EP2976063A1 - Préparation parentérale d'agent antibactérien à base de fluoroquinolone et procédé de préparation associé - Google Patents

Préparation parentérale d'agent antibactérien à base de fluoroquinolone et procédé de préparation associé

Info

Publication number
EP2976063A1
EP2976063A1 EP14722987.6A EP14722987A EP2976063A1 EP 2976063 A1 EP2976063 A1 EP 2976063A1 EP 14722987 A EP14722987 A EP 14722987A EP 2976063 A1 EP2976063 A1 EP 2976063A1
Authority
EP
European Patent Office
Prior art keywords
pharmaceutical composition
composition according
propylene glycol
aqueous
moxifloxacin
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.)
Withdrawn
Application number
EP14722987.6A
Other languages
German (de)
English (en)
Inventor
Evamgelos KARAVAS
Efthimios Koutris
Vasiliki SAMARA
Ioanna Koutri
Athina Iliopoulou
George GOTZAMANIS
Morfis Abatzis
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.)
Pharmathen SA
Original Assignee
Pharmathen SA
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 Pharmathen SA filed Critical Pharmathen SA
Publication of EP2976063A1 publication Critical patent/EP2976063A1/fr
Withdrawn legal-status Critical Current

Links

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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents

Definitions

  • the present invention relates to an aqueous pharmaceutical formulation comprising a fluoroquinolone antibacterial agent such as Moxifloxacin or pharmaceutical acceptable salt thereof and an effective amount of a tonicity agent such as propylene glycol, in order to achieve appropriate osmolality of the solution.
  • a fluoroquinolone antibacterial agent such as Moxifloxacin or pharmaceutical acceptable salt thereof
  • a tonicity agent such as propylene glycol
  • Parenteral routes of administration can have significant advantages over oral delivery in some situations.
  • Parenteral administration routes result in a higher blood serum concentration in a shorter amount of time, when compared to oral administration of the same drug.
  • the expected drug serum concentration can be more predictable and the dose can be much lower than other routes of administration because of elimination of loss" of the drug due to metabolism, binding to food and other drugs.
  • This method of administration is preferred in emergency situations and when subjects being treated are unconscious, uncooperative, or unwilling to accept oral medication.
  • Intravenous administration in which the medication is directly administered into the vein of the patient either by injection or infusion, is a very common method of parenteral administration.
  • the whole amount of drug can either be injected directly into the vein, or it can be infused over a longer period of time.
  • Active ingredients that are administered intravenously are almost always in the form of an aqueous solution, therefore the active ingredient needs to be characterized by sufficient water solubility.
  • Sufficient water solubility means that the quantity of the active ingredient necessary for successful treatment can be dissolved completely in the aqueous medium to be administered to the patient. Poorly or very poorly water soluble active ingredients can only be administered to the patient by other methods of administration as the volume of aqueous medium required to dissolve them would be no longer suitable for intravenous administration. In addition, miscibility of the administered solution with the patient's blood is another prerequisite for an active ingredient to be administered by intravenous administration, otherwise the patient runs the risk of severe-embolism or severe necrosis.
  • Moxifloxacin is an antibiotic from the class of quinolones carboxylic acids of the following formula:
  • EP 1 225898B1 claims an aqueous formulation comprising Moxifloxacin hydrochloride, xanthan gum as tonicity agent and an amount of a water soluble calcium salt.
  • Another object of the present invention is to provide an aqueous pharmaceutical formulation comprising a fluoroquinolone antibacterial agent such as Moxifloxacin or pharmaceutical acceptable salt thereof for parenteral use that effectively address issues related to the solubility of the active substance, stability of the dosage form as well as physiological acceptability by the patient.
  • a fluoroquinolone antibacterial agent such as Moxifloxacin or pharmaceutical acceptable salt thereof
  • a further approach of the present invention is to provide a method for the preparation of an aqueous pharmaceutical formulation comprising a fluoroquinolone antibacterial agent such as Moxifloxacin or pharmaceutical acceptable salt thereof that deals with the major consideration of sterility when manufacturing dosage forms for parenteral administration.
  • a fluoroquinolone antibacterial agent such as Moxifloxacin or pharmaceutical acceptable salt thereof
  • an aqueous pharmaceutical formulation comprising a fluoroquinolone antibacterial agent such as Moxifloxacin or pharmaceutical acceptable salt thereof as an active ingredient and an effective amount of a pharmaceutically acceptable tonicity agent such as propylene glycol, in order to achieve adequate osmolality of the pharmaceutical dosage form.
  • a fluoroquinolone antibacterial agent such as Moxifloxacin or pharmaceutical acceptable salt thereof
  • a pharmaceutically acceptable tonicity agent such as propylene glycol
  • a process for the preparation of an aqueous pharmaceutical formulation comprising a fluoroquinolone antibacterial agent such as Moxifloxacin or pharmaceutical acceptable salt thereof, which comprises:
  • parenteral administration is non-enteral or non-oral and, therefore, includes all products administered other than by the oral route.
  • the parenteral composition of the present invention is injectable or infusible and is administered via the intravenous (IV), subcutaneous or intramuscular route.
  • IV intravenous
  • a parenteral composition should have a pH close to physiological levels. However, most of the products have a pH value that is a compromise between physiological acceptability, solubility of the active substance and stability of the finished dosage form. Thus, great majority of the marketed products have a pH of between 2 and 12. Additionally, a parenteral product should have an osmolality of between 240mOsm/L to 340mOsm/L in order to be isotonic.
  • the present invention provides an aqueous parenteral formulation comprising from 0.1% (w/v) to 0.2% (w/v) (on dry bases) of Moxifloxacin hydrochlorideand 1.5% (w/v) to 2.0% (w/v) of propylene glycol. "% (w/v)" is the weight in gr per 100ml of volume, unless otherwise stated.
  • the present invention provides an aqueous pharmaceutical formulation comprising a fluoroquinolone antibiotic agent of the class such as Moxifloxacinand salts thereof for parenteral use having a pH value of from 4 to 5.
  • a fluoroquinolone antibiotic agent of the class such as Moxifloxacinand salts thereof for parenteral use having a pH value of from 4 to 5.
  • This pH value provides the optimum area where the active pharmaceutical ingredient dissolves but also can be by human body without any irritation or pain associated with the administration.
  • the present invention provides a process for preparing the aqueous pharmaceutical formulation of Moxifloxacin or salt thereof by dissolving the total amount of active ingredient in water for injection and propylene glycol is then added and dissolved.
  • Containers suitable in accordance with the present invention refer to containers which do not interact chemically with the solution for injection in any way to alter the strength, quality, or purity beyond the official requirements under the ordinary conditions of handling, shipment, storage, sale and use.
  • aqueous pharmaceutical compositions were prepared using different tonicity agents.
  • the process used for manufacturing was the same for all of them and comprised the steps of:
  • composition 1 was stored in stability chambers in long term conditions (25°C/60%RH) and in accelerated conditions (40oC/75%RH) in the final package (glass vial and butyl rubber stopper).
  • composition 1 for parenteral administration. Additionally, there were no particles or sedimentation observed in that period and the microbiological test confirmed the sterility of the product.

Abstract

La présente invention concerne une préparation pharmaceutique aqueuse de moxifloxacine, ou d'un sel de qualité pharmaceutique de celui-ci, et de propylène glycol à utiliser pour le traitement d'infections chez les humains ou les animaux. La présente invention concerne également un procédé de conception d'une telle préparation.
EP14722987.6A 2013-03-14 2014-03-13 Préparation parentérale d'agent antibactérien à base de fluoroquinolone et procédé de préparation associé Withdrawn EP2976063A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GR20130100156A GR1008168B (el) 2013-03-14 2013-03-14 Παρεντερικο σκευασμα αντιβακτηριακου παραγοντα φθοριοκινολονης και μεθοδος για την παρασκευη αυτου
PCT/EP2014/000668 WO2014139677A1 (fr) 2013-03-14 2014-03-13 Préparation parentérale d'agent antibactérien à base de fluoroquinolone et procédé de préparation associé

Publications (1)

Publication Number Publication Date
EP2976063A1 true EP2976063A1 (fr) 2016-01-27

Family

ID=50687438

Family Applications (1)

Application Number Title Priority Date Filing Date
EP14722987.6A Withdrawn EP2976063A1 (fr) 2013-03-14 2014-03-13 Préparation parentérale d'agent antibactérien à base de fluoroquinolone et procédé de préparation associé

Country Status (3)

Country Link
EP (1) EP2976063A1 (fr)
GR (1) GR1008168B (fr)
WO (1) WO2014139677A1 (fr)

Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110319502A1 (en) * 2010-06-25 2011-12-29 Coffey Martin J Compositions and Methods for Enhancing Reduction of Spore-Forming Microorganisms

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3906365A1 (de) 1988-07-15 1990-01-18 Bayer Ag 7-(1-pyrrolidinyl)-3-chinolon- und -naphthyridoncarbonsaeure-derivate, verfahren sowie substituierte (oxa)diazabicyclooctane und -nonane als zwischenprodukte zu ihrer herstellung, und sie enthaltende antibakterielle mittel und futterzusatzstoffe
IL109626A0 (en) * 1993-05-15 1994-08-26 Abbott Lab Stable quinolone and naphthydridine premix formulations
JPH0782141A (ja) * 1993-09-17 1995-03-28 Tanabe Seiyaku Co Ltd 動物用注射剤
DE19937116A1 (de) 1999-08-06 2001-02-08 Bayer Ag Moxifloxacin Kochsalzformulierung
CN1384745A (zh) 1999-11-01 2002-12-11 爱尔康公司 含有一种氟喹诺酮抗生素和黄原酸胶的药物组合物
US6872723B2 (en) * 2002-01-28 2005-03-29 Wyeth Stabilized difloxacin injectable solution
US20070197548A1 (en) * 2006-02-17 2007-08-23 Murthy Yerramilli V S Fluoroquinolone compositions
DE102006010642A1 (de) * 2006-03-08 2007-09-27 Bayer Healthcare Aktiengesellschaft Arzneimittelformulierungen, enthaltend Fluorchinolone
CA2660151C (fr) * 2006-08-07 2012-04-17 Bausch & Lomb Incorporated Compositions et procedes pour traiter, controler, reduire ou ameliorer les infections et les sequelles de celles-ci
JPWO2008044734A1 (ja) * 2006-10-12 2010-02-18 杏林製薬株式会社 ガチフロキサシン含有水性液剤
BRPI0818483A2 (pt) * 2007-11-01 2015-04-14 Bausch & Lomb Método para preparar uma composição farmacêutica, composição farmacêutica, e, uso da mesma.

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20110319502A1 (en) * 2010-06-25 2011-12-29 Coffey Martin J Compositions and Methods for Enhancing Reduction of Spore-Forming Microorganisms

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See also references of WO2014139677A1 *

Also Published As

Publication number Publication date
WO2014139677A1 (fr) 2014-09-18
GR1008168B (el) 2014-04-08

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