WO1994012198A1 - Injectable taxol composition - Google Patents

Injectable taxol composition Download PDF

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Publication number
WO1994012198A1
WO1994012198A1 PCT/AU1993/000599 AU9300599W WO9412198A1 WO 1994012198 A1 WO1994012198 A1 WO 1994012198A1 AU 9300599 W AU9300599 W AU 9300599W WO 9412198 A1 WO9412198 A1 WO 9412198A1
Authority
WO
WIPO (PCT)
Prior art keywords
acid
solution
taxol
injectable
composition according
Prior art date
Application number
PCT/AU1993/000599
Other languages
English (en)
French (fr)
Inventor
Robyn Louise Elliott
Gregory Paul Handreck
David Carver
Timothy Prout
Hernita Ewald
Original Assignee
F.H. Faulding & Co. 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 F.H. Faulding & Co. Limited filed Critical F.H. Faulding & Co. Limited
Priority to AU55538/94A priority Critical patent/AU5553894A/en
Publication of WO1994012198A1 publication Critical patent/WO1994012198A1/en

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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • 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
    • A61K47/06—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
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • 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
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin

Definitions

  • Taxol is a compound extracted from the bark of a western yew, Taxus brev ⁇ folxa and known for its antineoplastic activity. It is described for example in the Merck Index, Eleventh Edition 1989, monograph 9049.
  • taxol was chosen for development as an antineoplastic agent because of its unique mechanism of action and good cytotoxic activity against IP. implanted bl6 melanoma and the human MX-1 mammary tumor xenograft. Taxol is believed to function as a mitotic spindle poison and as a potent inhibitor of cell replication in vitro. Other mitotic spindle poisons (colchicine and podophyllotoxin) inhibit microtubule assembly. Taxol employs a different mechanism of action since it appears to shift the equilibrium of polymerization/depolymerization toward polymer assembly and to stabilize microtubules against depolymerization under conditions which would cause rapid disaggregation of microtubules.
  • taxol entered clinical trials in 1983. Over the past few years, taxol has demonstrated good response rates in treating both ovarian and breast cancer patients who were not benefiting from vinca alkaloid or cisplatin therapy. It has also shown encouraging results in patients with other types of cancer including lung, melanoma, lymphoma, head and neck.
  • NCI National Cancer Institute
  • a known formulation contains taxol, cremophor EL (a polyethoxylated castor oil which acts as a solubilizer) and ethanol. It is a disadvantage of the known formulation that the taxol therein degrades, unless stored at or below 8°C, with the result that the shelf life of the formulation is unsatisfactory, and there is therefore a need for a taxol solution of improved stability.
  • cremophor EL a polyethoxylated castor oil which acts as a solubilizer
  • the invention provides a solution containing taxol, a pharmaceutically acceptable solubilising agent (for example a polyethoxylated castor oil), and a pharmaceutically acceptable organic solvent (such as ethanol), characterized in that the pH of the solution has been adjusted to a pH less than 8.1, preferably into the range 1 to 8 by addition of an acid.
  • a pharmaceutically acceptable solubilising agent for example a polyethoxylated castor oil
  • a pharmaceutically acceptable organic solvent such as ethanol
  • Acids in the form of powders for example citric acid, are preferred over those which contain water, for example sulphuric acid.
  • the most preferred acid for use in accordance with the present invention is anhydrous citric acid but a wide range of acids may be used including the following: Citric acid - Monohydrous
  • taxol Due to its limited solubility in water, taxol is usually prepared and administered in a vehicle containing cremophor EL (a polyethoxylated castor oil which acts as a solubiliser) and ethanol.
  • a solution prepared by the formulation as stated in the NCI Taxol Clinical brochure has a pH of 9.1.
  • the invention essentially teaches addition of an acid to a taxol formulation to adjust its pH into the range below 8.1, preferably 1 to 8, and more preferably 5 to 7.5.
  • Citric acid was dissolved in ethanol (absolute alcohol), using a ratio of 8 mis of absolute alcohol to 1 gram of citric acid, and the solution was stirred for fifteen (15) minutes.
  • Cremophor EL was weighed out into the main mixing vessel.
  • Solution 1 was added to solution 2, and the container used for solution 2 was washed with a minimum quantity of absolute alcohol to ensure complete transfer of the citric acid.
  • Solution 3 was mixed and bubbled with nitrogen for at least 15 minutes.
  • the taxol was weighed out and slurried using absolute alcohol, using a ratio of 8 ml of absolute alcohol to 1 gm of taxol.
  • the slurried taxol was added to solution 3 and the slurrying vessel was washed with a minimum quantity of absolute alcohol.
  • Solution 3 was adjusted to 75% of required volume using absolute alcohol, and thoroughly stirred for at least 45 minutes until completely dissolved. Once completely dissolved, the volume was made up with absolute alcohol and the final solution stirred for 5 minutes.
  • Citric Acid (Anhydrous) 2.O g Taxol 6.Omg Absolute Alcohol to 1.0OmL
  • Cremophor EL 0.5mL Taxol 6mg
  • the solution was filled into clear type 1 glass 5mL vials and sealed with rubber bungs.
  • the solution was stored at 40°C for 7 days.
  • citric acid which is preferably used in the anhydrous form, at pH 5 to 7.5, the formulation at pH 6.1 showing the lowest levels for both total and individual major impurities.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Dermatology (AREA)
  • Medicinal Preparation (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
PCT/AU1993/000599 1992-11-27 1993-11-25 Injectable taxol composition WO1994012198A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU55538/94A AU5553894A (en) 1992-11-27 1993-11-25 Injectable taxol composition

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
AUPL607492 1992-11-27
AUPL6074 1992-11-27

Publications (1)

Publication Number Publication Date
WO1994012198A1 true WO1994012198A1 (en) 1994-06-09

Family

ID=3776561

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/AU1993/000599 WO1994012198A1 (en) 1992-11-27 1993-11-25 Injectable taxol composition

Country Status (8)

Country Link
KR (1) KR100371062B1 (enrdf_load_stackoverflow)
CN (2) CN1096673A (enrdf_load_stackoverflow)
AU (1) AU5553894A (enrdf_load_stackoverflow)
IL (2) IL107776A0 (enrdf_load_stackoverflow)
IN (1) IN176188B (enrdf_load_stackoverflow)
NZ (1) NZ258044A (enrdf_load_stackoverflow)
WO (1) WO1994012198A1 (enrdf_load_stackoverflow)
ZA (1) ZA938844B (enrdf_load_stackoverflow)

Cited By (20)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2710534A1 (fr) * 1994-09-28 1995-04-07 Bristol Myers Squibb Co Solvant de stabilisation, composition pharmaceutique le contenant, et son procédé de préparation.
EP0674510A4 (en) * 1992-11-27 1995-08-12 Napro Biotherapeutics Inc INJECTABLE COMPOSITION.
NL9500340A (nl) * 1995-02-22 1996-10-01 Yew Tree Pharmaceuticals B V Gestabiliseerde paclitaxel-oplossing en farmaceutisch preparaat dat deze oplossing bevat.
ES2095802A1 (es) * 1993-09-29 1997-02-16 Bristol Myers Squibb Co Composicion farmaceutica estabilizada y solvente de estabilizacion.
US5686488A (en) * 1995-08-25 1997-11-11 Alcon Laboratories, Inc. Polyethoxylated castor oil products as anti-inflammatory agents
WO1997041850A1 (en) * 1996-05-02 1997-11-13 Yeong Wook Song Paclitaxel for the treatment of rheumatic diseases
WO1998053810A1 (en) * 1997-05-30 1998-12-03 Man Woo Han Pharmaceutical injection solution containing taxol
WO1998057630A1 (fr) * 1997-06-13 1998-12-23 Laboratoires Thissen (L.T.B.) Forme pharmaceutique pour l'administration de paclitaxel, procede de preparation d'une composition de paclitaxel prete a l'emploi et utilisation de cette composition
EP0876145A4 (en) * 1995-12-21 1999-04-21 Genelabs Tech Inc TAX COMPOSITION AND PROCEDURE
US6045808A (en) * 1997-01-31 2000-04-04 Pharmacia & Upjohn Company Method for removing high boiling solvents from drug formulations by vacuum drying
WO2000032186A3 (en) * 1998-12-02 2000-11-16 Mylan Pharmaceuticals Inc Stabilized injectable pharmaceutical compositions containing taxoid anti-neoplastic agents
KR100330373B1 (ko) * 1996-05-28 2002-11-07 주식회사한국신약 탁솔을 함유한 주사용 약제 조성물
KR100358934B1 (ko) * 1996-09-13 2003-01-29 주식회사한국신약 탁솔을함유한주사용약제조성물
WO2003022247A1 (en) * 2001-09-10 2003-03-20 Choongwae Pharma Corporation Injectable composition of paclitaxel
US6919370B2 (en) 2000-11-28 2005-07-19 Transform Pharmaceuticals, Inc. Pharmaceutical formulations comprising paclitaxel, derivatives, and pharmaceutically acceptable salts thereof
JP2005534656A (ja) * 2002-06-10 2005-11-17 プリヴァ−ラチェマ アー．エス． ポリオキシエチル化ひまし油に基づく安定化医薬組成物およびその製造方法
EP1904052A4 (en) * 2005-06-17 2008-12-10 Hospira Australia Pty Ltd LIQUID PHARMACEUTICAL COMPOSITIONS OF DOCATEXEL
JP2012072188A (ja) * 2002-06-26 2012-04-12 Medigene Ag 脂肪親和性化合物を含む陽イオン性リポソームの製法
US9308180B2 (en) 2005-08-31 2016-04-12 Abraxis Bioscience, Llc Compositions and methods for preparation of poorly water soluble drugs with increased stability
US11529441B2 (en) 2015-09-15 2022-12-20 W. L. Gore & Associates, Inc. Drug composition and coating

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19536165A1 (de) * 1995-09-28 1997-04-03 Basf Ag Verfahren zur Reinigung von alkoxylierten Fetten
CN1101677C (zh) * 1997-05-30 2003-02-19 韩万愚 含有紫杉醇的药用注射溶液
DE10115740A1 (de) * 2001-03-26 2002-10-02 Ulrich Speck Zubereitung für die Restenoseprophylaxe
CN101396354B (zh) * 2007-09-30 2010-12-01 江苏恒瑞医药股份有限公司 一种稳定的塔三烷类化合物液体组合物及其制备方法和其应用
CN101829051B (zh) * 2010-05-31 2012-09-12 南昌弘益科技有限公司 1’-乙酰氧基胡椒酚乙酸酯注射液
CN103432109B (zh) * 2013-09-01 2015-09-23 吴静 紫杉醇的药物组合物

Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1990010443A1 (en) * 1989-03-09 1990-09-20 University Of Kansas Derivatives of taxol, pharmaceutical compositions thereof and methods for the preparation thereof
EP0428376A1 (en) * 1989-11-14 1991-05-22 Florida State University Method for preparation of taxol using an oxazinone
EP0505047A1 (en) * 1991-03-18 1992-09-23 Virginia Tech Intellectual Properties, Inc. Rearranged taxol compounds and method of using in testing of in vivo activity
US5157049A (en) * 1988-03-07 1992-10-20 The United States Of America As Represented By The Department Of Health & Human Services Method of treating cancers sensitive to treatment with water soluble derivatives of taxol
AU1888792A (en) * 1991-04-19 1992-11-17 University Of Mississippi, The Methods and compositions for isolating taxanes

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2601675B1 (fr) * 1986-07-17 1988-09-23 Rhone Poulenc Sante Derives du taxol, leur preparation et les compositions pharmaceutiques qui les contiennent
NZ224497A (en) * 1987-05-18 1990-04-26 Janssen Pharmaceutica Nv Pharmaceutical composition comprising flunarizine

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5157049A (en) * 1988-03-07 1992-10-20 The United States Of America As Represented By The Department Of Health & Human Services Method of treating cancers sensitive to treatment with water soluble derivatives of taxol
WO1990010443A1 (en) * 1989-03-09 1990-09-20 University Of Kansas Derivatives of taxol, pharmaceutical compositions thereof and methods for the preparation thereof
EP0428376A1 (en) * 1989-11-14 1991-05-22 Florida State University Method for preparation of taxol using an oxazinone
EP0505047A1 (en) * 1991-03-18 1992-09-23 Virginia Tech Intellectual Properties, Inc. Rearranged taxol compounds and method of using in testing of in vivo activity
AU1888792A (en) * 1991-04-19 1992-11-17 University Of Mississippi, The Methods and compositions for isolating taxanes

Cited By (32)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1500393A1 (en) * 1992-11-27 2005-01-26 Mayne Pharma (USA) Inc. Injectable composition containing taxol
EP0674510A4 (en) * 1992-11-27 1995-08-12 Napro Biotherapeutics Inc INJECTABLE COMPOSITION.
US6306894B1 (en) 1992-11-27 2001-10-23 Napro Biotherapeutics, Inc. Injectable composition
EP1384474A1 (en) * 1992-11-27 2004-01-28 Napro Biotherapeutics, Inc. Injectable composition containing taxol
US6140359A (en) * 1992-11-27 2000-10-31 Napro Biotherapeutics, Inc. Injectable composition
EP0835657A1 (en) * 1992-11-27 1998-04-15 Napro Biotherapeutics, Inc. Injectable composition
US5977164A (en) * 1992-11-27 1999-11-02 Napro Biotherapeutics, Inc. Stabilized pharmaceutical composition
US5972992A (en) * 1992-11-27 1999-10-26 Napro Biotherapeutics, Inc. Injectable composition
ES2095802A1 (es) * 1993-09-29 1997-02-16 Bristol Myers Squibb Co Composicion farmaceutica estabilizada y solvente de estabilizacion.
FR2710534A1 (fr) * 1994-09-28 1995-04-07 Bristol Myers Squibb Co Solvant de stabilisation, composition pharmaceutique le contenant, et son procédé de préparation.
NL9500340A (nl) * 1995-02-22 1996-10-01 Yew Tree Pharmaceuticals B V Gestabiliseerde paclitaxel-oplossing en farmaceutisch preparaat dat deze oplossing bevat.
US5686488A (en) * 1995-08-25 1997-11-11 Alcon Laboratories, Inc. Polyethoxylated castor oil products as anti-inflammatory agents
EP0876145A4 (en) * 1995-12-21 1999-04-21 Genelabs Tech Inc TAX COMPOSITION AND PROCEDURE
WO1997041850A1 (en) * 1996-05-02 1997-11-13 Yeong Wook Song Paclitaxel for the treatment of rheumatic diseases
KR100330373B1 (ko) * 1996-05-28 2002-11-07 주식회사한국신약 탁솔을 함유한 주사용 약제 조성물
KR100358934B1 (ko) * 1996-09-13 2003-01-29 주식회사한국신약 탁솔을함유한주사용약제조성물
US6045808A (en) * 1997-01-31 2000-04-04 Pharmacia & Upjohn Company Method for removing high boiling solvents from drug formulations by vacuum drying
WO1998053810A1 (en) * 1997-05-30 1998-12-03 Man Woo Han Pharmaceutical injection solution containing taxol
WO1998057630A1 (fr) * 1997-06-13 1998-12-23 Laboratoires Thissen (L.T.B.) Forme pharmaceutique pour l'administration de paclitaxel, procede de preparation d'une composition de paclitaxel prete a l'emploi et utilisation de cette composition
BE1011216A3 (fr) * 1997-06-13 1999-06-01 Thissen En Abrege L T B Lab Forme pharmaceutique pour l'administration de paclitaxel, procede de preparation d'une composition de paclitaxel prete a l'emploi et utilisation de cette composition.
WO2000032186A3 (en) * 1998-12-02 2000-11-16 Mylan Pharmaceuticals Inc Stabilized injectable pharmaceutical compositions containing taxoid anti-neoplastic agents
US6919370B2 (en) 2000-11-28 2005-07-19 Transform Pharmaceuticals, Inc. Pharmaceutical formulations comprising paclitaxel, derivatives, and pharmaceutically acceptable salts thereof
KR100774366B1 (ko) * 2001-09-10 2007-11-08 주식회사 중외제약 파클리탁셀 주사제 조성물
US7186751B2 (en) 2001-09-10 2007-03-06 Choongwae Pharma Corporation Injectable composition of paclitaxel
WO2003022247A1 (en) * 2001-09-10 2003-03-20 Choongwae Pharma Corporation Injectable composition of paclitaxel
JP2005534656A (ja) * 2002-06-10 2005-11-17 プリヴァ−ラチェマ アー．エス． ポリオキシエチル化ひまし油に基づく安定化医薬組成物およびその製造方法
JP2012072188A (ja) * 2002-06-26 2012-04-12 Medigene Ag 脂肪親和性化合物を含む陽イオン性リポソームの製法
EP1904052A4 (en) * 2005-06-17 2008-12-10 Hospira Australia Pty Ltd LIQUID PHARMACEUTICAL COMPOSITIONS OF DOCATEXEL
EP2138164A1 (en) * 2005-06-17 2009-12-30 Hospira Australia Pty Ltd Liquid pharmaceutical formulations of docetaxel
EP2308467A3 (en) * 2005-06-17 2011-06-22 Hospira Australia Pty Ltd Liquid pharmaceutical formulations of docetaxel
US9308180B2 (en) 2005-08-31 2016-04-12 Abraxis Bioscience, Llc Compositions and methods for preparation of poorly water soluble drugs with increased stability
US11529441B2 (en) 2015-09-15 2022-12-20 W. L. Gore & Associates, Inc. Drug composition and coating

Also Published As

Publication number Publication date
IL107776A0 (en) 1994-02-27
AU5196793A (en) 1994-06-09
KR100371062B1 (ko) 2003-04-21
AU5553894A (en) 1994-06-22
AU667142B2 (en) 1996-03-07
NZ258044A (en) 1995-12-21
CN1095266A (zh) 1994-11-23
IN176188B (enrdf_load_stackoverflow) 1996-02-24
CN1096673A (zh) 1994-12-28
ZA938844B (en) 1994-08-02
CN1047305C (zh) 1999-12-15
IL126178A0 (en) 1999-05-09

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