WO2009143558A1 - Formulations injectables - Google Patents

Formulations injectables Download PDF

Info

Publication number
WO2009143558A1
WO2009143558A1 PCT/AU2009/000646 AU2009000646W WO2009143558A1 WO 2009143558 A1 WO2009143558 A1 WO 2009143558A1 AU 2009000646 W AU2009000646 W AU 2009000646W WO 2009143558 A1 WO2009143558 A1 WO 2009143558A1
Authority
WO
WIPO (PCT)
Prior art keywords
solution
paracetamol
pyrrolidone
analgesic
antipyretic
Prior art date
Application number
PCT/AU2009/000646
Other languages
English (en)
Inventor
Alexander James Kelly
Original Assignee
Silphion Pty 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
Priority claimed from AU2008902603A external-priority patent/AU2008902603A0/en
Application filed by Silphion Pty Limited filed Critical Silphion Pty Limited
Publication of WO2009143558A1 publication Critical patent/WO2009143558A1/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
    • A61K9/0012—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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
    • 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
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A61P29/02—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] without antiinflammatory effect

Definitions

  • the invention described herein relates generally to administration of analgesics and antipyretics by injection.
  • the invention is directed to an injectable formulation comprising the analgesic or antipyretic and a pyrrolidone, although the scope of the invention is not necessarily limited thereto.
  • Analgesics and antipyretics are regularly needed in a hospital environment. It is therefore highly desirable to have these drugs in a stable, soluble, injectable formulation, for rapid intravenous administration, or for intravenous perfusion.
  • One such drug of extensive use is paracetamol and non-steroidal anti-inflammatory drugs (NSAIDs).
  • WO 02/072080 describes the addition of ascorbic acid or a derivative thereof for stabilization of aqueous solutions of paracetamol.
  • EP 0916347 discloses solutions of paracetamol in water and alcoholic solvents, with the addition of metabisulf ⁇ te as antioxidant.
  • Injectable formulations cannot contain the above additives as these present a health risk to many patients due to the potential toxicity of the additives.
  • their stability depends on the exclusion of oxygen and oxidation agents from the aqueous solution, thereby severely restricting their storage options.
  • the invention provides an injectable solution of an analgesic or antipyretic comprising water and a pyrrolidone.
  • the injectable solution can be any practicable concentration.
  • a solution of low volume and high concentration is preferable for injection.
  • Solutions of in the order of Ig/ 1OmL are preferred for formulations of the invention.
  • the solution can be packaged in any practicable manner, for example in type 1 glass vials, ampoules, pre-filled syringes, plastic blow-fill-seal ampoules or other packaging as used for such pharmaceutical preparations.
  • the analgesic or antipyretic can be any such drug, including NSAIDs.
  • the drug is preferably paracetamol.
  • the pyrrolidone can be any pyrrolidone, such as 2-pyrrolidone, but is preferably N- methyl-2-pyrrolidone. These solvents enable the drug to be solubilised at high concentration, and corresponding low volume, which is highly desirable for an injectable solution.
  • the relative concentration of the drug is preferably at least 1:10 w/v.
  • the concentration of the drug is preferably at least 100 mg/mL.
  • the injectable solution of the invention can optionally include excipients such as mannitol, sorbitol, sucrose, glycerol, ethanol, polyethylene glycol and propylene glycol. Addition of the excipients assists with increasing the stability of the high concentration of the drug in the solution, with time and temperature, including at refrigeration temperatures and normal storage temperatures for an injection. Alteration of the solution, including precipitation of the drug, is prevented using the solution of the invention.
  • excipients such as mannitol, sorbitol, sucrose, glycerol, ethanol, polyethylene glycol and propylene glycol.
  • the injectable solution can be administered to a patient in any appropriate manner, including by direct intravenous injection, injection by intravenous push, by continuous (drip) means, by injection of the formulation of the invention into a PCA/pump for automatic treatment or by dilution into a carrying solution for intravenous administration, for example 5% dextrose or isotonic saline.
  • a carrying solution for intravenous administration for example 5% dextrose or isotonic saline.
  • the injectable formulations of the invention are solutions of analgesics and antipyretics, and in particular paracetamol, which are highly concentrated and stable under storage and transportation conditions.
  • the formulations are appropriate for injection as they are non-toxic, highly concentrated, and stable.
  • the invention therefore has provided a significant advance in the area of intravenous pain and fever relief, with the provision of the formulations of the invention.

Abstract

L'invention porte sur des solutions injectables d'un analgésique ou d'un antipyrétique comprenant de l'eau et un pyrrolidone, en particulier sur des solutions injectables hautement concentrées de paracétamol.
PCT/AU2009/000646 2008-05-26 2009-05-25 Formulations injectables WO2009143558A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AU2008902603A AU2008902603A0 (en) 2008-05-26 Injectable Formulations
AU2008902603 2008-05-26

Publications (1)

Publication Number Publication Date
WO2009143558A1 true WO2009143558A1 (fr) 2009-12-03

Family

ID=41376465

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/AU2009/000646 WO2009143558A1 (fr) 2008-05-26 2009-05-25 Formulations injectables

Country Status (1)

Country Link
WO (1) WO2009143558A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20150027160A (ko) * 2012-06-29 2015-03-11 신테티카 에스에이 척추 투여용 과포화 아세타미노펜 주사 용액

Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR920006911B1 (ko) * 1989-06-14 1992-08-22 신풍제약 주식회사 안정한 피록시캄 주사액 조성물 및 그의 제조방법
JPH1029937A (ja) * 1996-05-15 1998-02-03 Kobayashi Seiyaku Kogyo Kk メフェナム酸水溶液製剤
EP1002531A1 (fr) * 1998-01-12 2000-05-24 Panacea Biotec Limited Composition miscible à l'eau d'anti-inflammatoires non stéroidiens
WO2002041899A1 (fr) * 2000-11-27 2002-05-30 Phoenix Scientific, Inc. Preparation antibiotique/analgesique et procede d'elaboration de cette preparation
WO2003097054A1 (fr) * 2002-05-20 2003-11-27 Schering-Plough Ltd. Compositions et procede pour traiter les infections chez le bovin et chez le porc
US20050069591A1 (en) * 2003-09-30 2005-03-31 Howard Bernstein Injectable, oral, or topical sustained release pharmaceutical formulations
WO2007053197A2 (fr) * 2005-06-03 2007-05-10 Elan Pharma International, Limited Preparations nanoparticulaires a base d'acetaminophene

Patent Citations (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR920006911B1 (ko) * 1989-06-14 1992-08-22 신풍제약 주식회사 안정한 피록시캄 주사액 조성물 및 그의 제조방법
JPH1029937A (ja) * 1996-05-15 1998-02-03 Kobayashi Seiyaku Kogyo Kk メフェナム酸水溶液製剤
EP1002531A1 (fr) * 1998-01-12 2000-05-24 Panacea Biotec Limited Composition miscible à l'eau d'anti-inflammatoires non stéroidiens
WO2002041899A1 (fr) * 2000-11-27 2002-05-30 Phoenix Scientific, Inc. Preparation antibiotique/analgesique et procede d'elaboration de cette preparation
WO2003097054A1 (fr) * 2002-05-20 2003-11-27 Schering-Plough Ltd. Compositions et procede pour traiter les infections chez le bovin et chez le porc
US20050069591A1 (en) * 2003-09-30 2005-03-31 Howard Bernstein Injectable, oral, or topical sustained release pharmaceutical formulations
WO2007053197A2 (fr) * 2005-06-03 2007-05-10 Elan Pharma International, Limited Preparations nanoparticulaires a base d'acetaminophene

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
KR20150027160A (ko) * 2012-06-29 2015-03-11 신테티카 에스에이 척추 투여용 과포화 아세타미노펜 주사 용액
KR102118227B1 (ko) 2012-06-29 2020-06-03 신테티카 에스에이 척추 투여용 과포화 아세타미노펜 주사 용액
US11344517B2 (en) 2012-06-29 2022-05-31 Sintetica S.A. Injectable supersaturated acetaminophen solution for spinal administration

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