WO2013151518A1 - Formulations de capsule comprenant du ceftibutène - Google Patents

Formulations de capsule comprenant du ceftibutène Download PDF

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Publication number
WO2013151518A1
WO2013151518A1 PCT/TR2013/000109 TR2013000109W WO2013151518A1 WO 2013151518 A1 WO2013151518 A1 WO 2013151518A1 TR 2013000109 W TR2013000109 W TR 2013000109W WO 2013151518 A1 WO2013151518 A1 WO 2013151518A1
Authority
WO
WIPO (PCT)
Prior art keywords
formulation
formulation according
ceftibuten
agent
range
Prior art date
Application number
PCT/TR2013/000109
Other languages
English (en)
Inventor
Mahmut Bilgic
Original Assignee
Mahmut Bilgic
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 Mahmut Bilgic filed Critical Mahmut Bilgic
Priority to EP13724914.0A priority Critical patent/EP2833874A1/fr
Publication of WO2013151518A1 publication Critical patent/WO2013151518A1/fr

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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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4858—Organic compounds
    • 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
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
    • A61K31/546—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin
    • 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
    • A61K9/4866—Organic macromolecular 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
    • A61K9/14—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
    • A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
    • 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

Definitions

  • the present invention relates to pharmaceutical formulations comprising ceftibuten for use in treatment of upper and lower respiratory tract and urinary system infections. Said formulations are characterized in being in capsule form. Ceftibuten was first disclosed in the application numbered US 4634697.
  • ceftibuten is indicated for infections such as abscesses caused by susceptible bacteria, bronchitis, dermatitis, otitis, empyema, enteritis, gastroenteritis, nasopharyngitis, osteomyelitis, pneumonia, pneumonitis, pustulosis, pyelonephritis, respiratory tract infections, rhinitis, septicemia, tonsillitis, ulcer, urinary system infections, wound and soft tissue infections.
  • infections such as abscesses caused by susceptible bacteria, bronchitis, dermatitis, otitis, empyema, enteritis, gastroenteritis, nasopharyngitis, osteomyelitis, pneumonia, pneumonitis, pustulosis, pyelonephritis, respiratory tract infections, rhinitis, septicemia, tonsillitis, ulcer, urinary system infections, wound and soft tissue infections.
  • Ceftibuten is present in 200 and 400 mg tablet forms on the market.
  • ceftibuten is stabile in dihydrate and trihydrate forms. Furtermore, it is also disclosed in said patents that dihydrate and trihydrate forms of ceftibuten can be filled into hard gelatin capsules for oral administration.
  • ceftibuten formulations are formulated in capsule form, low solubility of the capsules in gastro-intestinal liquid in body and difficulties of dissolution of ceftibuten decreases absorption of the medicine and leads to loss of effectiveness of the treatment. Therefore, there is still need for new approaches in order to develop ceftibuten formulations produced in capsule form which can disperse easily and fast in body, have high absorption and bioavailability during oral use.
  • ceftibuten capsule forms which comprise a composition of at least two different pH agents having high water solubility as pH agent wherein the ratio of the first pH agent to the second pH agent composing this composition is in the range of 1 :5 to 5: 1 by weight disperse easily and fast in body and absorption and thus bioavailability of the drug is high.
  • the present invention relates to capsule formulations comprising ceftibuten and is characterized in that said formulations comprise a composition of at least two different pH agents having high solubility in aqueous solutions and the ratio of the first pH agent to the second pH agent composing this composition is in the range of 1 :5 to 5:1 by weight.
  • the ratio of the first pH agent to the second pH agent in the composition comprising at least two different pH agents is preferably in the range of 1 :3 to 5: 1 , more preferably in the range of 1 :2 to 4: 1 by weight.
  • the first and the second pH agents composing the composition comprising at least two different pH agents having high solubility in aqueous solutions to be used in the formulations of the present invention can be selected from a group comprising tribasic calcium phosphate, monosodium glutamate, potassium citrate, trisodium citrate, sodium hydroxide, dibasic sodium phosphate, monobasic sodium phosphate, disodium hydrogen phosphate, sodium bicarbonate or combinations thereof.
  • the first pH agent in the composition comprising at least two different pH agents having high solubility in aqueous solutions that shall be used in the formulations of the present invention can be disodium hydrogen phosphate.
  • the second pH agent in the composition comprising at least two different pH agents having high solubility in aqueous solutions that shall be used in the formulations of the present invention can be sodium bicarbonate.
  • the ratio of the two different pH agents disodium hydrogen phosphate and disodium sodium bicarbonate having high solubility in aqueous solutions to be used in the formulations of the present invention to each other can be in the range of 1 :5 to 5: 1 , preferably in the range of 1 :3 to 5 : 1 , more preferably in the range of 1 :2 to 4: 1 by weight.
  • the present invention relates to capsule formulations comprising ceftibuten and another characteristic feature of said formulations is that the capsule formulations in which the ceftibuten formulation is filled is prepared from titanium dioxide, gelatin or a combination thereof.
  • Solid dosage forms of the molecule ceftibuten having low water solubility present weak dispersibility and solubility characteristics and this results in decrease in absorption of the drug and thus effectiveness of the treatment.
  • the inventors have observed that capsule formulations comprising ceftibuten present optimum dispersibility and solubility in the case that the ratio of ceftibuten to the pH agent composition comprising at least two different pH agents having high solubility in aqueous solutions is in the range of 1 : 1 to 15:1, preferably in the range of 3: 1 to 10:1.
  • capsule formulations of the present invention comprise at least one pharmaceutically acceptable excipient in addition to ceftibuten and pH agent composition.
  • the pharmaceutically acceptable excipients that can be used in the formulations of the present invention can be selected from a group comprising disintegrant, glidant, lubricant and binder.
  • the disintegrant that can be used in the capsule formulations of the present invention comprising ceftibuten can be selected from a group comprising carboxymethyl cellulose calcium, carboxymethyl cellulose sodium, microcrystalline cellulose, silicon dioxide, croscarmellose sodium, crospovidone, hydroxypropyl cellulose, methylcellulose, povidone, magnesium aluminium silicate, starch.
  • croscarmellose sodium can be used as the disintegrant in the capsule formulations of the present invention comprising ceftibuten.
  • the glidant that can be used in the capsule formulations of the present invention comprising ceftibuten can be selected from a group comprising magnesium silicate, silicon dioxide, colloidal silicon dioxide, starch, talc, tribasic calcium phosphate or a combination thereof.
  • the lubricant that can be used in the capsule formulations of the present invention comprising ceftibuten can be selected form a group comprising calcium stearate, magnesium stearate, sodium stearyl fumarate, polyethylene glycol, PEG 6000, polyvinyl alcohol, potassium benzoate, sodium benzoate.
  • the binder that can be used in the capsule formulations of the present invention comprising ceftibuten can be selected from a group comprising ethyl cellulose, gelatin, hydroxyl ethyl cellulose, hydroxyl methyl cellulose, hydroxyl propyl cellulose, hypromellose, magnesium aluminium silicate, methyl cellulose, povidone.
  • capsule formulations of the present invention comprising ceftibuten
  • said formulations comprise ceftibuten in the range of 5-99%, preferably in the range of 10-95%, more preferably in the range of 30-90% by weight in proportion to total weight of the unit dose amount.
  • ceftibuten in the form of its pharmaceutically acceptable solvates, monohydrate form, dihydrate form, trihydrate form, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms.
  • ceftibuten in the capsule formulations of the present invention comprising ceftibuten, can preferably be in hydrate form, more preferably in dihydrate form.
  • the formulations prepared according to the present invention can comprise 5-25% pH agent, 1-15% binder, 0.5-5% disintegrant, 0.01-0.5% glidant, 0.1-1.5% lubricant by weight in proportion to total weight of the unit dose amount.
  • wet granulation method is used for preparation of the formulation of the present invention.
  • ceftibuten is granulated with the granulation solution and the obtained granules are dried.
  • the pH agent, disintegrant and glidant are added to the sieved granules and they are mixed together.
  • the mixture is sieved again, lubricated adding the lubricant and then filled into capsules.
  • the capsules are blistered and put into cartons.
  • capsule formulations of the present invention comprising ceftibuten are used for production of a medicament effective in treatment of pharyngitis in children and/or adults; tonsillitis, sinusitis, red fever; upper respiratory tract infections such as otitis media in children, acute bronchitis, acute exacerbations of chronic bronchitis in adults; and lower respiratory tract infections such as pneumonia in patients suitable for oral treatment; urinary system infections such as acute and chronic pyelitis, cystopyelitis, cystitis, urethritis in adults and children.
  • the examples below are given in order to explain the pharmaceutical compositions of the present invention and their preparation methods, yet the invention cannot be limited to these.
  • the formulation given above is prepared by using wet granulation method. According to this, ceftibuten dihydrate is granulated with a granulation solution comprising binder. The obtained granules are dried, sieved and mixed with the pH agents, disintegrant and glidant. At the last phase, lubrication is applied with the lubricant and mixture is filled into capsules. Capsules are blistered and put into cartons.

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Preparation (AREA)

Abstract

La présente invention concerne des formulations pharmaceutiques comprenant du ceftibutène destinées à être utilisées dans le traitement d'infections des voies respiratoires supérieures et inférieures et du système urinaire. Lesdites formulations sont caractérisées en ce qu'elles sont sous la forme d'une capsule.
PCT/TR2013/000109 2012-04-04 2013-04-03 Formulations de capsule comprenant du ceftibutène WO2013151518A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP13724914.0A EP2833874A1 (fr) 2012-04-04 2013-04-03 Formulations de capsule comprenant du ceftibutène

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TR2012/03836 2012-04-04
TR201203836 2012-04-04

Publications (1)

Publication Number Publication Date
WO2013151518A1 true WO2013151518A1 (fr) 2013-10-10

Family

ID=48485412

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/TR2013/000109 WO2013151518A1 (fr) 2012-04-04 2013-04-03 Formulations de capsule comprenant du ceftibutène

Country Status (2)

Country Link
EP (1) EP2833874A1 (fr)
WO (1) WO2013151518A1 (fr)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106397457A (zh) * 2016-09-21 2017-02-15 临沂草之美医药科技有限公司 一种治疗外科手术感染的药物头孢布烯晶体化合物
CN106432272A (zh) * 2016-09-21 2017-02-22 临沂草之美医药科技有限公司 一种制备治疗外科手术感染的药物头孢布烯晶体化合物的方法
CN106432271A (zh) * 2016-09-21 2017-02-22 临沂草之美医药科技有限公司 一种治疗外科手术感染的药物头孢布烯晶体化合物
CN106432270A (zh) * 2016-09-21 2017-02-22 临沂草之美医药科技有限公司 一种制备治疗外科手术感染的药物头孢布烯晶体化合物的方法

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4634697A (en) 1983-10-04 1987-01-06 Shionogi & Co., Ltd. Carboxyalkenamidocephalosporins
GB2192183A (en) * 1986-07-02 1988-01-06 Shionogi & Co A crystalline oral cephalosporin hydrate and its compositions
US20080305160A1 (en) * 2004-11-24 2008-12-11 Flamel Technologies Oral Medicament For The Modified Release Of At Least One Active Principle, In Multimicrocapsule Form
US20090258069A1 (en) * 2008-04-15 2009-10-15 John Burnier Delivery of LFA-1 antagonists to the gastrointestinal system

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4634697A (en) 1983-10-04 1987-01-06 Shionogi & Co., Ltd. Carboxyalkenamidocephalosporins
GB2192183A (en) * 1986-07-02 1988-01-06 Shionogi & Co A crystalline oral cephalosporin hydrate and its compositions
US4812561A (en) 1986-07-02 1989-03-14 Shionogi & Co., Ltd. Crystalline hydrate of oral cephalosporin and its composition
US4933443A (en) 1986-07-02 1990-06-12 Shionogi & Co., Ltd. Method for preparing crystalline hydrate of oral celphalosporin and its composition
US20080305160A1 (en) * 2004-11-24 2008-12-11 Flamel Technologies Oral Medicament For The Modified Release Of At Least One Active Principle, In Multimicrocapsule Form
US20090258069A1 (en) * 2008-04-15 2009-10-15 John Burnier Delivery of LFA-1 antagonists to the gastrointestinal system

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN106397457A (zh) * 2016-09-21 2017-02-15 临沂草之美医药科技有限公司 一种治疗外科手术感染的药物头孢布烯晶体化合物
CN106432272A (zh) * 2016-09-21 2017-02-22 临沂草之美医药科技有限公司 一种制备治疗外科手术感染的药物头孢布烯晶体化合物的方法
CN106432271A (zh) * 2016-09-21 2017-02-22 临沂草之美医药科技有限公司 一种治疗外科手术感染的药物头孢布烯晶体化合物
CN106432270A (zh) * 2016-09-21 2017-02-22 临沂草之美医药科技有限公司 一种制备治疗外科手术感染的药物头孢布烯晶体化合物的方法

Also Published As

Publication number Publication date
EP2833874A1 (fr) 2015-02-11

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