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WO2007096900A1 - Composition pharmaceutique stable de taxanes - Google Patents

Composition pharmaceutique stable de taxanes Download PDF

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Publication number
WO2007096900A1
WO2007096900A1 PCT/IN2007/000052 IN2007000052W WO2007096900A1 WO 2007096900 A1 WO2007096900 A1 WO 2007096900A1 IN 2007000052 W IN2007000052 W IN 2007000052W WO 2007096900 A1 WO2007096900 A1 WO 2007096900A1
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WO
WIPO (PCT)
Prior art keywords
solvent
ionic
water
pharmaceutical composition
cremophor
Prior art date
Application number
PCT/IN2007/000052
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English (en)
Inventor
Dinesh Kumar
Santosh Kumar Deolia
Rajeev Kumar Yadav
Rajesh Singh Tomar
Original Assignee
Dabur Pharma 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 Dabur Pharma Limited filed Critical Dabur Pharma Limited
Priority to AU2007219104A priority Critical patent/AU2007219104B2/en
Priority to EP07706195A priority patent/EP1998808A1/fr
Priority to CA2642324A priority patent/CA2642324C/fr
Publication of WO2007096900A1 publication Critical patent/WO2007096900A1/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
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
    • 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
    • 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
    • A61P35/00—Antineoplastic agents

Definitions

  • the present invention relates to a stable pharmaceutical composition of taxanes and a method for preparation thereof.
  • the present invention relates to a stable pharmaceutical composition of Paclitaxel and a method for preparation thereof.
  • the present invention also relates to a non-ionic solvent having a conductivity value of less than or equal to 5.0 micro semens, which is capable of providing a stabilized pharmaceutical composition comprising a taxane and methods for the preparation of such solvents.
  • Taxane derivatives have found wide acceptance for treatment of variety of tumors, especially ovarian cancer, breast cancer, lung cancer, prostate cancer and AIDS related kaposi's sarcoma. Taxanes have also been shown to be effective against other type of cancers, such as melanoma, lymphoma, and those developed in the neck and head.
  • the scientific literature is replete with reports of the efficacy of taxanes in the treatment of variety of unrelated conditions viz. neoplasm in the skin, gastric cancer, polycystic kidney disease etc. Their wide spectrum in vivo activity against malignant tumors has enabled them to be studied as a key therapeutic agent in the treatment of diseases resistant to other anticancer therapies.
  • Taxane derivatives currently in clinical practice include Paclitaxel (Wani MC, et al., JAm Chem Soc, 1971, 9JL 2325-2327) and Docetaxel (US 4,814,470), which are marketed under the brand name of Taxol ® and Taxotere ® respectively.
  • a marketed Taxol ® composition is a solution for injection comprising Paclitaxel, cremophor EL and ethanol in a vial, wherein the concentrated solution must be further diluted with normal saline (NS), 5% dextrose in water (D5W) and 5% dextrose in normal saline (D5NS) prior to administration.
  • a marketed Taxotere ® composition is a solution for injection comprising of Docetaxel and Polysorbate 80. This concentrate is mixed with an initial diluent (13% ethanol in water for injection) supplied in another vial and further diluted with 0.9% sodium chloride or 5% dextrose prior to injection.
  • Cremophor EL is commercially available polyoxyethylated castor oil supplied by M/s BASF. The use of cremophor EL has distinct advantages such as stimulating haemopoiesis reconstituting capacity in mammals and promotes protection in mammals, subjected to anticancer treatments such as radiation and/or chemotherapy, as described by Bertoncello Ivan in WO 91/02531.
  • cremophor EL is not only effective in solubilizing Paclitaxel but also offers a distinct advantage of stimulating haemopoiesis reconstituting capacity, however, its use is associated with certain toxic and hypersensitive reactions, which limits the use of cremophor-paclitaxel formulation in various clinical settings. Further,
  • Paclitaxel precipitates upon dilution with infusion fluid and exhibit a loss of potency of greater than 60% after storage for 12 weeks at 5O 0 C. The loss of potency is attributed to the decomposition of paclitaxel during storage. It was further reported that taxane compositions using crude polyoxyethylated castor oil or Polysorbate as disclosed by
  • cremophor El has other limitations such as presence of high ionic content, metallic and oxidizing impurities, which further destabilizes the paclitaxel in a pharmaceutical composition thereby rendering it unsafe for patient administration.
  • the final pH of the formulation goes invariably to an acidic range, which in turn could cause administration site reactions, thereby further causing patient discomfort.
  • Prescribing information of Taxol ® which has pH in the acidic range, indicates that the said formulation causes injection site reactions in approximately 13% of patients and includes erythema, tenderness, skin discoloration, or swelling at the injection site.
  • the aforementioned methods wherein an acid is added further has the limitation that pH of the formulation needs to be maintained constantly within a range of 4-6. Deviation of pH to higher (alkaline) values, results in degradation of the taxane composition. Thus it provides only a narrow pH range to work on.
  • Zhang et al in WO 2001/072300 disclose a taxane formulation in polyethoxylated castor oil, which is stabilized by addition of a metal salt of an acid.
  • Preferred acids are gluconic acid, amino acid, ascorbic acid, pamitic acid, citric acid, an alpha or beta hydroxy acid, sulfuric acid, hydrochloric acid, hydrobromic acid, hydroiodic acid, hydrofluoric acid, alpha-hydroxy methyl sulfinic acid, benzoic acid, sulfonic acid, and the metal salt is iron, copper, zinc, magnesium, calcium, manganese, aluminum, tin, platinum etc.
  • the carboxylate anion content is lowered by either contacting the cremophor El with an aluminum oxide bed to separate the carboxylate anions as well as other impurities or by the addition of an acid, particularly a mineral acid such as hydrochloric acid or nitric acid to the formulation.
  • an acid particularly a mineral acid such as hydrochloric acid or nitric acid to the formulation.
  • adsorbents such as aluminum oxide
  • adsorbing agents when used for purification of cremophor require critical monitoring for their presence in the final preparation.
  • Theses adsorbing agents if present, even in traces, may have detrimental effect rendering such formulations highly toxic for human administration.
  • use of these adsorbing agents calls for use of specific filters or purification process, which not only makes the entire process complex but also costly. Moreover, needless to mention, this would increase the cost of manufacturing.
  • Kysilka et al in US 2005/0142225 disclose use of a silica gel column to reduce the content of acidic and basic compounds present in polyoxyethylated castor oil for producing a stable taxane composition.
  • Dralle-Voss et al disclose a process for purification of cremophor by treating it with a mixture of adsorbents such as aluminium oxide and silicate.
  • Anevski et al. in US 6,388,112 disclose yet another method for purification of cremophor which involves use of an activated carbon and an ion exchange resin column for reducing the amount of salts, acids and various other ionic impurities present in cremophor.
  • Burman et al in US 2005/0016926 disclose use of reverse-phase chromatography to reduce the ionic, metallic and oxidizing impurities content of the cremophor.
  • James et al in NL 95/00340 disclose a stabilized, pharmaceutically acceptable composition of Paclitaxel and disclose that pre-treatment of the surfactant with a molecular sieve material preferably a porous aluminium oxide that allows a paclitaxel solution having long-term stability to be formed.
  • ionic exchange resin, chromatographic columns or reverse phase column chromatographic technique for the purification of cremophor requires judicious selection of solvent systems, resins and columns.
  • Kang Hoon Seok et al in KR 2000061111 disclose a pharmaceutical composition of paclitaxel injection comprising ethyl acetate fractional extract of cremophor, povidone, polyethylene glycol and assistant emulsifier.
  • the KR 2000061111 discloses that when only ethyl acetate fractional extract of cremophor is utilized in preparation of paclitaxel injection, it showed inferior stability than that of a marketed formulation. In order to improve the stability, use of various vegetable oils or polyethylene glycol ester of mixed fatty acids originated from vegetable oil as assistant solubilizer is recommended.
  • the disclosed method suffers from the limitation that the desired stability is achieved in this method only by addition of various vegetable oils or polyethylene glycol ester of mixed fatty acids originated from vegetable oil as assistant solubilizer. Additions of such extraneous additives are frowned upon by Health authorities, rendering such compositions unacceptable.
  • a stabilized formulation of paclitaxel is obtained either by addition of an extraneous agent such as acidifying, chelating, solubilizing or stabilizing agents into the pharmaceutical composition of paclitaxel in alcohol and cremophor EL or by utilization of a purified cremophor.
  • an extraneous agent such as acidifying, chelating, solubilizing or stabilizing agents
  • the present invention is a step forward in this direction in providing a novel, simple and economical method for a stable taxane composition.
  • An object of the present invention is to provide a stabilized taxane composition suitable for parenteral administration.
  • Another object of the present invention is to provide a stabilized taxane composition suitable for parenteral administration, which avoids addition of any extraneous agents such as stabilizing agents, chelating agents, acidifying agents and co- solubilizing agents for stabilizing taxane formulation.
  • Still another object of the present invention is to provide a stabilized taxane composition suitable for parenteral administration, which utilizes non-ionic solvents, purified by a method, which is simple, convenient, economical and patient friendly.
  • Yet another object of the present invention is to provide a stabilized taxane composition suitable for parenteral administration, which utilizes non-ionic solvents purified by a method free from the limitations associated with the prior art methods.
  • a further object of the present invention is to provide a stabilized paclitaxel composition suitable for parenteral administration.
  • a still further object of the present invention is to provide a stabilized paclitaxel composition suitable for parenteral administration, which avoids addition of any extraneous agents such as stabilizing agents, chelating agents, acidifying agents and co- solubilizing agents for stabilizing the paclitaxel formulation.
  • Yet further object of the present invention is to provide a stabilized paclitaxel composition suitable for parenteral administration, which utilizes non-ionic solvents, purified by a method, which is simple, convenient, economical and patient friendly.
  • Still another object of the present invention is to provide a stabilized paclitaxel composition suitable for parenteral administration, which utilizes non-ionic solvents purified by a method free from the limitations associated with the prior art methods.
  • Yet another object of the present invention is to provide a simple, convenient and economical method for purification of non-ionic solvents, which renders such non- ionic solvents suitable for utilization in manufacture of a stable pharmaceutical composition of taxanes .
  • Yet further object of the present invention is to provide a method for purification of non-ionic solvents, which is free from the limitations associated with the prior art methods.
  • Still further object of the present invention is to provide a method for treatment of cancer comprising administration of such stable formulation of taxane to the human or animal in need of such treatment.
  • the present invention is directed to purification of non-ionic solvents suitable for preparation of stabilized injection compositions containing at least a taxane. Accordingly, it is a primary aspect of the present invention to provide a method for preparing a purified non-ionic solvent, which when used in a taxane composition has a stabilizing effect on such composition.
  • the present invention also provides a method for preparation of a stabilized pharmaceutical composition using such purified non-ionic solvents.
  • the stabilized pharmaceutical compositions produced using the purified non- ionic solvent of the present invention have been shown to have a shelf life greater than the compositions produced from untreated/unpurified non-ionic solvents.
  • solvent extraction technique could be used as a selective separation procedure for isolating and concentrating a valuable, non- ionic, non-polar solvent from impurities present therein, with the aid of a two layer solvent system having an aqueous or polar phase and a non-aqueous or non-polar water-immiscible organic phase.
  • the purification of non-ionic solvents by the method of the present invention utilizing an aqueous and a water-immiscible organic solvent phases involves no critical process steps, and no particular significance need to be given for pH modification of the final formulation, for obtaining a stabilized formulation of taxanes.
  • a stable formulation of paclitaxel can be obtained by utilization of a simple purification technique of cremophor as disclosed herein and utilizing such purified cremophor for preparation of paclitaxel composition, involving neither addition of any extraneous agent such as stabilizing agent, chelating agent, oxidizing agent, preservatives nor adjustment of pH with a pharmaceutically acceptable pH modifier.
  • the commercially available non-ionic solvent is dissolved in a water- immiscible organic solvent, which is then washed with fractions of more polar, aqueous solvent.
  • the two liquid phases are then allowed to separate.
  • the addition of an aqueous phase to an organic phase containing non-ionic solvent selectively removes all impurities leaving behind the pure solvent in the organic phase.
  • the degradation products of paclitaxel include Baccatin II, ethyl ester side chain of paclitaxel, 10-deacetyl paclitaxel (DAP), lO-deacetyl-7-epi-paclitaxel (10-DA-7epi- T) and 7-epi-paclitaxel (7-epi-T). From Table -I, it would be abundantly evident that the formulation of paclitaxel prepared by using cremophor purified by the method of the present invention shows highly superior stability profile in terms of degradation products. Thus, in essence the present invention provides a simple, convenient, less time consuming and economical process for purification of cremophor.
  • the present invention provides a pharmaceutical composition of paclitaxel prepared using such purified cremophor.
  • a pharmaceutical composition of paclitaxel prepared using such purified cremophor.
  • the present invention provides a stabilized taxane composition, particularly a stabilized paclitaxel composition suitable for parenteral administration.
  • the present invention provides a stabilized taxane composition suitable for parenteral administration, which avoids addition of any extraneous agents such as stabilizing agents, chelating agents, acidifying agents and co-solubilizing agents for stabilizing taxane formulation.
  • the present invention provides a stabilized taxane composition suitable for parenteral administration, which utilizes non-ionic solvents, purified by a simple, convenient and economical method, comprising the steps of: a) dissolving the non-ionic solvent in an water-immiscible organic solvent; b) adding an aqueous solvent to the solution of step (a) to form a biphasic system; c) extracting/ selectively partitioning the non-ionic solvent into the organic phase; d) allowing the two immiscible phases to stand; e) separating the aqueous and organic phases; f) optionally, washing the organic phase with the aqueous solvent once more or twice; g) optionally, extracting the combined aqueous phase of step (e) and (f) with the water-immiscible organic solvent; h) combining all the water-immiscible organic phases of steps (e), (f) and (g); and i) evaporating the organic solvent to
  • the present invention provides a stabilized paclitaxel composition suitable for parenteral administration, which avoids addition of any extraneous agents such as stabilizing agents, chelating agents, acidifying agents and co- solubilizing agents for stabilizing the paclitaxel formulation.
  • the present invention provides a stabilized paclitaxel composition suitable for parenteral administration, which utilizes non-ionic solvents, purified by a simple, convenient, economical and patient friendly method, comprising the steps of: a) dissolving the non-ionic solvent in an water-immiscible organic solvent; b) adding an aqueous solvent to the solution of step (a) to form a biphasic system; c) extracting/ selectively partitioning the non-ionic solvent into the organic phase; d) allowing the two immiscible phases to stand; e) separating the aqueous and organic phases; f) optionally, washing the organic phase with the aqueous solvent once more or twice; g) optionally, extracting the combined aqueous phase of step (e) and (f) with the water-immiscible organic solvent; h) combining all the water-immiscible organic phases of steps (e), (f) and (g); and i) evaporating the
  • the present invention provides a method for selectively removing the impurities from non-ionic solvents.
  • the present invention provides a method to obtain a purified non-ionic solvent system, which has a conductivity value of less than or equal to 5.0.
  • the present invention is primarily directed to a method of purification of non- ionic solvents and their utilization in preparation of a stabilized pharmaceutical composition of taxanes.
  • the present invention is directed towards a solvent extraction process comprising two immiscible liquid phases; an aqueous solvent and a water-immiscible organic solvent, which selectively removes the impurities from the non-ionic solvents and results in purified non-ionic solvent, which has reduced conductivity.
  • non-ionic solvent refers to a condensation product of an alkylene oxide and a lipid or fatty acid.
  • the preferred non-ionic solvent includes a polyoxyethylated castor oil such as that sold by M/s BASF under the trade name Cremophor EL ® or Cremophor ELP ® .
  • water-immiscible organic solvent refers to an organic solvent, which is immiscible with water.
  • water-immiscible solvents are, but not limited to, halogentated hydrocarbon solvents such as
  • Dichloromethane Carbon tetrachloride, Chloroform, 1,2-dichloroethane, lower chlorinated alkanes containing 1 to 4 carbon atoms etc. and non-halogenated hydrocarbon solvents such as cyclohexane, n-hexane, n-heptane etc.
  • the hydrocarbon solvents the halogenated hydrocarbon solvents are more preferred and amongst the halogenated hydrocarbon solvents, Dichloromethane is highly preferred.
  • aqueous solvent refers to water containing solvents. Water is a preferred solvent, whereas de-ionized water is more preferred and Milli-Q water of HPLC grade is highly preferred aqueous solvent.
  • conductivity refers to the ability of a solvent to conduct electric current. Since the charge on ions in solution facilitates the conductance of electrical current, the conductivity of a solution is proportional to its ionic concentration. Even though, the conductivity is roughly proportional to the concentration of ions in solution, but all ions do not conduct equally. Ions that move through solution easily conduct better.
  • cremophor Normally, after purifying the crude cremophor by the method described in the present invention, a solution of cremophor in water is prepared. Normally, the ratio of cremophor to water is 10:1 w/w. then the two electrodes are placed in the sample and current flowing through the sample is measured. Normally, at least 25% drop in conductivity is observed.
  • conductivity capacity of the commercially available non-ionic solvents, particularly, cremophor increases on storage.
  • the commercially available cremophor has a conductivity value of at least 5.5, normally in the range of 5.5 to 7.5, which could further increase depending on the storage duration. It was found that, the cremophor purified by the method of the present invention, has a conductivity value of less than or equal to 5 micro Semens.
  • cremophor purified by the method of the present invention produces a stable pharmaceutical composition of paclitaxel.
  • the purified cremophor having a conductivity value in the range of 2.0 to 3.5 are preferred and those having a conductivity values below 2.5 are highly preferred for preparation of a stable pharmaceutical composition of paclitaxel.
  • the process employed for the purification of non-ionic solvents, liquid-liquid extraction process is carried out according to the well-established protocols of liquid extractions. However, standard deviation form this procedure, further enhancing efficiency of liquid-liquid extraction method are possible and therefore, the procedural steps should be not construed as limiting the scope of the invention.
  • the non-ionic solvent is first dissolved in a water- immiscible organic solvent.
  • both, the non-ionic solvent and water-immiscible organic solvent are used in 1:1 ratio.
  • Suitable methods to enhance the dissolution rate such as mixing could be employed to get a uniform solution.
  • Aqueous solvent, preferably Milli-Q water is added to the above uniform solution to form a biphasic system. It is highly preferred to add the aqueous solvent in 1: 1 ratio of water- immiscible organic solvent. Further, stirring or agitation could be employed to effect the extraction of non-ionic solvent in two immiscible liquid phases.
  • a continuous stirring with the help of mechanical stirrer for about 2 to 30 minutes with 10 to 250 rpm is employed to perform the extraction.
  • the biphasic mixture is allowed to stand for phase separation.
  • 12 hrs or more are required to have a clear phase separation at room temperature, when a biphasic system using dichloromethane as water-immiscible organic solvent and Milli-Q water as aqueous solvent is utilized in purification of commercially available cremophor.
  • the two different layers of water- immiscible organic solvent and aqueous solvent are separated.
  • the organic phase is further washed with equal volumes of aqueous solvent once more or twice.
  • the combined aqueous phases obtained during the abovementioned process could further be extracted with equal volumes of water-immiscible organic solvent. Then, all the fractions of water-immiscible organic phases are combined and the organic solvent is evaporated to obtain the purified non-ionic solvent, having a conductivity of below 5.0. The obtained, purified non-ionic solvent is further dried under vacuum at temperature of about 50 0 C to remove residual organic solvents and moisture to obtain a dried, purified non-ionic solvent.
  • the weight ratio of non-ionic solvent to organic phase is 1 :1 and it is further highly preferred that both the liquid phases viz., the aqueous phase and immiscible organic phase are used in 1:1 ratio.
  • the method of the present invention reduces the conductivity of the commercially available cremophor to a value of below 5.0 from an intial value of 5.5 to 7.5, thereby rendering it suitable for preparation of a pharmaceutical composition of paclitaxel.
  • the present invention also provides a pharmaceutically stable formulation of paclitaxel made using a purified non-ionic solvent and alcohol.
  • the stabilized pharmaceutical composition of paclitaxel produced using the non-ionic solvent purified by the method of the present invention has been shown to have a shelf life greater than the compositions produced from commercially available non-ionic solvent.
  • the stabilized formulation of paclitaxel includes an alcohol, which may be added to the non-ionic solvent before or after combining the said solvent with paclitaxel.
  • the alcohol may be a dehydrated alcohol.
  • Compositions suitable for parenteral administration such as injection or infusion may be prepared by diluting the compositions with a suitable parenteral fluid prior to parenteral administration, injection or infusion.
  • each ml contains 6 mg of paclitaxel, and 527 mg of purified cremophor and 49-50% v/v dehydrated alcohol.
  • Example -1 is intended to demonstrate the preferred embodiment of the invention. One skilled in the art will readily recognize that numerous embodiments of the invention can be practiced to achieve the stabilizing effect.
  • Example -1 is intended to demonstrate the preferred embodiment of the invention. One skilled in the art will readily recognize that numerous embodiments of the invention can be practiced to achieve the stabilizing effect.
  • Example -1 is intended to demonstrate the preferred embodiment of the invention. One skilled in the art will readily recognize that numerous embodiments of the invention can be practiced to achieve the stabilizing effect.
  • the obtained cremophor was further dried under vacuum at temperature of about 50 0 C to get the pure and dry cremophor.
  • the obtained pure cremophor is then further subjected to various chemical tests.
  • a comparative analysis of the obtained properties of purified cremophor with that of commercially available cremophor is presented in Table- II.
  • the conductivity was measured with a conductivity meter of Ecoscan (CON-5). The two electrodes are immersed in the non-ionic solvent and a constant voltage is applied to two electrodes and the resulting current is measured.
  • Paclitaxel formulation was prepared by dissolving paclitaxel to get a final concentration of 6 mg/ml in 50:50 v/v mixture of cremophor purified by the method of the present invention and absolute ethanol.
  • a paclitaxel formulation was also prepared similarly, to serve as a control by utilizing commercially available Cremophor and ethanol.
  • Each ml of the prepared formulations contains 6 mg of paclitaxel, and 527 mg of either purified cremophor or commercially available cremophor.

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  • General Chemical & Material Sciences (AREA)
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  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
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Abstract

La présente invention concerne un solvant non ionique de valeur de conductivité inférieure ou égale à 5,0 microsiemens, et permettant d'obtenir une composition pharmaceutique stabilisée qui comprend un taxane. La présente invention concerne également une composition pharmaceutique stable de taxanes ainsi qu'une méthode d'élaboration de ladite composition.
PCT/IN2007/000052 2006-02-21 2007-02-07 Composition pharmaceutique stable de taxanes WO2007096900A1 (fr)

Priority Applications (3)

Application Number Priority Date Filing Date Title
AU2007219104A AU2007219104B2 (en) 2006-02-21 2007-02-07 Stable pharmaceutical composition of taxanes
EP07706195A EP1998808A1 (fr) 2006-02-21 2007-02-07 Composition pharmaceutique stable de taxanes
CA2642324A CA2642324C (fr) 2006-02-21 2007-02-07 Composition pharmaceutique stable de taxanes

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Application Number Priority Date Filing Date Title
IN473DE2006 2006-02-21
IN473/DEL/2006 2006-02-21

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WO2007096900A1 true WO2007096900A1 (fr) 2007-08-30

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EP (1) EP1998808A1 (fr)
AR (1) AR059452A1 (fr)
AU (1) AU2007219104B2 (fr)
CA (1) CA2642324C (fr)
WO (1) WO2007096900A1 (fr)

Cited By (5)

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US7771751B2 (en) 2005-08-31 2010-08-10 Abraxis Bioscience, Llc Compositions comprising poorly water soluble pharmaceutical agents and antimicrobial agents
US7981445B2 (en) 2005-08-31 2011-07-19 Abraxis Bioscience, Llc Compositions and methods for preparation of poorly water soluble drugs with increased stability
US8940786B2 (en) 2012-10-01 2015-01-27 Teikoku Pharma Usa, Inc. Non-aqueous taxane nanodispersion formulations and methods of using the same
CN107929750A (zh) * 2017-12-20 2018-04-20 江苏九旭药业有限公司 一种抗肿瘤的药物组合物及其制备方法与应用
US10842770B2 (en) 2010-05-03 2020-11-24 Teikoku Pharma Usa, Inc. Non-aqueous taxane pro-emulsion formulations and methods of making and using the same

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US4814470A (en) 1986-07-17 1989-03-21 Rhone-Poulenc Sante Taxol derivatives, their preparation and pharmaceutical compositions containing them
WO1999033780A1 (fr) * 1997-12-24 1999-07-08 Schein Pharmaceutical, Inc. Nouvelle huile de ricin polyethoxylee, procede de fabrication et formulations a base de cette derniere
WO2000023070A1 (fr) * 1998-10-20 2000-04-27 Ben Venue Laboratories, Inc. Procede de purification de solvants s'utilisant pour la preparation de compositions pharmaceutiques
WO2004100994A2 (fr) * 2003-05-19 2004-11-25 Ebewe Pharma Ges.M.B.H. Nfg.Kg Procede de preparation d'une composition injectable stable de substances actives antineoplasiques difficilement solubles
US20050016926A1 (en) * 2003-07-24 2005-01-27 Dabur Research Foundation Stabilized formulation
EP1690551A2 (fr) * 2005-02-10 2006-08-16 Sindan Pharma Srl Purification d'un tenside par ultrafiltration

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Publication number Priority date Publication date Assignee Title
US2561330A (en) * 1948-03-25 1951-07-24 Phillips Petroleum Co Process for refining soybean oil
US4814470A (en) 1986-07-17 1989-03-21 Rhone-Poulenc Sante Taxol derivatives, their preparation and pharmaceutical compositions containing them
WO1999033780A1 (fr) * 1997-12-24 1999-07-08 Schein Pharmaceutical, Inc. Nouvelle huile de ricin polyethoxylee, procede de fabrication et formulations a base de cette derniere
WO2000023070A1 (fr) * 1998-10-20 2000-04-27 Ben Venue Laboratories, Inc. Procede de purification de solvants s'utilisant pour la preparation de compositions pharmaceutiques
WO2004100994A2 (fr) * 2003-05-19 2004-11-25 Ebewe Pharma Ges.M.B.H. Nfg.Kg Procede de preparation d'une composition injectable stable de substances actives antineoplasiques difficilement solubles
US20050016926A1 (en) * 2003-07-24 2005-01-27 Dabur Research Foundation Stabilized formulation
EP1690551A2 (fr) * 2005-02-10 2006-08-16 Sindan Pharma Srl Purification d'un tenside par ultrafiltration

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WANI MC ET AL., JAM CHEM SOC., vol. 93, 1971, pages 2325 - 2327

Cited By (10)

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US7771751B2 (en) 2005-08-31 2010-08-10 Abraxis Bioscience, Llc Compositions comprising poorly water soluble pharmaceutical agents and antimicrobial agents
US7981445B2 (en) 2005-08-31 2011-07-19 Abraxis Bioscience, Llc Compositions and methods for preparation of poorly water soluble drugs with increased stability
US8034765B2 (en) 2005-08-31 2011-10-11 Abraxis Bioscience, Llc Compositions and methods for preparation of poorly water soluble drugs with increased stability
US9308180B2 (en) 2005-08-31 2016-04-12 Abraxis Bioscience, Llc Compositions and methods for preparation of poorly water soluble drugs with increased stability
US10842770B2 (en) 2010-05-03 2020-11-24 Teikoku Pharma Usa, Inc. Non-aqueous taxane pro-emulsion formulations and methods of making and using the same
US8940786B2 (en) 2012-10-01 2015-01-27 Teikoku Pharma Usa, Inc. Non-aqueous taxane nanodispersion formulations and methods of using the same
US9308195B2 (en) 2012-10-01 2016-04-12 Teikoku Pharma Usa, Inc. Non-aqueous taxane formulations and methods of using the same
US9763880B2 (en) 2012-10-01 2017-09-19 Teikoku Pharma Usa, Inc. Non-aqueous taxane formulations and methods of using the same
CN107929750A (zh) * 2017-12-20 2018-04-20 江苏九旭药业有限公司 一种抗肿瘤的药物组合物及其制备方法与应用
CN107929750B (zh) * 2017-12-20 2021-06-08 江苏九旭药业有限公司 一种抗肿瘤的药物组合物及其制备方法与应用

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CA2642324A1 (fr) 2007-08-30
EP1998808A1 (fr) 2008-12-10

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