 Altana Pharma Ag Forme posologique orale contenant un inhibiteur de type 4 de pde en tant qu'ingredient actif et du polyvinylpyrrolidone en tant qu'excipient
US8067395B2 (en) * 2006-01-13 2011-11-29 Pharmacyclics, Inc. Inhibitors of tyrosine kinases and uses thereof

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003070279A1 (fr) * 2002-02-20 2003-08-28 Altana Pharma Ag Forme posologique orale contenant un inhibiteur de type 4 de pde en tant qu'ingredient actif et du polyvinylpyrrolidone en tant qu'excipient
US8067395B2 (en) * 2006-01-13 2011-11-29 Pharmacyclics, Inc. Inhibitors of tyrosine kinases and uses thereof

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